Dr Rajiv Desai

An Educational Blog

ALLERGY

ALLERGY:

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Prologue:

Medical representatives of pharmaceutical industry frequently visit doctors to promote their products and shower doctors with drug samples, gifts and tours. One medical representative gifted me a perfume to promote his new product. I do not use perfumes. However, human mind is curious and when a perfume was given to me as a gift, I thought why not use it. Two weeks after using perfume, I developed itching skin rash over my body known as ‘Urticaria’ and dermatologist diagnosed it as allergy to perfume. The priciest perfumes and skin care products can cause allergic reactions because of the chemicals that give them their scent. In one fragrance, there may be as many as 26 allergens. The figure above shows urticarial skin rash in another patient. Allergy is not a disease but a mechanism which may play a role in a number of disorders. You can be allergic to anything right from water to semen, from pollen to fruits and from milk to alcohol. It is estimated that 30-40% of the world population is now affected by one or more allergic conditions. A high proportion of the increase in allergic disease is in young people. In the near future, the burden of allergic diseases is expected to greatly increase as these patients become adults. Complex allergies involving polysensitization and multiple organ involvement are increasing in prevalence, with a high morbidity placing a higher demand on health care delivery services. Allergies can cause a broad spectrum of disease with symptoms ranging from mildly irritating to extremely debilitating and even fatal. On average, someone with allergic disorders experiences a quality of life 35 percent less than the general population.   

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Allergic diseases are common, and their prevalence is increasing. Accurate diagnosis of triggering or causative allergens is essential for appropriate advice for avoidance and environmental control measures. Although allergic diseases can occur at almost any age, some allergies are most likely to develop for the first time in particular age groups. Allergy to environmental agents can affect almost every organ of the body. Although allergic rhinitis is the commonest manifestation, the lower respiratory tract, the conjunctiva, the skin, and the gastrointestinal tract are frequently affected by allergic disease. Common causes of allergy symptoms include food allergies such as peanut allergy or milk allergy, and seasonal allergies resulting from grass, weed, tree pollen, or various molds. Cat allergies and dog allergies can also cause miserable symptoms such as itchy eyes, sneezing, nasal congestion, and wheezing. Allergic skin conditions can cause a rash and itchy skin. Allergic disease is estimated to affect around 15-20% of the population of the western world, with a two- to three-fold increase being seen in the past 20-30 years (Royal College of Physicians, 2003). It is a condition that has a huge impact on the lives of those who experience it. Allergic diseases have risen dramatically during the last decades. They represent a major health problem and may affects up to one third of the whole population. While increasing pollution is considered to be one of the reasons, there are theories that growing up in cleaner and more germ free atmospheres could be responsible for the over-reactivity of the immune system to generally harmless foreign proteins.

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Allergies are among the most common of medical disorders. It is estimated that more than one in every five people suffer from some form of allergy throughout the world. Numerically this is more than heart disease, diabetes, and cancer combined. If left untreated, allergies can lead to impaired quality of life, including sleep disturbances and missed days of school or work. Allergy is the single largest reason for school absence and is a major source of lost productivity in the workplace. About 30,000 Americans per year go to the emergency room due to severe allergic reactions to food, and as many as 200 die every year from food allergies, according to the Food Allergy and Anaphylaxis Network. 

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The Asthma and Allergy Foundation (AAFA) states allergies affect 60 million Americans, is the fifth leading chronic disease in the U.S., and the third leading among children. More than 40 million people have indoor/outdoor allergies as their primary allergy. More than 17 million people visit their doctor for allergies annually. Up to 6 percent of the general population suffers from an allergy to latex, and children with spina bifida who have had multiple surgical procedures are at higher risk for allergic reactions to latex. Atopic dermatitis is one of the most common skin conditions and occurs commonly in infants and children, and its prevalence in the United States is about 10 percent. Food allergies occur in 8 percent of children aged six years and younger. Peanut or other nut allergies affect about 3 million Americans and produce the most severe reactions. Acute allergic hives affect from 10 percent to 20 percent of Americans at some time during their lifetime, and half of those affected have symptoms for more than six months. Allergies to stinging insects occur in about 3.5 percent of Americans.

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In the United Kingdom a quarter of individuals suffer from an allergy at some time in their lives and many of these are children. This number is on the rise. A recent review of UK epidemiological data has revealed that there has been an inexorable rise in the prevalence of allergic disorders. Allergic pathophysiology can cause a spectrum of diseases in individuals, which may vary in severity. Atopy – a tendency to produce the IgE antibody in response to low doses of aeroallergens – is known to increase risk of developing allergic disorders such as food allergy, atopic eczema/dermatitis, allergic rhinitis and asthma. Data from blood measurements taken as part of the Health Survey for England in 2001 revealed that 42% of boys and 24% of girls aged 11–15 years were sensitive to the house dust mite (HDM) allergen (≥0.4kU/l HDM specific IgE) indicating the very high proportion of young people who are at high risk of manifesting allergic problems.

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Cost of allergy:

Allergies and their complications are expensive. According to the Asthma and Allergic Foundation of America (2002) allergies are the sixth largest cause of chronic disease in the United States. Yearly, allergies cost an estimated $18 Billion to the U.S.  The economic cost of allergic disease in Australia is estimated to be $9.4 billion from direct and indirect cost of medical care and loss of income and reduced productivity, with an additional $21.3 billion from lost wellbeing (disability and premature death).  

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Hypersensitivity:

Hypersensitivity causes objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus that is tolerated by normal subjects. When the term is used without context, it means immune hypersensitivity.

Non-allergic hypersensitivity:

Non-allergic hypersensitivity is the preferred term to describe hypersensitivity in which immunological mechanisms cannot be proven.  

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Definition of allergy: 

An allergy is a hypersensitivity disorder of the immune system.  Allergic reactions occur when a person’s immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen.  Allergy is one of four forms of hypersensitivity and is formally called type I (or immediate) hypersensitivity. Allergic reactions are distinctive because of excessive activation of certain white blood cells called mast cells and basophils by a type of antibody called Immunoglobulin E (IgE). This reaction results in an inflammatory response which can range from uncomfortable to dangerous. There is no consensus among medical researchers and immunologists regarding definition of allergy. Some may call allergy as any hypersensitive immunological reaction to foreign substance no matter whether it is mediated by IgE or not, and no matter whether it is immediate hypersensitivity or delayed hypersensitivity. In non-IgE-mediated allergy the antibody can belong to the IgG isotype, eg, anaphylaxis due to immune complexes containing dextran, and serum sickness. Both IgE and IgG antibodies are found in allergic bronchial pulmonary aspergillosis (ABPA). Allergic contact dermatitis is representative of allergic diseases mediated by lymphocytes (type 4 hypersensitivity).

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Allergies are an overreaction of the body’s immune system to specific substances that it misidentifies as harmful. This overreaction of the body’s immune system is known as an allergic reaction and the substances that cause it are called allergens. Allergic reaction can be provoked by skin contact with poison plants, chemicals and animal scratches, as well as by insect stings. Ingesting or inhaling substances like pollen, animal dander, molds and mildew, dust, nuts and shellfish, may also cause allergic reaction. Medications such as penicillin and other antibiotics are also to be taken with care, to assure an allergic response is not triggered. Whatever the allergen, allergic reaction symptoms can be miserable, ranging from a runny nose and watery eyes to breathing problems, diarrhea, hives, and even death.  

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An allergy is an adverse reaction to a protein in our environment, such as those found on pets, and in pollen or nuts. These proteins are called allergens and are normally harmless. In people with an allergy, the body reacts to a specific allergen by releasing histamine from mast cells in the skin, lungs, nose or intestine. This causes inflammation and swelling.  Symptoms can include itchy skin, tissue swelling and wheezing. In severe cases it can lead to full-blown anaphylaxis or even death. Common allergic diseases include hay fever, asthma, eczema and urticaria. In most cases, treatment is available to successfully manage or treat allergy symptoms. Severe allergic reaction such as anaphylaxis requires urgent medical attention.

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Age when certain allergies are likely to occur for first time:  

  • Neonates—Atopic dermatitis, food allergies (milk, egg, nuts)
  • Early childhood—Asthma (house dust mite, pets)
  • Teenagers—Allergic rhinitis (grass and tree pollens)
  • Early adulthood—Urticaria, angio-oedema (aspirin intolerance)
  • Adulthood—Allergy to venom (bee, wasp); nasal polyps

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Children and adolescents with allergies are not equally sensitive to all allergens. Some may have severe allergic rhinitis but no food allergies, for instance, or be extremely sensitive to nuts but not to any other food. Allergies may get worse over time. For example, childhood ragweed allergy may progress to dust and pollen allergy. On the other hand, a child may outgrow allergic sensitivity. Infant or childhood atopic dermatitis disappears in almost all people. More commonly, what seems to be loss of sensitivity is instead a reduced exposure to allergens or an increased tolerance for the same level of symptoms.

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History of allergy:

The concept of “allergy” was originally introduced in 1906 by the Viennese pediatrician Clemens von Pirquet, after he noted that some of his patients were hypersensitive to normally innocuous entities such as dust, pollen, or certain foods. Pirquet called this phenomenon “allergy” from the Ancient Greek words allos meaning “other” and ergon meaning “work”. He proposed that the term should apply to the ‘uncommitted’ biological response which in the individual may lead either to immunity (which is beneficial) or allergic disease (which is harmful). All forms of hypersensitivity used to be classified as allergies, and all were thought to be caused by an improper activation of the immune system. Later, it became clear that several different disease mechanisms were implicated, with the common link to a disordered activation of the immune system. In 1963, a new classification scheme was designed by Philip Gell and Robin Coombs that described four types of hypersensitivity reactions, known as Type I to Type IV hypersensitivity. With this new classification, the word “allergy” was restricted to type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions. A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled immunoglobulin E (IgE) – Kimishige Ishizaka and co-workers were the first to isolate and describe IgE in the 1960s.This binds to the surface of special large cells (mast cells), stimulating them to secrete histamine, serotonin, and prostaglandins. These are the chemicals that produce the allergic reactions such as inflammation of the nasal membranes in hay fever or the contraction of the tubes leading to the lungs which causes asthma. Such responses include the classic allergic disorders of asthma, eczema, hay fever and urticaria. These disorders may be triggered by pollen, house dust, fungi, drugs, air pollutants, and some food constituents. The specific allergy-causing substance (allergen) provokes an immunological reaction in skin-prick tests.

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Epidemiology:

Many diseases related to inflammation such as type 1 diabetes, rheumatoid arthritis, and allergic diseases — hay fever and asthma — have increased in the Western world over the past 2-3 decades. Rapid increases in allergic asthma and other atopic disorders in industrialized nations, it is estimated, began in the 1960s and 1970s, with further increases occurring during the 1980s and 1990s, although some suggest that a steady rise in sensitization has been occurring since the 1920s. The incidence of atopy in developing countries has, in general, remained much lower. Although genetic factors fundamentally govern susceptibility to atopic disease, increases in atopy have occurred within too short a time frame to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes. Several hypotheses have been identified to explain this increased prevalence; increased exposure to perennial allergens due to housing changes and increasing time spent indoors, and changes in cleanliness or hygiene that have resulted in the decreased activation of a common immune control mechanism, coupled with dietary changes, obesity and decline in physical exercise. The hygiene hypothesis maintains that high living standards and hygienic conditions expose children to fewer infections. It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away from TH1 type responses, leading to unrestrained TH2 responses that allow for an increase in allergy. Changes in rates and types of infection alone however, have been unable to explain the observed increase in allergic disease, and recent evidence has focused attention on the importance of the gastrointestinal microbial environment. Evidence has shown that exposure to food and fecal-oral pathogens, such as hepatitis A, Toxoplasma gondii, and Helicobacter pylori (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%, and an increased prevalence of parasitic infections has been associated with a decreased prevalence of asthma. It is speculated that these infections exert their effect by critically altering TH1/TH2 regulation. Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm. [Hygiene hypothesis-vide infra]

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Immune system:

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The figure below shows overview of immune system response to foreign substance.

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The immune system, which can be further divided into innate or adaptive sections, is the body’s key mechanism of defense against infection, but also the system responsible for pathological allergic reactions to harmless substances. Because the immune system can easily damage cells it is important to limit the response to just those things which are harmful to the body, and prevent the immune system attacking harmless substances as in allergic reactions. Both the innate and adaptive immune systems play a role in allergy, which occurs as a result of sensitization to harmless substances in the environmental (e.g. dust and pollen), and hypersensitive reactions upon subsequent exposure to these particles.

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The figure below shows overview of innate & adaptive immune system.

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Innate immune system:

The innate (also called non-specific) immune system acts in response to all foreign particles entering the body and involves:

•Epithelial barriers (skin and mucous membranes which line the bodies cavities including the nose, mouth and bowel);

•Body encasements such as the scull and thoracic cage which protect the internal organs from exposure to pathogens;

•Inflammatory responses involving proteins produced by body cells which mount an attack on pathogens which enter the body.

While anatomical barriers of the innate immune system can be seen with the naked eye, the innate immune system also functions at the cellular and molecular level. Important cells and molecules involved in innate immune responses include:

•Phagocytic cells which are white blood cells and include neutrophils, eosinophils and macrophages. These cells are attracted to foreign pathogens in the body by inflammation and remove harmful pathogens in the blood by ingesting them;

•Inflammatory mediators including basophils and mast cells. These cells regulate the body’s inflammatory responses and signal the body to mount an inflammatory response if a foreign particle invades. The inflammatory response catalyses other immune responses, such as activation of phagocytic cells;

•Natural killer cells which are also involved in adaptive immune processes. In the innate immune system these cells recognize cells under stress or invasion from pathogens and binds to them. The natural killer cells are capable of inducing apoptosis (death, or the last phase of the cell cycle) in the stressed cells and the pathogens they contain; and

•Immune Molecules including complement proteins and cytokines. These Molecules are produced by the cells of the human body but also influence responses of the immune system. For example, pro-inflammatory cytokines are pro-inflammatory stimulate inflammatory processes and anti-inflammatory cytokines inhibits inflammatory process.

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Adaptive immune system:

The adaptive immune system is typically involved in immune responses to bacteria, bacterial toxins and virus antigens. It involves the production of antibodies (also called immunoglobulins) against a specific target as well as effector T cells to neutralize the invading foreign agent. Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies (immunoglobulins) that destroy substances containing antigens. The adaptive immune response is specific. For example, an antibody produced to mount an attack on the bacteria salmonella will only attack salmonella and not other types of bacteria.  

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The figure below is an overview of factors influencing immune system.

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Lymphocytes are a fundamental component of the immune system, and when they make a mistake it can create an allergic response.

There are two types of lymphocytes:

  • B-lymphocytes (B-cells)
  • T-lymphocytes (T-cells)

Both types help guard your body against foreign substances such as invading bacteria, viruses and toxins. They move freely through and among the tissues of the body, travel through the walls of blood vessels, and move between the various lymph nodes and lymph channels. B-cells and T-cells go everywhere. Lymphocytes act like traveling customs agents. Everywhere they go, they are busy checking the passports of every cell they encounter. Whenever they discover a cell that seems threatening, they immediately begin countermeasures against it. The biochemical process behind these countermeasures is amazing! B cells produce antibodies, which are proteins that bind to and destroy or neutralize antigens. T cells do not produce antibodies; instead, they produce cytokines — soluble molecules mediating interaction between cells. T cells also bind directly to an antigen and initiate an attack on it by ‘presenting’ parts of it to B cells, to stimulate antibody production.

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Allergic Threats:

When a lymphocyte encounters a particle or cell with surface marker molecules that identify it as a foreign invader, it performs a microscopic version of taking fingerprints and mug shots of the invader. Because these foreign invaders cause the production of antibodies, they are called antibody generators, or antigens. After a B-cell identifies an antigen, it will make its way back to a lymph node, change into a plasma cell and produce antibodies specifically engineered to fight that particular threat.

There are five basic types of antibodies, called immunoglobulins, or Igs. Each is classified by type with a letter suffix:

  • IgA
  • IgD
  • IgE
  • IgG
  • IgM

The Ig responsible for allergic reactions is IgE.

 In a properly functioning immune system, the genetic code contains enough information to enable the lymphocytes to distinguish between threatening and non-threatening proteins. In an allergic person’s immune system, the lymphocytes can’t tell that the protein ingested as part of a meal containing shellfish isn’t invading the body. The B-cells of an allergic person — “misinformed” at the genetic level — cause the production of large quantities of IgE antibodies that attach themselves to mast cells and basophils throughout the body. This is known as the sensitizing exposure (vide infra).

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The job of the antibodies is to detect and help destroy substances that cause disease and sickness. An allergic reaction is the body’s way of responding to an “invader.” When the body senses a foreign substance, called an antigen, the immune system is triggered. The immune system normally protects the body from harmful agents such as bacteria and toxins. Its overreaction to a harmless substance (an allergen) is called a hypersensitivity reaction, or an allergic reaction. In allergic reactions, the antibody is called immunoglobulin E or IgE. This antibody promotes production and release of chemicals and hormones called “mediators.” Mediators have effects on local tissue and organs in addition to activating more white blood cell defenders. It is these effects that cause the symptoms of the reaction. Histamine is one of the better-known mediators produced by the body. If the release of the mediators is sudden or extensive, the allergic reaction may also be sudden and severe, and anaphylaxis may occur. Bee stings, fire ant stings, penicillin, and peanuts are known for causing dramatic reactions that can be serious and involve the whole body. Minor injuries, hot or cold temperatures, exercise, stress, or emotions may trigger allergic reactions. Often, the specific allergen cannot be identified unless you have had a similar reaction in the past. Allergies and the tendency to have allergic reactions run in some families.  Many people who have one trigger tend to have other triggers as well. People with certain medical conditions are more likely to have allergic reactions.

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The figure below shows overview of main mechanisms of allergies and their diseases:

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Allergic reactions:

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The figure below shows algorithm of immune hypersensitivity. The classical allergy is immediate hypersensitivity mediated by IgE but some researchers also include non-IgE mediated hypersensitivity as allergy. 

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Is Allergy = Hypersensitivity reaction mediated by immunological mechanisms?

The term allergy can be used quite broadly, to include contact hypersensitivity responses, such as to poison ivy or detergents. Such reactions do not develop immediately in sensitized subjects but hours or a few days after exposure to the antigen. These are examples of ‘delayed hypersensitivity reactions’, in which T lymphocytes (which must be recruited to sites of antigen challenge) are actively involved. In its most narrow usage, the term allergy refers to immune responses in which IgE antibodies play an important part. People with such allergies can experience reactions within minutes of allergen challenge. It’s not easy to see how such a potentially costly immune response as the allergic reaction could have evolved.  Hypersensitivity (also called hypersensitivity reaction) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. The traditional classification for hypersensitivity reactions is that of Gell and Coombs and is currently the most commonly known classification system.  It divides the hypersensitivity reactions into the following 4 types:

  • Type I reactions (i.e., immediate hypersensitivity reactions) involve immunoglobulin E (IgE)–mediated release of histamine and other mediators from mast cells and basophils.
  • Type II reactions (i.e., cytotoxic hypersensitivity reactions) involve immunoglobulin G or immunoglobulin M antibodies bound to cell surface antigens, with subsequent complement fixation.
  • Type III reactions (i.e., immune-complex reactions) involve circulating antigen-antibody immune complexes that deposit in postcapillary venules, with subsequent complement fixation.
  • Type IV reactions (i.e., delayed hypersensitivity reactions, cell-mediated immunity) are mediated by T cells rather than by antibodies.

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Comparison of Different Types of hypersensitivity
characteristics type-I
(anaphylactic)
type-II
(cytotoxic)
type-III
(immune complex)
type-IV
(delayed type)
antibody IgE IgG, IgM IgG, IgM None
antigen exogenous cell surface soluble tissues & organs
response time 15-30 minutes minutes-hours 3-8 hours 48-72 hours
appearance weal & flare lysis and necrosis erythema and edema, necrosis erythema and induration
histology basophils and eosinophil antibody and complement complement and neutrophils monocytes and lymphocytes
transferred with antibody antibody antibody T-cells
examples allergic asthma, hay fever erythroblastosisfetalis, Goodpasture’s nephritis SLE, farmer’s lung disease tuberculin test, poison ivy, granuloma

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Depending on whether the antigen triggers a response by B cells or T cells, hypersensitivity reactions can have immediate or delayed effects. They are classified as Type I, II, III, and IV. Type I, II, and III hypersensitive reactions are the products of B cell stimulation and, as a result of antibody-antigen responses, these reactions take immediate effect. Different types of reaction may occur together — for example, in asthma, bronchial reactions to allergens show both an immediate and a late-phase response.

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Type I reactions; which include hay fever and insect venom allergy, involve the class of antibodies known as immunoglobulin E (IgE). IgE molecules are bound to mast cells, which are found in connective tissue. When enough antigen has bound with the IgE antibodies, the mast cells release granules of histamine and heparin and produce other substances that cause inflammation. These potent chemicals dilate blood vessels and constrict bronchial air passages. Histamine is responsible for the visible symptoms of an allergic attack, such as running nose, wheezing, and tissue swelling.  In severe allergic reactions, ‘complement’ fragments (anaphylatoxins) — proteins circulating in the blood — stimulate a more massive release of substances from mast cells which dilate blood vessels and constrict bronchioles. This sequence of events results in the collapse of the circulatory system, together with respiratory symptoms, leading to a potentially fatal reaction — anaphylactic shock.

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Type II reactions involve different immunoglobulins, known as IgG or IgM, which are antibodies against antigens on the surface of certain ‘target’ cells or in their immediate environment. These antigens may be natural components of healthy cells, or they may be extrinsic components induced by drugs or infectious microbes. The resulting antigen-antibody complex activates the complement system: a series of potent enzymes that destroy the target cell. An example of Type II reactions is autoimmune haemolytic anaemia. In patients with this condition, antibodies destroy their own red blood cells, leading to anaemia.

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Type III reactions result when the antigen- antibody complexes (immune complexes) become deposited on the walls of the small blood vessels. Normally, phagocytes remove immune complexes effectively. However, if this mechanism is overloaded, the immune complexes persist and are eventually deposited in a range of tissues and organs. These complexes then trigger the complement system, resulting in damage to blood vessels and inflammation; an example is glomerulonephritis, when the ‘filtering’ components of the kidneys are affected.

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Type IV reactions are the only ones that involve delayed hypersensitivity. These reactions are caused by the actions of T cells. Here the antigens are trapped inside macrophages and cannot be cleared. T cells are then activated to produce cytokines, which mediate a range of inflammatory responses. In contrast to the rapid responses mediated by B-cell antibodies, T cells take longer to accumulate at the site where the antigen is present. Thus the hypersensitive responses are delayed and appear 12 to 24 hours or more after exposure to an appropriate antigen. Contact dermatitis is one example, in which the skin responds to allergens such as nickel and rubber accelerators. These substances penetrate the skin and become linked to a carrier protein, capable of producing allergic reactions. Hypersensitivity involving T-cell-mediated immunity occurs also in some chronic diseases due to infectious agents such as the mycobacteria that cause leprosy and tuberculosis, and parasitic worms such as schistosomiasis. Organ transplantation (of kidney, heart, or lungs, respectively) is increasingly used to save patients with renal failure, cardiac failure, or cystic fibrosis. Unfortunately, T cells of the recipients can recognize and respond to foreign antigens of the grafts, leading to their eventual destruction. Immunosuppressive drugs such as steroids and cyclosporin are successful in preventing rejection. However, these drugs do not work specifically against the particular unwanted functions of macrophages or T-cells, and may reduce the patients’ resistance to infections.

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Some authors believe this classification system may be too general and favor a more recent classification system proposed by Sell et al. This system divides immunopathologic responses into the following 7 categories:

  • Inactivation/activation antibody reactions
  • Cytotoxic or cytolytic antibody reactions
  • Immune-complex reactions
  • Allergic reactions
  • T-cell cytotoxic reactions
  • Delayed hypersensitivity reactions
  • Granulomatous reactions

This system accounts for the fact that multiple components of the immune system can be involved in various types of hypersensitivity reactions. For example, T cells play an important role in the pathophysiology of allergic reactions. In addition, the term immediate hypersensitivity is somewhat of a misnomer because it does not account for the late-phase reaction or for the chronic allergic inflammation that often occurs with these types of reactions. Allergic reactions manifest clinically as anaphylaxis, allergic asthma, urticaria, angioedema, allergic rhinitis, some types of drug reactions, and atopic dermatitis. These reactions tend to be mediated by IgE, which differentiates them from pseudoallergic (formerly called anaphylactoid) reactions that involve IgE-independent mast cell and basophil degranulation. Such reactions can be caused by iodinated radiocontrast dye, opiates, or vancomycin and appear similar clinically by resulting in urticaria or anaphylaxis.  Patients prone to IgE-mediated allergic reactions are said to be atopic. Atopy is the genetic predisposition to make IgE antibodies in response to allergen exposure.

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What is an IgE-mediated allergy?

Allergy is classically defined as an exaggerated, pathological, specific immunologic reaction to foreign (exogenous) substances. As the body of evidence in immunology and immunopathology grows, the term ‘allergy’ is increasingly being confined to denote type I hypersensitivity reactions. However, there is as yet no consensus about definitions. In a somewhat narrower sense, allergy is defined as a condition triggered by a specific, acquired immune response to a harmless, non-pathogenic antigen. The allergic reaction results from the production of specific IgE antibodies directed against innocuous and typically widespread antigens. An antigen in this type of hypersensitivity reaction is called an ‘allergen’. The most important allergens include airborne allergens such as grass, tree or weed pollen, as well as moulds (or rather their spores), which are mainly released in summer and autumn. Patients often show cross-reactions to foods, the so called pollen-associated food allergy or oral allergy syndrome (OAS). The spectrum of perennial allergens includes mainly house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, and cat allergens. Less frequent are perennial reactions to other furry animals and moulds. This means that an allergen is a non-infectious agent that triggers an IgE antibody response and hence a type I hypersensitivity reaction. Type I reactions are the classical immediate reactions that occur seconds to minutes after allergen exposure. They include the pattern of symptoms seen in allergic rhinitis and conjunctivitis, allergic asthma, urticaria, and food and insect venom allergies. Anaphylaxis is considered the most severe form of an acute allergic immediate reaction and, in a narrower sense, is typically IgE-mediated.

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Non-atopic (non-IgE mediated) allergy: 

However, allergy is not as simple as above discussion seems to suggest. Some conditions are not dependent on IgE but still involve an abnormal immune response to a wide variety of external environmental agents. These conditions are known as non-atopic (non-IgE-mediated). The mechanisms of non-atopic disease are less clearly understood but some disorders (i.e. contact dermatitis) may involve a different subset of immune cells known as T helper 1 (Th1). Non-IgE mediated immediate hypersensitive immune response is discussed later on in the paragraph on ‘pseudoallergy’.  

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Not all IgE associated ‘allergic’ reactions occur in ‘atopic’ subjects. Also, non-atopic individuals do suffer from IgE mediated allergy.

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Th1-Th2 system:

Th stands for T helper type white blood cells. Immune responses can be classified as Th1 or Th2 based on the type of inflammation and molecules secreted after stimulation. Th1 immune responses traditionally fight intracellular infections such as bacterial and viral infections, whereas Th2 responses are specialized for large parasites such as worms. Asthma and allergic disease result from an improper Th2 immune response. At birth, the immune system switches to be either allergy prone (TH2) or non-allergy prone (TH1), depending on genetics and environment. Th1 immunity is good for fighting bacteria and viruses, and protecting against allergies. Th2 immunity is good at fighting parasite infections, but makes us more vulnerable to develop allergies. If there’s a family history of allergies, a child is much more likely to switch on TH2 immunity. This promotes the manufacture of excessive amounts of allergy-related immunoglobulin E (IgE) in the bloodstream. This IgE latches on to harmless allergens and triggers allergic reactions. If an inhaled pollen micro-particle gets attached to IgE in the nasal membranes, for example, this combined IgE/pollen complex causes mast cells to release naturally occurring defence chemicals called histamine. This leads to profuse nasal itching, tickling, sneezing and a watery mucus discharge.

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It turns out that IgE-associated allergic reactions (type-1) and delayed hypersensitivity reactions (type-4) are examples of two types of immune response that are directed by two distinct subtypes of helper T lymphocyte (Th cells). These responses also can be mobilized against pathogens. In subjects with helminthic parasites, such as intestinal worms, the immune responses are dominated by the actions of one subtype of helper T cell, Th2 cells. Th2 cells produce interleukin-4 (IL-4), IL-13 and other cytokines. These both drive the production of IgE and other antibodies, and promote the development and function of the effector cells of these responses, including mast cells, basophils and eosinophils (another type of leukocyte that can express FceRI). By contrast, in infections with intracellular pathogens (including viruses and certain bacteria or single-cell parasites) and in delayed hypersensitivity reactions, the immune responses are regulated primarily by Th1 cells. Th1 cells produce a different pattern of cytokines than Th2 cells, including interferon gamma, that not only promote host defense mechanisms against intracellular pathogens but also can suppress the activities of Th2 cells and the effector cells of Th2-driven responses. Thus, patients with IgE-associated allergies or helminthic parasites can be thought of as having a ‘Th2-based’ immune system.

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The figure below shows regulation of Th1 & Th2 system. 

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In IgE-mediated immediate reactions, there is an imbalance between T-helper cell (Th) subpopulations Th1 and Th2 cells with a preponderance of Th2 cells and a simultaneously attenuated Th1 reaction. These two cell types secrete different cytokines that are important to the course of antibody production and hence to antibody class lineage choice. Following specific stimulation by an antigen/allergen, TH1 cells release interferon-gamma and interleukin-2 (IL-2), which cause B-cells to predominantly produce IgG antibodies. Th2 cells, on the other hand, produce IL-4 and IL-13, which lead to increased IgE synthesis by B-cells. Th2 cells also secrete IL-5, which has a stimulatory effect on eosinophils. Moreover, recent studies have shown that allergic patients also have a relative deficiency of regulatory T-cells (T-regs) and the cytokines formed by T-regs including TGF-beta and IL-10. This may cause suppression of immunomodulatory allergen tolerance induction. IL-10 induces the synthesis of IgG4 and TGF-beta induces the synthesis of IgA. Increased production of IgG4 during high-dose specific immunotherapy (SIT), for example, has been suggested as an immunologic marker of allergen tolerance induction as a result of treatment.

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Remember, Th1 system is involved in type-4 delayed hypersensitivity reaction to non-self antigens and same system is involved in autoimmune disorders to self antigens. Th2 system is involved in type-1 immediate hypersensitivity reactions (formal allergy) and response to parasites.

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Allergens:

In the realm of immunology, substances that cause immune responses or allergic reactions are known as antigens. Specific antigens that provoke an allergic reaction are called allergens. Typical allergens include pollens, house-dust mites, animal dander, bacteria, foods, drugs, and chemicals. At present, we do not know why, in similar amounts and circumstances, these substances are harmless to most people but can cause health hazards in others. Avoidance of known allergens is the best protection against such reactions.

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Many allergens are soluble proteins which often have enzymatic function, such as proteolytic activity, in their natural state. Allergenic properties may be related to the latter (e.g. the augmentation of mucosal permeability) and to aerodynamic properties which in turn depend on particle size. The major allergens of Western industrialised countries are Der p 1 and Der p 2 from house dust mite (Derntatophagoides pteronyssinus), Fel d 1 from cat (Felis domesticus), several tree allergens including Bet v 1 from birch tree (Betula verrucosa) and many grasses such as Phi p 1 and Phi p 5 from timothy grass (Phleum pratense). The ragweed allergens; Amb a 1, a 2, a 3, a 5 and a 6 from short ragweed {Ambrosia artemisiifolia) and Amb t 5 from giant ragweed (Ambrosia trifida) are important seasonal allergens in North America. Allergies to Hev b 1-7 from latex, the milky sap harvested from the rubber tree (Hevea brasiliensis), and Ara h 1-3, which are highly allergenic peanut proteins, are increasingly important problems.

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A large variety of substances may cause allergies: pollens, animal proteins, molds, foods, insect venoms, foreign serum proteins, industrial chemicals, and drugs. Most natural allergens are proteins or polysaccharides of moderate molecular size (molecular weights of 10,000 to 200,000). Chemicals or drugs of lower molecular weight (haptens) have first to bind to the body’s own proteins (carriers) in order to become fully effective allergens. In the case of allergic contact dermatitis, the classical allergens are low molecular weight chemicals, e.g., chromium, nickel and formaldehyde, reacting with T cells.  For the development of the hypersensitivity state underlying clinical allergies, repeated contact with the allergen is required. Duration of the sensitization period is usually dependent upon the sensitizing strength of the allergen and the intensity of exposure. Some allergens (for example, saliva, urine, and hair proteins of domestic animals) are more sensitizing than others. In most instances, repeated contact with minute amounts of allergen is required; several annual seasonal exposures to grass pollens or ragweed pollen usually occur before an overt manifestation of hay fever. On the other hand, allergy to cow milk proteins in infants can develop within a few weeks. When previous contacts with allergens have not been apparent (for example, antibiotics in food), an allergy may become clinically manifest even upon the first conscious encounter with the offending substance. Besides the intrinsic sensitizing properties of allergens, individual predisposition of the allergic person to become sensitized also plays an important role. Clinical manifestations, such as hay fever, allergic asthma, and atopic (endogenous) dermatitis, occur more frequently in some families. In other clinical forms of allergy, genetic predisposition, though possibly present as well, is not as evident.

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Allergens as eukaryotic proteins lacking bacterial homologues:

Only a small number of protein homologues cause the majority of allergies. There is no consensus structure or other obvious common denominator discriminating the few proteins that are allergens from thousands of other, non-allergenic proteins. By database sequence homology searching, researchers have shown that to date known allergen sequences have no or few bacterial homologues, in contrast to randomly selected control protein sequences. This finding suggests a novel common denominator for allergens of potential use for allergen prediction programs. A possible interpretation of this finding is that allergens are proteins which are exposed to the immune system and which lack bacterial homologues. In other words, bacterial homologue proteins stimulate Th1 type immunity while non-bacterial homologue proteins stimulate Th2 type immunity. This interpretation is indeed relevant to many observations that allergies coincide with a delayed establishment of infant gut flora.

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Mistaken identity:

Allergy is the result of mistaken identity. An allergen enters the body and is wrongly identified by the immune system as a dangerous substance. In response, the immune system makes an antibody to attack the allergen. These are specific antibodies of the IgE class. When an allergen is found, IgE antibodies trigger a cascade of immune system reactions, including the release of chemicals known as mast cell chemicals. These are substances that the body normally uses to destroy micro-organisms. The most common of these is histamine. In small amounts, histamine causes itching and reddening of the local area. In large amounts, the nearby blood vessels become dilated and the area swells with accumulated fluid.

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Sensitization:

Allergic reactions do not happen the first time you come into contact with an allergen, but at a later point of contact. This is because the body’s immune system has to develop sensitivity to the allergen before you can become allergic to it. In other words, your immune system needs to recognize and memorize the allergen (for example, pet hair or pollen) and then make antibodies against it. This process is known as sensitization. The time taken to become sensitized to an allergen varies from days to years. Some people stop in the sensitization phase, experiencing symptoms but never fully developing an allergy to the allergen.

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The figure below shows how first time exposure to allergen cause sensitization:

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The figure below describes in detail how allergen is processed to develop type-1 hypersensitivity:

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The binding of IgE to human mast cells and basophils, a process termed sensitization, prepares these cells for subsequent antigen-specific activation. The sensitization of the high-affinity Fc receptor for IgE, designated FcRI, also stabilizes the cellular expression of the receptor. FcRI is composed of one, one, and two disulfide-linked chains, which together cross the plasma membrane seven times. The chain is responsible for IgE binding, and the end chains provide for signal transduction that follows the aggregation of the sensitized tetrameric receptors by polymeric antigen. Signal transduction is initiated through the action of an Src family–related tyrosine kinase, termed Lyn, that is constitutively associated with the chain. Lyn transphosphorylates the canonical immunoreceptor tyrosine-based activation motifs (ITAMs) of the end chains of the receptor, resulting in recruitment of more active Lyn to the chain and of Syk tyrosine kinase. The phosphorylated tyrosines in the ITAMs function as binding sites for the tandem src homology two (SH2) domains within Syk. Syk activates not only phospholipase C, which associates with the Linker of Activated T Cells at the plasma membrane, but also phosphatidylinositol 3-kinase to provide phosphatidylinositol-3,4,5-trisphosphate, which allows membrane targeting of the Tec family kinase Btk and its activation by Lyn. In addition, the Src family tyrosine kinase Fyn becomes activated after aggregation of IgE receptors and phosphorylates the adapter protein Gab2 that enhances activation of phosphatidylinositol 3-kinase. Indeed, this additional input is essential for mast cell activation, but it can be partially inhibited by Lyn, indicating that the extent of mast cell activation is in part regulated by the interplay between these Src family kinases. Activated phospholipase C cleaves phospholipid membrane substrates to provide inositol-1,4,5-trisphosphate (IP3) and 1,2-diacylglycerols (1,2-DAGs) so as to mobilize intracellular calcium and activate protein kinase C, respectively. The subsequent opening of calcium-regulated activated channels provides the sustained elevations of intracellular calcium required to recruit the mitogen-activated protein kinases, ERK, JNK, and p38 (serine/threonine kinases), which provide cascades to augment arachidonic acid release and to mediate nuclear translocation of transcription factors for various cytokines. The calcium ion–dependent activation of phospholipases cleaves membrane phospholipids to generate lysophospholipids, which, like 1,2-DAG, may facilitate the fusion of the secretory granule perigranular membrane with the cell membrane, a step that releases the membrane-free granules containing the preformed mediators of mast cell effects.

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Sensitization means a person’s immune system produces a specific antibody to an allergen. It does not mean the person will experience allergy symptoms [vide infra].

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Allergic cascade:

Although mast cells are found in connective tissue and basophils are a type of white blood cell, they have one thing in common to the allergy sufferer. They contain histamine, an important weapon in the body’s arsenal for fighting infection. Unfortunately, when released into the body inappropriately or in too high a quantity, histamine is a potentially devastating substance. It takes between a week and 10 days of sensitizing exposure for the mast cells and basophils to become primed with IgE antibodies. Then, if the allergen comes along again, it triggers a destructive domino effect within the system called the allergic cascade. Whether it’s a protein molecule on a ragweed pollen particle that has been inhaled, or the injected protein in the venom of a wasp, the same sequence of events takes place:

  • The IgE antibodies bound to the surfaces of basophils and mast cells recognize the protein surface markers of the allergen.
  • The IgE antibodies react by binding to the protein surface markers while remaining attached to the mast cells or basophils.
  • This binding alert a group of special proteins called the complement complex that circulates in the blood.

There are about 20 proteins in this family of proteins, at least nine of which are involved in the allergic-response mechanism. After the IgE antibody (which is already attached to a mast cell or basophil) encounters and binds to its specific allergen, the first complement protein attaches itself to the site. This alerts the next complement protein in the sequence, which joins and alerts the next, and so on. When the string is complete, the offending cell is destroyed. This is fine in a normal immune system, as IgG antibodies latch onto surface markers of disease cells and cause their destruction. But in an allergic episode, the cells involved are mast cells and basophils. When mast cells and basophils are destroyed, their stores of histamine and other allergy mediators are released into the surrounding tissues and blood. This causes dilation of surface blood vessels and a subsequent drop in blood pressure. The spaces between surrounding cells fill with fluid.

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The figure below shows primary mediators released by mast cells after allergens interact with IgE bound on its membrane:

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Secondary mediators:

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The table below shows effects of primary &secondary mediators:

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Atopy:

The term atopy from the Greek atopos, meaning ‘out of place’ is often used when describing IgE-mediated diseases. Thus, atopic individuals have a hereditary predisposition to produce IgE antibodies against common environmental allergens and have clinical manifestations of one, or more, atopic diseases (i.e. allergic rhinitis, asthma and atopic eczema). Some allergic diseases (e.g. contact dermatitis and hypersensitivity pneumonitis) operate through IgE-independent mechanisms and in this sense may be considered as non-atopic, allergic conditions.

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The majority of people who suffer from IgE-mediated allergy are said to be “atopic”. The European Academy of Allergology and Clinical Immunology (EAACI) defines atopy as “a personal or familial tendency to produce IgE antibodies in response to low doses of allergens, usually proteins, and as a consequence, to develop typical symptoms such as asthma, rhinoconjunctivitis or the atopic eczema/dermatitis syndrome (AEDS).” This means that atopic individuals are more likely to develop these allergic conditions than non-atopic individuals. However, not all atopic individuals do so. Atopy is associated with disorders such as hay fever, allergic asthma and eczema. The disorders discussed in this article are mainly atopic in nature, so when the term allergy is used in an unqualified way, it refers to atopic allergy. However, individuals without an atopic background may also develop hypersensitivity reactions, particularly urticaria and anaphylaxis, associated with the presence of IgE.

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The figure below shows overview of atopic allergy disease: 

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Atopy and Th2 cells:

All of us inhale aero-allergens such as those derived from pollen, house dust mite and cat. In general, non-atopic adults and children mount a low grade immunological response; they produce allergen-specific IgG antibodies and in vitro their T cells respond to the allergen with a modest degree of proliferation and production of interferon-gamma which is typical of Th1 cells. Atopic individuals, by contrast, mount an exaggerated allergen-specific IgE response; they have elevated serum levels of IgE antibodies and positive skin tests to extracts of common aeroallergens. Several studies have shown that T cells from the peripheral blood respond to allergen in vitro by producing cytokines of the Th2-type, i.e. interleukin-4 (IL-4), IL-5 and IL-135-7, rather than cytokines of the Th1-type (IFN gamma and IL-2). There are many exceptions to this rule. For example, T cells from atopic subjects have been found to produce a mixed (Th0) cytokine pattern when challenged in vitro by an allergen from house dust mite. Nevertheless, the immunopathological hallmark of allergic disease is the infiltration of affected tissue by cells with a Th2-type cytokine profile.

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T cells from virtually all new-born infants are primed in utero to common environmental allergens and produce an immune response that is dominated by Th2 cells. It has been proposed that during subsequent development the normal (i.e. nonatopic) subject’s immune system there is a shift in favor of a Th1 response to inhalant allergen (a process termed ‘immune deviation’). On the other hand, in potential atopies, there is further boosting of fetally primed Th2-polarized immunity. It has been suggested that the major stimulus for developing protective Th1-like immunity is microbial exposure. Engulfment by macrophages of a wide range of microbes, including Mycobacteria and Lactobacilli, leads to the secretion of IL-12. IL-12 (by inducing Th1 cells and natural killer cells to produce IFN-gamma) drives the immune system to an ‘allergy-protective’ Th1 response. Other factors may also influence whether Th1 or Th2 cells dominate the response, including the dose of allergen and length of exposure as well as the avidity of allergen-specific interactions between T cells and antigenpresenting cells. Anjana Rao and Orly Avni describe the molecular aspects of T cell differentiation in terms of signaling pathways and transcription factors underlying the Th1 and Th2 response (vide supra). There is evidence that cytokine gene expression is, in part, ‘epigenetic’, i.e. at the level of chromatin accessibility through modification of nucleosomal histones. 

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Pathophysiology of allergy:

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The figure below shows overview of pathophysiology of allergy:

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Acute response:

In the early stages of allergy, a type I hypersensitivity reaction against an allergen encountered for the first time and presented by a professional Antigen-Presenting Cell causes a response in a type of immune cell called a Th2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4). These Th2 cells interact with other lymphocytes called B cells, whose role is production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE. Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a kind of Fc receptor called FceRI) on the surface of other kinds of immune cells called mast cells and basophils, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage are sensitized to the allergen. If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule, and activates the sensitized cell. Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation, and smooth muscle contraction. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems; asthma is localized to the respiratory system and eczema is localized to the dermis.

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Late-phase response:

After the chemical mediators of the acute response subside, late phase responses can often occur. This is due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils and macrophages to the initial site. The reaction is usually seen 4–24 hours after the original reaction. Cytokines from mast cells may also play a role in the persistence of long-term effects. Late phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils, and are still dependent on activity of TH2 cells.

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The figure below shows acute and late phase, type 1 immune hypersensitive reaction being visualized in allergic skin test because skin testing is a biologic test that mimics the actual type I reaction.

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The late phase of Type 1 reaction (which develops 4–24 hours after exposure to allergen and is mediated by eosinophils, basophils, Th2 cells and mast cells) should not be confused with delayed hypersensitivity Type IV reaction (which takes 48–72 hours to develop and is mediated by Th1 cells).  

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In a nutshell what allergy means is depicted in the figure below:

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In a nutshell what allergy means is explained below:

In pre-disposed individuals, initial exposure(s) to allergen leads to the activation of allergen-specific T helper 2 (Th2) cells and IgE synthesis, which is known as allergic sensitization. Subsequent exposures to allergen cause inflammatory-cell recruitment and activation and mediator release, which are responsible for early (acute) allergic responses (EARs) and late allergic responses (LARs). In the EAR, within minutes of contact with allergen, IgE-sensitized mast cells degranulate, releasing both pre-formed and newly synthesized mediators in sensitized individuals. These include histamine, leukotrienes and cytokines, which promote vascular permeability, smooth-muscle contraction and mucus production. Chemokines released by mast cells and other cell types direct recruitment of inflammatory cells that contribute to the LAR, which is characterized by an influx of eosinophils and Th2 cells. Eosinophils release an array of pro-inflammatory mediators, including leukotrienes and basic proteins (cationic proteins, eosinophil peroxidase, major basic protein and eosinophil-derived neurotoxin), and they might be an important source of interleukin-3 (IL-3), IL-5, IL-13 and granulocyte/macrophage colony-stimulating factor. Neuropeptides are also proposed to contribute to the pathophysiology of allergic symptoms.

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Acute and chronic allergic reaction:

Atopic allergic conditions arise when individuals produce increased amounts of the allergic antibody immunoglobulin E (IgE), a type of antibody which binds particularly strongly to specific receptors on mast cells (specialised cells found in connective tissue and airways). When the cell-associated IgE comes into contact with the specific allergen against which it is directed, the molecules of IgE become “cross-linked” by that allergen, and the mast cell becomes activated. This results in the release of inflammatory chemicals such as histamine and leukotrienes. Acute symptoms of allergy such as sneezing, spasm of the airways, itching, rash and tissue swelling are caused by histamine, and when there is a large release into the circulation, as in anaphylaxis, histamine causes a fall in blood pressure. Leukotrienes have a more prolonged course of action, causing airway narrowing and swelling which leads to shortness of breath and wheeze. The symptoms of chronic allergic disorders, such as a continuous blocked nose or on-going wheeziness, may result from another molecular pathway involving immune cells known as T helper 2 (Th2) cells. This pathway involves the release of cytokines and chemokines, small messenger proteins which recruit other cells into the reaction. Chronic allergic reactions as well as late phase of acute allergic reactions are mediated by similar pathways.

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The figure below shows pathways leading to acute and chronic allergic reactions:

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Pathophysiology of allergic inflammation:

Allergic inflammation is due to a complex interplay between several inflammatory cells, including mast cells, basophils, lymphocytes, dendritic cells, eosinophils, and sometimes neutrophils. These cells produce multiple inflammatory mediators, including lipids, purines, cytokines, chemokines, and reactive oxygen species. Allergic inflammation affects target cells, such as epithelial cells, fibroblasts, vascular cells, and airway smooth muscle cells, which become an important source of inflammatory mediators. Sensory nerves are sensitized and activated during allergic inflammation and produce symptoms. Allergic inflammatory responses are orchestrated by several transcription factors, particularly NF-kB and GATA3. Inflammatory genes are also regulated by epigenetic mechanisms, including DNA methylation and histone modifications. There are several endogenous anti-inflammatory mechanisms, including anti-inflammatory lipids and cytokines, which may be defective in allergic disease, thus amplifying and perpetuating the inflammation. Better understanding of the pathophysiology of allergic inflammation has identified new therapeutic targets but developing effective novel therapies has been challenging. Corticosteroids are highly effective with a broad spectrum of anti-inflammatory effects, including epigenetic modulation of the inflammatory response and suppression of GATA3.

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Eosinophils:

Eosinophil granulocytes, usually called eosinophils, are white blood cells that are one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood. Eosinophils along with basophils and mast cells are important mediators of allergic responses and asthma pathogenesis and are associated with disease severity. An increase in eosinophils, i.e., the presence of more than 500 eosinophils/microlitre of blood is called an eosinophilia, and is typically seen in people with a parasitic infestation of the intestines, a collagen vascular disease (such as rheumatoid arthritis), malignant diseases such as Hodgkin’s disease, extensive skin diseases (such as exfoliative dermatitis), Addison’s disease, in the squamous epithelium of the esophagus in the case of reflux esophagitis, eosinophilic esophagitis, and with the use of certain drugs such as penicillin. In the Western World, allergic or atopic diseases are the most common causes, especially those of the respiratory or integumentary systems. In the developing world, parasites are the most common cause. 

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Role of Eosinophils in allergy:  

For over 100 years, the eosinophil has been associated with allergic disease. At present, eosinophils appear to be associated pathologically with asthma, atopic dermatitis, allergic rhinitis, eosinophilic gastroenteritis, and certain eye diseases. The effector functions of eosinophils appear to be derived primarily from release of lipid mediators and proteins, including cytokines and granule proteins. Eosinophil degranulation results in the release of several cytotoxic cationic granule proteins. Furthermore, release of cytokines by eosinophils and other cells involved in inflammation amplifies and regulates localized immune responses. Altogether, the eosinophil’s capacity to release and be influenced by a variety of mediators, including the granule proteins and cytokines, implicates this cell in the pathology of inflammation and in the perpetuation of the inflammatory response.

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Infiltration of eosinophils to the lung is one of the hallmark characteristics of allergic asthma in humans and animal models alike; however, until recently the function of these cells in asthma has been a mystery. Traditionally, researchers have thought that eosinophils were recruited to the lung by T cells as end stage effector cells. High levels of IL-5 are found in the blood and bronchoalveolar lavage fluid (BAL) of patients with eosinophilic esophagitis and allergic asthma (Hogan, 2008). Atopic asthmatics also harbor large numbers of eosinophil progenitors expressing IL-5 receptor alpha in the bone marrow, that when cultured with IL-5 ex vivo, develop into eosinophils (Sehmi et al., 1996). Although eosinophils, a type of immune cell, have long been considered to mediate allergic and asthmatic Th2 immune responses, they may also play a role in determining the switch between Th1 and Th2 immune responses. Tulic et al therefore examined the development of eosinophils in human children. They observed an age-dependent decrease in the number of eosinophils in the thymus, an organ where early Th1/Th2 differentiation may occur, suggesting an early role of eosinophils in Th2 bias. Dr. Moqbel’s group suggests that “functional thymic IDO+ eosinophils during human infant life may have an immunomodulatory role in Th2 immune responses.”

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Are eosinophils mere bystanders or bio-markers of allergic response?  

A hallmark of allergic disease is infiltration of the tissues with increased numbers of eosinophils. This is the result of the coordinated action of cytokines, particularly IL-5, CCR3 binding chemokines and the adhesion molecules P-selectin and VCAM-1, acting in concert to cause selective trafficking of eosinophils into allergic tissue. This process is orchestrated by the Th-2 allergen specific lymphocyte. While there is little data to support the view that eosinophils ameliorate the allergic process, although they could have an important role in the disordered repair that leads to permanently impaired function in some allergic diseases, the evidence that they cause many of the pathophysiological features of allergic disease, while strong, remains circumstantial. Much of the data could be interpreted just as easily to suggest that eosinophils are bystander cells; markers of a certain type of pathological process, but not impinging upon it. The most direct evidence for a pathological role rests on the toxicity of the eosinophil granule proteins for bronchial epithelium and the bronchoconstrictor actions of the sulphidopeptide leukotrienes. The actions of LT antagonists in asthma which are certainly beneficial, but in most cases are not as effective as glucocorticoids, could be interpreted both for and against the eosinophil. In a study researchers have focused on the question of whether eosinophils are important effector cells in the pathogenesis of allergic disease. They conclude with a qualified affirmative. Even if they are only bystander cells they remain clinically important as diagnostic markers and a guide to the management of allergic disease. The current evidence is consistent with a role for eosinophils simply as markers of the inflammatory process, but not impinging upon it. Even if they are just markers, eosinophils are so closely related to at least asthma that they remain extremely useful as indicators of diagnosis and response to treatment in allergic diseases. The evidence would also be entirely consistent with eosinophils being important effector cells. Perhaps the most likely answer is that eosinophils are part of a complex inflammatory process in which they favor one aspect of the pathophysiology, cough for example or airway wall remodeling. If this is the case, using anti-eosinophilic drugs to assess their role may be more difficult than simply measuring FEV1 or BHR in short-term studies.

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Mast cells:

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A mast cell (also known as mastocyte) is a resident cell of several types of tissues and contains many granules rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens. The mast cell is very similar in both appearance and function to the basophil, a type of white blood cell. However, they are not the same, as they arise from different cell lines. Many forms of cutaneous and mucosal allergy are mediated for a large part by mast cells; they play a central role in asthma, eczema, itch (from various causes) and allergic rhinitis and allergic conjunctivitis. The secretory granule of the human mast cell has a crystalline structure, unlike mast cells of lower species. IgE-dependent cell activation results in solubilization and swelling of the granule contents within the first minute of receptor perturbation; this reaction is followed by the ordering of intermediate filaments about the swollen granule, movement of the granule toward the cell surface, and fusion of the perigranular membrane with that of other granules and with the plasmalemma to form extracellular channels for mediator release while maintaining cell viability.

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Systemic mastocytosis:

Systemic mastocytosis is defined by a clonal expansion of mast cells that in most instances is indolent and nonneoplastic. The prevalence of systemic mastocytosis is not known, a familial occurrence is rare, and atopy is not increased. The mast cell expansion is generally recognized only in bone marrow and in the normal peripheral distribution sites of the cells, such as skin, gastrointestinal mucosa, liver, and spleen. Mastocytosis occurs at any age and has a slight preponderance in males. The prevalence of systemic mastocytosis is not known, a familial occurrence is rare, and atopy is not increased. The pharmacologically induced manifestations are pruritus, flushing, palpitations and vascular collapse, gastric distress, lower abdominal crampy pain, and recurrent headache. The increase in local cell burden is evidenced by the lesions of urticaria pigmentosa at skin sites and is a direct cause of bone pain and/or malabsorption. Mast cell-mediated fibrotic changes occur in liver, spleen, and bone marrow but not in gastrointestinal tissue or skin. In some patients, flushing and recurrent vascular collapse are markedly aggravated by an idiosyncratic response to a minimal dosage of NSAIDs. The management of systemic mastocytosis uses a stepwise and symptom/sign-directed approach that includes an H1 antihistamine for flushing and pruritus, an H2 antihistamine or proton pump inhibitor for gastric acid hypersecretion, oral cromolyn sodium for diarrhea and abdominal pain, and aspirin for severe flushing with or without associated vascular collapse, despite use of H1 and H2 antihistamines, to block biosynthesis of PGD2. Systemic glucocorticoids appear to alleviate the malabsorption.

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IgE:

Immunoglobulin E (IgE) is a class of antibody that has been found only in mammals. IgE’s main function is immunity to parasites such as parasitic worms like Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE may also be important during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE also plays an essential role in type I hypersensitivity, which manifests various allergic diseases, such as allergic asthma, allergic rhinitis, food allergy, and some types of chronic urticaria and atopic dermatitis. IgE also plays a pivotal role in allergic conditions, such as anaphylactic reactions to certain drugs, bee stings, and antigen preparations used in specific desensitization immunotherapy. IgE primes the IgE-mediated allergic response by binding to Fc receptors found on the surface of mast cells and basophils. Fc receptors are also found on eosinophils, monocytes, macrophages and platelets in humans. Atopic individuals can have up to 10 times the normal level of IgE in their blood (as do sufferers of hyper-IgE syndrome). However, this may not be a requirement for symptoms to occur as has been seen in asthmatics with normal IgE levels in their blood – recent research has shown that IgE production can occur locally in the nasal mucosa. IgE that can specifically recognize an “allergen” (typically this is a protein, such as dust mite DerP1, cat Fel d 1, grass or ragweed pollen, etc.) has a unique long-lived interaction with its high-affinity receptor FceRI so that basophils and mast cells, capable of mediating inflammatory reactions, become “primed”, ready to release chemicals like histamine, leukotrienes, and certain interleukins. These chemicals cause many of the symptoms we associate with allergy, such as airway constriction in asthma, local inflammation in eczema, increased mucus secretion in allergic rhinitis, and increased vascular permeability; it is presumed, to allow other immune cells to gain access to tissues, but which can lead to a potentially fatal drop in blood pressure as in anaphylaxis. The anti-IgE antibody drug omalizumab recognizes IgE not bound to its receptors and is used to neutralize or mop-up existing IgE and prevent it from binding to the receptors on mast cells and basophils.

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Evolutionary perspective of IgE:

IgE is an evolutionary conserved member of the immunoglobulin (Ig) family. Immunoglobulins are antibodies, which play a key function in immune response. Compared to all other immunoglobulin classes, which are present in concentrations of micrograms to milligrams per ml serum, the titre of IgE is very low (nano- to micrograms per ml range) in plasma of normal healthy individuals and of normal laboratory mouse strains. IgE is most prominent in epitheliae and mucosae where it is bound to specific receptors on highly potent effector cells like eosinophilic granulocytes and mast cells. Bound to these cells IgE has a long half-life (weeks to months), while free in plasma the half-life is very short (~ 6 hours). This suggests that IgE plays a role in local immune defence mechanisms. However, the core function for IgE is still unknown. From an evolutionary point of view, IgE is conserved and can be found in all mammalia. It therefore originated at least 160 million years ago, possibly even more than 300 million years ago, from a gene duplication of IgY, in which the anaphylactic and opsonic activities of IgY were separated, giving rise to IgE and IgG, respectively. IgG now represented the opsonic activities, which are needed to label antigens with antibodies and complement factors to enable scavenger cells to recognizes and destroy the enemy. IgE was responsible for anaphylactic activities, which represent another way of immune defense, which may involve the whole body. Apparently, in an evolutionary sense, anaphylactic defense mechanisms are needed, but at a potentially high price to the organism. The division of anaphylactic and opsonic activities in separate genes allowed principally a tighter and more specific control of both immune mechanisms. In these days IgE is best known for its strong, unwanted effector functions, in the form of allergic reactions. These can range from annoying, local symptoms, like hay fever, to life-threatening, systemic reactions like anaphylactic shock. This underlines the potential hazard of high systemic IgE titres. Remarkably, over the last four decades the incidence of allergic disease has risen. This represents an intriguing problem from a medical, epidemiological, immunological, genetic and evolutionary view. Unfortunately, it is also a major socio-economic problem. Researchers’ interpretation of these data is that control mechanisms, that were adequate in the past and honed in evolution, are failing. In the recent past they have described several B cell specific control mechanisms that indicate a tight control of the IgE response. The understanding of these mechanisms, combined with the analysis of the biological function of the IgE molecule during an immune response are the prerequisite for the establishment of new systemic IgE targeted therapeutic strategies in the future.

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Immunoglobulin E (IgE) antibodies and mast cells have been so convincingly linked to the pathophysiology of anaphylaxis and other acute allergic reactions that it can be difficult to think of them in other contexts. However, a large body of evidence now suggests that both IgE and mast cells are also key drivers of the long-term pathophysiological changes and tissues remodeling that are associated with chronic allergic inflammation in asthma and other settings. Such potential roles include IgE-dependent regulation of mast-cell functions, actions of IgE that are largely independent of mast cells and roles of mast cells that do not directly involve IgE. In a review study, researchers supported the conclusion that IgE and mast cells can have both interdependent and independent roles in the complex immune responses that manifest clinically as asthma and other allergic disorders.

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Cross-reactivity of allergy:

A cross-reactivity allergy is present when the antibodies against a specific allergen are also capable of identifying other allergens from other allergen sources and may thus induce an allergic reaction to those allergens as well. The reason for the cross-reactions lies in the structural similarities among proteins of diverse sources, such as pollens and foods. Cross-reactions are frequently seen between certain pollen types and foods. This is called “oral allergy syndrome” [vide infra]. For example, some people reacting allergic to birch pollen may not tolerate apples as well.  Antibodies targeting a birch pollen allergen detect a similar protein in the apple. The result is that people suffering from birch pollen allergy may react to the consumption of apples with allergic symptoms such as swelling, redness and itching of the oral mucosa, although their original immune response was not targeting the apple antigen but the main allergen in birch pollen. Latex-fruit syndrome is another example of cross-reactivity of allergy. 

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New immune cells and allergy:

Researchers at the Malaghan Institute of Medical Research in Wellington and the Centenary Institute in Sydney have discovered of a unique type of immune cell in the skin. The new cell type is part of a family known as group 2 innate lymphoid cells (ILC2) which was discovered less than five years ago in the gut and the lung, where it has been linked to asthma. But this is the first time such cells have been found in the skin, and they are relatively more numerous there. The significance of which is the compelling evidence that these cells can drive the development of allergic skin disease. They have used the most cutting-edge cell analysis and transgenic reporter gene technologies currently available to identify these cells in the skin. They were able to see how these immune cells move through the skin, what they interact with and for how long. This has been crucial in building up a picture of what these cells are actually doing. Critically, researchers have been able to show that these cells have the potential to cause skin allergy in experimental models. By being able to link this new cell type to skin allergy, there is a greater possibility they can now find ways to stop the onset of allergic disease. Future research will now focus on learning more about these cells and how they could be exploited to stop allergic disease.  

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Allergies and Autoimmune Disease – An Immune System Imbalance:

The immune system is a complex network of organs, tissues, cells, and proteins that fights off invaders. The immune system must strike a balance between a strong enough response to prevent infection and cancer and a response too strong which will damage cells and tissues. Allergy and autoimmune disorders result when the immune system overreacts or reacts inappropriately. Examples include hay fever, systemic lupus erythematosus, and rheumatoid arthritis. Hyperactivity and hypersensitivity of certain facets of the immune system often result in exaggerated immune responses.  Allergies and autoimmune diseases fall into this category.  Each type of exaggerated immune response involves a different cascade of events. One event in the cascade of events of an allergy is the release of histamine by mast cells. An antihistamine inhibits the action of histamine, thus relieving the symptoms of the allergy. In the case of autoimmune disease, one event in the cascade of events is the release of proinflammatory cytokines by T-Cells. Drugs used to combat rheumatoid conditions target these T-Cells, specifically inhibiting the release of these cytokines by various mechanisms.  In the case of both allergy and autoimmune disease, suppression of histamine action or proinflammatory cytokines respectively, do not cure the disease. Suppression of these immune components merely suppresses the symptoms. The cure can only be found in restoring the proper function of the immune system. When the different facets of the immune system are brought back into balance, exaggerated immune responses do not generally occur. Allergies occur when an exaggerated immune response occurs in reaction to an allergen. The most common types of allergic diseases occur when the immune system responds to a false alarm. In an allergic person, a normally harmless material such as grass pollen, food particles, mold, or house dust mites is mistaken for a threat and attacked. Allergic responses come in many different varieties.  Environmental allergies, food allergies, and allergies to medications are among the most commonly seen. Allergies involve both genetic and environmental factors. Research into the genetic basis of allergies, however, has not been accomplished to the extent that it has with autoimmune diseases. T-Cells, specifically Th2 cells (Thymus Helper Type 2 Cell), play a significant role in the allergic response. Various interleukins and immunoglobulins are also involved in the cascade of events of the allergic response. The types of immunoglobulins, and the type of immune system cells involved determine the type of allergy. Autoimmune diseases result when a different portion of the immune system has become hyperactive; attacking the body’s tissues as if the tissue itself was a foreign invader. [Self is perceived as non-self] Sometimes the immune system’s recognition apparatus breaks down, and the body begins to manufacture T cells and antibodies directed against self antigens in its own cells and tissues. As a result, healthy cells and tissues end up being attacked by the immune system.  Misguided T cells and autoantibodies, as they are known, contribute to many autoimmune diseases. Misguided T cells can attack insulin-producing cells of the pancreas, contributing to an autoimmune form of diabetes. In addition, an antibody known as rheumatoid factor is common in people with rheumatoid arthritis. People with systemic lupus erythematosus (SLE) have antibodies to many types of their own cells and cell components. SLE patients can develop a severe rash, serious kidney inflammation, and disorders of other important tissues and organs. As often seen with allergies, autoimmune diseases require both a genetic and environmental factor in order to be expressed.  Autoimmune disorders are often referred to as the family of inflammatory disorders because inflammation of a particular tissue occurs as part of the disorder. The possibility exists for certain facets of the immune system to exhibit exacerbated responses while other facets are functioning at a normal level. In the individual with autoimmune disorders, the Th1 (Thymus Helper Type 1 Cell) response of secreting cytokines is greatly exaggerated. These cytokines, released during the cascade of events associated with autoimmune disorders, play a major role in the inflammatory response found with autoimmune disease. Th1 and Th2 immune cells have a natural balance to them. Autoimmune diseases occur as a result of an exaggerated Th1 associated immune system response. Allergies, on the other hand, occur as a result of an exaggerated Th2 associated immune system response.  If the Th1 / Th2 balance was restored, autoimmune diseases and allergies would cease, or at least alleviated to great extent.  Restoration of Th1 / Th2 balance, in fact, has been shown to benefit both the allergy and autoimmune patient. The question arises of what actually caused the imbalance in the first place.  While multiple factors are known to influence immune system function, the specific factors involved in Th1 / Th2 balance are well documented.

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Involvement of both ‘allergic’ and ‘autoimmune’ mechanisms in EAE, MS and other autoimmune diseases:

Allergic and autoimmune diseases have been considered to be at the opposite sides of the spectrum of the immune response. Autoimmune diseases, such as multiple sclerosis (MS), rheumatoid arthritis and type 1 insulin-dependent diabetes mellitus, are considered T helper 1 (Th1)-mediated diseases, and allergic disorders, such as asthma, food allergy or rhinitis, are considered to be Th2-mediated. In a study, researchers present evidence for the hypothesis that, elements of the immune response classically associated with allergy, importantly contribute to the pathogenesis of autoimmune demyelinating diseases of the central nervous system (CNS), in both the human disease, MS, and its animal model, experimental autoimmune (formerly ‘allergic’) encephalomyelitis (EAE). Autoimmune demyelinating diseases of the CNS, and other autoimmune diseases, can reflect the interplay of both Th1- and Th2-associated mechanisms.

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Is celiac disease a wheat allergy?

No. Celiac disease is not a wheat allergy, nor is it a gluten allergy. Celiac disease is an autoimmune disorder triggered by eating gluten. In celiac disease, gluten stimulates (because of genetic predisposition) the production of immunoglobulins that attack the villi lining the small intestine (that is, the body’s own normal tissues). Celiac disease is often confused for an allergic illness because (like an allergy) it requires a foreign substance to trigger it.

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Difference between allergy and autoimmune disease using celiac disease as example:

In earlier paragraph, I have discussed differences between allergy and autoimmune disorders. Another important difference between autoimmune conditions and allergies is that autoimmune disorders are never outgrown; they persist for life. Allergies can sometimes be outgrown. Also, autoimmune conditions can result in long-term damage to the body. For instance, because celiac disease damages the small intestine, people with celiac disease are at risk for malabsorption, nutritional deficiencies, iron-deficiency anemia, and osteoporosis. People with celiac disease are also at risk for other autoimmune conditions, such as thyroid disease, diabetes, and liver disease. In addition, in untreated celiac disease, a type of white blood cell called the T lymphocyte is activated, along with other parts of the immune system, putting patients at increased risk to develop gastrointestinal lymphomas. A wheat allergy, in contrast, would not put patients at risk for any of these problems. In general, allergies usually result in only temporary symptoms without long-term damage, unless they produce a fatal anaphylactic reaction. 

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The rise of allergy and autoimmune disease is not an evolutionary accident or malfunction.  These disorders aren’t the consequence of novel substances in our environment.  Rather, they are the result of an unprecedented disappearance of an important part of our immune system — the friendly organisms with which we’ve co-evolved, and to which we had outsourced the regulation or our inflammatory immune response.  While we might not depend on any single organism, never before in our evolutionary history have our bodies and our daily environment become so devoid of these helpers. The result is that we are increasingly victims of an overactive and unmodulated inflammatory response that often shows up as friendly fire against our own tissues.    

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Epidemiologic studies point to a decreased frequency of allergy in patients with autoimmune diseases. However, recent studies suggest that IL-17 and related cytokines, which play a central role in autoimmunity, might also promote allergy.  

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The table below shows comparison of allergy with other bodily responses to antigens, self or non-self.

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Comparison of allergy with other responses:

Antigen source Mechanism Manifestation Result
Foreign Immunologic Allergy Disease
Foreign Immunologic Immunity Prophylaxis
Self Immunologic Autoimmunity Disease
Foreign Toxic Toxicity Disease

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Somatosensory pathways in allergic immunity:

One research paper hypothesize that noxious substances, including allergens, can be detected by somatosensory neurons to elicit protective reflexes, including itch, coughing, sneezing, vomiting and diarrhoea. These pathways can also elicit aversive behaviors that enforce avoidance of allergens in future.

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Route of entry of allergens:

Allergens enter the body through four main routes: the airways, the skin, the gastrointestinal tract, and the circulatory system.

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The table below shows overview of various clinical syndromes arising out of allergy:

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Inhalation route:

Airborne allergens cause the sneezing, runny nose, and itchy, bloodshot eyes of allergic rhinitis (hay fever). Airborne allergens can also affect the lining of the lungs, causing asthma, or the conjunctiva of the eyes, causing allergic conjunctivitis. The most common airborne allergens are the following:

•plant pollens

•animal fur and dander

•body parts and excrement from dust mites (microscopic creatures found in all houses)

•excrement from cockroaches

•house dust

•mold spores

•cigarette smoke

•solvents

•cleaners

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Ingestion route:

Allergens in food can cause itching and swelling of the lips and throat, cramps, and diarrhea. When absorbed into the bloodstream, they may cause hives (urticaria) or more severe reactions involving recurrent, non-inflammatory swelling of the skin, mucous membranes (angioedema). Some food allergens may cause anaphylaxis, a potentially life-threatening condition marked by tissue swelling, airway constriction, and drop in blood pressure. Common food allergens include the following:

•nuts, especially peanuts, walnuts, and brazil nuts

•fish, mollusks, and shellfish

•eggs

•wheat

•milk

•food additives and preservatives

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Contact route:

In contact with the skin, allergens can cause reddening, itching, and blistering, called contact dermatitis. Skin reactions can also occur from allergens introduced through the airways or gastrointestinal tract. This type of reaction is known as atopic dermatitis. Dermatitis may arise from an allergic response (such as from poison ivy) or exposure to an irritant causing nonimmune damage to skin cells (such as soap, cold, and chemical agents).

Common causes of contact dermatitis include the following:

•poison ivy, oak, and sumac

•nickel or nickel alloys

•latex

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Injection route:

Injection of allergens, from insect bites and stings or drug administration, can introduce allergens directly into the circulation, where they may cause system-wide responses (including anaphylaxis), as well as the local ones of swelling and irritation at the injection site. Insects and other arthropods whose bites or stings typically cause allergy include the following:

•bees, wasps, and hornets

•mosquitoes

•fleas

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Indoor vs. outdoor allergens:

Allergens in the home (indoor allergens):

The following are examples of allergens present in most homes throughout the year. They can cause constant irritation and inflammation of the nose, airways and skin.

•House dust mite droppings – these tiny, spider-like creatures are found all around the home, particularly in bedding (the average mattress contains about 10,000), carpets and soft furnishings

•Animal dander – tiny skin flakes covered in dried sweat and saliva, carried on the fur of cats, dogs, hamsters, guinea pigs, mice, rabbits and gerbils

•Bird feathers, cockroach droppings and mould or mildew spores

•Nuts, eggs, fish and milk in the diet

•Hair dyes, jewellery and leather goods

Tobacco smoke aggravates asthma and nasal allergies.

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Outdoor allergens:

During spring and early summer – from March to May – tree pollens are the main outdoor allergen. Silver birch pollen is the most profuse tree pollen allergen, followed by ash, London plane and oak. Grass pollens predominate from May to August, causing summer hay fever. Timothy and rye grasses produce large amounts of pollen, especially during hot sunny days following rainfall. Oil seed rape pollen, although commonly implicated, isn’t usually a cause of allergies. It’s the volatile organic compound (VOC) chemicals released by rape flowers that cause nose and eye irritation during the summer. In late summer, common weed pollens such as nettle, ragweed and dock may cause allergic symptoms. Outdoor mould, such as cladosporium spores, grows on fallen leaves in autumn and can trigger seasonal outbreaks of asthma. Horse hair is a potent allergen and exposure at stables or on riding equipment may trigger asthma, rhinitis and even urticaria.

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Allergens in hospital:

Latex rubber, found in surgical gloves, catheters, syringes and many medical appliances, can provoke allergies while in hospital or undergoing surgery. Fluids given by intravenous drip, x-ray dyes, iodine used to sterilise skin and animal proteins in vaccines can all potentially cause allergies. Medications are a common cause of allergies in hospital, especially penicillin, aspirin and anaesthetics.

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Signs and symptoms of allergy:

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The immune system normally responds to harmful substances such as bacteria, viruses and toxins by producing symptoms such as runny nose and congestion, post-nasal drip and sore throat, and itchy ears and eyes. An allergic reaction can produce the same symptoms in response to substances that are generally harmless, like dust, dander or pollen. The sensitized immune system produces antibodies to these allergens, which cause chemicals called histamines to be released into the bloodstream, causing itching, swelling of affected tissues, mucus production, hives, rashes, and other symptoms.

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Symptoms vary in severity from person to person. Symptoms depend on the allergy, but may include:

  • Sneezing
  • Runny nose
  • Red, watery and itchy eyes
  • Wheezing
  • Coughing
  • Breathing problems
  • Headache
  • Skin rash
  • Stomach pains
  • Vomiting and diarrhoea.

Do not self-diagnose. The symptoms and signs of allergies are common to many other medical conditions. It is important to see your doctor for professional diagnosis and treatment.

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Symptoms depend on the specific type of allergic reaction. Allergic rhinitis is characterized by an itchy, runny nose, sneezing, and often a scratchy or irritated throat due to postnasal drip. Inflammation of the thin membrane covering the eye (allergic conjunctivitis) causes redness, irritation, and increased tearing in the eyes. Asthma causes wheezing, coughing, and shortness of breath. Symptoms of food allergies depend on the tissues most sensitive to the allergen and whether the allergen spread systemically by the circulatory system. Gastrointestinal symptoms may include swelling and tingling in the lips, tongue, palate or throat; nausea; cramping; diarrhea; and gas. Contact dermatitis is marked by red, itchy, weepy skin blisters, and an eczema that is slow to heal. It sometimes has a characteristic pattern from the object containing the allergen, such as a glove allergy with clear demarcation on the hands, wrist, and arms where the gloves are worn, or on the earlobes by wearing earrings.

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Whole-body or systemic reactions may occur from any type of allergen but are more common following ingestion or injection of an allergen. Skin reactions include the raised, red, and itchy patches called hives that characteristically blanch with pressure and resolve within 24 hours. A deeper and more extensive skin reaction, involving more extensive fluid collection and pain, is called angioedema. This response usually occurs on the extremities, fingers, toes, and parts of the head, neck, and face. Anaphylaxis is marked by airway constriction, blood pressure drop, widespread tissue swelling, heart rhythm abnormalities, and in some cases, loss of consciousness. Other symptoms may include dizziness, weakness, seizures, coughing, flushing, or cramping. The symptoms may begin within five minutes after exposure to the allergen up to one hour or more later. Commonly, this is associated with allergies to medications, foods, and insect venoms. In some individuals, anaphylaxis can occur with exercise, plasma exchange, hemodialysis, reaction to insulin, radiocontrast media used in certain types of medical tests, and on rare occasions during the administration of local anesthetics.

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How to spot Allergic child:

Children with allergies tend to have an unhealthy looking pale complexion called ‘white dermatographism’ and are often small for their age.

Particular features, listed below, may indicate how prone your child is to allergies.

Allergic shiners:

Allergic children and adults have typical darkening around the eyes called allergic shiners. This blue discoloration is caused by congested veins and looks like smudged mascara.

Dennie-Morgan lines:

Young children with nasal and chest allergies have characteristic Dennie-Morgan lines. These are crease-like wrinkles that form under the lower eyelid folds.

Long face syndrome:

Children with asthma and nasal allergies have so-called long face syndrome: a high-arched palate and protruding upper teeth. This develops after years of constant nasal blockage. The nasal mucous membranes (turbinates) swell from irritation, so much so that the nasal passages become completely blocked. These children are forced to breathe through their mouths, which also affects tooth growth.

Nasal salute:

Intense nasal itching leads to the ‘nasal salute’ – the child tends to rub their nose with the palm of the hand, usually in an upward direction. This constant rubbing leads to a crease or wrinkle across the bridge of the nose.

Facial tics:

Children with nasal allergies tend to pull funny faces, as their noses are always itching. They may then go on to develop uncontrollable facial tics or twitches and constantly sniff, making strange noises. Teachers often complain they’re being naughty and fooling around, when the real cause is an untreated nasal allergy.

Keratosis pilaris:

Children with allergies, and potential eczema sufferers, have characteristic dryness and roughness of the skin, particularly on the cheeks, upper arms and chest. This dryness is called xerosis and usually has a sandpaper-like texture called keratosis pilaris, which reduces the skin barrier to irritants and infection.

Atopic eczema:

Atopic eczema may develop as a consequence of dry skin, especially in the elbow and knee joints of children. Children with eczema constantly fidget and scratch, leading to a misdiagnosis of being hyperactive, when in fact it’s their itchy skin distracting them.

Conjunctivitis:

With chronic eye allergies, the inner parts of the eyelids develop a swollen, cobblestone-like appearance from allergic conjunctivitis. Children also tend to rub away the outer third of their eyebrows.

Glue ear:

Children with nasal allergies may develop glue ear, when mucous becomes trapped behind the eardrum in the middle ear. This results in temporary deafness, discomfort and a poor attention span.

Postnasal drip:

Children may experience a constant postnasal drip and repeated sore throats from allergic mucous building up and being discharged into the throat. Serious nasal allergies also reduce children’s senses of taste and smell. 

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 Frequency in population:

  • Approximately 70% of individuals with food allergies also have other allergies, including hay fever.
  • Hay fever (allergic rhinitis) occurs in 15-20% of the population and about 50% of these will have some form of mouth (oral allergy syndrome; food contact hypersensitivity) or, less frequently, intestinal allergic reaction.
  • Birch pollen allergy is the form of hay fever most commonly accompanied by food allergies in the Western developed world – in up to 80%.
  • Between 30-80% of individuals with latex allergy have associated allergic reactions to food [vide infra].
  • Cross-reactivity between shellfish and house mite allergy is quite common.
  • Children with atopic dermatitis / eczema have a high prevalence (at least 30%) of food allergies, predominantly cow’s milk, egg and peanut.
  • The incidence of food-induced asthma in children is about 6% (rarer in adults), with the most frequent offending food allergies being milk, eggs, and peanuts. 

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Various allergy syndromes can be classified in two broad groups:

1. Clinical allergic syndrome where a patient presents with constellation of signs & symptoms no matter the etiology of allergy; for example allergic rhinitis may occur due to pollen or mould spore.

2. Etiological allergy syndrome where a patient presents with definite etiology of allergy with varied manifestations; for example you are allergic to pea nuts and may present with diarrhea or hives.

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Clinical allergic syndromes:

Main clinical allergic syndromes are allergic rhinitis, allergic conjunctivitis, allergic bronchial asthma, anaphylactic shock, urticaria & angioedema and allergic dermatitis.   

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Allergic rhinitis:

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Allergic rhinitis is an allergic inflammation of the nasal airways. It occurs when an allergen, such as pollen, dust or animal dander (particles of shed skin and hair) is inhaled by an individual with a sensitized immune system. In such individuals, the allergen triggers the production of the antibody immunoglobulin E (IgE), which binds to mast cells and basophils containing histamine. When caused by pollens of any plants, it is called pollinosis, and if specifically caused by grass pollens, it is known as hay fever. IgE bound to mast cells are stimulated by pollen and dust, causing the release of inflammatory mediators such as histamine (and other chemicals). This usually causes sneezing, itchy and watery eyes, swelling and inflammation of the nasal passages, and an increase in mucus production. Symptoms vary in severity between individuals. Very sensitive individuals can experience hives or other rashes. Particulate matter in polluted air, and chemicals such as chlorine and detergents, which can normally be tolerated, can greatly aggravate allergic rhinitis.

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Key clinical features of allergic rhinitis include sneezing, itching, nasal discharge and impaired nasal breathing. Depending on the time pattern of symptoms, and hence on the triggering allergen, a distinction is made between seasonal allergic rhinitis (pollinosis, hay fever) and perennial allergic rhinitis. Recent reports in the literature have also suggested a distinction between intermittent allergic rhinitis (symptoms less often than on 4 days/week or in less than consecutive 4 weeks) and persistent allergic rhinitis (>4 days/week and > consecutive 4 weeks). In seasonal allergic rhinitis, symptoms are limited to periods of pollination, but, in patients with multiple sensitizations, may be protracted over longer periods of time in spring and/or summer. Seasonal allergic rhinitis in particular may include eye reactions (conjunctivitis). The chief complaint in perennial rhinitis is impaired nasal breathing. Perennial allergic rhinitis occurs year-round and can result from sensitivity to pet hair, mold on wallpaper, houseplants, carpeting, and upholstery. Some studies suggest that air pollution such as automobile engine emissions can aggravate allergic rhinitis. Allergic rhinitis is accompanied by general symptoms such as sleep disorders or difficulty concentrating and, especially in children, may also be accompanied by increased susceptibility to upper and lower respiratory tract infections. Although bacteria is not the cause of allergic rhinitis, one medical study found a significant number of the bacteria Staphylococcus aureus in the nasal passages of patients with year-round allergic rhinitis, concluding that the allergic condition may lead to higher bacterial levels, thereby creating a condition that worsens the allergies. Patients who suffer from recurring bouts of allergic rhinitis should observe their symptoms on a continuous basis. If facial pain or a greenish-yellow nasal discharge occurs, a qualified ear, nose, and throat specialist can provide appropriate sinusitis treatment. Quality of life is significantly impaired. In addition, the chronic inflammatory reaction in allergic rhinitis substantially increases the risk of asthma. Therefore, allergic rhinitis is a condition that should be taken seriously.

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Hay fever:

As discussed earlier, hay fever is allergic rhinitis caused by grass pollen but colloquially hay fever is caused by breathing in any pollen particles and by pollen getting into the eyes. You can get hay fever at any time from early spring to late summer, depending on which pollen or pollens you’re allergic to. The pollens most likely to cause problems in early spring are those from trees such as the silver birch, ash, oak and London plane. Grasses pollinate during mid-summer from May to August. The most profusely pollinating grasses are timothy, rye, cocksfoot, meadow and fescue. Occasionally, in late summer and autumn, weeds such as nettles and dock as well as mugwort and plantain can trigger hay fever. The condition tends to occur in atopic allergy-prone families and usually starts in the early teens, with symptoms peaking in the 20s. Remember; hay fever isn’t caused by hay and does not exhibit symptoms of fever, but since grasses shed their pollens into the air at about the same time that hay is being cut, the common term hay fever is used.  

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Oral allergy syndrome:

Some people with hay fever develop oral allergies to certain fruits, vegetables and nuts. This is also called pollen-food or oral allergy syndrome (OAS). OAS can occur anytime of the year but is most prevalent during the pollen season. Individuals with OAS usually develop symptoms within a few minutes after eating the food. People with OAS typically develop hay fever in early spring and notice itching and swelling of the mouth and throat when they eat fresh fruit and vegetables. This is due to the food containing a protein similar to the allergy-provoking protein in the pollen. The hay fever usually first appears in the teens, with oral allergies developing in the 20s. It doesn’t usually progress beyond oral irritation. Those who are allergic to silver birch pollen develop oral allergies to apples, peaches, cherries, carrots, celery, hazelnuts, peanuts and walnuts. People allergic to grass pollen may develop oral allergies to tomato, melon and watermelon. Mugwort pollen allergy cross-reacts with apple, celery and carrot. Ragweed pollen allergy cross-reacts with bananas, melon and honey. People don’t react to cooked or canned foods because this alters the allergen, rendering it less able to provoke an allergy. OAS is perhaps the most common food-related allergy in adults. OAS is not a separate food allergy, but rather represents cross-reactivity between distant remnants of tree or weed pollen still found in certain fruits and vegetables. Therefore, OAS is typically only seen in tree and weed allergic patients, and is usually limited to ingestion of only uncooked fruits or vegetables. In adults up to 60% of all food allergic reactions are due to cross-reactions between foods and inhalative allergens. OAS is a Type 1 or IgE-mediated immune response, which is sometimes called a “true allergy”. The body’s immune system produces IgE antibodies against pollen; in OAS, these antibodies also bind to (or cross-react with) other structurally similar proteins found in botanically related plants.

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Non-Allergic Rhinitis does not depend on the presence of IgE and is not due to an allergic reaction. The symptoms can be triggered by cigarette smoke and other pollutants as well as strong odors, alcoholic beverages, and cold. Other causes may include blockages in the nose, a deviated septum, infections, and over-use of medications such as decongestants.

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Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis:

IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. Researchers have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occurs in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Researchers’ detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and epsilon circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and epsilon circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.

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Allergic conjunctivitis:

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Allergic conjunctivitis is inflammation of the conjunctiva (the membrane covering the white part of the eye) due to allergy. Usually associated with allergic rhinitis, conjunctivitis is triggered by mast cells located mainly in the eyelids and in the conjunctiva of the eye whose activation causes symptoms such as itching, burning, redness and increased tearing. Eye symptoms are frequent harbingers of an immediate-type allergic reaction of the airways. If allergen exposure persists, or in case of particularly intense allergen exposure, patients may develop chemosis (swelling of the bulbar conjunctiva), which may involve the cornea. Although allergens differ between patients, the most common cause is hay fever. Symptoms consist of redness (mainly due to vasodilation of the peripheral small blood vessels), oedema (swelling) of the conjunctiva, itching and increased lacrimation (production of tears). If this is combined with rhinitis, the condition is termed allergic rhinoconjunctivitis. The symptoms are due to release of histamine and other active substances by mast cells, which stimulate dilation of blood vessels, irritate nerve endings and increase secretion of tears.

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Allergic bronchial asthma:

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It is estimated that as many as 300 million people of all ages, and all ethnic backgrounds, suffer from asthma and the burden of this disease to governments, health care systems, families, and patients is increasing worldwide. It is estimated by WHO that 250,000 avoidable asthma deaths occur in the world each year. The cardinal symptom of bronchial asthma is sudden-onset breathlessness (dyspnoea) with expiratory stridor (wheezing) and a troublesome cough.The attack often begins with a sensation of tightness and dry cough. Auscultation reveals characteristic rhonchi, wheezing and sonorous rales. The sputum, often copious and expectorated with difficulty, is typically viscous. Pulmonary function testing reveals obstructive impairment of ventilation with increased airway resistance and reduced forced expiratory volume in one second (FEV1).  Regardless of the cause or pathomechanism, bronchial asthma is characterized by increased airway reactivity (bronchial hyperresponsiveness) to various stimuli: many patients with bronchial asthma report increased airway sensitivity to non-specific stimuli such as fog, smoke, exhaust fumes or pungent odors. Bronchial asthma is now defined as a chronic inflammatory airway disease on the basis of bronchial hyperreactivity. The underlying pathophysiology is highly complex, and a basic distinction is made between extrinsic allergic bronchial asthma (extrinsic = exogenously triggered asthma) and intrinsic bronchial asthma (post-infectious asthma). Allergic bronchial asthma tends to be a disease of the first half of life, typically manifesting before age 30. The most common triggers are airborne allergens such as pollen and house dust mites, as well as animal danders and mould spores. A specific form is occupational asthma, which is caused by allergens on the job and whose incidence is on the rise. Triggering allergens include plastics such as epoxy resins, rubber ingredients, latex, “baking additives”, flours or metal salts. In allergic bronchial asthma, the allergic immediate reaction in the lower respiratory tract is accompanied by airway obstruction produced by mucosal oedema and contraction of airway smooth muscle (bronchospasm). Its onset is a few minutes after allergen exposure. Approximately 6–10 hours after allergen contact, a second episode of bronchoconstriction may occur as part of the late-phase reaction and be accompanied by infiltration, mainly of neutrophils and eosinophils, resulting in bronchial hyperresponsiveness for days or weeks. Therefore, even brief allergen exposure may lead to sustained exacerbation of symptoms. An elevated IgE level may suggest allergic asthma. The differential blood count shows an increased number of eosinophils, which can also be detected by cytology in sputum.

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Study finds up to 75 percent of asthmatic adults have an allergy:

Previously it was thought that underlying allergies were only prevalent in children with allergies. In fact, almost 80 percent of children with asthma have underlying allergies, so perhaps that was not necessarily the case with adults with asthma. However, a new study published in Annals of Allergy, Asthma and Immunology found that about 75 percent of asthma sufferers aged 20 to 40 years old and 65 percent of asthmatic adults aged 55 years and older, have at least one confirmed allergy. The older asthmatic adults studied were found to be sensitive to indoor house dust mites (36 percent), followed by grass pollen (33 percent), cats (27 percent), dog (24 percent), and cockroaches (11 percent). The allergic sensitivities in those asthmatics studied in the 20-to 40-year-old groups were different: These younger patients were found to be sensitive to dogs (50 percent) and house dust mites (45 percent). The medical community has long understood the relationship between having allergies and the risk of developing asthma especially in the younger population.  However, asthma is often not well diagnosed in older adults, and so many go untreated or under-treated. This study underscores the importance of looking at allergic triggers in older and younger individuals, as well as looking at genetic history and environmental modification in evaluating and treating asthmatic individuals. Testing for possible allergies and subsequent counseling regarding environmental allergy exposures need to be strongly considered in older patients with asthma. For a long time it was considered that older patients with asthma were more likely to be characterized as being “non-allergic.” It appears from this review and others, there is increasing evidence of older individuals with asthma who are more likely to have underlying allergies. The take-home message from this study shows an even higher number of older adults with underlying allergies, clearly a significant part of their day-to-day asthma.

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Allergies and asthma: They often occur together:

Who’s at risk of allergic asthma?

A family history of allergies is a major risk factor for allergic asthma. Having hay fever or other allergies also increases risk of getting asthma.

Is all asthma caused by allergies?

Though allergic asthma is very common, there are other types of asthma with different kinds of triggers. For example, for some people, asthma can be triggered by exercise, infections, cold air, gastroesophageal reflux disease or stress. Many people have more than one kind of asthma trigger. 

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It would be inapt to discuss everything about asthma in this article as focus is on allergy and not asthma. Hence details of asthma diagnosis and management are not discussed.

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Anaphylaxis:

Anaphylaxis is an acute, potentially life-threatening hypersensitivity reaction, involving the release of mediators from mast cells, basophils and recruited inflammatory cells. Anaphylaxis is defined by a number of signs and symptoms, alone or in combination, which occur within minutes, or up to a few hours, after exposure to a provoking agent. It can be mild, moderate to severe, or severe. Most cases are mild but any anaphylaxis has the potential to become life-threatening. Anaphylaxis develops rapidly, usually reaching peak severity within 5 to 30 minutes, and may, rarely, last for several days. The term anaphylaxis is often reserved to describe IgE-mediated immunological reactions. A second term, non-IgE mediated anaphylaxis, describes clinically identical reactions that are not IgE mediated but yet serious and life threatening.   

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Anaphylaxis is classified as grades I to IV based on the intensity of clinical symptoms (see Table below). 

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The term comes from the Greek words ana, against, and phylaxis, protection. Anaphylaxis is the most severe form of an immediate allergic reaction and may involve the entire body. Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Worldwide 0.05–2% of people are estimated to have anaphylaxis at some point in their life and rates appear to be increasing. It typically causes a number of symptoms including an itchy rash, throat swelling, and low blood pressure. Common causes include insect bites/stings, foods, and medications. Classically, the term anaphylaxis is confined to denote the IgE-mediated immediate reaction. However, specific IgG and IgM antibodies may, via the formation of circulating immune complexes, also trigger similar, complement-dependent symptoms (immune complex anaphylaxis). Non-immunologic anaphylaxis includes non-immunologic mechanisms involved substances that directly cause the degranulation of mast cells and basophils. These include agents such as contrast medium, opioids, temperature (hot or cold), and vibration.

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The triggering molecule is usually taken up percutaneously or orally, but entry from the air is also possible.

Common triggers include:

  • foods
  • insect venoms
  • drugs
  • additives
  • natural latex
  • airborne allergens

Physical triggers like cold or exercise (exercise-induced anaphylaxis) or anaphylaxis of unknown origin have also been described. Moreover, allergen application during specific immunotherapy may rarely trigger severe systemic allergic reactions. In many cases, anaphylactic symptoms occur only in response to the combined exposure to different stimuli, such as allergen exposure in combination with physical exercise, additional emotional stress or acute infection. This phenomenon is referred to as augmentation or summation. The use of beta-blockers and possibly also of ACE inhibitors may lead to exacerbation of anaphylactic symptoms. Anaphylaxis typically presents with many different symptoms over minutes or hours with an average onset of 5 to 30 minutes if exposure is intravenous and 2 hours for foods. The most common areas affected include: skin (80–90%), respiratory (70%), gastrointestinal (30–45%), heart and vasculature (10–45%), and central nervous system (10–15%) with usually two or more being involved.

Symptoms include:

  • on the skin: itching, erythema (flushing), urticaria and angioedema
  • in the oral cavity: itching of the palate and tingling in the throat; these are often the initial symptoms of anaphylaxis
  • in the respiratory tract: rhinorrhea, hoarseness and bronchospasm to the point of respiratory arrest
  • in the gastrointestinal tract: nausea, vomiting, cramps and defecation
  • in the cardiovascular system: tachycardia, blood pressure drop, occasionally also transient blood pressure increase, shock and arrhythmia to the point of circulatory arrest. Great fluctuations of central venous pressure are characteristic.

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Urticaria and angioedema:

An immediate allergic reaction on the skin or mucous membranes may manifest as urticaria or angioedema or both.

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Angioedema:

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Angioedema is the rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis. The term angioneurotic oedema was used for this condition in the belief that there was nervous system involvement, but this is no longer thought to be the case. Cases where angioedema progresses rapidly should be treated as a medical emergency, as airway obstruction and suffocation can occur. The skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue, swell up over the period of minutes to several hours. The swelling can also occur elsewhere, typically in the hands. The swelling can be itchy or painful. There may also be slightly decreased sensation in the affected areas due to compression of the nerves. Urticaria (hives) may develop simultaneously. In severe cases, stridor of the airway occurs, with gasping or wheezy inspiratory breath sounds and decreasing oxygen levels. Tracheal intubation is required in these situations to prevent respiratory arrest and risk of death. The hereditary form (HAE) often goes undetected for a long time, as its symptoms resemble those of more common disorders, such as allergy or intestinal colic. An important clue is the failure of hereditary angioedema to respond to antihistamines or steroids, a characteristic that distinguishes it from allergic reactions.  

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Urticaria:

Urticaria (from the Latin urtica meaning nettle) commonly referred to as hives, is a kind of skin rash notable for pale red, raised, itchy bumps. Hives might also cause a burning or stinging sensation. Symptoms of urticaria include characteristic wheals from oedema of the upper cutis, surrounded by erythema, and localised itching or burning. This wheal-and-flare reaction may develop within a matter of minutes and typically resolves spontaneously after a few hours. The same wheals are observed following the injection of histamine or allergens into the skin, and this is made use of in the diagnosis of allergic conditions. There are various forms of urticaria, and immunologic and non-immunologic forms can be distinguished. A possible classification of urticaria is based on clinical course: acute urticaria lasts less than six weeks, while chronic urticaria lasts more than six weeks. Intermediate forms are acute intermittent urticaria (several acute episodes) and chronic recurrent urticaria (continual episodes separated by brief asymptomatic intervals of one to two days). The most likely triggers for acute urticaria are allergies to pets, horses, latex and foods, such as shellfish and nuts in adults and eggs and cow’s milk in children.  Other possible causes include bee or wasp stings, and allergies to medicines such as antibiotics, blood pressure pills and aspirin. Viral infections, such as glandular fever and herpes, dental and sinus infections, fungal infections, blood transfusions and vaccines can also cause acute urticaria. Acute viral infection is a common cause of acute urticaria (viral exanthema). The cause of chronic urticaria is often more difficult to identify. Chronic urticaria is rarely due to an allergy. The majority of chronic hives cases have an unknown (idiopathic) cause. In perhaps as many as 30 to 40% of patients with chronic idiopathic urticaria, it is caused by an autoimmune reaction. Chronic bacterial and parasitic infections, long-term use of blood pressure drugs, underlying thyroid disease and autoimmune diseases such as lupus can provoke urticaria.  Chronic urticaria is often accompanied by coexistent physical urticaria, triggered by environmental exposure to heat, cold, sunlight, vibration, pressure on the skin or even exercise. Most people with urticaria have such sensitive skin that any rubbing will cause raised red lines to develop. This is called dermatographism.  Physical urticaria is triggered by physical factors and lasts only an hour or two.  Urticaria may occur as part of immediate-type reactions concomitantly with allergic airway symptoms. Oedema of the pharynx and larynx including the glottis are particularly serious because of the potential risk of suffocation. If tissue oedema occurs in the subcutis, the condition is referred to as angiooedema (angioneurotic oedema). It commonly occurs on the lips, eyelids and genitals

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Hives (urticaria) are raised, red, itchy welts, as seen in the figure above. The majority of urticaria develops as a result of allergic reactions. Occasionally they may be associated with autoimmune diseases, infections (parasitosis), drugs, malignancy, or other causes.

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Allergic contact dermatitis:

Allergic contact dermatitis (ACD) is a form of contact dermatitis that is the manifestation of an allergic response caused by contact with a substance; the other type being irritant contact dermatitis (ICD). Although less common than ICD, ACD is accepted to be the most prevalent form of immunotoxicity found in humans. By its allergic nature, this form of contact dermatitis is a hypersensitive reaction that is atypical within the population. As such, ACD is termed a Type IV delayed hypersensitivity reaction involving a cell-mediated allergic response. Contact allergens are essentially soluble haptens (low in molecular weight) and, as such, have the physico-chemical properties that allow them to cross the stratum corneum of the skin. They can only cause their response as part of a complete antigen, involving their association with epidermal proteins forming hapten-protein conjugates. This, in turn, requires them to be protein-reactive. The conjugate formed is then recognized as a foreign body by the Langerhans cells (LCs) (and in some cases other Dendritic cells (DCs)), which then internalize the protein; transport it via the lymphatic system to the regional lymph nodes; and present the antigen to T-lymphocytes. This process is controlled by cytokines and chemokines – with tumor necrosis factor alpha (TNF-alpha) and certain members of the interleukin family (1, 13 and 18) – and their action serves either to promote or to inhibit the mobilization and migration of these LCs. As the LCs are transported to the lymph nodes, they become differentiated and transform into DCs, which are immunostimulatory in nature. Once within the lymph glands, the differentiated DCs present the allergenic epitope associated with the allergen to T lymphocytes. These T cells then divide and differentiate, clonally multiplying so that if the allergen is experienced again by the individual, these T cells will respond more quickly and more aggressively. Common allergens include nickel, gold, some drugs etc.

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Atopic dermatitis: 

This condition (also called atopic eczema or infantile eczema) affects people with dry and rough skin (keratosis pilaris) and may be caused by a variety of allergens. Atopic dermatitis (eczema with demonstrable IgE association) is an inflammatory, relapsing, non-contagious and pruritic (itchy) skin disorder. With a prevalence of 2-5% (in children and young adults approximately 10%), atopic eczema is one of the most commonly seen dermatoses.  Atopic dermatitis is caused by allergens introduced through the airways or gastrointestinal tract and it is a type-1 immediate hypersensitive reaction. The skin of a patient with atopic dermatitis reacts abnormally and easily to irritants, food, and environmental allergens and becomes very itchy, which leads to scratching, redness, and flaky skin. It often starts in early childhood, around three months of age, and tends to run in atopic families. Atopic eczema is the most common inflammatory skin disease of childhood in developed countries. The cause of atopic eczema is probably due to a combination of genetic and environmental factors. Atopic eczema varies in severity, often from one hour to the next and the disease can be associated with complications such as bacterial and viral infections.

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The figure below shows atopic dermatitis in a baby:

 

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Possible causes of atopic dermatitis include:

•Food allergy, which plays an important role in children under one year but not in adults

•Cow’s milk, hen’s eggs and peanuts are the foods most likely to exacerbate infantile eczema

•House dust mites tend to aggravate eczema in older children and adults

•Pet dander exposure, such as to cats, dogs and other furry animals, may play a role

•Certain bacteria may cause sudden, severe outbreaks of eczema

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Pediatric and adult eosinophilic esophagitis (EoE):

Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th2)-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen–driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. 

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Allergic March:

The “Allergic March” is a term that describes how allergic diseases progress throughout one’s life. Numerous studies have shown that allergic diseases can progress from one form to another throughout a child’s life – a phenomenon termed the ‘allergic march’, which now affects 15-30% of children in Western countries. The term “allergic march” [also called atopic march] refers to the natural history of atopic manifestations, which is characterized by a typical se­quence of immunoglobulin E (IgE) antibody responses and clinical symptoms that appear early in life, persist over years or decades, and often remit spontaneously with age. Although the production of IgE starts in the 11th week of gestation, no specific sensitization to food or inhalant allergens can be detected in cord blood with standard methods for measuring elevated serum IgE antibodies. Skin allergy or eczema is usually the first sign of allergic disease in young infants and is often associated with an underlying food allergy. These children are then more likely to go on to develop respiratory allergies, such as asthma and hay fever. If your infant has eczema or egg allergy, it doesn’t necessarily mean that they will go on to develop other, more serious allergic conditions. However, it does mean that they have an increased risk of following the allergic march. Up to 20% of children with eczema go on to develop peanut allergy by the age of 3, and 80% of these children will remain allergic for life. Scientists now believe that prevention of allergic diseases early in life can pay dividends by preventing progression along the allergic march. Since allergic disease is immune-mediated, the most obvious target for new therapies is the earliest stages of the allergic immune response. 

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The range of allergic disorders:

Allergy plays a role in various disorders and allergic reactions can be acute, chronic, mild or severe. For conditions such as asthma, rhinitis, eczema and urticaria, commonly regarded as allergic in origin, allergy plays a role in some patients but not in others. As an example, asthma may be triggered by allergy, but can also be caused by viral infections, pollution and stress. Skin disorders such as dermatitis, urticaria and angioedema, can be caused by both atopic and non-atopic allergic mechanisms as well as non-allergic pathways. Thus, although swelling, itching and redness are found in many of these conditions it is often very difficult to establish a clear association between a specific allergy and the skin disease. The Royal College of Physicians’ report noted that the importance of allergy may also change with time. For example, milk and egg allergy are prevalent in young children but these are often replaced by other allergies as the individual ages. Throughout this article the term “allergic disorders” is used as a generic term to refer to disorders in which allergy can play a role.

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Etiological allergy syndromes:

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Drug allergy:

Reactions to medication are extremely common. In fact, 15-30% of all hospitalized patients will experience an unintended reaction as a result of medications. However, true allergic reactions to medications only occur in about 1 of 10 of all adverse drug reactions. 

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There is a popular misconception that adverse drug reaction (ADR) means drug allergy. The table below shows various ADRs with allergy being only one of the causes of ADR.

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Drug allergies are a group of symptoms caused by an allergic reaction to a medication. Not every adverse reaction to a drug, however, is a drug allergy. Adverse, or negative, reactions to drugs can, according to the World Allergy Organization, be divided into predictable reactions (pharmacologic actions of the drug in an otherwise ‘normal’ person) and unpredictable reactions (related to an individual’s immune response in susceptible patients). A drug allergy is a type of unpredictable reaction, and is much less common than other adverse reactions. In fact, the Organization notes, that adverse drug reactions account for 3-6% of all hospital admissions, but drug allergies comprise fewer than 10% of all adverse reactions. A drug allergy differs from drug intolerance. Drug intolerance, or an adverse side effect from a drug, doesn’t involve the immune system at all. Common drug intolerance is stomach upset. As opposed to an allergic situation, however, you may be able to continue taking your medication if you have a drug intolerance. Sometimes taking the medicine with food or taking a lower dose alleviates the symptom. Often drug intolerance will dissipate as you continue to take your medication. 

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Drugs that cause allergic reactions include:

  • Antibiotics – penicillin, sulphonamides, tetracycline, chloramphenicol and cephalosporins
  • Heart drugs – ACE inhibitors, quinidine, amiodarone, methyldopa
  • Anaesthetic drugs – muscle relaxants, thiopentone, halothane
  • Morphine derivatives – morphine, pethidine and codeine
  • Aspirin-like drugs – diclofenac, ibuprofen, indomethacin
  • Cancer chemotherapy drugs – cisplatin, cyclophosphamide, methotrexate
  • Antiseptics – chlorhexidine, iodine
  • Vaccines – such as tetanus toxoid and diphtheria vaccine
  • Preservatives and colourings in medication – such as sulphites, sodium benzoate and tartrazine
  • Anti-epileptic, anti-tuberculosis medication, heparin, insulin, enzymes and latex

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The World Allergy Organization notes that risk factors for a drug allergy include both drug factors and host factors.

Drug risk factors include:

  1. the nature of the drug (penicillins, aspirin and sulfonamides make up over 80% of allergic drug reactions), degree of exposure, with higher drug doses and longer administration causing more severe reactions,
  2. the route of administration, with topical application causing the highest degree of allergy-related issues (for this reason penicillin is no longer used topically at all.) and injections posing a greater risk than oral medication, and
  3. ‘cross-sensitization,’ meaning that once a reaction to a certain drug has taken place, the likelihood of a reaction to drugs with similar chemical structures increases.

Host (the individual taking the drug) risk factors include:

  1. age (some allergic reactions are less common among children due the immaturity of the immune response system and the lack of repeated exposure to drugs necessary to set the body off),
  2. genetic factors,
  3. co-morbid illnesses  (those with compromised immune systems are at greater risk), and
  4. previous drug exposure (those who have been allergic to drugs in the past may have a greater likelihood of developing allergies to new drugs).

Also a history of other allergies, even hay fever, increases your likelihood of an allergic reaction, as does taking several drugs at the same time. Additionally, those with asthma, heart disease and high blood pressure are at a greater risk for developing a more severe reaction.

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Most true allergic reactions to drugs affect the skin (although other organs may also be involved), but serious cutaneous reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome are rare. Skin responses caused by drug allergy often resemble those occurring in the absence of drug exposure, and a detailed medical history exploring the temporal relationship to the drug exposure is vital. The range of allergic skin responses, their identification, causes and treatment are described by Ardern-Jones & Friedmann. By contrast, non-cutaneous severe allergic reactions such as anaphylaxis are infrequent, perhaps accounting for only 10% of all allergic responses. Importantly, even these reactions can be mimicked by pseudoallergic responses to drugs.

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Food allergy:

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The figure below shows that perception of food allergy is far higher than actual food allergy.

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Reactions to food are common. These reactions range from mild to severe, and may result from your body’s negative response to certain foods or from a true food allergy.  A wide variety of foods can cause allergic reactions, but 90% of allergic responses to foods are caused by cow’s milk, soy, eggs, wheat, peanuts, tree nuts, fish and shellfish. Other food allergies, affecting less than 1 person per 10,000 population, may be considered “rare”. Egg allergies affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5. The sensitivity is usually to proteins in the white rather than the yolk. Milk allergies are the most prevalent in children. Some sufferers are unable to tolerate milk from cows, goats, or sheep, and many sufferers are also unable to tolerate dairy products such as cheese. Lactose intolerance, a common reaction to milk, is not a form of allergy, but rather due to the absence of an enzyme lactase in the digestive tract. Food allergy is thought to develop more easily in patients with the atopic syndrome, a very common combination of diseases: allergic rhinitis and conjunctivitis, eczema and asthma. The syndrome has a strong inherited component; a family history of allergic diseases can be indicative of the atopic syndrome.

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The most common food allergies in adults are shellfish, peanuts, tree nuts, fish, and egg. The most common food allergies in children are milk, eggs, peanuts, and tree nuts. Six to eight percent of children under the age of three have food allergies and nearly four percent of adults have food allergies. But people of any age can have sudden allergic reactions to a food that had previously not been a problem for them. Some children seem to grow out of their sensitivity to certain foods, often by age 4. Allergies to peanuts, tree nuts and shellfish usually do not go away, though. For reasons that are not entirely understood, the diagnosis of food allergies has apparently become more common in Western nations in recent times. In the United States, food allergy affects as many as 5% of infants less than three years of age and 3% to 4% of adults. There is a similar prevalence in Canada.

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Food allergy statistics in the U.S.

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Most known food allergens are proteins. However, carbohydrate epitopes can also act as allergens, as is seen with delayed immunoglobulin E (IgE)-mediated reactions to galactose-alpha-1,3-galactose (alpha-gal) in meat. A second carbohydrate allergen has been identified in several case series of patients with acute allergic reactions to beverages containing short-chain galactooligosaccharide (scGOS), a prebiotic used as a supplement in cow’s milk formula and other beverages. The patients in these case series all tolerated other dairy products and had no history of cow’s milk allergy. All reported cases occurred in Southeast Asia in patients who were over two years of age, suggesting that there is a primary sensitizing agent (e.g., aeroallergen) specific to the region. 

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The Food Allergy Pyramid:

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The pyramid depicts the most allergic food groups at the top, and the rest in descending order. The severe allergens are reactive for most people. The strong and moderate food groups are reactive for many people. And the mild food groups are usually safe for most people. However, rare individuals can have life-threatening reactions to seafood, nuts and beans. So take this also into consideration. Scores are based on the Biotype Research, which includes 4 kinds of food allergies.

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 What are the symptoms of food allergy?

Reactions can affect different body systems:

•The digestive tract, which first comes into contact with food. Some symptoms, such as swelling and itching of the lips, the lining of the mouth as well as throat tightness and hoarseness may occur quickly. When the food enters the stomach and then the intestines, nausea, cramping, pain, vomiting and diarrhea may occur.

•Body systems, such as the skin, lungs and blood vessels, that are affected after the food leaves the digestive tract. These reactions can occur in minutes or within two hours. Often, hives and swelling of the skin occur. Anaphylaxis, the most dangerous and life-threatening result of a food allergy, usually occurs within minutes after consuming the food. When this happens, blood vessels widen so much that blood pressure falls. Symptoms include wheezing, difficulty breathing, throat tightness, nausea, rapid pulse, flushing, faintness, itching of the palms and sole of the feet and even passing out. Without speedy treatment, this intense allergic reaction can cause death.

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The typical allergic reaction to a food occurs within four hours after it has been eaten. Occasionally, there is a delay of about eight hours, but symptoms that occur a day or more after exposure are rarely from an allergy. The picture is further confused by the unpredictability of food allergies. A food does not necessarily cause the same symptoms in everyone who is allergic to it: some people might experience mild itching and others cardiovascular collapse. In addition, a person might not react to each exposure, depending on the amount of the food consumed, how often it is eaten and coincidental exposure to other allergy triggers, such as pollen. Even vigorous exercise, when done soon after eating a particular food, can intensify an allergic reaction, perhaps by speeding the absorption of the food.  

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What can be done to avoid developing Food Allergies?

To prevent or modify the development of food allergy, identify early in life people who are most at risk:

  • Those with a family history of allergy
  • Babies with allergy antibodies in their umbilical cord blood or serum
  • Infants less than 12 months old with antibodies to egg and other foods including peanut, codfish and milk

Consult a doctor about whether to test an infant for allergy antibodies. If positive, talk with the doctor about how to decrease the incidence and severity of the food allergy. Allergic reactions to cow’s milk or soy formula can appear within days or months after birth. There is evidence that infants who are breast-fed exclusively during their first six to 12 months of life develop fewer allergies by age one or two than infants fed with formula. The American Academy of Pediatrics (AAP) recommends exclusive breast-feeding as ideal nutrition for about the first six months of life. Furthermore, a maternal diet that avoids eggs, cow milk, peanuts and fish while nursing may help reduce eczema in infants. It’s important for a doctor to review cases of food allergy on a regular basis. Some types can change and improve over time, especially in the case of children, who often grow out of sensitivities such as cow’s milk protein allergy. Checking will mean you don’t keep imposing an unnecessary dietary restriction on yourself.

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Latex allergy:

Common latex products include

  • Gloves
  • Condoms
  • Balloons
  • Rubber bands
  • Shoe soles
  • Pacifiers

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Latex can trigger an IgE-mediated cutaneous, respiratory, and systemic reaction. The prevalence of latex allergy in the general population is believed to be less than one percent. In a hospital study, one in 800 surgical patients (0.125 percent) report latex sensitivity, although the sensitivity among healthcare workers is higher, between seven and ten percent. Researchers attribute this higher level to the exposure of healthcare workers to areas with significant airborne latex allergens, such as operating rooms, intensive-care units, and dental suites. These latex-rich environments may sensitize healthcare workers who regularly inhale allergenic proteins. The most prevalent response to latex is an allergic contact dermatitis, a delayed hypersensitive reaction appearing as dry, crusted lesions. This reaction usually lasts 48 to 96 hours. Sweating or rubbing the area under the glove aggravates the lesions, possibly leading to ulcerations.  Anaphylactic reactions occur most often in sensitive patients, who have been exposed to the surgeon’s latex gloves during abdominal surgery, but other mucosal exposures, such as dental procedures, can also produce systemic reactions.  

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The most common clinical presentation of latex reaction is a nonimmunologic, irritant dermatitis of the hand. Contact dermatitis (type IV delayed hypersensitivity reactions to rubber additives) is the most common immunologic manifestation of latex rubber allergy. Type I allergic responses are less common and include contact urticaria, rhinoconjunctivitis, asthma, and anaphylaxis. Seven percent to 10% of health care workers regularly exposed to latex and 28% to 67% of children with spina bifida have a positive skin test result to latex proteins indicating increased blood levels of IgE antibody. About one third of patients with positive skin test results, however, do not yet have symptoms of latex allergy. Systemic (life-threatening) anaphylactic shock can occur intraoperatively in highly sensitive patients because of mucosal absorption of latex protein allergens from the surgeon’s gloves. The present treatment for latex allergy is careful avoidance of latex materials. In addition, the use of powder-free latex gloves can eliminate airborne latex exposure and can allow health care workers with inhalant allergic reactions to return to work. A reduction of the total protein level on latex rubber devices may prevent further sensitization and eliminate latex allergic reactions.

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Latex-Fruit Syndrome and Class 2 Food Allergy:

It is estimated that 50-70 % of latex-allergic people have IgE antibodies cross-reactive to the antigens coming from some vegetable foods. In addition, increasing numbers of plant-derived foods are suspected to cross-react with latex antigens. Fruits are especially notorious for their frequent cross-reactivity, which is referred to as “latex-fruit syndrome”. Besides various plant-derived foods, latex-allergic people are occasionally affected by some kinds of pollen and medical plants. These patients often have perioral itching and local urticaria. Only occasionally have these food-induced allergies induced systemic responses. Researchers suspect that the cross-reactivity of latex with banana, avocado, kiwifruit, and chestnut occurs because latex proteins are structurally homologous with some plant proteins. This extensive cross-reactivity of latex-allergic patients is due to the fact that major latex allergens are defense-related proteins of a rubber tree. Higher plants universally induce such protective proteins under certain conditions, and their structures are relatively conserved during the course of evolution. These features of defense-related proteins provide common epitopes for IgE antibodies. In other words, it is considered that the defense-related proteins of the rubber tree and of cross-reactive plants act as pan-allergens responsible for the extensive cross-reactivity of latex-sensitized people. List of the Suspected Vegetable, tree, pollen include banana, avocado, potato, tomato, kiwi, chestnut, walnut, passion fruit, pear, grapefruit, mushroom, bell pepper, mango, pineapple, celery, cantaloupe, apple, papaya, almond, buckwheat, fig, lettuce, peach, orange, peanut, strawberry, pepper, mustard, watermelon, bamboo shoot, carrot, coconut, apricot, loquat, peppermint, soybean, cherry, nectarine, ragweed, mugwort, timothy, Kentucky blue grass, Condurango bark, Cannabis, …..

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Latex-fruit syndrome and oral allergy syndrome are class 2 food allergy as shown in the figure above.

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Mold Allergy:

Molds are a kind of fungus, the most common found on earth. There are 1.5 million species of mold, making up 25 percent of the earth’s biomass. However, only 80 species are known to trigger allergic reactions. Many types of molds (microscopic fungi) live in our environment. Mold grows in indoor and outdoor areas that are warm, dark and/or moist. Molds reproduce and grow by sending tiny spores into the air. Inhaled spores cause allergy and asthma symptoms. Examples of allergy symptoms include itchy eyes, runny nose and rash. Mold grows easily in most humid, warm conditions, but it also can occur in conditions that are cool and, rarely, even dry. A common name for mold found indoors is mildew. Mold spreads by way of spores, which are like tiny airborne seeds. Most molds in the home originate outdoors. Mold spores can waft in, or be carried in on clothes. Mold finds hospitable ground and colonizes in wet basements, humid crawl spaces, and anywhere leaks, high humidity or condensation are present. The microscopic spores that mold uses to spread and reproduce are the primary culprits in mold allergies. When inhaled, they can cause respiratory allergic symptoms and, potentially, other health problems. Although mold growth isn’t a reason to panic, large areas of mold growth may require a special cleanup in order for a residence to be habitable.

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Venom allergy:

An initial sting by a wasp or honeybee causes a person to become sensitised. It may take up to six weeks for someone to become fully reactive. This means their first sting may have no ill effects, but subsequent stings are likely to cause an allergic reaction. An enzyme in sting venom provokes the allergic reaction. Wasps can inflict multiple stings, while a bee leaves its stinger in the skin and dies immediately. Venom allergic reactions usually occur within ten minutes of the sting. Life-threatening reactions may occur in highly allergic individuals, older people and those with heart and respiratory diseases, especially if someone experiences multiple stings. Stings on the face and neck may react worse than stings on a finger or toe. Bee keepers and gardeners are high-risk groups for bee sting anaphylaxis. Such people ought to carry injections of epinephrine, sometimes through a device known as the EpiPen or Twinject auto-injector for emergency treatment of anaphylaxis.

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Cockroach allergy:

Cockroach allergies are remarkably common, and some researchers believe the incidence is rising. One-third of people with other documented allergies are sensitive to cockroaches, but so are up to 12 percent of individuals without any other known allergies. Cockroach allergies may be dangerous to people with asthma, as exposure may cause severe attacks in over half of those diagnosed. Even if you’ve never seen a cockroach in your home, the allergen may be present. It is not necessarily a reflection of the cleanliness of your home. Cockroaches live in walls and other places you cannot see or easily clean. Cockroach allergies can cause sneezing, wheezing, itchy eyes, cough and other symptoms common to allergic rhinitis. As in other common allergies, symptoms can range from mild to severe. But cockroach allergies may have especially dangerous health consequences to children. One study showed that kids who were allergic to cockroaches were hospitalized for asthma 3.3 times more often than other children—including children with allergies to dust mites or cats. Twenty-three percent to 60 percent of city dwellers with asthma are allergic to cockroaches. Some researchers believe that the rise in cases of asthma among urban children is due to increased contact with cockroach allergens, especially since kids play indoors more than they used to. Proteins in cockroach feces, saliva and bodies are thought to be the major culprit in triggering allergic responses.

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Pet allergy:

Pet allergy is an allergic reaction to proteins found in an animal’s skin cells, saliva or urine. Signs of pet allergy include those common to hay fever, such as sneezing and runny nose. Some people may also experience signs of asthma, such as wheezing and difficulty breathing. These reactions can make asthma, rhinitis, and/or eczema (atopic dermatitis) symptoms worse in some people. Most often, pet allergy is triggered by exposure to the dead flakes of skin (dander) a pet sheds. Any animal with fur can be a source of pet allergy, but pet allergies are most commonly associated with cats, dogs, rodents and horses. A person can develop allergies with repeated exposure.

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Pets have allergies too:

Common allergens affecting pets are the pollens from trees, grass and weeds, mold spores, house dust and dust mites. Even that wool rug that your pug likes to curl up on may be causing her allergy symptoms. Airborne allergies usually start early in a pet’s life and are associated with irritation in certain parts of the body. In dogs these areas present as skin irritations around the eyes and mouth, ears, armpits, feet legs and around the anus. Owners of pets with allergy seek relief for their pets’ allergy symptoms. Short courses of steroids, antihistamines, medicated shampoos all help short term but do not address the underlying problem and that are the allergy itself.

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Dust Mite Allergy:

Dust mites are microscopic animals, too small to be seen with the naked eye, that feed on human skin scales. They persist in bedding, carpets, stuffed furniture, old clothing and stuffed toys. Dust mites are most common in humid climates, and they don’t survive when the humidity is below 50 percent. If droppings of dust mites are inhaled or come in contact with the skin, they may cause allergic symptoms and aggravate asthma and/or eczema. Examples of allergy symptoms include itchy eyes, runny nose and rash. 

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The figure below shows dust mite allergy cycle.

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Pollen Allergy (vide supra):

Pollen from trees, grasses and weeds can be inhaled and cause allergy and asthma symptoms. Pollen may travel many miles in the wind, so trees, grasses and weeds beyond your immediate area can cause allergy and asthma symptoms. Pollen allergies are often seasonal, and allergy and asthma symptoms occur when the amount of pollen in the air is high. Examples of allergy symptoms include itchy eyes, runny nose and sneezing. Examples of asthma symptoms can be coughing, wheezing and difficulty breathing. These symptoms may vary depending on weather conditions and where you live. Once an allergy has been identified, your healthcare provider may recommend medications or therapies to control symptoms. The next step is to decrease or eliminate exposure to the allergen. This is called environmental control. Evidence shows that allergy and asthma symptoms may improve over time if the recommended environmental control changes are made.

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Pollen count;

As a ritual, each spring summer and fall, tiny particles known as pollen are released from trees, grasses and weeds. Pollen is transported by air currents and enters human noses and throats, triggering an allergic reaction named allergic rhinitis. According to the National Institute of Allergies and Infectious Diseases, a branch of the National Institute of Health, approximately 35 million Americans complain from upper respiratory symptoms related to pollen. Pollen count is a measure of how much pollen is in the air in a certain area at a specific time. It is expressed in grains/spores of pollen per cubic meter of air collected over 24 hours. Pollen counts tend to be highest early in the morning on warm, breezy days and lowest during chilly, wet periods. Weather conditions during pollination can affect the amount of pollen produced and its distribution. Thunderstorms can precipitate respiratory difficulties. Initially, windy conditions that usually precede storms stir dust, mold, pollen and this may activate allergies. Later on, heavy rains tend to break pollen into small particles, allowing the smaller pieces to be inhaled deeper into the lungs and causing more significant symptoms. Due to climate change, pollen counts are expected to more than double by 2040.

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Pollen Graph & Chart:

Pollen count is the measurement of the number of grains/spores of pollen in a cubic meter of air. The higher the number, the more people will suffer if they are allergic to a particular pollen (hay fever). Usually, the counts are announced for specific plants such as grass, ash or olive. These are tailored to what is usually a common plant in the area being measured. The purpose of the pollen graph is to quickly inform the reader of the day’s pollen/spore conditions. The pollen graph also provides the reader with a reference point so the count can be interpreted. In each daily count the average grains/spores per meter3 of each category of pollen/spores (trees, grasses, weeds and molds) will be calculated.  The calculated numbers will be compared against the chart below and graphed accordingly. 

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Range

Low

Medium

High

Very High

Percentile

(<50th)

(50th-75th)

(75th-99th)

(>99th)

Trees

<15

15-91

91-1500

>1500

Grasses

<10

10-50

51-500

>500

Weeds

<10

10-50

51-500

>500

Molds

<900

900-2500

2501-25000

>25000


The chart was adapted from an article in The Pollen Monitor by David A. Frenz.  Frenz’s chart was derived from pollen and mold counts in 51 cities in the United States by Burge (1992).  Frenz arranged the count data for each pollen/spore class in descending order and divided the data into four classes (low, medium, high and very high) according to the percentile.  

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Seasonal allergy (due to pollens):

It takes repeated exposure for allergies to develop fully, so several seasons might pass before a condition like hay fever sets in―which is why most kids don’t develop allergies until they’re 4 or 5. Seasonal allergies continue to develop throughout life.  New allergies can occur in any decade, but generally they tend to peak at around age 20. The season typically begins in early spring, when trees, including oak, cedar, elm, birch, ash, maple, and walnut, start to pollinate. Grasses, such as timothy, Bermuda, orchard, and some bluegrasses, germinate in late spring and early summer. Weeds, like sagebrush, tumbleweed, and ragweed―by far the most prevalent seasonal allergen, affecting 75 percent of sufferers―kick in during late summer and early fall. (Goldenrod, often confused with ragweed, is sometimes blamed for allergy symptoms, but it actually produces sticky, nonairborne pollen.) Many people think that if they can just make it to fall, they’re in the clear. Unfortunately for some, moldy leaves, an often overlooked allergen, can extend symptoms almost until winter.

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Cold urticaria:

Cold urticaria is an allergy to cold temperatures. With cold urticaria, exposure to cold temperatures causes redness, itching, swelling and hives on the skin that has been in contact with the cold. As much as possible, people with cold urticaria should avoid exposure to cold air and cold water. For example, swimming in cold water is the most common cause of a severe, whole-body reaction — leading to fainting, shock and even death. Mycoplasma pneumonia and mononucleosis have been linked to cold urticaria. The disease is classified as chronic when hives appear for longer than 6 weeks; they can last for life, though their course is often unpredictable. This disorder, or perhaps two disorders with the same clinical manifestations, can be inherited (familial cold urticaria) or acquired (primary acquired cold urticaria). The acquired form is most likely to occur between ages 18–25. Known as secondary acquired urticaria, this less common type of cold urticaria can be caused by an underlying health problem, such as rheumatoid arthritis, hepatitis or cancer.

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Researcher Joshua Milner may know at least part of the reason. In a study published by the New England Journal of Medicine, Milner and his colleagues found a genetic mutation in 27 people from three families who all had cold urticaria mixed with other immune system abnormalities and disorders. In trying to understand the link between this group of conditions — autoimmunity, chronic infections and cold urticaria — researchers not only identified a disease-causing mutation but uncovered a unique and fascinating genetic mechanism at the crux of allergy, immune defense and self-tolerance.

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Heat allergy:

Just as you can be allergic to cold, you can also be allergic to heat. People with heat urticaria develop itchy, red, swollen skin and welts when they’re exposed to temperatures above 109.4 degrees Fahrenheit. These reactions typically occur from an increase in body heat brought on by exercise, hot showers, saunas, blankets or even spicy foods.

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Sun allergy:

Sun allergy is a problem, which is triggered by exposure to sunlight. The different types of sun allergy include polymorphic light eruption (PMLE), actinic prurigo, chronic actinic dermatitis (CAD) and solar urticaria. The symptoms that you experience depend on the particular type of sun allergy you have. Sunlight Allergies may affect up to 20 Percent of the world’s population. The polymorphous light eruption — PMLE –is a condition that’s estimated to affect 5 to 20 percent of the global population. Women seem to be more susceptible than men, and in some cases, there can be a hereditary or genetic component. The condition often arises in early adulthood, but young children sometimes contract a related allergy — juvenile spring eruption — that tends to attack the ears and face. Childhood sun allergies usually improve with increased sun exposure and disappear with age. Not so for adult-onset sun allergies. There is little connection between solar allergies and skin color.  Sun allergies are unrelated to how light your skin is or how easily you sunburn. PMLE symptoms are rarely life threatening, and they typically vanish within hours, unlike sunburn, which often doesn’t appear until 24 hours after sun exposure, and can last for weeks. Though some medical experts don’t recognize PMLE as a true allergy, the body’s immune system identifies a foreign invader — in this case sun-altered skin — and unleashes a defense in the form of antibodies. Both topical and oral medications can cause allergic reactions when skin is exposed to sunlight. Sunscreens and products that contain chemical sunblock rather than mineral sunblock are often the culprit in breakouts as well. That means slathering on sunscreen containing zinc oxide or titanium dioxide whenever you go out or plan to spend time near windows. Besides being a potential allergen, chemical-based sunscreens don’t block the entire spectrum of UVA rays. Clothing is the best defense because it really, truly covers you. It doesn’t wear off, and you can’t miss a spot. A more severe form of a solar allergy-like condition called porphyria can cause blisters, swelling, cramping, paralysis — and in extreme cases, psychosis.

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Contact lens allergy:

Contact lens wearers may develop giant papillary conjunctivitis, triggered by constant local irritation by the contact lenses on the conjunctival surfaces. The lining of the upper eyelid is usually most affected. Disposable contact lenses may help settle symptoms, but occasionally wearing contact lens has to be suspended. Never use steroid eye drops unless under the direct supervision of a doctor. Although they’re effective for treating eye allergies, they can lead to unwanted side-effects such as glaucoma and cataract formation. They may also encourage infections of the eye, with resultant corneal scarring.

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Alcohol Allergies:

Although a true alcohol allergy is rare but real, and the reaction can be severe, most allergic reactions to alcohol are due to an ingredient in alcohol. Every person’s body chemistry and make-up is different and so how a person responds to alcohol can vary greatly. A true alcohol allergy tends to be inherited.  Although research is limited, people with a true allergy to alcohol should avoid drinking. Research indicates that the enzyme, Aldehyde Dehydrongenase metabolizes alcohol in the liver into acetic acid (vinegar). A person who has an allergy to vinegar can have a severe reaction to the alcohol. It is important to remember that alcohol can increase the likelihood of severe allergic reactions (anaphylaxis) to other foods. Alcohol can exacerbate underlying conditions such as asthma, urticaria and rhinitis. Alcohol also increases the permeability of the gut, which allows more food molecules into the body. This may explain the reactions of mildly food sensitive individuals who may not react to the food alone but only when it is combined with alcohol.

Common Ingredients used in Alcoholic Beverages that are Common Allergens:

This list is not all inclusive but simply gives same examples.

  • yeast
  • hops
  • barley
  • rye
  • sodium metabisulphite
  • egg protein or seafood proteins (used to fine some beers)
  • histamines are common in red wines, sulphites (higher in white wines)
  • grapes (due to the chemicals used to dust the grapes)
  • gluten
  • wheat

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Alcohol intolerance can cause immediate, unpleasant reactions after you consume alcohol. The most common signs and symptoms of alcohol intolerance are nasal congestion and skin flushing. This condition is sometimes inaccurately referred to as an alcohol allergy. Alcohol intolerance is caused by a genetic condition in which the body is unable to break down alcohol. Such people have an alteration called a polymorphism, in the ALDH gene which renders the enzyme aldehyde dehydrongenase inactive and makes it impossible for them to convert alcohol into acetic acid. Alcohol is converted into acetaldehyde by enzyme alcohol dehydrogenase and acetaldehyde is converted into acetic acid by enzyme aldehyde dehydrogenase. When enzyme aldehyde dehydrogenase is inactive, acetaldehyde accumulate in body producing signs of alcohol intolerance. This intolerance is more common with the Asian population and symptoms may include flushing, nausea, and rapid heartbeat. The only way to prevent alcohol intolerance is to avoid alcohol altogether. In some cases, what may seem to be alcohol intolerance is caused by a reaction to something else in an alcoholic beverage — such as chemicals, grains or preservatives. In other cases, reactions are caused by combining alcohol with certain medications. In rare instances, reactions to alcohol can be a sign of a serious underlying health problem that requires diagnosis and treatment.

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Cell Phones allergy:

Normally we’re pretty careful about the kinds of things we let touch our faces, but how often has that concern come to mind when that thing is your cell phone?  In recent years, dermatologists have begun to see an increasing number of contact dermatitis patients who are allergic to their cell phones, or more specifically the nickel in their cell phones. Some people are extremely nickel-sensitive. Nickel is a metal that’s used in a wide variety of products, including jewelry, belt buckles and watch bands. It’s the most common cause of contact dermatitis in the developed world. The symptoms of a nickel reaction range from redness to a more obvious rash, even blisters. Not all cell phones contain nickel. In an attempt to get an idea of how many phones might have the metal, Bercovitch tested 22 models and published the results in the Canadian Medical Association Journal in January 2008. Ten devices were positive for the metal. In some, the nickel showed up around the menu buttons. In others, it appeared near the decorative logos, around the edge of the screen or on a part of the handset where paint was chipped.  However, there are also people who may be allergic to the electromagnetic emissions from cellphones. Nickel allergy affects about 17 percent of women and 3 percent of men — women develop cellphone rash more often because they’re more likely to have been sensitized to nickel through ear piercing.

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Exercise allergy:

It’s the perfect excuse: I can’t exercise because I’m allergic to it.  Sure, it sounds like a joke but a rare condition called exercise-induced anaphylaxis can result in an allergic reaction during exercise, and it can be severe enough to kill the exerciser. Most often reported with running or jogging, the exercise-allergic person might get hives, swelling, trouble breathing, low blood pressure, itching, nausea, a headache or wheezing. Because some of the symptoms occur commonly during normal exercise, some people with exercise-induced anaphylaxis might not realize they have the problem. In addition, for some people, the reaction only comes when exercise is combined with a certain food. Casale noted several early reports of exercise-induced anaphylaxis from people who ate celery before they exercised.  “They could exercise, they were fine. They could eat celery, they were fine. They eat celery, then they exercise — then they have an anaphylactic reaction,” said Casale, who studied the phenomenon in the 1980s.   

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Touch allergy:

People with dermatographia are sensitive to pressure and touch (rubbing), and depending on the severity of the case, occasionally even a slight touch can trigger an allergic episode that creates a raised, itchy red rash. It is unknown why this allergy occurs, but it’s estimated that 2 to 5 percent of the population has it. Because words and designs can easily be scratched on the skin, the condition is often referred to as “skin writing disease”.

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Sex allergy:

Believe it or not, there are people who are allergic to sex — kind of. Semen allergy also known as seminal plasma hypersensitivity can make sex unbearable for about women, who may experience symptoms like swelling, burning and hives. The problem is estimated to affect about 20,000-40,000 women in the US. This type of allergy is usually treated by identifying which of the proteins in the man`s semen are causing the woman`s allergic reaction, then using a desensitization process to build up tolerance. Symptoms include burning sensations, rashes and welts, which is why the allergy can often be misdiagnosed as a sexually transmitted disease. The only real signifier of a semen allergy is that that symptoms appear within minutes of contact. Treatments range from always using condoms to desensitization by exposing a person to small amounts of semen and gradually increasing the amount as the body becomes accustomed to it.

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Allergic to Water?

Imagine being allergic to a substance that makes up about 70 percent of the earth and almost as much of our bodies. But for some, a rare allergy to water is harsh reality. Water induced urticaria is very unusual — there are not many cases ever reported. The mechanism has not really been defined. It is certain, however, that people with aquagenic urticaria produce histamine from mast cells in the skin which causes redness, rashes and hives if they touch water. Dutton’s sensitivity is such that she can only bathe for about 10 seconds each week and cannot drink water, juice, tea or coffee, opting for diet cola instead. She is also restricted from eating certain fruits and vegetables.  It’s not a problem with water in the body. It’s when [water] is applied on top of the body, citing additives as a possible cause for the allergic reaction seen on the skin. This may also be the effect of different temperatures of water, such as cold or hot and can flare with chemicals such as fluorine and chlorine.

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Occupational Allergy:

Occupational allergic diseases represent an important public health issue due to their high prevalence and their socio-economic burden. Occupational asthma (OA) contributes significantly to the global burden of asthma, since the condition accounts for approximately 15% of asthma amongst adults. Allergic contact dermatitis (ACD) is one of the most common occupational diseases. Occupational allergic diseases remain largely under-recognized by physicians, patients, and occupational health policy makers. Occupational allergic diseases can result in long-term health impairment, especially when the diagnostic and avoidance measures are delayed. Occupational allergic diseases lead to important adverse consequences in terms of healthcare resources, employment, earning capacity and quality of life. Occupational allergic diseases are associated with a  substantial adverse financial impact for affected workers, insurance or compensation schemes, health services, and employers. Occupational allergic diseases are, by definition, preventable diseases and their burden should be minimized by appropriate preventative strategies.  

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Reactions to vaccine components during child vaccination program:

Vaccines are of major importance in controlling the spread of infectious diseases, but use of some vaccines was linked to allergic and autoimmune phenomena in healthy and often in certain high risk populations. Allergic reactions to different vaccines may result from reactions to the common components of these vaccines. Two main components that were identified are gelatin and egg protein. Careful examination of the literature shows such reactions are rare and life threatening event are extremely uncommon. Although severe allergic adverse events attributable to vaccination are extremely rare, all serious allergic reactions should be further assessed to detect the likely causative vaccine component, including egg protein and gelatin. The risks of not vaccinating children, however, far outweigh the risk for allergy. Therefore, childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed for allergy. The possibility of vaccination triggering or unmasking autoimmunity in genetically susceptible individuals cannot be ruled out, but for the general population the risk: benefit ratio is overwhelmingly in favor of vaccinations.  

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 Multiple allergies:

The presence of one allergic disorder significantly increases the risk of developing other allergic disorders affecting different organ systems. This has been attributed to the shared predisposition and mechanism for development of these diseases, whereby an immunological response to environmental allergens is driven by type 2 T cell cytokines. A study found that Recorded incidence and lifetime prevalence of multiple allergic disorders in England have increased substantially in recent years. The age–sex standardized incidence of multiple allergic disorders was 4.72 per 1000 person-years in 2001 and increased by 32.9% to 6.28 per 1000 patients in 2005 (p<0.001). A small group of highly atopic individuals develop severe allergies from an early age. They may have infantile food allergies (commonly cow’s milk, egg and nuts) usually associated with extensive eczema.  Many have cross-reactions to other foods – latex allergy may react with avocado, banana, kiwi and chestnuts, for example. They then develop childhood allergic asthma, allergic rhinitis and remain highly allergic to numerous foods and environmental allergens. Both patients and healthcare providers find managing multiple allergies to be particularly problematic, with patients often requiring referrals to a number of different specialists. They need ongoing supervision at a combined allergy care clinic under the care of a consultant immunologist, dermatologist, dietician, chest physician, paediatrician and ear, nose and throat specialist. However, vast majority of people with allergies have only a few allergies, which are well controlled by specific allergen avoidance and regular long-term allergy preventer medication.

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Causes and risk factors of allergy:

Risk factors for allergy can be placed in two general categories, namely host and environmental factors. Host factors include heredity, gender, race, and age, with heredity being by far the most significant. However, there have been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.

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Host factors:

Allergic diseases are strongly familial: identical twins are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in non-identical twins. Allergic parents are more likely to have allergic children, and those children’s allergies are likely to be more severe than those in children of non-allergic parents. Some allergies, however, are not consistent along genealogies; parents who are allergic to peanuts may have children who are allergic to ragweed. It seems that the likelihood of developing allergies is inherited and related to an irregularity in the immune system, but the specific allergen is not. Atopy in parents or siblings is a strong indicator of allergy risk. Allergies are likely to occur in atopic families where there’s early childhood exposure to certain allergens. You’re at increased risk of allergies if you have family members with asthma or allergies such as hay fever, hives or eczema. The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk. Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years. The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10. Although you can become allergic to something at any age, children are more likely to develop an allergy than are adults. Children sometimes outgrow allergic conditions as they get older. However, it’s not uncommon for allergies to go away and then come back sometime in the future. Overall, boys have a higher risk of developing allergies than girls, although for some diseases, namely asthma in young adults, females are more likely to be affected. Sex differences tend to decrease in adulthood. Also an allergic mother who smokes puts a child at even greater risk of allergy. Ethnicity may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to migration. It has been suggested that different genetic loci are responsible for asthma, to be specific, in people of European, Hispanic, Asian, and African origins. Allergy is much less common in younger children in large families than in their older siblings. This is probably due to viral infections being passed more often from one child to another in large families, which may influence the subsequent dominance of Th1 driven rather than Th2 driven immune responses. Having asthma increases your risk of developing an allergy. Also, having one type of allergic condition makes you more likely to be allergic to something else.

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Who’s at risk of allergies statistically?

  • Children from non-allergic families have a 12 per cent risk of developing an allergy
  • If one parent has allergies, this risk increases to 20 per cent
  • If both parents have allergies, the risk is more than 40 per cent
  • If both parents have the same allergy (such as asthma, hay fever or eczema) the child has a 70 per cent risk of having the same allergy

Other factors that may promote allergies include:

  • Birth by caesarean section
  • Frequent courses of antibiotics
  • Coming from a smaller family, with just one or two children
  • Passive cigarette smoke inhalation
  • Being overweight – obese children are more prone to asthma

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Environmental basis of allergy:

Hygiene hypothesis:

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Allergic diseases are inflammatory disorders that develop on the basis of complex gene–environment interactions. The prevalence of allergies is steadily increasing and seems to be associated with modern lifestyle. Therefore, it was hypothesized that high living standards and hygienic conditions are correlated with an increased risk for the development of an allergic disease. This so-called “hygiene hypothesis” states that due to reduced exposure to microbial components, the proposed allergy-preventing potential of these factors is no more present in sufficient qualities and/or quantities, which leads to an imbalance of the immune system with a predisposition to the development of allergic disorders.  Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a Th2-mediated immune response. Many bacteria and viruses elicit a Th1-mediated immune response, which down-regulates Th2 responses. The first proposed mechanism of action of the hygiene hypothesis was that insufficient stimulation of the Th1 arm of the immune system leads to an overactive TH2 arm, which in turn leads to allergic disease. The current view of cellular and molecular mechanisms responsible for these phenomena includes changes in the fine balancing of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) responses which are triggered by altered or missing innate immune cell activation. In fact, proper activation of cells of the innate immune system via their so-called pattern recognition receptors has been demonstrated to play a crucial role in early shaping of the immune system and suppression of the development of Th2-driven allergic immune responses. These processes start already in utero and prenatal as well as early postnatal developmental stages seem to represent a certain ‘window of opportunity’ for allergy-preventing environmental influences. In other words, individuals living in too sterile an environment are not exposed to enough pathogens to keep the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when they are not exposed to this level, the immune system will attack harmless antigens and thus normally benign microbial objects — like pollen — will trigger an immune response.

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The hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were, it is presumed, exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. It is used to explain the increase in allergic diseases that have been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents.

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Epidemiological data support the hygiene hypothesis. Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world. Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner. The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases. The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by Caesarean section rather than vaginal birth. Does this mean that our children should play in kitty litter boxes and not get vaccinated against childhood diseases? Absolutely not. It probably means that we’re trading potentially life-threatening infections for a shift in our immune systems towards allergies.

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The ‘hygiene hypothesis’ as originally formulated by Strachan, proposes that a cause of the recent rapid rise in atopic disorders could be a lower incidence of infection in early childhood, transmitted by unhygienic contact with older siblings. Use of the term ‘hygiene hypothesis’ has led to several interpretations, some of which are not supported by a broader survey of the evidence. The increase in allergic disorders does not correlate with the decrease in infection with pathogenic organisms, nor can it be explained by changes in domestic hygiene. A consensus is beginning to develop round the view that more fundamental changes in lifestyle have led to decreased exposure to certain microbial or other species, such as helminths, that are important for the development of immunoregulatory mechanisms. Although this review concludes that the relationship of the hypothesis to hygiene practice is not proven, it lends strong support to initiatives seeking to improve hygiene practice. It would however be helpful if the hypothesis were renamed, e.g. as the ‘microbial exposure’ hypothesis, or ‘microbial deprivation’ hypothesis, as proposed for instance by Bjorksten. Avoiding the term ‘hygiene’ would help focus attention on determining the true impact of microbes on atopic diseases, while minimizing risks of discouraging good hygiene practice.

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The adaptive immune cells (B and T) cells develop normal responses only if they are stimulated by exposure to foreign substances…Children get primed with IgG antibodies from their mother and IgA antibodies from breast milk which provide “passive” immunity for the first two years of life.  After that, children need to begin activating their own adaptive immunity – their own IgMs and IgGs….If this process of educating the adaptive immune system is not sufficiently activated in early childhood, the immune system of the adolescent or adult remains underdeveloped.  Then the response to foreign bodies relies more on the “emergency” system, using IgE antibodies instead of IgG, IgA, or IgM antibodies. It is these IgE antibodies that tend to overreact, causing allergies. Essentially, an “under-trained” adaptive immune system, such as that of someone raised in a sterile environment, is more prone to confuse harmless foreign bodies like pollen, dog hair, peanuts, eggs, or insect venom, for parasites. Their IgEs become sensitized towards these allergens, attach themselves to the mast cells on mucous membranes or beneath the skin.  Once the allergen reappears, a full-blown chemical attack, including histamine release, is initiated.

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Rising trends in allergic disease in western nations:  

The British Allergy Foundation believes that the incidence of allergies is growing at five per cent each year.  The marked increase in the prevalence of atopic disease in Western Europe, the US and Australasia during recent years indicates the importance of environmental influences. The role of various outdoor and indoor factors is discussed by Strachan. An interesting example of environmental as opposed to genetic changes is the incidence of seasonal allergic rhinitis and asthma after the unification of Germany. These disorders were less common in East Germany than West Germany before unification, whereas after unification the prevalence of atopy and hay fever, but not asthma, has increased in children who spent their early childhood in East Germany. This phenomenon raises the possibility that a ‘Westernized life-style’ accounts for the increases in prevalence. It has been suggested that in Western countries the developing immune system is deprived of the microbial antigens that stimulate Th1 cells, because the environment is relatively clean and because of the widespread use of antibiotics for minor illnesses in early life. Several epidemiological studies support this theory. For example, evidence for bacteria colonising the gastrointestinal tract preventing atopic sensitization was provided by studies by 1-year-old infants living in countries with a low (Estonia) and high (Sweden) prevalence of atopy.  Lactobacilli and Eubacteria predominated in Estonian infants whereas Clostridia were more frequent in Swedish infants. At 2 years of age, allergic children were colonised less often by Lactobacilli, and harboured higher counts of aerobic bacteria (coliforms, Staphylococcus aureus) than non-allergic children. Moreover, atopy and allergic asthma were less frequent in people exposed to agents in soil, air and water such as H. pylori, T. gondii, hepatitis A virus. Therefore, these microbes, by producing an IL-12-rich environment could drive a Th1 response. Such findings may explain, for instance, why in Europe and Africa, a farming life-style, where there is increased exposure to bacteria in stables where livestock is kept, is protective against the development of atopic disease. Other related factors which may encourage the Th2 phenotype include a date of birth around the pollen season, and alterations in infant diet. Furthermore, atopic allergic diseases are less common in younger siblings, having three or more older siblings, and in those who have had measles and hepatitis A indicating that repeated ‘immune stimulation’ {e.g. by viruses) may be protective. This is supported by the study of Ball et alp who provided evidence that exposure of young children to older children at home, or to other children at day-care centers, protected against the development of asthma and frequent wheezing in childhood. Set against the hygiene hypothesis is the finding of increased prevalence, among poor blacks in the US, of atopic asthma in association with sensitization to cockroaches and the house dust mite. However, more data are required on infection by foodborne and orofaecal microbes on inhabitants of inner American cities before these apparent inconsistencies can be explained. Thus, poor inner city dwellers may have the compounding effect of gut flora that do not protect against atopy and heavy exposure to allergens which may explain this paradox. The development of specific allergic diseases may be related to alterations in the target organ. For example, the co-factors required for the development of an asthmatic attack may include respiratory virus infections and exposure to increased allergens, tobacco smoke, and air pollutants. These factors alone, or in combination, may alter immunoregulatory mechanisms at mucosal surfaces in ways that promote a Th2 cell-mediated allergic inflammatory response. 

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Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study:

Researchers found that atopy and respiratory allergies were inversely related to a gradient of exposure to orofecal or foodborne infections (T gondii, hepatitis A virus, and H pylori) but not to viruses transmitted through other routes—that is, mumps, rubella, chickenpox, herpes simplex virus type 1, and cytomegalovirus.  Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries. The decline of orofecal and foodborne infections and changes in the overall pattern of commensals and pathogens that stimulate gut associated lymphoid tissue may be strong determinants of the epidemic of allergic rhinitis and asthma in developed countries. Although further studies are required to verify this conclusion, it is not inconceivable that we may soon use certain microbes or their molecules to prevent atopy without causing infectious disease. 

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Studies using microorganisms to prevent allergy:

If the hygiene hypothesis is true, what can we do? Lessening our fanatical attention to hygiene might help, but could also lead to more colds and flu. Instead, we may have to look at dosing ourselves with the bacteria and parasites we’ve been trying to avoid. Could this work? Well, a study of Japanese children who were given a tuberculosis vaccine made from a weakened form of TB bacteria (a mycobacteria, related to soil bacteria) discovered they had a much lower rate of allergies and asthma than kids who didn’t receive the vaccine. Studies are underway to see if inhaling or injecting mycobacteria can prevent asthma attacks, and preliminary results are promising. In an even stranger study, patients with Crohn’s disease, a chronic inflammation of the intestines, have been given drinks laced with the eggs of parasitic worms. Crohn’s disease was first identified in the 1930s, and it is far more common in developed, urbanized areas than in poor, undeveloped areas. Until the 1930s, most kids in North America had intestinal worms; most kids in underdeveloped countries still do. Statistical studies indicate that any country that gets rid of worms begins to see more cases of inflammatory bowel disease. So Dr. Joel Weinstock, a parasitologist, has recruited volunteers with Crohn’s disease to swallow the eggs of a pathogen-free species of pig whipworm (which can’t grow to full size in a human). All the patients, who were resistant to all other forms of treatment, went into remission. Some of the patients have now been in remission for up to a year with doses of worm eggs every three weeks. So studies do show that stimulation of immunity by microorganisms does reduce allergy and autoimmune diseases.

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Foreign-Born American children have fewer childhood Allergies:

Atopic disease is more common among children who are born in the U.S. than among those who move here, according to a JAMA Pediatrics study. Researchers reviewed data from some 80,000 participants in a national survey of child health. The information collected included the children’s and parents’ birthplaces, and whether the child had ever been diagnosed with asthma, eczema, hay fever, or food allergy. Birth outside the U.S. was associated with a roughly 50% decreased risk for having an atopic disorder. A foreign-born child with foreign-born parents was at even lower risk, but not for eczema or food allergies. Living in the U.S. for more than 10 years blunted the effect, however. The authors say their results support the “hygiene hypothesis” that early childhood microbial exposures protect against atopic disorders.  

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Parasites and allergy: conflicting relationship:

Recent research has shown that some common parasites, such as intestinal worms (e.g., hookworms), secrete chemicals into the gut wall (and, hence, the bloodstream) that suppress the immune system and prevent the body from attacking the parasite. This gives rise to a new slant on the hygiene hypothesis theory — that co-evolution of man and parasites has led to an immune system that functions correctly only in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive. In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in infants. However, the research to support this theory is conflicting, with some studies performed in China and Ethiopia showing an increase in allergy in people infected with intestinal worms. Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies. It may be that the term ‘parasite’ could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work.

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The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 and T helper 2 that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward Th1, which counterbalance proallergic responses of Th2 cells. Thus, a reduction in the overall microbial burden will result in weak Th1 imprinting and unrestrained Th2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of Th1-autoimmune diseases is also increasing and that Th2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.

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The immunoepidemiological interactions between intestinal worm (or geohelminth) infections and allergy are of great interest to parasitologists, immunologists, and allergists because of the close similarities between the human immune response to geohelminth parasites and environmental allergens. Allergic diseases appear to be most rare in populations living in the rural tropics with high rates of infection with geohelminth parasites, and this has led to suggestions that the relationship between geohelminth infections and allergy may be causal. Allergic sensitization and disease results from a complex interaction between environmental exposures and genetic background, and the numerous epidemiological studies that have investigated the relationship between allergy and geohelminth infections have provided conflicting findings. The strongest epidemiological evidence for a causal association is provided by intervention studies that demonstrate evidence for an effect of anthelmintic treatment on atopy or asthma risk. There is evidence also for an inverse relationship between geohelminth infection and either atopy or asthma symptoms from cross-sectional studies that have been conducted in areas of high infection prevalence. Chronic geohelminth infections could affect allergy risk by modulation of the immune response to environmental allergens, and an area of great research activity at present is the investigation of the role of regulatory T cells in modulating host inflammatory responses. However, a causal association between geohelminth infections and allergy remains to be proven, and prospective and intervention studies are required that investigate the development of allergy in early life at a time when humans are first exposed to geohelminth parasites and their antigens.

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Worms and asthma are associated with a Th 2 immune response, but evidence has accumulated that helminth infection is negatively associated with atopy, prevalence of allergic diseases and severity of asthma. One important difference between these polarized type Th 2 responses is that in allergy, modulation of the immunological response is not appropriate, whereas in infection with helminths, several host mechanisms down-regulate the host immune response. As a result, patients infected with worms have a decrease in both type Th1 and type Th2 responses. The main mechanism involved in this down-modulation is increased production of IL-10, but expansion of regulatory T cells and NKT cells may also participate. Regarding the interaction between worms and allergy, a few variables need to be taken in account: phase (acute or chronic) of helminth infection, parasite load and species of helminth. In animals and humans, acute helminth infection may increase manifestations of allergy, whereas chronic infection with parasites decreases atopy. The modulation of the immune response by helminths is dependent on having an adequate parasite load. Moreover, although several helminth species have been shown to modulate immune responses, most in vitro and in vivo studies have focused on the importance of Schistosoma mansoni in down-modulating allergic reactions.

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Race and allergy:

Research conducted at Henry Ford Hospital shows that race and possibly genetics play a role in children’s sensitivity to developing allergies. Researchers found:

  • African-American children were sensitized to at least one food allergen three times more often than Caucasian children.
  • African-American children with one allergic parent were sensitized to an environmental allergen twice as often as African-American children without an allergic parent.

The study was presented at the American Academy of Allergy, Asthma and Immunology annual meeting. The findings suggest that African Americans may have a gene making them more susceptible to food allergen sensitization or the sensitization is just more prevalent in African American children than white children at age 2. More research is needed to further look at the development of allergy.

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Allergies, Asthma affected by Geographic Factors:

Those living near the equator may find themselves sneezing and wheezing more than usual. And the reason may not be due to increasing pollen counts. According to a new study released in the issue of Annals of Allergy, Asthma & Immunology, the scientific journal of the American College of Allergy, Asthma and Immunology (ACAAI), living in locations closest to the equator can put you at increased risk of developing allergy and asthma. UV-B rays exposure is higher for people living in areas closer to the equator. This increase in UV-B may be linked to vitamin D, which is thought to modify the immune system. These modifications can lead to an elevated risk of developing allergy and asthma. Previous studies have shown that latitude can reflect a variation in airborne allergens due to climate, housing and social and cultural differences. This study is one of the first using the individuals latitude location and UV-B exposure to examine the association with allergy and asthma.

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Air Pollution and Allergies: A Connection?

Does the “air we breathe” have an impact on the rising incidence of allergies and asthma? Hay fever was rare in Japan before World War II. However, pollen allergy is now common and mostly affects those living in Japanese cities and near highways. Allergic disease is also more common in highly developed countries in North America and Europe and less common in Third World countries. This suggests that there must be something about modern, urban life that promotes allergy. Let us examine the impact of air pollution. By far the most important indoor pollutant is tobacco smoke, which is strongly associated with allergic sensitization, asthma, and other respiratory illnesses. Exposure to smoke results in the body’s enhanced ability to produce IgE (the allergy antibody) that attaches to allergens (e.g. pollen, dust mites and dander). The IgE response is a key trigger of allergic reactions. Parental smoking increases the risk of their children having many respiratory illnesses, including bronchitis, chronic cough, and asthma. The increased rates of allergy and asthma in city environments and in those living close to highways have drawn attention to the role of outdoor pollution. Common air pollutants, such as ozone, sulfur dioxide, and nitrogen dioxide probably act more as irritants than as promoters of sensitization. We know that nitrogen dioxide, ozone and diesel exhaust particulate matter in air pollution can predispose to increased respiratory infections, aggravate asthma, bronchiectasis and chronic bronchitis (COPD), but any link to actually triggering allergic sensitization is less clear. However, epidemiological and toxicological research suggests a causative relationship between air pollution and the increased incidence of asthma, allergic rhinitis, and other allergic disorders. These include ozone, nitrogen dioxide and, especially particulate matter, produced by traffic-related and industrial activities. Strong epidemiological evidence supports a relationship between air pollution and the exacerbation of asthma and other respiratory diseases. Among the effects that pollution of the air causes on human health, irritation of the exposed mucosa is the earliest and the most obvious one. Pollutants damage the anatomical and functional integrity of the primary airways; in particular they cause alteration of the mucociliary system. The mucosa undergoing continuous aggression by an aerosol loaded with pollutants assumes the characteristics of a tissue with chronic inflammatory processes with dysepithelialised areas that could be an easy entrance for airborne allergens. The loss of integrity of epithelial lining, the interference with the repulsion of extraneous particles trapped in the mucus, the infiltration of the inflammatory cells and lymphocytes called into action by the phlogistic reaction multiply the occasion of meeting between environmental allergens and the immunological system of the host and basically of setting in motion the process of sensitization. So in my view, pollution itself can cause or worsen allergy. Also, diesel exhaust particles have been shown to absorb grass pollen grains and increase the pollen load in the nose and lungs, thus making hay fever and hay asthma symptoms worse for city dwellers and those living near motorways. Around 250 million people are suffering from various allergies in India owing to the rise in pollution level. This is especially important as due to poor hygiene, poor sanitation, poverty and overpopulation, infections are very common in Indian population since infancy and Th1 immune system is predominant, yet pollution could cause allergy in sizable population. Pollution would make hygiene hypothesis hollow. 

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Global warming and allergy:

The planet is getting warmer, and human behavior is responsible. The changing climate has brought early spring, late-ending fall, and large amounts of rain and snow. All of that, combined with historically high levels of carbon dioxide in the air, nourishes the trees and plants that make pollen, and encourages more fungal growth, such as mold, and the release of spores. Pollen counts will increase by 30 percent by 2020 and will double by 2040 because of climate change. And pollen production is only part of the impact that global warming is going to have on allergies and asthma — and our health overall. In areas of the country experiencing prolonged heat and drought, dust will worsen air pollution, exacerbating asthma and other respiratory diseases. In other regions, climate change will affect the insect population — their stings and bites can provoke fatal allergic reactions in sensitive individuals — as well as the proliferation of such vines as poison ivy. Poison ivy thrives with increased carbon dioxide, and as a result, now makes a far more potent urushiol — the oil that causes poison-ivy-triggered rashes — than in the past. In fact, one study published in the Journal of Allergy and Clinical Immunology called climate change “potentially the largest global threat to human health ever encountered,” predicting more injury, disease and death from natural disasters, heat waves, infections and widespread malnutrition, as well as more allergic and air-pollution illnesses and death.  

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Other environmental factors: 

International differences have been associated with the number of individuals within a population that suffer from allergy. Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined. Exposure to allergens, especially in early life, is an important risk factor for allergy.     

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Family food habits and allergy in children: 

How higher peanut eating in a family led to peanut protein in infant’s bed dust led to peanut allergy in child:

A higher level of peanut protein in an infant’s home environment is correlated with an increased household consumption of peanuts and activated basophils of children who had a peanut allergy, a small study found. Peanut protein levels were significantly higher in the infant’s bed and play area in high peanut-consuming households (P<0.001), defined as consumption greater than or equal to 10 grams per week, when compared with lower peanut-consuming households. Furthermore, in a multivariate regression model examining clinical, behavioral, and household factors associated with peanut protein levels in the infant’s bed dust, only household peanut consumption remained significant (Coefficient=0.492, P=0.020), the researchers reported in the Journal of Allergy and Clinical Immunology. In addition, researchers showed that dust samples with high peanut protein content triggered a dose-dependent activation of peanut-allergic children’s basophils, as indicated by the upregulation of the CD63 activation marker, a finding not observed in non-allergic children’s basophils. This finding led authors to speculate about the ability of peanut allergens in house dust to interact with immune cells and initiate a response leading to allergic sensitization. This is the first study to demonstrate that peanut protein levels in an infant’s home environment are positively correlated with household peanut consumption and that peanut protein in household dust is biologically active. Extrapolating from this study, one can hypothesize that family food habits may have a role in developing allergy in a child growing up in that family.  

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The genetic and environmental basis of atopic diseases:

The prevalence of atopic diseases has increased abruptly in recent years in most Westernized societies, making the question why this happened the topic of a heated debate. The best paradigm available to date to explain this steep rise, the ‘hygiene hypothesis’, supports that it is the excess ‘cleanliness’ of our environments that has led to the decline in the number of infectious stimuli that are necessary for the proper development of our immune system. Recent findings support that it is the combined effect that not only pathogenic, but also non-pathogenic microorganisms, and even their structural components, can exert on the immune system that deters from the development of atopic responses. Adding to these results are intriguing new findings on the effect different gene polymorphisms can have on an individual’s predisposition to allergic diseases. The most important linkages produced, to date, include those among the genes for IL-4, IL-13, HLA-DRB, TNF, LTA, FCER1B, IL-4RA, ADAM33, TCR alpha/theta, PHF11, GPRA, TIM, p40, CD14, DPP10, T-bet, GATA-3, and FOXP3 and allergic disorders. The two parallel research efforts, epidemiologic and genetic, are only recently starting to converge, producing fascinating results on the effect particular gene-environment interactions might have in the development of atopy. The most important lesson learned through this tremendous research effort is that not only a small number but thousands and millions of separate risk factors act in concordance in the production of the allergic phenotype.  

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The figure below shows interplay of genes and environment in development of allergies: 

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Diagnosis of allergy:

An immediate relation between exposure to potential allergens and the development of symptoms makes both the diagnosis and identification of allergy straightforward. In 25-50% of cases the predominant symptoms develop 1-10 hours after exposure (late phase reactions), obscuring the allergic nature of the illness. In allergic diseases of occupational etiology the first symptom may be exercise induced asthma or night-time waking with cough. The longer such symptoms have been present the more likely they are to persist when exposure ceases. Effective management of allergic diseases relies on the ability to make an accurate diagnosis. Allergy testing can help confirm or rule out allergies.  Correct diagnosis, counseling and avoidance advice based on valid allergy test results will help reduce the incidence of symptoms, medications and improve quality of life. For assessing the presence of allergen-specific IgE antibodies, two different methods can be used: a skin prick test or an allergy blood test. Both methods are recommended and have similar diagnostic value. Skin prick tests and blood tests are equally cost-effective and health economic evidence show that both the IgE antibody test and the skin prick test were cost effective compared with no test. Also, earlier and more accurate diagnoses save cost due to reduced consultations, referrals to secondary care, misdiagnosis and emergency admissions.

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Taking a clinical history

  • A detailed clinical history is vital for diagnosing an allergy
  • Taking a history requires experience, time, and patience
  • Patients should be allowed to give their own account of their symptoms in their own time
  • Structured questions about the patients’ history (with particular emphasis on previous allergic diseases—such as childhood eczema, hay fever, and asthma) should be asked
  • Frequency, severity, duration, and seasonality of symptoms should be ascertained, with particular reference to triggering factors, life threatening events, and effects of avoidance measures
  • Patients should be asked about diet; food exclusion; and intolerance to aspirin, colorings, and preservatives
  • Family history should be explored
  • Home, work, and outdoor environmental risk factors should be discussed
  • Groups at particular risk of allergy—such as healthcare and rubber industry workers and children with spina bifida, in whom latex allergy is particularly prevalent—should be identified
  • Patients should be asked about any treatment they are currently using, particularly about antihistamines, topical and oral corticosteroids, and adrenalin autoinjectors

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Laboratory Studies:

Anyone who suffers from an allergy knows it can be a question of trial and error before finding out what triggers a reaction. Some laboratory tests may be helpful in determining whether a reaction is truly allergic in nature. Obtaining a serum tryptase level soon after the onset of symptoms can be helpful in differentiating anaphylaxis from other forms of shock and from other symptom complexes that may be confused with anaphylaxis. The tryptase level can be elevated, which is indicative of mast cell degranulation. False-negative results can occur. Ideally, the tryptase level should be drawn within 4 hours after the event, but it can be drawn up to 15 hours later. Measurement of urinary histamine may also be useful. An elevated eosinophil count may be observed in patients with atopic disease. IgE levels may be elevated in patients who are atopic, but the level does not necessarily correlate with clinical symptoms. The radioallergosorbent test (RAST) and other in vitro IgE assays measure antigen-specific IgE and can be useful in identifying which allergens are causing symptoms for the patient. More sensitive tests have been available in recent years and have a greater positive predictive value for foods. These tests can sometimes detect clinically irrelevant allergens, however, creating false-positive results to some foods. Molecular diagnostic tests are now available that can detect allergenicity to specific food protein molecules known to trigger IgE-mediated reactions.

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Allergy blood test:

An allergy blood test is quick & simple and can be ordered by a licensed health care provider e.g. an allergy specialist, GP or PED. Unlike skin-prick testing, a blood test can be performed irrespective of age, skin condition, medication, symptom, disease activity and pregnancy. Adults and children of any age can take an allergy blood test. For babies and very young children, a single needle stick for allergy blood testing is often more gentle than several skin tests. An allergy blood test is available through most laboratories, and a sample of the patient’s blood is sent to a laboratory for analysis and the results are sent back a few days later. Multiple allergens can be detected with a single blood sample. Allergy blood tests are very safe, since the person is not exposed to any allergens during the testing procedure. The test measures the concentration of specific IgE antibodies in the blood. Quantitative IgE test results increase the possibility of ranking how different substances may affect symptoms. A general rule of thumb is that the higher the IgE antibody value, the greater the likelihood of symptoms. Allergens found at low levels that today do not result in symptoms can nevertheless help predict future symptom development. The quantitative allergy blood result can help determine what a patient is allergic to, help predict and follow the disease development, estimate the risk of a severe reaction and explain cross-reactivity. A low total IgE level is not adequate to rule out sensitization to commonly inhaled allergens. Total IgE is not useful to rule out sensitization to common inhalant allergens. High total IgE may indicate a high probability of sensitization and may be useful to decide whether further investigation is warranted in patients with negative specific allergy tests to a panel of common inhalant allergens. Total IgE levels can be affected by race, smoking history, age, season, and non-atopic disease.  30-40% of patients with allergic disease may have “normal” IgE levels. 

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Total IgE determination constitutes a good method for the screening of atopic diseases, though its actual value is controversial because normal values of total IgE do not exclude the existence of atopic disease, and high values of total IgE are not pathognomonic of atopy by themselves. The first step in identifying an atopic individual as such, after doing his anamnesis, can be carried out by means of total IgE determination. Most atopic individuals have high IgE values, but a normal result must be carefully interpreted: age and season-related variations must be considered. In general, atopic patients with IgE values greater than 1000 Ul/ml, always have positive specific IgE against some allergen. Antigen-specific IgE will be the next step in the in vitro identification of the responsible allergen. Nowadays, there are more than 400 characterized allergens available for in vitro diagnostic tests and several useful methodologies for specific IgE determination. Specific IgE results obtained with the different methods vary significantly, with absolute agreement in 55-65% of the cases, differences in one IgE class in 20-30% of the cases and differences in more than two classes in 5-10%. The specificity of the anti-IgE antibody used in the assay is of critical importance because any contaminant antibody can render unspecific results. On the other hand, it must be pointed out that there is a compromise between specificity and sensitivity, such that an increase in the sensitivity of a technique leads to a decrease in its specificity. It cannot be said that there is one method which is better than the others; it is better to examine them individually, allergen by allergen. Thus, specific IgE determination varies depending on the type of allergen. In general terms, for inhalant allergens, specificity and sensitivity of the methods are within the range of 85-95%, but these values (especially the specificity) decrease in the case of food allergens, and they are still lower when the allergen is a beta-lactam drug. There is a good correlation between clinical history and specific IgE against inhalant allergens, and a lower correlation in the case of food allergens. Due to the fact that most food allergens are not standardized, the definitive diagnosis of food hypersensitivity is achieved by means of provocation tests. Nevertheless, negative specific IgE (7-18% of the cases) does not rule out a sensitization against the tested allergen, and a positive specific IgE without symptoms must be carefully interpreted because it can be due to a low degree of sensitization, unable to express clinical symptoms at this moment, but useful in the future as a guide on the disease course. In the evolutive period of the disease, specific IgE levels can be modified in a natural way (in beta-lactam allergy, 50% of the cases with specific IgE become negative after a year), or as an effect of the treatment (e.g., after immunotherapy in the case of Hymenoptera venom allergy), or it can remain positive for a long time, as in the case of pollinosis. On the other hand, the cutoff of the method, and subsequently the range of values to be considered as positive, will depend on the allergen studied. While inhalant allergens (with the exception of some molds) offer relatively high mean values of specific IgE, food and drug allergens yield less significant values. 

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Blood tests are available that measure levels of immunoglobulin E (IgE) against specific allergens such as foods, inhalants, medications, latex, and venoms. These tests can confirm the diagnosis of an allergic disorder, supplementing a clinical history consistent with an immediate allergic reaction. They are particularly useful when skin testing cannot or should not be performed.

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1. Specific IgE levels higher than 0.35 kU/L suggest sensitization, but that is not synonymous with clinical disease.

2. Prospective studies have identified IgE levels that can predict clinical reactivity with greater than 95% certainty for certain foods, but similar studies have not been performed for most other foods, drugs, latex, or venom.

3. The likelihood of an IgE-mediated clinical reaction often increases with the level of specific IgE, but these levels do not predict severity or guarantee a reaction will occur.

4. The sensitivity of allergy blood tests ranges from 60% to 95%, and the specificity ranges from 30% to 95%.

5. In the appropriate setting, these tests can help in identifying specific allergens and assessing allergic disease.

6. Neither allergy blood testing nor skin testing should be used for screening: they may be most useful as confirmatory tests when the patient’s history is compatible with an IgE-mediated reaction.

7. Health care providers often need to evaluate allergic disorders such as allergic rhinoconjunctivitis, asthma, and allergies to foods, drugs, latex, and venom, both in the hospital and in the clinic.

8. Unfortunately, some symptoms, such as chronic nasal symptoms, can occur in both allergic and nonallergic disorders, and this overlap can confound the diagnosis and therapy. Studies suggest that when clinicians use the history and physical examination alone in evaluating possible allergic disease, the accuracy of their diagnoses rarely exceeds 50%.

9. Blood tests are now available that measure immunoglobulin E (IgE) directed against specific antigens. These in vitro tests can be important tools in assessing a patient whose history suggests an allergic disease. However, neither allergy skin testing nor these blood tests are intended to be used for screening: they may be most useful as confirmatory diagnostic tests in cases in which the pretest clinical impression of allergic disease is high.

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Most tests for “allergy” are actually tests for allergic sensitization, or the presence of allergen-specific IgE. Most patients who experience symptoms upon exposure to an allergen have demonstrable allergen-specific IgE that specifically recognizes that allergen, making these tests essential tools in the diagnosis of allergic disorders. The demonstration of sensitization is not sufficient to diagnose an allergy, however, because a sensitized individual may be entirely asymptomatic upon exposure to the allergen in question. Venom- and food-specific IgE has been reported in up to 25 and 60 percent of the general population, respectively. Less commonly, patients who react to an allergen may not have any allergen-specific IgE that is detectable with routine testing. Furthermore, IgE molecules recognizing specific epitopes of an allergen may differ in their ability to trigger allergic reactions, and the currently available tests do not distinguish among them.  

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Advantages of allergic blood testing:

In theory, allergy blood testing may be safer, since it does not expose the patient to any allergens. Another advantage of allergy blood testing is that it is not affected by drugs such as antihistamines or tricyclic antidepressants that suppress the histamine response, which is a problem with skin testing. Allergy blood testing may also be useful in patients on long-term glucocorticoid therapy, although the data conflict. Prolonged oral glucocorticoid use is associated with a decrease in mast cell density and histamine content in the skin, although in one study a corticosteroid was found not to affect the results of skin-prick testing for allergy. Thus, allergy blood testing can be performed in patients who have severe eczema or dermatographism or who cannot safely suspend taking antihistamines or tricyclic antidepressants.

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Limitations of allergic blood testing:

A limitation of allergy blood tests is that there is no gold-standard test for many allergic conditions. (Double-blind, placebo-controlled oral food challenge testing has been proposed as the gold-standard test for food allergy, and nasal allergen provocation challenge has been proposed for allergic rhinitis.)  Also, allergy blood tests can give false-positive results because of nonspecific binding of antibody in the assay. Of note: evidence of sensitization to a particular allergen (i.e., a positive blood test result) is not synonymous with clinically relevant disease (i.e., clinical sensitivity).  Conversely, these tests can give false-negative results in patients who have true IgE-mediated disease as confirmed by skin testing or allergen challenge. The sensitivity of blood allergy testing is approximately 25% to 30% lower than that of skin testing, based on comparative studies. The blood tests are usually considered positive if the allergen-specific IgE level is greater than 0.35 kU/L; however, sensitization to certain inhalant allergens can occur at levels as low as 0.12 kU/L. Specific IgE levels measured by different commercial assays are not always interchangeable or equivalent, so a clinician should consistently select the same immunoassay if possible when assessing any given patient over time. Levels of specific IgE have been shown to depend on age, allergen specificity, total serum IgE, and, with inhalant allergens, the season of the year. Other limitations of blood testing are its cost and a delay of several days to a week in obtaining the results.

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RAST:

Radiometric assays include the radioallergosorbent test (RAST) test method, which uses IgE-binding (anti-IgE) antibodies labeled with radioactive isotopes for quantifying the levels of IgE antibody in the blood. In the radioallergosorbent test (RAST) allergens (antigens) are chemically bound to an insoluble matrix such as plastic, cellulose nitrate, cellulose (paper), or agarose beads. When patients’ serum is added, allergen specific IgE binds to immobilized allergen. Radioactively labeled anti-IgE is then added, which attaches to the specific IgE already bound to the allergen. The amount of specific IgE in the patient’s blood can be estimated from the amount of bound radioactivity.  In another type of radioallergosorbent test (the CAP-RAST) system) the allergen is covalently coupled to a cellulose carrier with a large surface area. The patient’s serum containing IgE is then added and specific IgE reacts with bound allergen. After non-specific IgE has been washed away, enzyme labeled antibodies against human IgE are added, and the bound complex is then incubated with a fluorescence substrate, the developing agent.  An enzyme linked immunosorbent assay (ELISA) is a non-radioactive method which uses antigen in fluid phase and enzyme labeling of anti-IgE, which is detected by adding substrate for the enzyme, which produces color change detected photometrically. The radioactivity (radioallergosorbent test) fluorescence (CAP-RAST test), or color (ELISA)) of the eluate corresponds with the concentration of specific IgE in the patient’s blood. The advantages of measuring the concentration of allergen specific IgE are that (a) it is not influenced by any concurrent drug treatment, (b) it can be performed when there is widespread skin disease, (c) it is completely safe, (d) the specificity of the two radioallergosorbent tests can be as high as 90% for inhaled allergens. However, the results are not immediately available, and testing is expensive.

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American College of Allergy Asthma and Immunology (ACAAI) and the American Academy of Allergy Asthma and Immunology (AAAAI) issued the Joint Task Force Report “Pearls and pitfalls of allergy diagnostic testing” in 2008, and is firm in its statement that the term RAST is now obsolete: The term RAST became a colloquialism for all varieties of (in vitro allergy) tests. This is unfortunate because it is well recognized that there are well-performing tests and some that do not perform so well, yet they are all called RASTs, making it difficult to distinguish which is which. For these reasons, it is now recommended that use of RAST as a generic descriptor of these tests is abandoned. The new version, the ImmunoCAP Specific IgE blood test, is the only specific IgE assay to receive FDA approval to quantitatively report to its detection limit of 0.1kU/l. 

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Serum IgE and eosinophil count in allergic rhinitis—Analysis using a modified Bayes’ theorem: a study:

Eighty-nine of 125 patients were atopic by prick and/or intradermal skin testing. Using a modified version of Bayes’ theorem and positive and negative probability weights, calculations for different thresholds of Serum IgE and eosinophil counts were summated and a post test probability for atopy was calculated. Calculated post test probabilities varied according to the threshold used to determine a positive or negative test; however, IgE thresholds greater than 140IU/ml and eosinophil counts greater that 80cells/ml were found to have a high probability of predicting atopy in patients with rhinitis. Moreover, IgE had a greater influence than eosinophil count in determining post test probability of allergy in this population. Considerable differences were noted in the IgE levels of atopic and non-atopic patients, including those with asthma or a history of smoking. However, these differences were not observed with eosinophil levels. So using a modified version of Bayes’ theorem to determine post test probability, IgE threshold levels greater than 140IU/ml and eosinophil counts greater than 80cells/ml in an individual with clinical signs and symptoms of rhinitis are likely to correlate with an atopic aetiology. This model of probability may be helpful in evaluating individuals for diagnostic skin testing and certain types of allergy-modifying treatment.

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Allergy skin tests:

There are three different types of skin tests. The first is puncture, prick, or scratch test. This test includes tiny drops of the purified allergen being scratched or pricked into the surface of your skin.  This test is normally performed in order to identify the allergies to the mold, pollen, pet dander, foods, and dust mites. In an intradermal test, the purified allergen extracts are injected into the skin of your arm. This test will likely be administered if it is suspected that you are allergic to insect venom or penicillin. A patch test is one that does not use needles. The allergen is placed on a patch, which is then put on your skin. The test is utilized in order to identify the substances that are the cause of contact dermatitis. These causes may include fragrances, medications, hair dyes, preservative, metals, or resins. 

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The skin prick test is the most widely used allergy test and can be performed during the initial consultation with aqueous solutions of a variety of allergens. These include (a) common inhaled allergens (house dust mite, grass pollen, cat dander, dog hair); (b) occupational allergens (such as ammonium persulphate, platinum salts, antibiotics, and latex); and (c) food allergens  Skin prick testing requires control using diluent (negative control) and histamine solution (positive control). A drop of allergen solution is placed on the skin of the forearm. A sterile lancet or 25 gauge (orange) needle is used to prick the skin through the allergen solution (a separate needle is used for each allergen solution). The excess allergen solution is removed from the skin with an absorbent paper tissue. The reaction is evaluated after 30 minutes. The test should be performed with standardized allergen solutions, if possible. In general practice it may be sufficient to use four allergens (house dust mite, grass pollen, and cat and dog allergen) plus the positive and negative controls to confirm or exclude atopy and recognize the most common allergens encountered. Common areas for testing include the inside forearm and the back. If the patient is allergic to the substance, then a visible inflammatory reaction will usually occur within 30 minutes. This response will range from slight reddening of the skin to a full-blown hive (called “wheal and flare”) in more sensitive patients similar to a mosquito bite. Interpretation of the results of the skin prick test is normally done by allergists on a scale of severity, with +/- meaning borderline reactivity, and 4+ being a large reaction. Increasingly, allergists are measuring and recording the diameter of the wheal and flare reaction. Interpretation by well-trained allergists is often guided by relevant literature. Some patients may believe they have determined their own allergic sensitivity from observation, but a skin test has been shown to be much better than patient observation to detect allergy. If a serious life threatening anaphylactic reaction has brought a patient in for evaluation, some allergists will prefer an initial blood test prior to performing the skin prick test. Skin tests may not be an option if the patient has widespread skin disease or has taken antihistamines sometime the last several days.

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Positive reaction:

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A positive result is a skin weal >2mm greater than that observed with the negative control (allergen diluent) solution. However, the relation between a positive result and overt clinical disease caused by that allergen is not absolute. The result of the skin prick test should be interpreted in the light of the clinical history: if both the history of allergy and the test result are positive, atopy and the offending allergen are confirmed; if both are negative, allergy is excluded; in the case of perennial allergens, there may not be an immediate association between exposure and symptoms, resulting in a false negative history in the context of a positive test result; many patients with a positive test result do not have symptoms of allergy; if there is discordance between the history and the test result, referral to an allergy specialist is recommended.

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The advantages of skin prick testing are:

It is painless and has a low risk of side effects; it is informative to the patient; patient compliance is high; and the test can be performed in health centers.

The disadvantages are:

Systemic and topical antihistamines may suppress the weal and flare reaction; the test is less reliable with food allergens (which are less well standardized) than with inhaled allergens; itching causes a slight discomfort; and interpretation is difficult in patients with eczema or dermatographism.

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Caution:

Although skin prick testing with inhaled allergens is generally safe, occasional systemic reactions including anaphylaxis have been reported when food allergens are used; testing with food allergens should therefore be performed only in specialist centers. Adrenaline should always be available.

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Patch test:

The patch test is widely used in the diagnosis of allergic contact dermatitis. Several standardized series of contact allergens are available. Possible allergens are applied in a standardized form to a healthy area of the patient’s skin. The patch test can be performed either with the suspected chemicals or with the standard series of allergens. Eczematous reaction at the site of application 48-72 hours later shows that the patient is sensitized to that allergen. The reaction must be distinguished from simple irritant reactions. The patch test is the most important diagnostic tool in diagnosing contact allergic dermatitis. However, patch testing can cause a flare up reaction (of healed eczema) or persisting test reactions. It can also cause sensitization and subsequent allergic contact dermatitis. It is time consuming, and it requires specialist interpretation.

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At the present time, properly performed skin tests are the best available method for detecting the presence of allergen specific IgE. They are rapid, sensitive, and inexpensive on a per test basis. In vitro tests are acceptable substitutes for skin tests in some circumstances. If the patient does not have normal skin, cannot discontinue interfering medications, or is so sensitive by history that anaphylaxis seems possible, in vitro tests are preferred. In vitro tests are better when it is necessary to test a difficult patient such as a combative, mentally retarded adult. In vitro tests also have been invaluable in many allergy research studies. Physicians must remember that positive tests for allergen-specific IgE do not diagnose allergy. They only indicate the presence of IgE molecules with a particular immunologic specificity. A decision whether the specific IgE molecules are responsible for clinically apparent disease must be made by a well-trained physician. The ultimate standard for the diagnosis of allergic disease remains the combination of:

(1) Positive double-blind challenge,

(2) The presence of specific IgE, and

(3) Demonstration that the symptoms are the result of IgE-mediated inflammation.

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Food challenge:

  • Diagnosis of food allergy requires taking a careful history and, if necessary, altering the patient’s diet with the help of a skilled dietician. The consequence of correct diagnosis can be beneficial to patients but may disrupt their lifestyle.
  • A definite diagnosis of food allergy can be established by properly conducted blinded food challenges, which avoid any possible bias from patient or investigator.
  •  Removal of the food from the patient’s diet should eliminate symptoms
  • Ideally challenges should be conducted as double blind, placebo controlled challenges
  • If the suspected food, but not the inactive substance, causes an allergic reaction, the diagnosis is established
  • Food challenges must be performed under strict medical supervision and in hospital settings
  • Food challenges, however, may cause anaphylactic reaction, are time consuming, and require several challenges, with washout periods of days

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Skin-prick and radioallergosorbent tests for particular foods have about 85 percent sensitivity and 30 to 60 percent specificity. Intradermal testing has a higher false-positive rate and greater risk of adverse reactions; therefore, it should not be used for initial evaluations. The double-blind, placebo-controlled food challenge remains the most specific test for confirming diagnosis.

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Nasal smears:

Nasal smear tests are used to determine the number of eosinophils present in the nasal secretion. A cotton bud is inserted two or three times into each nostril, and the lining of the nose scraped with a firm, rolling movement. Secretions are spread gently on to a microscope slide and stained, and the cells are counted. The advantages of nasal smears are that the nose is readily accessible and the test can help to differentiate between eosinophilic rhinitis (allergic rhinitis and non-allergic rhinitis with eosinophilia, which respond well to topical corticosteroids) and rhinitis due to other causes. However, the disadvantages are a slight discomfort to the patient and a high risk of false negative results if the nasal smear is not properly obtained. If more than 10% of the stained cells in nasal smears are eosinophils this indicates a positive result compatible with nasal eosinophilia.

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Other tests:

Challenge testing:

Challenge testing is when small amounts of a suspected allergen are introduced to the body orally, through inhalation, or other routes. Except for testing food and medication allergies, challenges are rarely performed. When this type of testing is chosen, it must be closely supervised by an allergist.

Allergen provocation testing:

This is only performed in hospital, for aero-allergens as it can induce a severe reaction. The hospital medical staff performs provocation tests by introducing the suspected aero-allergen (pollen, dust mite, animal dander or mould extract) directly into the nose, lung or eye to see if they provoke an allergic reaction. This is then measured.  

Elimination/Challenge tests:

This testing method is used most often with foods or medicines. A patient with a suspected allergen is instructed to modify his/her diet to totally avoid that allergen for determined time. If the patient experiences significant improvement, he/she may then be “challenged” by reintroducing the allergen to see if symptoms can be reproduced.

Double-blind placebo-controlled food challenge (DBPCFC):

This may be performed in hospital for a suspected food allergy. The offending food is concealed in a capsule or broth and, under careful supervision, given to the patient to see if they react.

Cellular allergen stimulation test (CAST):

 Measures release of inflammatory chemicals called leukotrienes in a blood sample after exposure to specific allergens. Can help to identify allergens such as preservatives (sodium benzoate, sulphites, salicylates), food colourings (tartrazine), aspirin and some medications, where the reactions don’t involve IgE. It isn’t 100 per cent accurate and isn’t readily available.

Histamine release (HR):

Especially helpful in identifying allergic reactions that don’t involve IgE and can also help diagnose idiopathic urticaria. The blood sample has to be sent to a special reference laboratory in Denmark for testing.

Serum tryptase:

Histamine and tryptase are released into the bloodstream during allergic reactions. Histamine is rapidly metabolised and so is hard to measure, but tryptase can be measured in the blood for up to six hours after an allergic reaction. It can’t identify the allergen, but can confirm an allergic reaction took place.

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Tests for local IgE:

Many of us have seen patients like this: typical seasonal allergic rhinitis symptoms but negative skin tests. In many European countries, the standard practice is to follow up such a patient with series of nasal allergen challenges; they are often positive. IgE is the least abundant class of immunoglobulin in human serum, it is much more tissue based and bound to cell surfaces. Many authors have published studies demonstrating local production of IgE in nasal tissue in both allergic rhinitis and presumed non-allergic rhinitis.

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Pitfalls of allergy tests:

A positive test does not equal a diagnosis, which is the premise of the testing programs. These tests are fundamentally useless without a formal evaluation of the patient. The NIH guidelines indicate a growing awareness of false, easy-fix allergy diagnoses, but we’re still a long way from implementing an evidence-based standard for allergy testing. One study showed that in 103 out of 111 children who were avoiding foods based on allergy test results had no reaction to the food when they ate it during a carefully conducted food challenge. Such false diagnoses are disruptive. Special diets can be difficult to follow and restrictive diets can be more expensive. People can suffer unnecessary anxiety about accidentally eating the “wrong” thing.

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Differential diagnosis:

Before a diagnosis of allergic disease can be confirmed, other possible causes of the presenting symptoms should be considered. Vasomotor rhinitis, for example, is one of many maladies that shares symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis. Once a diagnosis of asthma, rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy.

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Differential Diagnoses of Immediate Hypersensitivity Reactions:

•Allergic and Environmental Asthma

•Anaphylaxis

•Angioedema

•Asthma

•Bronchitis

•Carcinoid Lung Tumors

•Cardiogenic Shock

•Chronic Obstructive Pulmonary Disease

•Emphysema

•Farmer’s Lung

•Food Allergies

•Food Poisoning

•Heart Failure

•Hereditary Angioedema

•Hypersensitivity Pneumonitis

•Irritable Bowel Syndrome

•Pulmonary Embolism

•Shock, Distributive

•Sinusitis, Acute

•Sinusitis, Chronic

•Syncope

•Upper Respiratory Tract Infection

•Urticaria

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Idiosyncratic drug reactions:

Idiosyncratic drug reactions are unpredictable reactions that can result in significant morbidity and mortality. Severe idiosyncratic drug reactions are often characterized by fever and internal organ involvement. Idiosyncratic reactions are qualitatively aberrant reactions that cannot be explained by the known pharmacologic action of the drug and occur only in a small percent of the population. A classic example of an idiosyncratic reaction is drug-induced hemolysis in persons with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In adverse drug reactions involving overdoses, the toxic effect is simply an extension of the pharmacological effect (Type A adverse drug reactions). On the other hand, clinical symptoms of idiosyncratic drug reactions (Type B adverse drug reactions) are different from the pharmacological effect of the drug. Clinical characteristics and circumstantial evidence suggest that idiosyncratic drug reactions are caused by reactive metabolites and are immune-mediated; however, there are few definitive data and there are likely exceptions. There are three principal hypotheses for how reactive metabolites might induce an immune-mediated idiosyncratic reaction: the hapten hypothesis, the danger hypothesis, and the p-i hypothesis. It has been proposed that some idiosyncratic reactions, especially those involving the liver, represent metabolic idiosyncrasy; however, there are even less data to support this hypothesis. The unpredictable nature of these reactions makes mechanistic studies difficult. There is a very strong association with specific human leukocyte antigen (HLA) genes for certain reactions, but this has only been demonstrated for very few drugs. Animal models represent a very powerful tool for mechanistic studies, but the number of valid models is also limited. There may be biomarkers of risk; however, much more work needs to be done. Despite progress in the identification of reactive metabolites believed to be the cause of idiosyncratic reactions, the basic mechanisms remain elusive. Furthermore, because of the lack of consensus regarding definition of these syndromes; reporting, and therefore epidemiological data, are often unreliable. Research is needed to explore further the pathophysiology of these reactions, so that better diagnostic tests and treatment methods can be developed.  

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Abacavir idiosyncratic reaction is immune hypersensitivity: 

The first unequivocal example of a type of drug hypersensitivity reaction described as “pharmacologic interaction of drugs with immune receptors” or the “p-i concept” has been described. The mechanism of abacavir hypersensitivity has been determined to involve binding of the drug to the antigen binding site of the HLA-B 57 molecule, which results in alteration of that site such that a different set of peptides is presented to T cells. Since T cells are tolerant only to those MHC-restricted peptides to which they were exposed during development in the thymus, the presentation of alternate peptides is interpreted as foreign and can result in an allo- or autoimmune like T cell reaction. This explains the strong association between this HLA allele and abacavir hypersensitivity. The p-i concept was first proposed in the 1990s to explain T cell mediated reactions with strong HLA associations.  

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Pseudoallergic reaction also known as anaphylactoid reactions are subset of idiosyncratic reactions.

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Nonallergic drug hypersensitivities also referred to as pseudoallergic or anaphylactoid reactions, have clinical manifestations that are often indistinguishable from allergic reactions. Nonallergic drug hypersensitivities do not involve either IgE-mediated (type 1) or delayed (type 4) hypersensitivity. Nonallergic hypersensitivities are commonly referred to as pseudoallergic or idiosyncratic reactions. The common nonallergic drug hypersensitivities are secondary to chemotherapeutic drugs, radiocontrast agents, vancomycin, nonsteroidal anti-inflammatory agents, local anesthetic reactions and opiates. Protocols for skin testing of radiocontrast, nonsteroidal anti-inflammatory agents, local anesthetics and chemotherapeutic agents have been developed, though most have not been validated or standardized. Other diagnostic tests include in vitro-specific IgE tests, and the current ‘gold’ standard is usually an oral challenge or bronchoprovocation test. In the case of aspirin, even though it is not believed to be IgE-mediated, a ‘desensitization’ protocol has been developed and utilized successfully, although the mechanism of this desensitization is unclear.

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Drug reaction syndromes with manifestations suggestive of or compatible with immunopathologic mechanisms but known to lack an immune basis are usefully aggregated under the term ‘non-allergic hypersensitivity reactions,’ also called ‘pseudoallergic drug reactions’. These reactions constitute a subset of idiosyncratic reactions and clinically must be distinguished from immunologic (allergic) reactions. The idiosyncratic reactions that mimic IgE-independent syndromes are often referred to as ‘anaphylactoid,’ a much-abused term. Most pseudoallergic reactions that qualify as anaphylactoid involve the same final common pathway as type I reactions. In these cases (e.g., radiocontrast media reactions, opiate-induced urticaria, aspirin-induced asthma), basophils and mast cells are activated and vasoactive mediators released by non-immune mechanisms. Common examples of drug hypersensitivity are shown in the table below. 

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Pseudoallergy:

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The figure below shows revision of type 1 hypersensitivity reaction differentiating allergy from pseudoallergy:

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A pseudoallergy is a condition named for its similar presentation to a true allergy, though due to different causes. It may be due to alterations in the metabolism of histamine. It can be the cause of some forms of food intolerance. The symptoms of a pseudoallergy are very similar to those of an allergy. However, in contrast to an allergic reaction, a pseudoallergic reaction causes symptoms directly, without the release of IgE antibodies. Because IgE antibodies must be present in order for a diagnosis to be made via skin or blood testing, it is not possible to test for a pseudoallergy. Pseudoallergies can only be diagnosed via a strict exclusion diet and subsequent provocation testing with suspected pseudoallergens. Typical triggers of a pseudoallergy include food additives such as coloring agents or preservatives, but also naturally occurring substances such as biogenous amines, benzoic acids and probably aromas. Because it is not clear whether all pseudoallergens have been identified, the exclusion diet is referred to as “low in pseudoallergens” and not “pseudoallergen-free”.

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Among the general public, the distinction is rarely made between allergies and pseudoallergies. Although pseudoallergies have symptoms very similar to “true” allergies, pseudoallergies are not involved with the IgE immune system. The allergy-like symptoms are not reactions with antibodies, rather, the substances cause the reactions directly or through complements. The severity of the reaction depends on the dose. Unlike “true” allergies, pseudoallergies do not have a sensitization phase. Symptoms occur even at the first exposure. The following substances are common causal agents of pseudoallergies:  

  • Various food additives such as certain colorings and the preservatives benzoic acid and sorbic acid
  • Histamines: Primarily found in fish such as tuna and sardines
  • Biogenous amines are breakdown products of certain food proteins. They are often present in microbe-derived foods like yeast extract. Biogenous amines are also found in foods like chocolate, avocado, and tomatoes.
  • Salicylic acid blocks fermentation and rotting in various fruits and is also present in wine. Salicylate derivatives are used in pharmaceuticals such as aspirin and anti-rheumatism drugs.

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Complements and pseudoallergy:

Hypersensitivity reactions (HSRs) have been traditionally categorized in four groups from I to IV by Coombs and Gell. However, it has increasingly been recognized that a substantial portion of acute allergic reactions, whose symptoms fit in Coombs and Gell’s Type I category, are actually not initiated or mediated by pre-existing IgE antibodies. Recent estimates suggest that these non-IgE-mediated “anaphylactoid, pseudoallergic or idiosyncratic” reactions may represent as high as 77% of all immune-mediated immediate HSRs (Demoly et al., 1999), implying hundreds of thousands of reactions and numerous fatalities every year (Szebeni, 2001). Known examples of pseudoallergy include the reactions caused by radiocontrast media (RCM), nonsteroidal anti-inflammatory drugs, analgetics, morphine and insect venoms, liposomes and micellar solvents, such as Cremophor EL (CrEL) in Taxol. While there is no known common underlying cause for most of these reactions, there is substantial evidence suggesting that the reactions caused by RCM, liposomes and CrEL have a common trigger mechanism: complement (C) activation. Gell and Coomb’s system of four categories (types I–IV) has serious limitations, including the fact that pseudoallergy cannot be fitted in any of the four types of HSRs. However, no consensus has been reached to date, how to replace this classification. Descotes and Choquet-Kastylevsky (2001) proposed the use of three major types, namely, pseudoallergy, immunoglobulin-mediated and cell-mediated HSRs.  

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Opioids: Allergy vs. Pseudoallergy:

There is growing evidence that numerous drug-induced allergies are not mediated by the pathogenic role of allergen-specific immunoglobulin E (IgE). The case for such non–IgE-mediated, or pseudoallergic, reactions is proposed on the basis of the mechanism of mast cell and basophil activation. The pseudoallergic symptoms can resemble those of a true allergy but are caused by histamine release from cutaneous mast cells. Oral and injectable opioids are among the drugs that cause these symptoms, but the symptoms may not be due to a true allergy. Therefore, in patients who show these reactions, it is important to choose a safe alternative drug. Remember that most patients who say they are allergic to an opioid have experienced only a side effect that has been misclassified as an allergy. Published data suggest that as many as nine out of 10 patients labeled with an opioid allergy do not have a true allergy. On the other hand, patients who are considered allergic to an opioid present a serious challenge to clinicians because pain is not always controlled with nonopioid alternatives such as NSAIDs.

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Allergy vs. sensitivity vs. intolerance:

The use of the word “allergy” has become a generic term used by the public to describe allergies, sensitivities and intolerances.

Allergy:

This is a reaction produced by the body’s immune system when it encounters a normally harmless substance by involving IgE.

Sensitivity:

 This is the exaggeration of a normal side effect produced by contact with a substance. For example, the caffeine in a cup of coffee may cause extreme symptoms, such as palpitations and trembling, when it would usually only has this effect when taken in much larger doses. “Sensitivity” is a reaction to a substance, which is an exaggeration of a normal side effect produced by that substance. For example, reliever inhalers used in asthma, if given at too high a dose in a particular individual may cause them to “shake”. Sensitivity involves no immune system response, but it can still yield a multiplicity of symptoms, ranging from issues in the digestive tract to neurological problems. Some of the issues associated with sensitivities can become life threatening, especially if someone is exposed to a substance repeatedly, which is why it is important to be aware of sensitivities. (Some researchers classify sensitivity as immune reaction involving IgG-vide infra)

Intolerance:

This is where a substance (such as lactose) causes unpleasant symptoms (such as diarrhoea) for a variety of reasons, but does not involve the immune system. An inability to absorb or metabolize something (i.e.: lactose). This is not an immune response and therefore not considered an allergy. People with intolerance to certain foods can typically eat a small amount without having any problems. In contrast, people with a food allergy will have a bad reaction even if they come into contact with a tiny amount of the food to which they are allergic. “Intolerance” happens when unpleasant symptoms occur after eating a substance, which your body cannot handle because the digestive system does not produce sufficient quantities of a particular enzyme/chemical, which is needed to break down the food and aid digestion.

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Remember:

Allergy is an immune response, while intolerance is a chemical reaction due to lack of substances necessary to process something.

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Food allergy, food sensitivity and food intolerance:

Food intolerances are much more common than food allergy. In fact, nearly everyone at one time has had an unpleasant reaction to something they ate. Some people have specific food intolerances. Lactose intolerance, the most common specific food intolerance, affects about 10 percent of Americans. There’s a lack of consensus about the definition of food intolerances and food allergies. Therefore, there’s overlap and interchangeability in the literature. In general though, adverse food reactions can be classified as immune and nonimmune. The immune category can be further subdivided into allergies and sensitivities by some researchers. Food sensitivities are frequently confused with food allergies although they involve different immune mechanisms and have different characteristics. One of the most common food intolerances is lactose intolerance. There’s a deficiency in the digestive enzyme lactase so the lactose in milk isn’t digested well. It can be difficult to tell the difference between the symptoms of food allergy and food intolerance. Usually, symptoms caused by food allergy develop very soon after consuming the food, but, while symptoms caused by food intolerance can be immediate, they may also take 12 to 24 hours to develop. Food intolerance reactions are usually related to the amount of the food consumed. They may not occur until a certain amount (threshold level) of the food is eaten, but this amount varies for each person. The symptoms of food allergy and intolerance can also be caused by other conditions, so it’s important to see your doctor for a medical diagnosis.
Symptoms of food intolerance can include:

  • Nervousness, tremor
  • Sweating
  • Palpitations
  • Rapid breathing
  • Headache, migraine
  • Diarrhoea
  • Burning sensations on the skin
  • Tightness across the face and chest
  • Breathing problems – asthma-like symptoms
  • Allergy-like reactions.

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The foods that tend to cause intolerance reactions in sensitive people include:

  • Dairy products, including milk, cheese and yoghurt
  • Chocolate
  • Eggs, particularly egg white
  • Flavor enhancers such as MSG (monosodium glutamate)
  • Food additives
  • Strawberries, citrus fruits and tomatoes
  • Wine, particularly red wine
  • Histamine and other amines in some foods.

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For certain foods, there are ways to manage intolerances. It’s estimated that 50 million Americans are lactose intolerant, meaning they have a hard time digesting any dairy products such as cheese or ice cream. But there are now products such as Lactaid available, which you take before consuming a dairy product, that help the body digest the lactose without bloating, gas or diarrhea. If you think you have a food allergy or intolerance, Marshall suggests you begin keeping a very accurate food diary. Make sure you include what you ate, when you ate it and how long after you ate it that you got a negative reaction. However, if you experience very severe reactions after eating a food, forget the diary and go to a doctor who can begin testing immediately. If the allergic reaction is severe, it may require emergency treatment.

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A food allergy is an immediate reaction where the offending food causes the IgE immune cells to respond immediately causing urticaria (hives), anaphylactic shock, rhinitis (runny nose) and stomach problems. Food sensitivity is a delayed reaction where the offending food causes IgG immune cells to react and may take up to 3-7 days for your body to feel the effects.

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The differences between the two kinds of immune-mediated adverse food reactions are summarized in the table below.

Item
Compared
Food
Sensitivities
Food
Allergies
Body Organs Involved Any organ system in the body can be affected Usually limited to airways, skin, gastrointestinal tract
Symptom Onset Occurs From 45 minutes up to 3 days after ingestion From seconds to 1 hour after ingestion
Are symptoms acute or chronic? Usually chronic, sometimes acute Usually acute, rarely chronic
Percentage of Population Affected  20-30% 1-2%
Immunologic Mechanisms White blood cells
Antibodies:
   IgG (and subclasses)
   IgM
C3, C4
IgE
Non-Immunologic Mechanisms Toxic , pharmacologic None
How much food is needed to trigger the allergy? From small amount to large amount; often dosage dependent 1 molecule of allergic food needed to trigger reaction

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Lactose Intolerance versus Milk Allergy:

Lactose Intolerance:

People who have lactose intolerance cannot digest the milk sugar, lactose, because they manufacture too small a quantity of the digestive enzyme, lactase. Too small is a relative term. If you drink only tiny amounts of milk, even a tiny amount of lactase is sufficient. Too much milk (or any dairy product) can overwhelm even a fairly large lactase supply. How much is too much? That depends on a dozen factors, and can be hard to judge, even from meal to meal. Undigested lactose sits in the intestines and does two things, both bad. It draws water into your intestines, producing diarrhea, and it gets fermented by the bacteria in your colon, producing gas. That’s why the symptoms of lactose intolerance include, in addition to gas and diarrhea, flatulence, bloating and cramps. Note that these are all symptoms of the lower intestines.

 Milk or Dairy Allergy:

A milk or dairy allergy is a reaction to the protein in milk. There are two milk proteins, casein and whey. Some people are allergic only to one or the other. Most are allergic to both. The safest course in either case is to avoid all dairy products. This is very different from lactose intolerance, in which most people can still have small or moderate amounts of milk.

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Sinus Infection vs. Allergies — How Do You Know?

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Thirty-five million Americans suffer from nasal allergies and 7 million suffer from chronic sinus infections, yet most people can’t tell the difference between these two conditions. There is abundant confusion between cold, sinus and allergy symptoms. This means that often these conditions get mistreated or go untreated, which can lead to “chronic nasal congestion and associated symptoms” that can affect quality of life as well as daytime performance.

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Acute sinusitis refers to sinusitis symptoms that last less than four weeks. Most acute sinusitis starts as a regular cold from the common cold viruses and then becomes a bacterial infection. Chronic sinusitis is when symptoms last three months or longer. The cause of chronic sinusitis is believed to be a combination of swelling and infection. Recurrent sinusitis occurs when three or more acute episodes happen in a year. Allergic rhinitis puts you at risk for developing sinusitis because allergies can cause swelling of the sinuses and nasal mucous linings. This swelling prevents the sinus cavities from draining, and increases your chances of developing secondary bacterial sinusitis. If you test positive for allergies, your allergist can prescribe appropriate medications to control your allergies, possibly reducing your risk of developing an infection. In rare cases, immune problems that harm your ability to fight common infections may present with chronic or recurrent sinusitis.

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Rhinosinusitis: Clarifying the Relationship between Sinuses and Rhinitis:

Recent studies by otolaryngologist–head and neck surgeons have better defined the association between rhinitis and sinusitis. They have concluded that sinusitis is often preceded by rhinitis and rarely occurs without concurrent rhinitis. The symptoms, nasal obstruction/discharge and loss of smell, occur in both disorders. Most importantly, computed tomography (CT scan) findings have established that the mucosal linings of the nose and sinuses are simultaneously involved in the common cold (previously, thought to affect only the nasal passages). Otolaryngologists, acknowledging the inter-relationship between the nasal and sinus passages, now refer to sinusitis as rhinosinusitis. The catalyst relating the two disorders is thought to involve nasal sinus overflow obstruction, followed by bacterial colonization and infection leading to acute, recurrent, or chronic sinusitis. Likewise, chronic inflammation due to allergies can lead to obstruction and subsequent sinusitis. Other medical research has supported the close relationship between allergic rhinitis and sinusitis. In a retrospective study on sinus abnormalities in 1,120 patients (from two to 87 years of age), thickening of the sinus mucosa was more commonly found in sinusitis patients during July, August, September, and December, months in which pollen, mold, and viral epidemics are prominent. A review of patients (four to 83 years of age) who had surgery to treat their chronic sinus conditions revealed that those with seasonal allergy and nasal polyps are more likely to experience a recurrence of their sinusitis.

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Both allergies and sinus infections can make you feel congested making it difficult to tell them apart. Sinus infections result from blocked mucus becoming infected in nasal and/or sinus passages. Allergies are a result of your immune system reacting to substance such as pollen or dust. The following is a list of symptoms associated with sinus infections, allergies, and colds:

SIGN / SYMPTOM SINUSITIS ALLERGY COLD
Facial Pressure / Pain Yes Sometimes Sometimes
Duration of Illness Over 10-14 days Varies Under 10 days
Nasal Discharge Whitish or colored Clear, thin, watery Thick, whitish or thin
Fever Sometimes No Sometimes
Headache Often Sometimes Sometimes
Pain in Upper Teeth Sometimes No No
Bad Breath Sometimes No No
Coughing Sometimes Sometimes Yes
Nasal Congestion Yes Sometimes Yes
Sneezing No Sometimes Yes

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Cold vs. allergy:

Common colds are caused by viruses, while seasonal allergies are immune system responses triggered by exposure to an allergen. The easiest way to tell the difference between the two is how long they last — which unfortunately doesn’t help when symptoms first strike! A common cold usually lasts no longer than ten days, while allergies can pester people for months on end. Seasonal allergies usually bloom the same time every year while colds are more prominent in the winter and fall. Colds last only one to two weeks, commonly cause cough, sore throat, and sometimes body aches and fever, but not itchy, watery eyes. Allergies can last for a month or more, commonly cause itchy eyes, and don’t cause fevers or body aches; plus, they tend to cause coughing only in those who have asthma. With a cold, coughing and congestion are almost always evident, whereas itchiness of the mouth, eyes, and throat are easy indicators of allergies. The type of mucus associated with each is particular, too. A yellowy mucus usually accompanies a cold, while people with allergies deal with thin, watery snot. Other symptoms unique to the common cold include muscle aches, fatigue, and fever, whereas an all day sneeze fest usually points to pollen. In terms of distinguishing between the two, the National Institute of Allergy and Infectious Diseases has made following chart which provides some clues.

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Vasomotor rhinitis vs. allergic rhinitis:

Vasomotor rhinitis affects millions of Americans and results in significant symptomatology. Characterized by a combination of symptoms that includes nasal obstruction and rhinorrhea, vasomotor rhinitis is a diagnosis of exclusion reached after taking a careful history, performing a physical examination, and, in select cases, testing the patient with known allergens. According to a 2002 evidence report published by the Agency for Healthcare Research and Quality (AHRQ), there is insufficient evidence to reliably differentiate between allergic and nonallergic rhinitis based on signs and symptoms alone.The minimum level of diagnostic testing needed to differentiate between the two types of rhinitis also has not been established. Vasomotor rhinitis is characterized by prominent symptoms of nasal obstruction, rhinorrhea, and congestion. These symptoms are excessive at times and are exacerbated by certain odors (e.g., perfumes, cigarette smoke, paint fumes, inks); alcohol; spicy foods; emotions; and environmental factors such as temperature, barometric pressure changes, and bright lights. Patients with vasomotor rhinitis are further divided into two subgroups: “runners,” who demonstrate “wet” rhinorrhea; and “dry” patients, who exhibit nasal obstruction and airflow resistance with minimal rhinorrhea. Many studies have attempted to clarify the pathogenic mechanisms for these subgroups. Current theories include increased cholinergic glandular secretory activity (for runners), and nociceptive neurons with heightened sensitivity to usually innocent stimuli (for dry patients). These theories have not been adequately proven. The vasomotor nasal effects of emotion and sexual arousal also may be caused by autonomic stimulation. In one small study, researchers concluded that autonomic system dysfunction is significant in patients with vasomotor rhinitis (P < .005). Possible compounding factors included previous nasal trauma and extraesophageal manifestations of gastroesophageal reflux disease. Whatever their causal mechanisms, the various rhinitis syndromes result in significant morbidity in the United States. The National Rhinitis Classification Task Force concluded that 17 million Americans have nonallergic rhinitis. An evidence report from the Agency for Healthcare Research and Quality (AHRQ) estimated that 20 to 40 million Americans have allergic rhinitis, making it the sixth most prevalent chronic illness. No specific test is available to diagnose vasomotor rhinitis. In studies and in practice, allergic rhinitis is excluded or implicated as the cause of symptoms by using conventional skin testing or by evaluation for specific IgE antibodies to known allergens. According to the AHRQ, the results of “only one small recent study suggest that total serum IgE may be as useful as specific allergy skin prick tests, which, in turn, are more useful than radioallergosorbent testing in confirming a diagnosis of allergic rhinitis.” The lack of sensitivity and specificity of nasal cytology, total serum IgE, and peripheral blood eosinophil counts, which have been favored in the past for differentiating among rhinitis syndromes, makes their clinical use problematic. The minimum level of testing needed to confirm or exclude a diagnosis of vasomotor rhinitis has not been established in the literature. Topical anticholinergics should be used for rhinorrhea caused by vasomotor rhinitis. Azelastine may be used for vasomotor rhinitis associated with rhinorrhea, sneezing, postnasal drip, and nasal congestion. Topical corticosteroids may be used for vasomotor rhinitis associated with nasal obstruction and congestion. Cromolyn sodium may be used for vasomotor rhinitis associated with sneezing and congestion in patients older than two years.

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Treatment of allergy:

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When to seek Medical Care:

Because allergic reactions can progress and worsen in minutes causing complications, medical attention is always recommended for all but the most minor and localized symptoms. If the symptoms of your reaction worsen over a few days, or if they do not improve with recommended treatment and removal of the allergen, call your health-care provider. Tell your health-care provider if you have any allergic symptoms after using a drug. Allergic reactions can be dangerous. Sudden, severe, widespread reactions require emergency evaluation by a medical professional. Call an ambulance if you or someone around you has any of the following with an allergic reaction:

  • sudden, severe, or rapidly worsening symptoms
  • exposure to an allergen that previously caused severe or bad reactions 
  • swelling of the lips, tongue, or throat
  • wheezing, chest tightness, loud breathing, trouble breathing, or hoarseness of voice
  • confusion, sweating, nausea, or vomiting
  • widespread rash or severe hives
  • lightheadedness, collapse, or unconsciousness

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Traditional medical treatment:

Traditional treatment and management of allergies consisted simply of avoiding the allergen in question or otherwise reducing exposure. For instance, people with cat allergies were encouraged to avoid them. However, while avoidance of allergens may reduce symptoms and avoid life-threatening anaphylaxis, it is difficult to achieve for those with pollen or similar air-borne allergies. Nonetheless, strict avoidance of allergens is still considered a useful treatment method, and is often used in managing food allergies.

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A Quick Guide to Allergy Relief:

Minimizing Symptoms:

  • Check the pollen count and try to stay inside when levels are high.
  • Close windows at night and delay morning jogs. Plants release pollen from 4 a.m. to 8 a.m., so the longer you stay inside during this period, the better.
  • Run the air conditioner and invest in a HEPA (high-efficiency particulate air) filter, which is required to capture 99.97 percent of the particles passing through it. Because pollen from shoes, animal paws, and other things can get embedded in carpets, consider replacing permanent carpets with washable throw rugs. Be wary of nonairborne allergens, such as dander, mold, and dust, which can aggravate seasonal allergies.
  • Keep your lawn mowed short to prevent it from sprouting pollen-producing buds. Consider substituting nonpollinating plants, like ivy and myrtle, for grass. Get rid of leaves and compost piles quickly, before molds form.
  • Wear natural fibers. Synthetics, such as polyester and nylon, can create a pollen-attracting electric charge when rubbed.
  • Shower and wash your hair before going to bed. Daytime pollen can collect on your body, meaning you’ll be breathing it in all night.
  • Breathe through your nose. When it comes to keeping out foreign bodies, noses are much better designed than mouths.
  • Avoid secondhand smoke. A study in the Journal of Allergy and Clinical Immunology found that exposure to secondhand smoke exacerbated allergic responses.

Clean the house often. Reducing the levels of pollen, dust, and mold in your home will reduce your symptoms. Use vacuums, mops, and microfiber dust cloths, which collect particles, rather than brooms, which recirculate them into the air. Buy pillowcases and mattress covers made from fabrics labeled “dustproof,” and wash them frequently at hot temperatures to eradicate dust mites and pollen. Don’t air-dry bedding or clothes, since damp cloth attracts pollen. And wipe down windowsills with a damp cloth before going to bed so you can breathe and rest easy at night.

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Take a night shower:

 Instead of taking a shower right when you wake up, take one at the end of the day. Why? This washes away all of the pollen that might be attached to your skin or hair, allowing you to have the best shot at getting a good allergy-free night of sleep.

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Food Allergy advice for Kids: Don’t delay Peanuts, Eggs:

Food allergies affect an estimated 5% of children under the age of 5 in the U.S., according to the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The prevalence of a food allergy for children under 18 increased by 18% from 1997 to 2007.  Infants at risk for food allergies should be gradually introduced to suspect foods to build up tolerance, according to new recommendations from a leading allergy doctor group. Parents trying to navigate the confusing world of children’s food allergies now have more specific advice to consider. Highly allergenic foods such as peanut butter, fish and eggs can be introduced to babies between 4 and 6 months and may even play a role in preventing food allergies from developing. These recommendations regarding children and food allergies—a rising phenomenon that researchers don’t fully understand—come from the American Academy of Allergy, Asthma & Immunology in a January article in the Journal of Allergy & Clinical Immunology: In Practice. The AAAAI’s Adverse Reactions to Foods Committee outlined how and when to introduce highly allergenic foods, which include wheat, soy, milk, tree nuts, and shellfish. A new report recommends introducing highly allergenic foods to children earlier. Highly allergenic foods such as peanut butter, fish and eggs can be introduced to babies between 4 and 6 months. The recommendations are a U-turn from 2000, when the American Academy of Pediatrics issued guidelines that children should put off having milk until age 1, eggs until 2 and peanuts, shellfish, tree nuts and fish until 3. One theory to explain why early introduction is important holds that if babies aren’t exposed early enough to certain foods, their immune systems will treat them as foreign substances and attack them, resulting in an allergy. Multiple studies have shown that early exposure to allergens is actually protective for avoiding allergies later in life.  

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Cow’s milk allergy:

Cow’s milk allergy is the most common food allergy in infants 12 months and under. It can cause digestive problems, breathing difficulties, rashes or swelling of the face. Recent studies suggest the severity and duration of cow’s milk allergy is increasing, which may limit an infant’s diet, potentially leading to growth, development and health issues. Allergy to cow’s milk requires a dairy-free diet. Cow’s milk is replaced with protein hydrolysate-based milk substitutes or amino-acid formulas (in case of allergy to hydrolysates). These milk substitute products are specifically made for infants – they have all the minerals, fats, carbohydrates and proteins your baby’s body and brain require for proper growth and development. These can be found in most pharmacies. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines recommend the use of an extensively hydrolyzed protein in most infants with cow’s milk allergy. Historically, children with cow’s milk allergy didn’t build tolerance until three to five years of age. An extensively hydrolyzed formula means it contains a milk protein that is broken down into tiny pieces to virtually eliminate allergic reactions.  

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A Study:

The open non-randomized 12-month trial evaluated the rate of tolerance to cow’s milk in 260 children aged one to 12 months diagnosed with cow’s milk allergy who were fed extensively hydrolyzed casein formula (n=55), extensively hydrolyzed casein formula plus Lactobacillus GG (n=71), hydrolyzed rice formula (n=46), soy formula (n=55) or amino acid based formula (n=33). Full clinical evaluations were performed at six and 12 months to evaluate whether subjects had achieved oral tolerance to cow’s milk protein. The rate of children building oral tolerance to cow’s milk at 12 months was significantly higher (p<0.05) in the groups receiving EHCF + LGG (78.9 percent) and EHCF (43.6 percent) compared with the other groups: RHF (32.6 percent), SF (23.6 percent) and AAF (18.2 percent). The study shows significantly more infants with cow’s milk allergy who received an extensively hydrolyzed formula that includes Lactobacillus rhamnosus GG, built a tolerance to cow’s milk than those fed other formulas in the study.

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An estimated 80 percent of your immune system is located in your gut, so supporting your digestive health is essential to also supporting your immune system, which is your primary defense system against all diseases. Processed food, genetically engineered ingredients and synthetic additives all decimate the beneficial bacteria in your gut, thereby having a negative effect on your immune system.

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General guidelines:

Make it a rule to keep your windows closed and the air conditioner on when it’s pollen season. Be sure to set the AC to “recirculate,” and if it’s not hot outside, you can keep it in filter-only mode. Using an air conditioner in your car can cut the amount of pollen you breathe by as much as 30 percent. If you love an outdoor workout, avoid the morning or early afternoon. Grasses and trees start releasing pollen at sunrise, with levels peaking in the late morning and early afternoon. It is suggested that people run after work in the late afternoon or evening. Exercising when pollen counts are lower can make an enormous difference. And if pollen counts are going to be high on a given day, opt for a less strenuous workout. Room air purifiers and filters are an extremely effective way to remove pollen, animal dander, dust, and other allergens from indoor air. But unless you close the doors and windows in the room where you’re using one, it’s basically useless because they’re only meant to filter room-size areas. Even if you’re not allergic to animals, pets can bring in pollen, dust, mold, and other allergens from the outdoors. It’s best to avoid letting your dog or cat hang out on your bed. Recent research has also found that junk food increases a child’s risk of asthma and allergies, so certainly, avoiding such foods can, at the very least, reduce your risk. Also genetically engineered (GE) foods, which are pervasive in the American diet, have been shown to cause food allergies. 

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A mask:

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 If your neighbor kid bails and you’re stuck doing outdoor chores that aggravate your pollen, grass, or mold allergies, wear a NIOSH 95 filter mask. You can find them online, in pharmacies, or in hardware stores. Your neighbors may think you’re overreacting to a flu outbreak, but who cares! You’ll be able to breathe easy when you go back inside. As an added precaution, you should wear glasses or sunglasses when outside to keep pollen from invading your eyeballs. When you go inside, take a shower, wash your hair, and change your outfit to get rid of residue pollens riding on your wardrobe.

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Home remedy for sinus congestion and hay fever symptoms: neti pots:

These symptoms often improve with saline nasal irrigation — rinsing out the sinuses with a salt and water solution. You can use a neti pot or a specially designed squeeze bottle to flush out thickened mucus and irritants from your nose.

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Neti pot:

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The oddly shaped vessel has been hailed as a miracle treatment by allergy sufferers across the globe by allowing people to rinse pollen and other irritants from their noses. The device is a great addition to allergy remedy arsenal. For people with sinus problems, it helps to flush out the nose and keep things open. The neti pot is also recommended by American Academy of Allergy, Asthma & Immunology (AAAAI) for allergy sufferers. The AAAAI even posted a recipe that allows you to create your own saline solution. People should always use distilled or boiled water when using the neti pot to avoid infection.

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The neti pot is shaped like a miniature teapot and is used to flush the sinuses with a gentle saline solution. The name of the neti pot comes from the Ayurvedic technique called “jala neti,” or nasal cleansing. Nasal cleansing is based in the yoga tradition and Eastern cultures have used the practice for centuries. In recent years, Western cultures have adopted the practice and the neti pot made its way to the United States in the 1970s. Today, you can find neti pots and neti pot solution in mainstream drug stores. A more biological explanation for how the Neti pot works has to do with tiny, hair-like structures called cilia that line the inside of the nasal and sinus cavities. These cilia wave back and forth to push mucus either to the back of the throat where it can be swallowed, or to the nose to be blown out. Saline solution can help increase the speed and improve coordination of the cilia so that they may more effectively remove the allergens and other irritants that cause sinus problems. Typically, to use the Neti pot or other nasal irrigation device you would mix about 16 ounces (1 pint) of lukewarm water with 1 teaspoon of salt. Some people add 1/2 teaspoon of baking soda to buffer the solution and make it gentler on the nose, but there isn’t any real proof that this improves the experience. Use distilled, sterile, or previously boiled water to make up the irrigation solution.  Once you’ve filled the Neti pot, tilt your head over the sink at about a 45-degree angle. Place the spout into your top nostril, and gently pour the saline solution into that nostril. The fluid will flow through your nasal cavity and out the other nostril. It may also run into your throat. If this occurs, just spit it out. Blow your nose to get rid of any remaining liquid, then refill the Neti pot and repeat the process on the other side. It’s important to rinse the irrigation device after each use and leave open to air dry. In studies, people suffering from daily sinus symptoms found relief from using the Neti pot or other nasal irrigation system daily. Three times a week was often enough once symptoms subsided. Research has found that the Neti pot is generally safe. About 10% of regular users experience mild side effects, such as nasal irritation and stinging. Nosebleeds can also occur, but they are rare. Reducing the amount of salt in the solution, adjusting the frequency of Neti pot use, and changing the temperature of the water appear to reduce side effects. When we are sick, the mucus tends to thicken in order to trap viruses and bacteria. Pollen is also very sticky and may cling to the nasal passages. The warm salt water flushes dust and other debris out of the sinuses that blowing your nose may miss. Salt also has mild antiseptic properties and can kill some bacteria on contact. The salt also has some mild detergent effects. 

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Saline drops:

Irrigating the nose with saline solution (salt water) may help soothe upper respiratory allergies by removing irritants that become lodged in the nose and cause inflammation. In fact, saline solution may even wash away some of the inflammatory cells themselves.

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Drink Peppermint Tea:

Allergy sufferers throughout the centuries have turned to hot tea to provide relief for clogged-up noses and irritated mucous membranes, and one of the best for symptom relief is peppermint tea. Peppermint’s benefits extend well beyond its delicious smell; the essential oil acts as a decongestant, and substances in peppermint contain anti-inflammatory and mild antibacterial constituents.

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Steam inhalation:

Breathing steam refreshes and soothes irritated sinuses, and it helps rid the nasal passages of mucus. While it takes some time, it will make you feel wonderful! Boil several cups of water and pour into a big bowl (or a plugged sink). Lean carefully over the bowl, and drape a towel over your head. Breathe gently for 5 to 10 minutes.

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Elimination & Rotational Diet:

If you suspect a potential allergy or food intolerance there is testing available through your family doctor or naturopath. These tests can sometimes be costly and don’t always test for all possible sensitivities. Alternatively you can identify potential triggers through an elimination diet. Essentially you eliminate all potentially reactive foods for several days and introduce them one group at a time to check for negative response.

The top 5 suspect foods are:

1. Dairy

2. Gluten (wheat)

3. Eggs

4. Corn

5. Night Shades (Tomatoes, eggplant, peppers, and potatoes)

People are often surprised that night shade vegetables make this list. Tomatoes, eggplant, peppers, and potatoes are known for triggering the inflammatory response which makes them suspect as potential sensitive foods. On an elimination diet you should first keep a food journal and eat regularly for one week. Make note of any symptoms, changes in mood, and energy level. Next remove all 5 food groups from your diet for 7 days. Following this reintroduce one food group per day. Eat something from that group several times in one day and wait for a response. If no reaction occurs you can keep this group in your diet and introduce the next group on the next day. If a reaction does occur, remove it from your diet and continue to reintroduce the next food groups. A rotational diet is more of a lifestyle change that helps to avoid overeating potentially reactive foods and therefore preserving enzymes. This is applicable for someone with food intolerance as opposed to a food allergy. You are allowed to eat certain food groups every 3-5 days and must avoid them the rest of the time. It is extreme and makes grocery shopping difficult but it can prove to be effective especially if you find you are sensitive to several food groups.

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Drug-Free remedies to relieve Allergies:

Some studies have found that those regularly eating foods rich in omega-3 fatty acids were less likely to have allergy symptoms. Foods including flaxseed oil, walnuts and cold-water fish may help to fight inflammation and the other results of having seasonal allergies. A dose of chili pepper, horse radish or wasabi added to your food can also be a natural, temporary decongestant. Quercetin is a natural substance found in fruits, vegetable, red wine, black tea and some grains. Some studies have found that it alleviates some of the effects of pollen by helping to block the release of histamine that causes inflammations. Derived from a common weed in Europe, butterbur does not cause sleepiness and seems to function as a leukotriene inhibitor, blocking some of the chemicals that cause swelling in the nasal passages. Some research suggests that extracts of butterbur root can be as effective at relieving nasal symptoms as antihistamines.

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House dust mite eradication:

House dust mite eradication measures can help if special attention is paid to the bedroom:

  • Synthetic pillows and duvets are better than feather fills
  • Old mattresses harbour up to 10,000 house dust mites, so use mite impermeable barrier mattress covers
  • Wash pillow cases and covers at 60°C
  • Use a vacuum cleaner fitted with a HEPA filter
  • Choose hardwood and laminate flooring, not heavy pile carpets
  • Discourage soft toys and clutter
  • Regularly air the bedroom to reduce humidity

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Medications:

Several antagonistic drugs are used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes. These include antihistamines, glucocorticoids, epinephrine (adrenaline), theophylline and cromolyn sodium. Anti-leukotrienes, such as Montelukast or Zafirlukast, are FDA approved for treatment of allergic diseases. Anti-cholinergics, decongestants, mast cell stabilizers, and other compounds thought to impair eosinophil chemotaxis, are also commonly used. These drugs help to alleviate the symptoms of allergy, and are imperative in the recovery of acute anaphylaxis, but play little role in chronic treatment of allergic disorders.

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Antihistamine drugs:

A histamine antagonist (commonly called an antihistamine or antihistaminic) is a pharmaceutical drug that inhibits the action of histamine by blocking it from attaching to histamine receptors; or it may inhibit the enzymatic activity of histidine decarboxylase, catalyzing the transformation of histidine into histamine (atypical antihistaminics). Antihistamines are commonly used for the relief of allergies caused by intolerance of proteins. Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells. They exert a competitive antagonism to histamines. Itching and sneezing are suppressed by antihistamine blocking of H1-receptors on nasal sensory nerves. In common use, the term antihistamine refers only to compounds that have inhibit action at the H1 receptor (and not H2, etc). Rather than “true” antagonists, H1-antihistamines are actually inverse agonists at the histamine H1-receptor. Clinically, H1 antagonists are used to treat allergic reactions. Sedation is a common side-effect, and some H1 antagonists, such as diphenhydramine and doxylamine, are also used to treat insomnia. However, second-generation antihistamines do not cross the blood–brain barrier, and as such do not cause drowsiness. H2 antagonists, like H1 antagonists, are also inverse agonists and not true antagonists. They act on H2 histamine receptors found principally in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H2 to stimulate acid secretion; drugs that block H2 signaling thus reduce the secretion of gastric acid. H2 antagonists are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease.

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Types of antihistamine:

There are a number of antihistamine medicines, which are classified in two groups. These are:

  • first-generation antihistamines, which cause symptoms of drowsiness in most people; they include diphenhydramine and chlorphenamine 
  • second-generation antihistamines, which do not usually causes symptoms of drowsiness and include loratadine and cetirizine

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What are the advantages and disadvantages of various antihistamines?

The first antihistamines, however, crossed too easily into the brain, and often caused quite severe adverse effects. The drugs were actually strong sedatives, so they made people very sleepy. Their beneficial effects also wore off so quickly that people needed to take these drugs several times a day. Newer generations of drugs that caused fewer adverse effects and had a longer-lasting positive effect were developed. Four of these drugs are now among the most commonly used drugs for the relief of allergy symptoms: cetirizine, desloratadine, fexofenadine and loratadine. Researchers from the Oregon Evidence-Based Practice Center in the USA looked for trials that compared these four drugs with each other, to see if any were more effective than others for allergic rhinitis or urticaria. Allergic rhinitis is the scientific name for both hay fever that happens most around springtime (seasonal allergic rhinitis) and the same symptoms of sneezing, runny nose and watery eyes occurring year-round (perennial allergic rhinitis). Urticaria (often called hives) is an itchy reaction on the skin that is often associated with red, swollen patches called wheals. The researchers found 46 trials in adults and 27 trials in children, as well as some trials that only studied results for less than two weeks. Although this seems like a lot of research, because there were so many drugs and different symptoms, many important questions remain unanswered. Most of the trials looked only at seasonal allergic rhinitis. It is not yet clear which of these drugs might be the most effective for each particular type of allergic reaction, with the least adverse effects. There was some evidence that loratadine might start working more quickly than other drugs in people with perennial allergic rhinitis. Loratadine might also be better at relieving urticaria than cetirizine. Cetirizine might also cause more sleepiness than some of the other drugs, but this is not certain.

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The older antihistamines are sedating, and they induce psychomotor impairment, including reduced eye-hand coordination and impaired automobile driving skills. Their anticholinergic (muscarinic) effects include visual disturbance, urinary retention, and constipation. Because the newer H1 antihistamines such as fexofenadine, loratadine, desloradine, cetirizine, levocetirizine, olopatadine, bilastine, and azelastine are less lipophilic and more H1 selective, their ability to cross the blood-brain barrier is reduced, and thus their sedating and anticholinergic side effects are minimized. These newer antihistamines do not differ appreciably in efficacy for relief of rhinitis and/or sneezing. Azelastine nasal spray may benefit individuals with nonallergic vasomotor rhinitis, but it has an adverse effect of dysgeusia (taste perversion) in some patients. Because antihistamines have little effect on congestion, adrenergic agents such as phenylephrine or oximetazoline are generally used topically to alleviate nasal congestion and obstruction.

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Local antihistaminic:

Antihistamine nasal sprays help relieve sneezing, itchy or runny nose, sinus congestion, and postnasal drip. Prescription antihistamine nasal sprays include azelastine and olopatadine. Side effects of antihistamine nasal sprays may include bitter taste, dizziness, drowsiness or fatigue, dry mouth, headache, nasal burning, nosebleed, nausea, runny nose, sore throat, and sneezing.

Antihistamine eye drops are often combined with other medications such as mast cell stabilizers or decongestants. Antihistamine eye drops can ease symptoms such as itching, redness and swollen eyes. You may need to use these medications several times a day, because the effects may last only a few hours. Over-the-counter examples include ketotifen and pheniramine. Prescription examples include emedastine and olopatadine. Side effects of these medications can include red eyes, watery eyes, mild stinging or burning and headache. Antihistamine eye drops increase the risk of eye inflammation when you’re wearing contact lenses.

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Decongestants:

Decongestants are used for quick, temporary relief of nasal and sinus congestion. You may need to avoid decongestants if you’re pregnant, if you’re an older adult or if you have high blood pressure. Check with your doctor to see which medications are safe for you.

  • Oral decongestants (pills and liquids) relieve nasal and sinus congestion caused by hay fever. Many decongestants are available over-the-counter. A common example is pseudoephedrine. A number of medications contain a decongestant such as pseudoephedrine combined with other medications; for example, pseudoephedrine and an antihistamine. Oral decongestants can cause a number of side effects, including irritability, fast or irregular heartbeat, dizziness, insomnia, headaches, anxiety, tremors, and increased blood pressure.
  • Nasal decongestant sprays and drops relieve nasal and sinus congestion. Examples include phenylephrine and oxymetazoline. Nasal decongestants can cause dryness, burning or stinging inside the nose, runny nose, and sneezing. Taking too much of a nasal decongestant can cause irritability, fast or irregular heartbeat, dizziness, insomnia, headaches, anxiety, tremors, and increased blood pressure. Don’t use a decongestant nasal spray for more than a week or so, or you may develop severe congestion as soon as you stop taking it (rebound congestion).
  • Decongestant eye drops (or combined decongestant-antihistamine eye drops) can temporarily ease symptoms such as red, itchy eyes. Available over-the-counter, examples include tetrahydrozoline and naphazoline. Side effects include persistent eye redness and damage to blood vessels in the eye when overused. In rare cases, decongestant eye drops can cause a type of sudden (acute) glaucoma.

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Corticosteroids:

 Steroids work by decreasing the inflammation caused by allergic reactions. They prevent and treat nasal stuffiness, sneezing, and itchy, runny nose due to seasonal or year-round allergies. They can also decrease inflammation and swelling from other types of allergic reactions. Corticosteroids help prevent the release of symptom-causing chemicals during an allergic reaction. Most corticosteroid medications require a prescription.

  • Nasal corticosteroid sprays prevent and relieve signs and symptoms of allergies such as allergic rhinitis (hay fever). These medications can help with nasal stuffiness, sneezing, and itchy, runny nose. Examples include fluticasone, mometasone, budesonide, triamcinolone and beclomethasone, fluticasone and ciclesonide. Side effects can include unpleasant smell or taste, nasal irritation and nosebleeds.
  • Inhaled corticosteroids are used to relieve symptoms triggered by airborne allergy-triggering substances (allergens). These medications are generally taken on a daily basis as part of asthma treatment. Examples include fluticasone, budesonide, mometasone, beclomethasone and ciclesonide. Side effects are generally minor and can include mouth and throat irritation and oral yeast infections.
  • Corticosteroid eye drops are used to treat severe eye irritation caused by hay fever and allergic conjunctivitis. Examples include dexamethasone, fluorometholone and prednisolone. These medications may cause blurred vision. Prolonged use may increase your risk of eye infections, glaucoma and cataracts.
  • Corticosteroid skin creams relieve allergic skin reactions such as scaling and itching. Some low-potency corticosteroid creams are available without a prescription, but talk to your doctor before using a topical corticosteroid for more than a few weeks. Examples include hydrocortisone and triamcinolone. Side effects can include skin irritation and discoloration. Long-term use, especially of stronger prescription corticosteroids, thins the top layer of the skin, resulting in easy bruising where the cream has been applied. Corticosteroids are available in liquid form that can be useful for skin conditions involving the scalp.
  • Oral corticosteroids (pills and liquids) are used to treat severe symptoms caused by all types of allergic reactions. Examples include prednisone. Because they can cause numerous short- and long-term side effects, oral corticosteroids are usually prescribed for short periods of time. Long-term use can cause cataracts, osteoporosis, muscle weakness, stomach ulcers and delayed growth in children. Oral corticosteroids can also worsen hypertension. In some situations, corticosteroids may be given as a shot (injection) rather than pills.

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Leukotriene inhibitors:

Montelukast is a prescription medication that blocks symptom-causing chemicals called leukotrienes. This oral medication relieves allergy signs and symptoms including nasal congestion, runny nose and sneezing. Side effects can include upper respiratory infection in adults, and headache, ear infection and sore throat in children. The Food and Drug Administration (FDA) has warned that in some people, leukotriene-blocking medications could possibly cause psychological symptoms, such as irritability, anxiousness, insomnia, hallucinations, aggression, depression, and suicidal thinking or behavior.

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Mast cell stabilizers:

Cromoglicate-based drugs (sodium cromoglicate, nedocromil) block a calcium channel essential for mast cell degranulation, stabilizing the cell and preventing release of histamine and related mediators.  Mast cell stabilizers appear to stabilize the mast cells to prevent degranulation and mediator release. These drugs are not usually classified as histamine antagonists, but have similar indications. Cromolyn is an over-the-counter nasal spray. It prevents the release of histamine and other symptom-causing chemicals during an allergic reaction. This medication works best when you take it before your symptoms start. Some people need to use the spray three or four times a day. Side effects may include nasal stinging or sneezing. Mast cell stabilizer eye drops prevent the release of symptom-causing chemicals such as histamine. These prescription medications reduce allergy symptoms such as red, itchy eyes. Examples include cromolyn, lodoxamide, pemirolast and nedocromil. These medications don’t usually cause significant side effects.

Examples:

Cromoglicate (cromolyn)

Nedocromil

Beta2-adrenergic agonist

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Medications used to treat cold urticaria include:

  • Antihistamines: These medications block the symptom-producing release of histamine.
  • Cyproheptadine: This medication is an antihistamine that also affects nerve impulses that lead to symptoms.
  • Doxepin (Silenor): Normally used to treat anxiety and depression, this medication can also reduce cold urticaria symptoms.

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Eye allergy treatments:

Regular use of anti-allergy eye drops such as sodium chromoglycate, nedocromil, olopatidine and lodoxamide can help to treat mild seasonal disease.  Non-sedating oral antihistamines – cetirizine, loratadine, mizolastine and fexofenadine – can also help, especially when there’s an associated nasal allergy.  Corticosteroid eye drops occasionally have to be used for more severe eye allergies, but this should be for short periods only.

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Generally, treatment of a drug allergy falls into three categories:

  • Mild allergy (localized hives and itching)
    • Treatment is aimed at caring for the symptoms and stopping the reaction caused by the drug.
    • Medications prescribed may include antihistamines,
    • You may be advised to stop taking the medication that caused the allergy.
  • Moderately severe allergy (all-over hives and itching)
    • Treatment is aimed at caring for the symptoms and stopping the reaction.
    • Usually the offending medication is stopped.
    • Medications prescribed may include antihistamines, oral steroids (prednisone).
  • Severe allergy(shortness of breath, throat tightness, faintness, severe hives, involvement of many organ systems)
    • Treatment includes strong medications to quickly reverse the dangerous chain of events.
    • The offending medication is stopped immediately and you are admitted in a hospital.
    • Medications prescribed may include antihistamines, oral or IV steroids such as prednisone or methylprednisolone.
    • Depending on the severity of other symptoms, other medications may be used including epinephrine (also called adrenaline), which is inhaled, given by IV/ IM, or injected under the skin.

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How many times have we heard patients say they are “allergic” to drugs like antihistamines and corticosteroids?  

Hypersenstivities to medications used to treat allergic diseases are fortunately uncommon. Both the allergy literature and the dermatology literature describe delayed (and even immediate) hypersensitivity reactions to corticosteroids. Corticosteroids were voted Allergen of the Year in 2005 by the American Contact Dermatitis Society. This was designed to draw attention to allergens that are very common, under-recognized, merit more attention because they are causing significant allergic contact dermatitis.  Allergic reactions to corticosteroids usually involve symptoms of contact dermatitis, but may be more severe, including urticaria and even anaphylaxis. Luckily, there are ways to diagnose steroid allergy, and most people with this unusual allergy can tolerate other types of corticosteroids. There are also reports of allergic reaction to diphenhyramine (Benadryl).

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Treatment of anaphylaxis:

Anaphylaxis is a medical emergency that may require resuscitation measures such as airway management, supplemental oxygen, large volumes of intravenous fluids, and close monitoring. Administration of epinephrine is the treatment of choice with antihistamines and steroids often used as adjuncts. A period of in hospital observation for between 2 and 24 hours is recommended for people once they have returned to normal due to concerns of biphasic anaphylaxis. Epinephrine (adrenaline) is the primary treatment for anaphylaxis with no absolute contraindication to its use. It is recommended that an epinephrine solution be given intramuscularly into the mid anterolateral thigh as soon as the diagnosis is suspected. The injection may be repeated every 5 to 15 minutes if there is insufficient response. A second dose is needed in 16-35% of episodes with more than two doses rarely required. The intramuscular route is preferred over subcutaneous administration because the latter may have delayed absorption. Minor adverse effects from epinephrine include tremors, anxiety, headaches, and palpitations. People on β-blockers may be resistant to the effects of epinephrine. In this situation if epinephrine is not effective intravenous glucagon can be administered which has a mechanism of action independent of β-receptors. Antihistamines (both H1 and H2), while commonly used and assumed effective based on theoretical reasoning, are poorly supported by evidence. A 2007 Cochrane review did not find any good-quality studies upon which to base recommendations and they are not believed to have an effect on airway edema or spasm. Corticosteroids are unlikely to make a difference in the current episode of anaphylaxis, but may be used in the hope of decreasing the risk of biphasic anaphylaxis. Their prophylactic effectiveness in these situations is uncertain. Nebulized salbutamol may be effective for bronchospasm that does not resolve with epinephrine. If death occurs, it is usually due to either respiratory (typically asphyxia) or cardiovascular causes (shock), with 0.7–20% of cases causing death. There have been cases of death occurring within minutes. Urinary and serum histamine levels and plasma tryptase levels drawn after onset of symptoms may assist in diagnosis.

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Consider other vasopressors (e.g., dopamine) if hypotension does not respond to the above measures. Norepinephrine may be used if dopamine is not effective. Importantly, isoproterenol should not be used because it is a peripheral vasodilator. Patients with beta-adrenergic blockade may be particularly difficult to treat. They have both chronotropic and inotropic cardiac suppression and may not respond to the above treatments. Glucagon has positive inotropic and chronotropic effects and is the drug of choice in these cases. Atropine can also be used but will only be effective in treating bradycardia.

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Early recognition of an anaphylactic reaction is mandatory, since death occurs within minutes to hours after the first symptoms. Mild symptoms such as pruritus and urticaria can be controlled by administration of 0.3 to 0.5 mL of 1:1000 (1 mg/mL) epinephrine SC or IM, with repeated doses as required at 5- to 20-min intervals for a severe reaction. If the antigenic material was injected into an extremity, the rate of absorption may be reduced by prompt application of a tourniquet proximal to the reaction site, administration of 0.2 mL of 1:1000 epinephrine into the site, and removal without compression of an insect stinger, if present. An IV infusion should be initiated to provide a route for administration of 2.5 mL epinephrine, diluted 1:10,000, at 5- to 10-min intervals, volume expanders such as normal saline, and vasopressor agents such as dopamine if intractable hypotension occurs. Replacement of intravascular volume due to postcapillary venular leakage may require several liters of saline. Epinephrine provides both alpha and beta adrenergic effects, resulting in vasoconstriction, bronchial smooth-muscle relaxation, and attenuation of enhanced venular permeability. When epinephrine fails to control the anaphylactic reaction, hypoxia due to airway obstruction or related to a cardiac arrhythmia, or both, must be considered. Oxygen alone via a nasal catheter or with nebulized albuterol may be helpful, but either endotracheal intubation or a tracheostomy is mandatory for oxygen delivery if progressive hypoxia develops. Ancillary agents such as the antihistamine diphenhydramine, 50-100 mg IM or IV, and aminophylline, 0.25-0.5 g IV, are appropriate for urticaria-angioedema and bronchospasm, respectively. Intravenous glucocorticoids are not effective for the acute event but may alleviate later recurrence of bronchospasm, hypotension, or urticaria.

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An epinephrine (adrenaline) will prevent death if it’s used within 20 minutes of exposure, but after that window, the reaction cannot always be halted. That is why parents of children having food allergy keep injection epinephrine in a pre-filled syringe (EpiPen) ready for emergency use as it takes time to reach hospital.  

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Treatment of angioedema:

In allergic angioedema, avoidance of the allergen and use of antihistamines may prevent future attacks. Cetirizine is a commonly prescribed antihistamine for angioedema. Some patients have reported success with the combination of a nightly low dose of cetirizine to moderate the frequency and severity of attacks, followed by a much higher dose when an attack does appear. Severe angioedema cases may require desensitization to the putative allergen, as mortality can occur. Chronic cases require steroid therapy, which generally leads to a good response. In cases where allergic attack is progressing towards airway obstruction, epinephrine may be life-saving. In hereditary angioedema, specific stimuli that have previously led to attacks may need to be avoided in the future. It does not respond to antihistamines, corticosteroids, or epinephrine. Acute treatment consists of C1-INH concentrate from donor blood, which must be administered intravenously. In an emergency, fresh frozen blood plasma, which also contains C1-INH, can also be used. However, in most European countries, C1-INH concentrate is only available to patients who are participating in special programs. Future attacks of hereditary angioedema can be prevented by the use of androgens such as danazol, oxandrolone or methyltestosterone. These agents increase the level of aminopeptidase P, an enzyme that inactivates kinins; kinins (especially bradykinin) are responsible for the manifestations of angioedema. In acquired angioedema, HAE types I and II, and nonhistaminergic angioedema, antifibrinolytics such as tranexamic acid or ε-aminocaproic acid may be effective. Cinnarizine may also be useful because it blocks the activation of C4 and can be used in patients with liver disease, while androgens cannot.

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Radiocontrast media reactions (RCM):

The case of patients with severe reactions to radiocontrast media should be identified by a thorough history that includes previous reactions. A specific guide to treating these patients is included below.

Pretreatment Protocol for Patients with Previous RCM Reactions:

Use a nonionic, lower osmolarity RCM.

 Pretreat with the following:

 1) Prednisone, 50 mg orally at 13, 7, and 1 hour before the procedure.

 2) Diphenhydramine (Benadryl), 50 mg at 1 hour before the procedure.

 3) Ephedrine, 25 mg orally at 1 hour before the procedure,† or a histamine H2-receptor antagonist 1 hour before the procedure.

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Anti-allergy immunotherapy: Allergy shots: Allergy vaccines:

Allergy shots are a form of treatment called immunotherapy. Each allergy shot contains a tiny amount of the specific substance or substances that trigger your allergic reactions. These are called allergens. Allergy shots contain just enough allergens to stimulate your immune system — but not enough to cause a full-blown allergic reaction. Over time, your doctor increases the dose of allergens in each of your allergy shots. This helps get your body used to the allergens (desensitization). Your immune system builds up a tolerance to the allergens, and your allergy symptoms diminish over time.  Allergy shots cannot be used for all types of allergies. For instance, they cannot be used for food allergies. Allergy injection treatment is more effective for allergy to pollen, cats and house dust mites than it is for mold allergy. This is fortunate for us in the desert, where mold allergy is less of a problem than in more humid climates and where both allergic rhinitis and allergic asthma are commonly triggered by pollen.  Immunotherapy appears to be less effective in the treatment of allergic asthma than in the treatment of allergic rhinitis, but patients who have both conditions usually benefit from immunotherapy.  Although immunotherapy never provides a permanent cure for asthma or allergic rhinitis, it reduces the need for medications in many patients with allergic rhinitis and asthma.  Because there is a risk of allergic reactions to the injections that varies from one patient to another, the allergist gives advice on the balance between benefits and risk before starting treatment.

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Desensitization or hyposensitization is a treatment in which the person is gradually vaccinated with progressively larger doses of the allergen in question. This can either reduce the severity or eliminate hypersensitivity altogether. It relies on the progressive skewing of IgG antibody production, to block excessive IgE production seen in atopys. In a sense, the person builds up immunity to increasing amounts of the allergen in question. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the development of new allergy. Meta-analyses have also confirmed efficacy of the treatment in allergic rhinitis in children and in asthma. A review by the Mayo Clinic in Rochester confirmed the safety and efficacy of allergen immunotherapy for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insect based on numerous well-designed scientific studies. In addition, national and international guidelines confirm the clinical efficacy of injection immunotherapy in rhinitis and asthma, as well as the safety, provided that recommendations are followed. Since improvement in symptoms is normally delayed for 9-12 months, medications taken before starting the injections must not be stopped during this period. Medication requirements usually decrease after one year of treatment, but some patients never become independent of medications. Allergy shot treatment is the closest thing to a ‘cure’ for allergic symptoms. This therapy requires a long-term commitment.

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Allergy shots may be a good treatment choice for you if:

  • It’s impossible to avoid the things that cause your allergic reactions — and allergy medications don’t control your symptoms well
  • Allergy medications cause bothersome side effects or interactions with other medications you need to take
  • You want to reduce your long-term use of allergy medication
  • You’re allergic to insect stings

Allergy shots can be used to control symptoms triggered by:

  • Seasonal allergies. If you have seasonal allergic asthma or hay fever symptoms, you may be allergic to pollens released by trees, grasses or weeds.
  • Indoor allergens. If you have year-round symptoms, you may be sensitive to indoor allergens, such as dust mites, cockroaches, mold or dander from pets, such as cats or dogs.
  • Insect stings. Allergic reactions to insect stings can be triggered by bees, wasps, hornets or yellow jackets.

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What are the concentrations of allergens used?

 After knowing your allergy profile, a diluted solution is made of allergens for which you are most susceptible. This is known as vaccine. Usual starting concentration is 1:5000 (one part allergens and 5000 part diluents). The concentration is later increased to 1:500 and then 1:50 as vaccination progresses.

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What is the dose schedule of the allergens used?

Initially about 9 doses of 1:5000 vaccine are given twice a week in increasing volume subcutaneously. Starting dose is usually 0.1 ml increased by 0.1 ml each time to 0.9 ml. Then 1:500 dose is started with the same dose schedule. After completion 1:50 conc. is started. Total of 9 doses are given at weekly interval. Next 9 doses are given at 15 days interval. Then maintenance dose is started at 0.9 ml to 1.0 ml once a month for 3 to 5 years.  

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The figure below shows how immunotherapy (allergy shots) works by modifying immune response:

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Peripheral (naturally occurring and adaptive) T- cell tolerance is the key immunological mechanism in healthy immune response to self- and non-infectious non-self-antigen. Changes in the balance between allergen-specific Treg and Th2, and/or Th1 cells are very crucial in the development and also treatment of allergic diseases. Understanding of the immunological mechanisms that lead to tolerance induction by allergy shots, in particular the role of regulatory T-cells in allergen-specific peripheral tolerance may lead to more rational and safer approaches that could result in prevention and cure of allergic diseases, including asthma.

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Research has found that treating allergies actually changes the genes by epigenetics (a chemical modification of the genes that does not affect the actual DNA sequence), so desensitizing children may reduce the likelihood that they will pass on the disease to their children.

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Most people don’t have much trouble with allergy shots. But they contain the substances that cause your allergies — so reactions are possible, and can include:

  • Local reactions, which can involve redness, swelling or irritation at the injection site. These common reactions typically begin within a few hours of the injection and clear up soon after.
  • Systemic reactions, which are less common — but potentially more serious. You may develop sneezing, nasal congestion or hives. More-severe reactions may include throat swelling, wheezing or chest tightness.
  • Anaphylaxis is a rare life-threatening reaction to allergy shots. It can cause low blood pressure and trouble breathing. Anaphylaxis often begins within 30 minutes of the injection, but sometimes starts later than that.

If you get weekly or monthly shots on a regular schedule without missing doses, you’re less likely to have a serious reaction. Taking an antihistamine medication before getting your allergy shot can reduce the risk of a severe reaction. Check with your doctor to see if this is recommended for you.

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Relative Contraindications to allergy immunotherapy:

  • Co-existent uncontrolled asthma (within the UK, presence of asthma is considered a relative contraindication).
  • Patients taking beta blockers
  • Patients with other medical/immunological disease
  • Small children (less than 5 years)
  • Pregnancy (maintenance injections may be continued during pregnancy)
  • Patients unable to comply with the immunotherapy protocol  

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Sublingual immunotherapy: Allergy drops:

An alternative to antigen-injection immunotherapy (allergy shots), aka, subcutaneous immunotherapy (SCIT), is sublingual/swallow immunotherapy (SLIT), which is currently being used with increasing frequency in Europe. Here patients are directed to put very, very small drops of an extract of their allergen (initially a 1:1,000 dilution) under their tongue for two minutes, and then swallow. It offers the advantage of a lower likelihood of systemic adverse effects and has been shown to reduce allergic rhinitis and asthma symptoms. The allergy drops used for sublingual immunotherapy (SLIT) are administered daily, or several times per week, over a period of years. Studies thus far, however, indicate that SCIT may have a more significant impact on these symptoms than SLIT. SLIT is still being evaluated for FDA approval in the United States. Sublingual immunotherapy is an orally-administered therapy that takes advantage of oral immune tolerance to non-pathogenic antigens such as foods and resident bacteria. This therapy currently accounts for 40 percent of allergy treatment in Europe. In the United States, sublingual immunotherapy is gaining support among traditional allergists and is endorsed by doctors treating allergy.

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Many people refer to this process as “allergy drops,” and it is an alternative treatment for allergy shots. Most studies have looked at swallowing the extract, which seems to work better. Immunotherapy by the oral route (swallowed and not kept under the tongue for any period of time), causes too many gastrointestinal side effects (nausea, vomiting, diarrhea), and therefore is not used. Most patients are able to self-administer SLIT at home. The immune system of the gastrointestinal tract tends to ‘tolerate’ foreign substances, meaning that it does not respond in an over-active way to swallowed material. When SLIT is administered into the gastrointestinal tract [via your mouth], the immune system tolerates the allergen, instead of the over-reactivity of the immune system, as with allergic disease. This results in less allergy symptoms when the body is exposed to the allergy source, such as airborne pollen or pet dander. SLIT appears to be effective in the treatment of allergic rhinitis, allergic conjunctivitis and, to a lesser degree, allergic asthma. Studies have looked at giving SLIT before a pollen season, during a pollen season, both, or year-round. It is not yet known what the best dosing regimen is for SLIT. While most studies on SLIT do show benefit in the treatment of allergic disease, the results are somewhat inconsistent, with up to one-third of studies showing no benefit over placebo treatment.

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Researchers at Johns Hopkins University reviewed 63 studies of sublingual immunotherapy conducted from 1990 to 2012 in the U.S., Canada, Europe and Asia. The studies involved 5,131 participants ages 4 to 74 with asthma and nasal allergy or rhinitis (inflammation of the nasal mucous membrane) symptoms. Allergy drops were taken daily or weekly in trials ranging from three months to five years. Studies were graded as weak if they reported symptom improvements of less than 15%, moderate for changes from 15% to 40% and strong for improvements greater than 40%. Thirteen of the studies involved only asthma patients. About 70% of these patients showed a strong decrease in symptoms by using allergy drops, compared with those using either a placebo or another medication, which included conventional allergy drugs, inhaled steroids and another sublingual intervention.

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Oral immunotherapy for food allergy in children:

Oral immunotherapy is still experimental and the patients are not cured; they are desensitized enough that they can tolerate their former allergens. The child must continue to eat a maintenance dose of the food every day to avoid regaining the allergy. If you get off it for three days, you may become sensitive again. An egg-allergy trial found that when patients were taken off the maintenance dose for a month, roughly 60 percent regained the allergy (and there was no way to predict who those patients would be).  

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Asthma: Can specific immunotherapy reduce the symptoms, and how safe is it?

The researchers found 88 trials of immunotherapy in asthma, involving just under 3,500 people. They only included trials of subcutaneous immunotherapy, where the solution was injected into the skin. Both adults and children took part in the trials. Specific immunotherapy can prevent asthma attacks in some people. The research showed that specific immunotherapy really can help people who have asthma: symptoms got worse in 6 out of 10 people who did not have immunotherapy (60%), compared to only 3 out of 10 people who had the “allergy shots” (30%). In other words, specific immunotherapy prevented some asthma attacks in 3 out of 10 people (30%). The treatment also had another effect: people who had specific immunotherapy needed less medication for their asthma symptoms overall. About 2 out of 10 people who had immunotherapy needed to use less medication (20%).  Although some trials have shown that the effects of specific immunotherapy in asthma last for several years, it is not known how long these effects actually last. 

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Rush Immunotherapy:

“Rush immunotherapy” is a series of allergy shots. They are given over 2 to 3 days in a row. This “rushes” the initial phase of the treatment. Increasing doses of allergen extract are given every 30 minutes to hourly instead of every few days or weeks. There is an increased risk of a reaction with this procedure. Therefore, rush immunotherapy should only be done in a hospital or high risk procedure area under very close supervision.

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Repetitive, increasing doses of daily milk for treatment of milk allergy:

To date, the only option to treat food allergy is strict avoidance of the food and carrying an epinephrine injector (Epipen/Twinject) in case of an allergic reaction. For a food like cow’s milk, avoidance is very difficult because it is found in many foods. The constant fear of accidentally eating or drinking cow’s milk and anxiety related to carrying an injector has negative effects on quality of life. Accidentally having milk can cause life‐threatening reactions. Oral immunotherapy involves initially taking a very small amount of the allergen, in the case of milk allergy, cow’s milk, and slowly increasing the amount each day until a full serving is reached. This may change the way the body’s immune system sees the allergen, thereby increasing the amount of milk that can be eaten or drunk with no reaction. Researchers identified randomized controlled trials that compared oral immunotherapy to placebo or continued avoidance diet in children and adults with cow’s milk allergy. Five studies satisfied inclusion criteria. In total there were 196 participants (106 in the treatment group and 90 in the control), all of whom were children. In general, the quality of the studies was low. Because the trials involved small numbers and there were problems with the way they were done, further research is needed. The current evidence shows that oral immunotherapy can help a majority of allergic children tolerate a full serving of milk, as long as they continue drinking this amount each day. However, it is not known if this protection is continued if the immunotherapy is stopped for some time. Side effects during oral immunotherapy are frequent and most patients will have at least some mild symptoms. In the studies researchers included, for every 11 patients who received oral immunotherapy, one needed to be treated with epinephrine injection at some point for a serious allergic reaction to the therapy.  

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Multiple allergen desensitization:

Could patients be desensitized to more than one allergen at a time? No one had ever tried it, but more than a third of children with food allergies are allergic to more than one food. If it was safe to give patients x milligrams of one allergen, would it be safe to give them one-fifth of x milligrams of five different allergens, as long as the total dose remained the same?  That would assume that allergens function in a linear, additive fashion — rather than a multiplicative one; it was also possible that they could interact with one another to produce a more severe reaction. Trials are continuing on multiple allergen desensitization. We await results.   

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Anti-IgE antibody: Omalizumab Therapy:

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It is given as a shot once every 2 to 4 weeks and reserved for the treatment of severe asthmatic patients whose symptoms are triggered by allergic reactions and unresponsive to other milder forms of therapy. Anti-IgE is only available by prescription. It is a form of immunotherapy involving intravenous injection of monoclonal anti-IgE antibodies. These bind to free and B-cell associated IgE; signaling their destruction. They do not bind to IgE already bound to the Fc receptor on basophils and mast cells, as this would stimulate the allergic inflammatory response. Although omalizumab neutralized IgE in blood and inhibited IgE production by B-cells, it did not activate mast cells, basophils or monocytes (i.e. was non-anaphylactogenic). It was shown to reduce symptoms of allergic rhinitis and corticosteroid requirements in chronic asthma. It also inhibited the allergen-induced early- and late phase asthmatic reactions as shown by tests of lung function. While this form of immunotherapy is very effective in treating several types of atopy, it should not be used in treating the majority of people with food allergies.

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Omalizumab therapy could soon replace other, more toxic treatments for chronic, severe hives and itch:

An international team of researchers has found that a once-a-month, high-dose injection of a commonly used asthma drug is highly effective in treating teens and adults chronically afflicted with hives and severe, itchy rash. The drug, omalizumab, was tested on 323 people at 55 medical centers for whom standard antihistamine therapy failed to quell their underlying, allergy-like reaction, known as chronic idiopathic urticaria or chronic spontaneous urticaria.  Physicians and patients may now have a fast, safe and well-tolerated treatment option to consider before prescribing even more antihistamines, which can be highly sedating. The research team’s findings were published in The New England Journal of Medicine, to coincide with their initial presentation at the annual meeting of the American Academy of Allergy, Asthma & Immunology in San Antonio, Texas.  Participants in the study, which ran from 2009 to 2011, were mostly women and between the ages of 12 and 75. Each was randomly assigned to take one of three dosing regimens of omalizumab, or placebo, after which they were monitored through regular checkups for four months. Neither researchers nor participants were aware of what specific dose was being taken by which subjects during the study.  All study participants had chronic hives and rash for at least six months, with many having suffered from the condition for more than five years. All had continued to experience hives or a severe itchy rash for a full week while taking antihistamines.  Patients suffering with this condition need more and better treatment options because chronic hives and rash are profoundly hard to treat and can be very debilitating. The new study results offer substantial evidence that this treatment option not only works, but does so more safely than other drugs, such as corticosteroids and the immunosuppressant cyclosporine, which carry risk of potentially severe and toxic side effects, including high blood pressure, bone thinning and even infection. By contrast, headache was the most severe side effect observed with omalizumab therapy. No study participants died or suffered anaphylactic shock, or had to withdraw because of any adverse effects or events. Chronic idiopathic urticaria affects some 3 million Americans, and may or may not involve swelling, with twice as many women as men suffering from these often socially isolating conditions. Some patients experience such severe swelling of their eyes, hands, face, lips and throat that they have difficulty breathing. Some refuse to leave home, losing several days at a time away from work during flare-ups.   

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Surgery to the inferior turbinate (lining of the nose) in order to relieve nose block in allergic rhinitis after failed medical treatment:

Inferior turbinate (lining of nose) surgery is a commonly performed procedure in ENT as shrinking the lining may reduce some of the symptoms of allergic rhinitis, particularly nose blockage. This procedure is carried out using a multitude of techniques including cautery, laser and plasma knife. Although unusual, there is the potential for complications such as excessive bleeding and dry nose from these procedures. Researchers set out to identify randomized controlled trials (RCTs) of inferior turbinate surgery compared to continued medical treatment in allergic rhinitis patients in whom medical treatment had failed to relieve symptoms. Researchers also looked for RCTs comparing one technique of turbinate surgery with another. Researchers concluded that the evidence in the literature is not robust enough about the usefulness of surgery using any technique for this condition.

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Advances in allergy treatment:

In recent times, there have been enormous improvements in the medical practices used to treat allergic conditions. With respect to anaphylaxis and hypersensitivity reactions to foods, drugs, and insects and in allergic skin diseases, advances have included the identification of food proteins to which IgE binding is associated with severe reactions and development of low-allergen foods, improvements in skin prick test predictions; evaluation of the atopy patch test; in wasp sting outcomes predictions and a rapidly disintegrating epinephrine tablet, and anti-IL-5 for eosinophilic diseases.

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An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective. EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by favoring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment of autoimmune diseases but is not approved by the U.S. Food and Drug Administration or of proven effectiveness.

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T cell peptide epitope immunotherapy involves the administration of short synthetic allergen-derived peptides which, on the one hand, induce T cell anergy or tolerance, but on the other are unable to cross-link IgE and induce anaphylaxis. Early clinical trials in patients with cat allergy showed that a course of T cell peptides gave limited protection against allergic symptoms following exposure to cats. Mixtures of allergen-specific peptides selected on the basis of their binding to common MHC class II molecules have potential for greater efficacy since they will be recognized by T cells of most individuals within a population.

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 The recent description of the crystal structure of the complex between IgE and FceR opens the way for the first structure-based design of small molecule inhibitors. Several ways of inhibiting IL-4 are currently under investigation. For example, soluble recombinant IL-4 receptor was shown to improve moderately severe atopic asthma in a placebo-controlled trial. Other approaches for functionally inhibiting IL-4R include anti-IL-4R antibodies and mutant IL-4 proteins. Transcription factors involved in EL-4 signaling such as STAT-6 and c-maf are also attractive molecular therapeutic targets. Interference with FceRI function, by for instance designing peptides that block IgE/FceRIa chain interactions or inhibitors of Syk (required for intracellular signaling through FceRIa) are therapeutic options for the future.

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 In theory, chronic allergic inflammation should be controlled by targeting IL-5. In non-human primates, an anti-IL-5 monoclonal antibody almost completely abrogated eosinophilia and airway hyperresponsiveness in an ascaris model of asthma. Recent preliminary studies in patients with mild asthma have shown that a high affinity humanized IgG anti-IL-5 monoclonal antibody abolished blood eosinophils and reduced sputum eosinophils but, surprisingly, had no apparent effect on the allergen-induced late-phase asthmatic reaction or non-specific airway hyper-responsiveness. Long-term studies, in which total inhibition of tissue eosinophilia is achieved, will be required to establish conclusively the role of eosinophils and IL-5 in chronic atopic allergic disease and asthma. Other strategies for reducing eosinophil numbers include inhibition of a4P, (VLA-4) or CCR3, the receptor on eosinophils which binds to eotaxin and other eosinophil chemotactic C-C chemokines.

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Anti-allergy DNA vaccines:

A drawback of immunotherapy is that it carries a significant risk of triggering an allergic reaction. So if the allergy-provoking part of the allergen could be removed, while retaining the part our immune system recognises, the ‘neutralised’ allergen could be successfully desensitised without the risk of an unwanted reaction when it’s administered. DNA vaccination is a technique for protecting an organism against disease by injecting it with genetically engineered DNA to produce an immunological response. Anti-allergy DNA vaccine is an attractive alternative for the prevention and treatment of allergic diseases. Codelivery of hypoallergenic DNA vaccines with potent adjuvants via a desirable delivery mode will help to fulfill the requirements for clinical application of anti-allergy DNA vaccines. Modified vaccines are now in Phase 2 clinical trials to evaluate their efficacy and safety, and could soon be mass produced for immunotherapy to many environmental allergens and foods. Researchers are also developing specific plasmid and short DNA protein vaccines, which appear even more effective if given while bound to ‘friendly’ probiotic or inactivated bacteria. DNA vaccines hold promise in the treatment of allergic diseases. Approaches include the use of CpG motifs such as GACGTC, which induce strong Thl responses, administered either alone or in combination with allergen proteins. Plasmid vectors containing allergen genes have been injected into animals, either before or after allergen challenge, and were shown to markedly abrogate Th2 and enhance Thl responses and to suppress the allergic response. Virus-like particles, such as the yeast-derived Ty can also induce IFN-y producing CD8+ cells, rather than a Th2-type response, in a construct expressing a Der p 1 peptide.

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Allergist:

An allergist / immunologist (commonly referred to as an allergist) is a physician specially trained to diagnose, treat and manage allergies, asthma and immunologic disorders including primary immunodeficiency disorders. These conditions range from the very common to the very rare, spanning all ages and encompassing various organ systems. In the United States physicians holding certification by the American Board of Allergy and Immunology (ABAI) have successfully completed an accredited educational program and an evaluation process, including a secure, proctored examination to demonstrate the knowledge, skills, and experience to the provision of patient care in allergy and immunology.     

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Allergists are likely to carry out procedures and interventions in the following areas:

  • Dermatology (eczema, urticaria and contact dermatitis).
  • ENT (evaluation and management of the upper respiratory tract).
  • Respiratory medicine (asthma, extrinsic allergic alveolitis and occupational lung disease).
  • Paediatrics (milestones, infant food allergy and substitute formulas, infant rhinitis, eczema and asthma).
  • Immunology (vasculitis and immunoglobulin deficiency).
  • Food allergy (diagnosis: skin prick test and challenge, dietary evaluation).
  • Drug allergy (diagnosis: skin prick test and challenge, treatment – desensitization).
  • Rhinoconjunctivitis (diagnosis – skin prick test, treatment – immunotherapy).

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Internet as a tool for beating allergies:

 Use your keyboard as a tool to combat itchy eyes and a scratchy throat. First, take the American College of Allergy, Asthma, and Immunology’s Relief Self-Test to figure out the severity of your problem. You can also keep an eye on pollen counts by checking with the American Academy of Allergy, Asthma and Immunology every day. You can also shop online for that new vacuum cleaner, if you don’t already have one equipped with a HEPA filter, something essential for allergy sufferers.

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Natural Allergy Relief: Alternative Allergy Therapies:

In recent years, complementary-alternative medicine (CAM) has become very popular, with approximately half of the population either currently using or having used CAM on at least one occasion. The most common forms of CAM include acupuncture, homeopathic remedies, herbal medicines, and yoga. This increased use of CAM seems to be based on distrust of conventional and scientific-based medicine, bad experiences with physicians, and/or belief that CAM is safe, natural, and without side effects. 

Acupuncture:

A review of the available well-controlled studies on acupuncture fails to show little, if any, benefit on the treatment of asthma. Studies on acupuncture in the treatment of allergic rhinitis are, for the most part, poorly designed, although a few show benefit over placebo. One study performed in children, using three months of acupuncture treatment and three months follow-up after treatment, did show benefit in those children who received the “real” acupuncture, although they still required the same amount of medication for their allergies as the placebo group.

Herbal medicine:

While herbal supplements do show promise in the treatment of asthma and allergic rhinitis, there are some clear drawbacks. Herbs are not without side effects (some extremely dangerous), and have known interactions with many prescription medications. Herbal supplements are not regulated by the Food and Drug Administration in the same manner as prescription medications, so purity is not guaranteed. Therefore, it makes little sense to take herbal supplements because they are safer than prescription medications.

Homeopathy:

Despite some encouraging results in some small, selected studies, the overall evidence for homeopathy is weak, while evidence for conventional medications in the treatment of allergic rhinitis and asthma is very strong.

Chiropractic-Spinal Manipulation:

More than 100 patients with asthma were studied while being treated with “real” or “fake” chiropractic techniques. There were no differences between the two groups in terms of their asthma symptoms. However, one of these studies did show that the patients who received real chiropractic treatment had decreased sensitivity to an irritant medication (methacholine) used to detect severity of asthma. Another poorly-designed study on chiropractic techniques in asthma showed mild increase in a measurement of lung function in the group receiving treatment, although no symptoms were measured.

Breathing Techniques/Yoga:

Breathing techniques and yoga can be beneficial in terms of mental well-being and improvement in quality of life scores for asthmatics. However, studies on techniques such as Buteyko breathing, Sahaja, Hatha & Pranayama yoga fail to show any consistent improvement in asthma symptoms or definite improvement in lung function testing. No studies are available for allergic rhinitis.

Biofeedback/Hypnosis:

All studies reviewed on the use of biofeedback and hypnosis in the treatment of asthma were of poor study design and failed to show any benefit.

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Prognosis of allergy:

Most allergies can be easily treated with medication. Some children may outgrow an allergy, especially food allergies. However, once a substance has triggered an allergic reaction, it usually continues to affect the person. Allergy shots are most effective when used to treat people with hay fever symptoms and severe insect sting allergies. They are not used to treat food allergies because of the danger of a severe reaction. Allergy shots may need years of treatment, but they work in most cases. However, they may cause uncomfortable side effects (such as hives and rash) and dangerous outcomes (such as anaphylaxis).

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Most allergic reactions respond well to medications.

  • Hives, swelling, breathing difficulties, even anaphylaxis often improve and disappear in minutes to hours.
  • Some rashes take several days to heal.
  • Your health-care provider may want to monitor you for a few hours.
  • A dangerous allergic reaction may warrant an overnight stay in the hospital.

Allergic reactions will continue with continued exposure to the allergen or trigger.

  • You need to avoid any triggers you know cause an allergic reaction.
  • Ingested, inhaled, or injected allergy triggers may take days for the body to eliminate.
  • Continued medical therapy is necessary for continued exposure.

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Complications of allergy:

While most allergies are treated with drugs, some allergies may result in further complications such as upper respiratory infections, asthma, anaphylactic shock, eczema and drowsiness & other side effects of medicines.

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Having an allergy increases your risk of certain other medical problems, including:

  • Anaphylaxis. If you have severe allergies, you’re at increased risk of this serious allergy-induced reaction. Anaphylaxis is most commonly associated with food allergy, penicillin allergy and allergy to insect venom.
  • Another allergy. Having one type of allergy also increases your risk of becoming allergic to something else.
  • Asthma. If you have an allergy, you’re more likely to have asthma — an immune system reaction that affects the airways and breathing. In many cases, asthma is triggered by exposure to an allergen in the environment (allergy-induced asthma).
  • Atopic dermatitis (eczema), sinusitis, and infections of the ears or lungs. Your risk of getting these conditions is higher if you have hay fever, a pet allergy or a mold allergy.
  • Fungal complications of your sinuses or your lungs. You’re at increased risk of getting these conditions, known as allergic fungal sinusitis and allergic bronchopulmonary aspergillosis, if you’re allergic to mold.

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Prevention of allergy:

General guidelines:

Parents may find it helpful to keep an allergy journal for their child to track occurrence of allergic responses. For seasonal allergic rhinitis, they may use a calendar to note when symptoms begin and end. Documenting the level of seasonal allergens at the time can help determine when seasonal allergies tend to occur and what allergens affect the child. Local weather reports on television and on Web sites provide detailed allergen maps of pollen and mold/mildew spores. Antihistamines can then be taken as a preventive measure before symptoms begin each season. For children with allergies to foods, keeping a journal of foods eaten can help identify specific food allergens.

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Avoidance of allergens:

In some cases, like food allergies, avoiding the allergen is a life-saving necessity. That’s because, unlike allergies to airborne particles that can be treated with shots or medications, the only way to treat food allergies is to avoid the allergen entirely. For example, people who are allergic to peanuts should avoid not only peanuts, but also any food that might contain even tiny traces of them. Avoidance can help protect people against non-food or chemical allergens, too. In fact, for some people, eliminating exposure to an allergen is enough to prevent allergy symptoms and they don’t need to take medicines or go through other allergy treatments.

Here are some things that can help you avoid airborne allergens:

  • Keep family pets out of certain rooms, like your bedroom, and bathe them if necessary. (But for some people with serious symptoms, keeping a pet may be altogether impossible.)
  • Remove carpets or rugs from your room (hard floor surfaces don’t collect dust as much as carpets do).
  • Don’t hang heavy drapes and get rid of other items that allow dust to accumulate.
  • Clean frequently (if your allergy is severe, you may be able to get someone else to do your dirty work!)
  • Use special covers to seal pillows and mattresses if you’re allergic to dust mites.
  • If you’re allergic to pollen, keep windows closed when pollen season’s at its peak, change your clothing after being outdoors — and don’t mow lawns.
  • If you’re allergic to mold, avoid damp areas, such as basements, and keep bathrooms and other mold-prone areas clean and dry.

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Preventing allergic reactions depends on the type of allergy you have. General measures include the following:

  • Avoid known triggers. Even if you get treatment for your allergy symptoms, you still need to try and avoid your triggers. Common triggers include airborne allergens outdoors, at home or at work, and certain foods, insects or medications. Some allergic reactions are triggered or worsened by temperature extremes or emotional stress.
  • Keep a diary. When trying to identify exactly what causes or worsens your allergic symptoms, try to track all of your activities, note when symptoms occur, and write down what seems to help. This may help you and your doctor identify triggers and the best steps to prevent and treat them.
  • Wear a medical alert bracelet. If you’ve ever had a severe allergic reaction. A medical alert bracelet (or necklace) lets others know that you have a serious allergy in case you have a reaction and you’re unable to communicate.

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Prevent allergy in children:

Breastfeeding can help prevent or decrease allergies when you feed babies this way only for 4 to 6 months. However, changing a mother’s diet during pregnancy or while breastfeeding does not seem to help prevent allergies. For most children, changing the diet or using special formulas does not seem to prevent allergies. If a parent, brother, sister, or other family member has a history of eczema and allergies, discuss feeding with your child’s doctor. There is also evidence that being exposed to certain allergens (such as dust mites and cat dander) in the first year of life may prevent some allergies. It came from the observation that infants on farms tend to have fewer allergies than those who grow up in more sterile environments. However, older children do not seem to benefit. Once allergies have developed, treating the allergies and carefully avoiding allergy triggers can prevent reactions in the future.

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According to a report issued by the American Academy of Pediatrics, “There is evidence that breastfeeding for at least 4 months, compared with feeding infants formula made with intact cow milk protein, prevents or delays the occurrence of atopic dermatitis, cow milk allergy, and wheezing in early childhood.”

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A number of factors reduce your risk of developing allergies:

  • Being born into a family with no history of allergies
  • Being breastfed exclusively for the first four months of life, with a mother who avoids egg, nuts and cow’s milk while breastfeeding
  • Early exposure to good probiotic bacteria in the infant diet
  • Plenty of vitamins C and E, and omega-3 polyunsaturated oils
  • Having two or more older brothers and sisters
  • Living on a livestock farm and getting grubby playing in the farmyard

Although breastfeeding hasn’t been convincingly shown to reduce inhalant allergies or asthma, it transfers protective IgA antibodies to the baby and delays the potential onset of cow’s milk allergy by deferring the introduction of cow’s milk formula.

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Preventing food allergy in children:

Allergy prevention in children is an active area of research. Findings to date indicate that:

  • Prenatal – there is no conclusive evidence that avoiding allergens in pregnancy will help prevent allergies in your child.
  • Postnatal – exclusive breastfeeding during the first four to six months appears to protect against the development of allergies in early childhood. Exposure to cigarette smoke and starting solids early can increase the risk of developing allergies in early childhood.
  • Breastfeeding – if a baby is known to be allergic to a particular food, a breastfeeding mother should avoid eating that food.
  • Soy formula – studies have shown that using soy milk formula does not prevent the development of allergies in children.
  • Partially or extensively hydrolysed formula – these are cow’s milk based and have been processed to break down most of the proteins that cause symptoms in infants who are allergic to cow’s milk. They reduce the risk of developing eczema and cow’s milk allergy in infancy and early childhood.

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Prevent pet allergy:

With pet allergies, it’s practical to remove the pet permanently from the home. If this proves too traumatic, try the following:

  • Keep pets outside as much as possible or limit them to one room only, preferably one without carpeting
  • Don’t allow pets into bedrooms, as skin flakes (dander) can remain airborne for long periods. Cat dander allergen can also be carried around on clothing into schools or the workplace
  • Try to wash pets regularly – fortnightly if possible
  • Female animals produce less allergen and castration will reduce the production of allergen by male cats and dogs

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Preventing hay fever:

If you have hay fever, there are steps you can take to avoid exposing yourself to pollen:

  • Keep an eye on the pollen count (often included in weather reports) and stay inside as much as possible when it’s high.
  • Wear wrap-around sunglasses to stop pollen getting in your eyes
  • Saline douches or a little Vaseline applied inside the nose will reduce symptoms
  • Keep car windows closed and switch on the air conditioning to prevent pollen entering the car
  • Keep bedroom doors and windows closed in mid-morning and early evening when pollen levels peak
  • Avoid areas such as parks or fields, particularly in the early evening when there’s a lot of pollen floating at nose level
  • Get someone else to mow the lawn and don’t lie on freshly cut grass
  • Change into clean clothes when you come home and wash the clothes you wore outside

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Management of allergy of mother during pregnancy:

Diagnosis:

1. Detailed medical history and symptom analysis

2. Diary of allergy symptoms and avoidance of specific allergens accompanied by monitoring of changes of allergic symptoms

3. Do not put the mother on a rigid elimination diet

4. In vitro diagnostic tools such as serological testing (e.g. RAST) are preferred to in vivo testing

5. Although not contraindicated, skin prick testing should be postponed until after birth

6. Also postpone in vivo tests (food challenge tests and patch tests)

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Treatment:

• Food allergy: avoid offending food

• Other allergens:  avoid allergen contact

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Recommendations for treatment of asthma and allergies in pregnancy:

Drugs preferred for use during pregnancy:

Anti-inflammatory: cromolyn beclomethasone, prednisone

Bronchodilator: inhaled β2-adrenergic agonist, theophylline

Antihistamine: chlorpheniramine, tripelennamine

Decongestant: pseudoephedrine, oxymetazoline

Cough: guaifenesin, dextromethorphan

Antibiotic: amoxicillin

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Drugs that generally should be avoided during pregnancy:

Alpha-Adrenergic compounds (other than pseudoephedrine)

Epinephrine (other than for anaphylaxis)

Iodides

Sulfonamides (in late pregnancy)

Tetracyclines

Quinolones

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Immunotherapy (allergy shots) to pregnant mothers:

1. Should not be initiated during pregnancy because of the risk of systemic reactions

2. Patients who were already on immunotherapy before the pregnancy, maintenance treatment may be continued

3. Allergen dose should not be increased during pregnancy but rather reduced if necessary

4. Don’t stop, don’t start, don’t increase dose!

5. Active or passive allergen-specific vaccination of mothers may represent a feasible strategy for the prevention of allergic sensitization in childhood

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Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child: a meta-analysis:

Evidence is inadequate to advise women to avoid specific foods during pregnancy or breastfeeding to protect their children from allergic diseases like eczema and asthma. Researchers included five trials, involving 952 participants. Trials of mothers’ avoidance of milk, eggs, and other potentially ‘antigenic’ foods during pregnancy or breastfeeding, or both, provide inadequate evidence about whether such avoidance helps prevent atopic eczema or asthma in the child. Women who avoided eating these foods gained significantly less weight during pregnancy in the one trial reporting on this outcome, raising the possibility of adverse nutritional effects on the mother or fetus. Finally, one small trial reported an inconclusive response of breastfed infants with atopic eczema when their mothers avoided consumption of cow milk and egg. Prescription of an antigen avoidance diet to a high‐risk woman during pregnancy is unlikely to reduce substantially her child’s risk of atopic diseases, and such a diet may adversely affect maternal or fetal nutrition, or both. Prescription of an antigen avoidance diet to a high‐risk woman during lactation may reduce her child’s risk of developing atopic eczema, but better\ trials are needed. Dietary antigen avoidance by lactating mothers of infants with atopic eczema may reduce the severity of the eczema, but larger trials are needed.

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Penicillin allergy overview:

The term “penicillin” is often used generically to refer to benzylpenicillin (penicillin G), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V).  Allergic reactions to penicillin antibiotic may occur in up to 1% of patients receiving that agent. The allergic reaction is a Type I hypersensitivity reaction. Anaphylaxis will occur in approximately 0.01% of patients. However, most people who believe they are allergic can take penicillin without a problem, either because they were never truly allergic or because their allergy to penicillin has resolved over time. People who have a remote history of allergic reaction to a medication may become less allergic as time passes. Only about 20 percent of people will be allergic to penicillin 10 years after their initial allergic reaction if they are not exposed to it again during this time period. Severe reactions have been noted following first dose penicillin who have never taken penicillin before. This is because many of us are exposed and slightly sensitized to airborne moulds that readily elaborate penicillin and penicillin like substances in foodstuffs like bread, fruits and milk.

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Penicillin is the most common cause of anaphylaxis, for whatever reason, not just drug-induced cases. Penicillin and other antibiotics are haptens, molecules that are too small to elicit immune responses but which may bind to serum proteins and produce IgE antibodies.Topical application of a drug is associated with a high incidence of sensitization and should be avoided with certain agents, especially on inflamed skin. Penicillin and sulfonamides are no longer used topically because of this risk. Serious reactions to penicillin occur about twice as frequently following intramuscular or intravenous administration versus oral administration, but oral penicillin administration may also induce anaphylaxis even though oral administration of a drug is generally safer than any type of parenteral administration. The increased use of penicillin orally may be a reason why the risk of penicillin sensitization has been decreasing. The intravenous route may be the least sensitizing form of parenteral administration although it has been associated with catastrophic anaphylactic reactions. Neither atopy, nor a genetic history of allergic rhinitis, asthma or eczema, is a risk factor for the development of penicillin allergy. 

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No proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis, or syphilis in pregnant women. Penicillin also is recommended for use, whenever possible, in HIV-infected patients. Of the adult U.S. population, 3%–10% have experienced an immunoglobulin E (IgE)-mediated allergic response to penicillin, such as urticaria, angioedema, or anaphylaxis (i.e., upper airway obstruction, bronchospasm, or hypotension). Readministration of penicillin to these patients can cause severe, immediate reactions. Because anaphylactic reactions to penicillin can be fatal, every effort should be made to avoid administering penicillin to penicillin-allergic patients, unless they undergo acute desensitization to eliminate anaphylactic sensitivity.   

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Is this patient Allergic to Penicillin?  An Evidence-Based analysis of the likelihood of Penicillin Allergy:

Only 10% to 20% of patients reporting a history of penicillin allergy are truly allergic when assessed by skin testing. Taking a detailed history of a patient’s reaction to penicillin may allow clinicians to exclude true penicillin allergy, allowing these patients to receive penicillin. Patients with a concerning history of type I penicillin allergy who have a compelling need for a drug containing penicillin should undergo skin testing. Virtually all patients with a negative skin test result can take penicillin without serious sequelae. If you’re allergic to one type of penicillin, you’re at risk of being allergic to all penicillin-related antibiotics. Also, patients on monthly benzathine penicillin injection must do skin test every time before administrating penicillin as patient may not be allergic to penicillin earlier but now has indeed become allergic.   

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Penicillin allergy testing:

Skin testing for penicillin allergy is the most reliable way to determine if a person is truly allergic to penicillin. Approximately ninety percent of people will test negative (meaning they do not have a penicillin allergy), because they either lost the allergy over time, or they were never allergic in the first place. There are some situations in which penicillin, which is generally safe and inexpensive, would be a suitable antibiotic, but a person with possible allergy is given a stronger drug with more side effects because their allergic status is unclear. Therefore, determining if someone can safely take penicillin can be useful.

Testing for penicillin allergy is especially important in the following situations:

  • People who have a suspected penicillin (or closely related antibiotic) allergy and require penicillin to treat a life-threatening condition for which no alternate antibiotic is appropriate.
  • People who have frequent infections and have suspected allergies to many antibiotics, leaving few options for treatment.

Penicillin skin testing does not provide any information about certain types of reactions. This includes severe reactions with extensive blistering and peeling of the skin (Stevens-Johnson syndrome or toxic epidermal necrolysis), a widespread sunburn-like reaction that later peeled (erythroderma) or a rash composed of small bulls-eyes or target-like spots (erythema multiforme). People with these types of reactions should never again be given the medication that caused the reaction. This applies to all situations since a second exposure could cause a severe progressive reaction and even death.

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The immunogenic components of penicillin, which result from the opening of the penicillin ring under physiologic conditions, have been well-defined. The major determinant is benzylpenicilloyl, whereas minor determinants are penicillin G (benzylpenicillin), penicilloate, and penilloate. The major determinant, conjugated to a polylysine carrier molecule, is again available as a commercial product (Pre-Pen) in the U.S. Minor determinants other than penicillin G is not commercially available. Some allergists, primarily in major medical centers, synthesize minor determinates and do have them available for skin testing. Testing with benzylpenicilloyl polylysine (Pre-Pen) alone reportedly identifies up to 90% of patients likely to have IgE-mediated reactions to penicillin. The addition of penicillin G to the testing regimen raises the predictive value to 97%. In India, penicillin skin test is done by preparing testing dose from the vial containing penicillin for therapeutic use. This obviates the major and the minor determinant confusion.  0.02ml of drop is injected intradermally containing benzylpenicillin 10,000 units per ml. So the penicillin from therapeutic vial must be diluted while preparing for penicillin skin test.

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Skin testing should be done by an allergist in an office or hospital setting. Testing usually takes about one hour to complete. The skin is pricked and injected with weak solutions of the various preparations of penicillin and observed for a reaction (intradermal injection and not subcutaneous injection). This may cause discomfort due to itching, although it is not painful. 0.02-mL intradermal injections of negative control and antigen solutions are made into the volar surface of the forearm by using a 26- or 27-gauge needle on a syringe. The margins of the wheals induced by the injections should be marked with a ball point pen. An intradermal test is positive if the average wheal diameter 15 minutes after injection is >2 mm larger than the initial wheal size and also is >2 mm larger than the negative controls. Otherwise, the tests are negative.  A positive skin reaction is an itchy, red bump that lasts about half an hour and then resolves. A positive test indicates that the person is truly allergic. People with a positive test should continue to avoid penicillins. If the patient completes the skin testing without a positive reaction (no skin reaction after 30 minutes of injection), a single oral dose of full strength penicillin is commonly given to confirm that the patient does not have an allergy to the medication. The oral dose is needed because medical tests, including skin testing, are rarely 100 percent accurate. About three percent or less of people with a history of penicillin allergy and a negative skin test will still experience an allergic reaction. However, these reactions are very mild. If a person has a negative skin test and has no reaction to an oral dose of the antibiotic, you can safely administer penicillin.

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Desensitization:

Patients who have a positive skin test to one of the penicillin determinants can be desensitized. This is a straightforward, relatively safe procedure that can be performed orally or IV. Although the two approaches have not been compared, oral desensitization is regarded as safer and easier to perform. Patients should be desensitized in a hospital setting because serious IgE-mediated allergic reactions can occur. Desensitization usually can be completed in approximately 4–12 hours, after which time the first dose of penicillin is administered. After desensitization, patients must be maintained on penicillin continuously for the duration of the course of therapy.

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Can Cephalosporins be prescribed safely for penicillin-allergic patients?

Despite myriad studies spanning decades and involving varied patient populations, results have not conclusively established that penicillin allergy increases the risk of an allergic reaction to cephalosporins, compared with the incidence of a primary (and unrelated) cephalosporin allergy. Most people produce IgG and IgM antibodies in response to exposure to penicillin that may cross-react with cephalosporin antigens. The presence of these antibodies does not predict allergic, IgE cross-sensitivity to a cephalosporin. Even penicillin skin testing is generally not predictive of cephalosporin allergy. Many recent studies have established that the rate of cross-reactivity between penicillin and cephalosporins has been grossly overestimated. In fact, the rate of cross-reactivity between penicillin/amoxicillin and second- or third-generation cephalosporins is very low and may actually be lower than that between penicillins and other classes of antibiotics. Penicillin skin testing in patients with a history of penicillin allergy does not reliably predict allergy to a cephalosporin unless the side chain of the penicillin or ampicillin reagent is similar to the cephalosporin side chain being tested. The positive and negative predictive values of skin testing results for cephalosporins are not well established; if the haptens that cause cephalosporin allergy were known, cross-reactivity with penicillins could be assessed directly. Cephalosporin skin testing works only for the specific drug and drugs with the same side chains, and can be done only if the drug is available in an IV or IM formulation. Even a positive result does not guarantee a clinical reaction. When penicillin and cephalosporin skin tests or radioallergosorbent tests (RASTs) are positive, a clinical reaction is observed in only 10% to 60% of patients, depending on the reagent and study. For example, among 19 well-characterized patients allergic to penicillin who were studied for their sensitivity to the cephalosporins, cephaloridine and cefamandole (which have identical or very similar side chains to penicillin and were therefore potentially cross-reactive) only 2 (10.5%) reacted to cefamandole, while the other 17 patients tolerated both agents. In another study of clinical cross-reactivity between amoxicillin and cefadroxil in patients allergic to amoxicillin with good tolerance of penicillin, only 12% had an immediate allergic reaction to cefadroxil, despite the two drugs sharing an identical side chain. In a third study, allergenic cross-reactivity with cefadroxil and cefamandole was studied among 21 patients selectively allergic to amoxicillin; 8 (38%) had a positive response to cefadroxil (same side chain) and none to cefamandole (different side chain).

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Recent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to certain cephalosporins in penicillin-allergic patients is smaller than previously postulated. Medline and EMBASE databases were searched using the following keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 to 2005. Among 219 articles retrieved, 106 served as source material for this review. A significant increase in allergic reactions to cephalothin, cephaloridine, cephalexin, cefazolin, and cefamandole was observed in penicillin-allergic patients; no increase was observed with cefprozil, cefuroxime, ceftazidime, or ceftriaxone. Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins. First-generation cephalosporins have a modest cross-allergy with penicillins, but cross-allergy is negligible with 2nd- and 3rd-generation cephalosporins. Particular emphasis is placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents. Conclusions of this meta-analysis are:

  • The widely quoted cross-allergy risk of 10% between penicillin and cephalosporins is a myth.
  • Cephalothin, cephalexin, cefadroxil, and cefazolin confer an increased risk of allergic reaction among patients with penicillin allergy. 
  • Cefprozil, cefuroxime, cefpodoxime, ceftazidime, and ceftriaxone do not increase risk of an allergic reaction.
  • The cross-reaction rate between third-generation cephalosporins and penicillin approaches 0%

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Interventions for preventing reactions to snake antivenom:

People die or can be seriously disabled after being bitten by a venomous snake. Different venomous snake species have different effects on the body, but initial treatment is similar ‐ to try and prevent venom entering the general circulation. If it becomes apparent that the venom has reached the bloodstream, the patients start becoming extremely unwell and in these circumstances health staff may give specific antivenom (made from horse serum). However, antivenom frequently causes adverse effects which can, in themselves, be severe and result in death. There are drugs that can be given with the antivenom to try to reduce these adverse effects, and these include adrenaline, antihistamines, and steroids. A review looked to assess the benefit of giving these drugs along with the antivenom. The review of trials found one trial of 105 people in Sri Lanka looking at adrenaline; and a second trial of 101 people in Brazil looking at an antihistamine (promethazine). Both trials were well designed. Adrenaline showed fewer allergic reactions. There was no benefit seen from giving promethazine, and no trials were found on late allergic responses, or on corticosteroids. Routine prophylactic adrenaline for polyvalent antivenom known to have high adverse event rates seems sensible, based on this one trial. If clinicians believe local factors do not justify routine adrenaline, then they should test their belief in a randomized trial. Antihistamine appears to be of no obvious benefit in preventing acute reactions from antivenoms.

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Vitamin D and allergy:

The recent discovery that every tissue in the human body has vitamin D receptors and that vitamin D has pleiotropic effects has prompted an increased interest in this hormone. Vitamin D deficiency is widespread and on the increase. There is no consensus on the serum vitamin D levels to consider appropriate for global health, the cutoffs for its deficiency, or the doses to use for its supplementation. Vitamin D seems to correlate closely with host reactions against various respiratory infections. Epidemiological studies have shown that low serum 25-hydroxyvitamin D levels are associated with a higher risk of upper and lower respiratory infections in children and a shortage of vitamin D may contribute to asthmatic patients’ symptoms and morbidity rates. There are studies highlighting associations between childhood asthma, fetal lung and/or immune development, and maternal vitamin D intake. An insufficiency of this vitamin also seems to be implicated in the onset of childhood atopy and food allergies. The hypothesis is that vitamin D could have a central role in these pathological situations and that it may represent a novel preventive and/or therapeutic strategy.

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There is plenty of evidence to show that vitamin D is closely related to host reactions against different infections, and the tissue-specific synthesis of the active form of vitamin D (25OHD3) is implicated for both the innate and the adaptive immune systems. It has been demonstrated that vitamin D has potent immunomodulatory properties, exerting an action on cells of the innate immune system to inhibit proinflammatory cytokine production and induce antimicrobial peptide synthesis . During a bacterial infection, macrophages acquire the capacity to convert circulating 25 vitamin D into 1,25 OH vitamin D, which is a direct inducer of the expression of genes encoding for antimicrobial peptides and cathelicidin antimicrobial peptide in particular. This peptide is central in host defense against respiratory tract pathogens; it is a vanguard of innate immune response and enhances the clearance of bacteria from various barrier sites and immune cells. There is also evidence of vitamin D strengthening the physical epithelial barrier by stimulating junction genes, thereby aiding natural defenses. In addition, vitamin D modulates the adaptive immune system via direct effects on T-cell activation and on the phenotype and function of antigen-presenting cells. Vitamin D is associated with a dose-dependent reduction in the transcription of Th-1 cytokines, such as IL-2, granulocyte–macrophage colony-stimulating factor, and interferon gamma, as well as with an increased expression of the Th-2 cytokines IL-4, IL-5, and IL-10 in adult peripheral blood cell cultures. Von Essen et al.  recently showed that vitamin D directly modulates the T-cell antigen receptor, which has a central role in T-cell activation. Most of these actions are mediated by VDRs and by the VDBP, a serum protein binding most of the circulating vitamin D. Active VDRs affect the transcription of at least 913 genes and have been recognized as having different genetic variants that can influence the antimicrobial action of vitamin D (via the regulation of T-helper cell development and the cytokine secretion profile), and different VDR variants may be involved in the development of vitamin-D-related diseases. Vitamin D-binding protein seems to have immunomodulatory functions relevant to lung biology, and variations within its gene seem to be associated with infectious airway diseases involving a different level and efficacy of macrophage activation and neutrophil chemotaxis. In conclusion, it has been established that vitamin D is a modulator of innate and adaptive immune system functions and has a key role in Th1–Th2 balance.

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Considering the pleiotropic effects of vitamin D (especially on the development of immune system tolerance and of the integrity of the epithelial barrier), recent studies have hypothesized a relationship between the hormone vitamin D and the rising incidence of food allergies and skin diseases. According to epidemiological studies, the incidence of food allergy is increasing among children and its pathogenesis remains unclear. In 2007, Camargo et al. observed a strong north–south gradient for the prescription of epinephrine autoinjectors (EpiPens) in the United States, hypothesizing a link between low vitamin D levels in the north and allergic disorders; other epidemiological north–south trends have been observed for vitamin D deficiency and food allergy (based on A&E department records and hospitalizations), which probably correlate with a different UVB exposure, although there is no direct evidence of such a causal link. A recent study by the National Health and Nutrition Examination Survey 2005–2006 found vitamin D deficiency (<15 ng/ml) associated with higher levels of IgE sensitization to food and environmental allergens in children and adolescents. Intestinal infections, abnormal barrier permeability, and the promotion of a prosensitization immune balance as a result of vitamin D deficiency may contribute to the onset of food allergy. Vitamin D also seems to be involved in the development of many skin diseases (psoriasis, eczema, etc.), and VDRs have been found in basal proliferating keratin cells. We know from experience that most atopic patients have fewer skin lesions in summer, and we cannot rule out a potential effect of exposure to sunlight and the consequent increase in vitamin D production. In a study conducted in children with atopic dermatitis, Peroni et al. found a clear association between vitamin D deficiency and severity of atopic dermatitis. Hata et al. published a study on vitamin D supplementation in patients with atopic dermatitis, measuring cathelicidin expression in normal and atopic skin biopsies before and after vitamin D supplementation (4000 IU a day for 21 days). They found that oral vitamin D supplementation can correct the cathelicidin deficiency in the innate immune system of atopic subjects. Thorp et al. demonstrated that adult patients with chronic urticaria have lower vitamin D levels than controls, supporting the conviction that vitamin D may be an important immunomodulator.

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Possible Link between High Vitamin D Levels in Expectant Mothers and Increased Infant Allergy Risks:

Pregnant women should avoid taking vitamin D supplements. Supplementation appears to raise the risk of children developing a food allergy after birth. This was the conclusion drawn from a new survey carried out by the Helmholtz Centre for Environmental Research and the Martin Luther University in Halle-Wittenberg in Germany which was published in the medical journal Allergy. Vitamin D has always had a good reputation: it strengthens bones, protects against infections particularly during the cold winter months and aids the nervous and muscular systems. Especially in the prevention and treatment of rickets, it has been given to babies and infants around the world for around 50 years. However, recent scientific investigations are increasingly questioning the positive aspect of the “bone vitamin”. At the end of the 1990’s, for the first time people’s attention was drawn to a link between high vitamin D levels and the development of allergies. To pursue the problem, together with Prof. Gabriele Stangl’s group from the Institute of Agricultural and Nutritional Sciences at the Martin-Luther University in Halle-Wittenberg, Dr. Kristin Weibe from the Helmholtz Centre for Environmental Research in Leipzig devoted herself to the following task: can it be proved that there is a correlation between the concentration of vitamin D in the blood of expectant mothers and in cord blood of the babies? The researchers from the UFZ in Leipzig were furthermore interested in the association between vitamin D levels during pregnancy and at birth, the immune status and allergic diseases of the children later in life. Or, in other words: does the vitamin D level of pregnant women affect the allergy risk of their children? To investigate the question, Dr. Kristin Weibe’s team from Leipzig used samples from the LiNA cohort that the Helmholtz Centre for Environmental Research (UFZ) had established together with the St. Georg municipal clinic between 2006 and 2008 headed by Dr. Irina Lehmann. In total, it was possible to include 622 mothers and their 629 children in the long-term study “Lifestyle and environmental factors and their impact on the newborn allergy risk”. The level of vitamin D was tested in the blood of the pregnant mothers and also in the cord blood of the children born. In addition to this, questionnaires were used to assess the occurrence of food allergies during the first two years of the children’s lives. The result was clear: in cases where expectant mothers were found to have a low vitamin D level in the blood, the occurrence of food allergies among their two-year old children was rarer than in cases where expectant mothers had a high vitamin D blood level. In reverse, this means that a high vitamin D level in pregnant women is associated with a higher risk of their children to develop a food allergy during infancy.  Furthermore, those children were found to have a high level of the specific immunoglobulin E to food allergens such as egg white, milk protein, wheat flour, peanuts or soya beans. The UFZ scientists also got evidence for the mechanism that could link vitamin D and food allergies. Dr. Gunda Herberth – also from the Department of Environmental Immunology at the UFZ – took a closer look at the immune response of the affected children and analyzed regulatory T-cells in cord blood in particular. The cells are capable of preventing the immune system from overreacting to allergens, with the result that they protect against allergies. The UFZ researchers know from earlier analyses that the allergy risk increases in cases where too few regulatory T-cells are present in cord blood. The interesting result of the current research project: the higher the level of vitamin D found in the blood of mothers and children, the fewer regulatory T-cells could be detected. The correlation could mean that vitamin D suppresses the development of regulatory T-cells and thus increases the risk of allergy.

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Dr. Allen believes there may be a link between food allergies and vitamin D. In a study in the Journal of Allergy and Clinical Immunology, researchers took blood samples from more than 5,000 babies and found that those with low vitamin D levels were three times more likely to have a food allergy.

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So in a nutshell, role of vitamin D vis-à-vis allergy is controversial. High maternal vitamin D is associated with high infant allergy risk and low vitamin D in infant blood was associated with high allergy risk. We need more research.

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Effect of cobalamin (B-12) on the allergic response in mice:

To clarify the role of B-12 in the immunological function, serum C3, IgM, IgG, IgE contents, splenocytes expression of CD4, CD8, and CD4 positive intracellular IFN-gamma and IL-4 were examined in B-12-deficient mice, and the effect of the administration of CH3-B-12 was also studied. Serum C3, IgM and IgG contents were lower in B-12-deficient mice than in the control mice. On the other hand, serum IgE content was significantly higher in B-12-deficient mice, and the value in CH3-B-12 administered mice, administered CH3-B-12 to B-12-deficient mice for 48 h before the end of feeding period, showed a tendency to recovery. CD4+CD8 cells and CD4+/CD8+ ratio in splenocytes were significantly higher in B-12-deficient mice than in control mice. CD4+IFN-gamma+ cells were significantly lower in B-12-deficient mice than in control mice, and CD4+IL-4+ were significantly higher in B-12-deficient mice than in control mice. These results suggest that B-12-deficiency causes CD4+CD8T cells shift from the T helper type 1 to the T helper type 2, which participate in the IgE production and elevates CD4+/CD8+ ratio. Thus, B-12 plays a role in maintaining the immune function in mice. We can extrapolate this finding in humans by giving vitamin B-12 to allergic patients to change immune response from Th2 to Th1.

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Probiotics and allergies:

Probiotics are harmless micro-organisms that live in our bowel. Synbiotics are a combination of probiotics and special sugars called prebiotics, which stimulate the growth of probiotics.  Studies show allergy-prone children have fewer probiotics in their bowel than non-allergic children. The probiotics Lactobacillus GG and Lactobacillus rhamnosus have been shown to improve eczema symptoms under the age of two and, if supplemented from early infancy, probiotics can reduce eczema attacks. Probiotics don’t seem to benefit asthma, but may influence the immune system. They may reduce general allergies and have a beneficial effect on immunity. For best results, pregnant women should take probiotics for the last few months of pregnancy and supplement the baby’s diet with probiotics and prebiotics. Caution should be taken if the child has a cow’s milk allergy, as cow’s milk residues may be present in supplements.

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Babies with high risk of allergy: Could prebiotics in infant formulas make a difference?

Infant formulas containing prebiotics might be able to prevent the development of eczema in babies who are at high risk of allergies, but they have not been tested enough to be sure. So far, none of the breast milk substitutes has been shown to provide better protection than breastfeeding.  Allergies are quite common in babies, but the risk largely depends on their genes: up to 7 out of 10 babies develop an allergy if both parents have allergies. For comparison: only 1 out of 10 babies develops an allergy if none of their close relatives has an allergy. Supplements are sometimes used in baby formulas in the hope that this could prevent babies from developing allergies. One of the supplements now used in some baby formulas are the so-called “prebiotics”. These are not bacteria like probiotics (often called “friendly bacteria”). Prebiotics are substances that the body cannot digest, so they reach the bowel intact. It is thought that they stimulate the development of friendly bacteria in the bowel, such as lactic acid bacteria, and reduce the kind of bacteria that can lead to allergies and food intolerance. Breastfed babies have a lot more lactic acid bacteria in their bowels than babies who are fed infant formula. It is thought this might be one of the reasons breastfeeding can help protect against the development of allergies. One kind of prebiotic used in infant formula is a type of carbohydrate (a sugar or starch) called oligosaccharides. Researchers from the Cochrane Collaboration analyzed the available trials on infant formulas containing prebiotics to see whether these products can prevent allergies, and to find out about possible adverse effects. They found 2 trials that tested the effect of prebiotics on allergies. The trials involved just over 400 babies. There were obvious differences between the trials. For example, one study only looked at babies who had a high risk of developing allergies. This means that more research is needed before we can be sure about what effects prebiotics in infant formulas have.

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Soy formula for prevention of allergy fails:

When babies are not exclusively breastfed, evidence suggests that using a soy formula instead of a cow’s milk formula does not reduce allergies in infants and children. Infant formulas have been designed to try to lower the chances of developing allergy. These formulas include hydrolysed cow’s milk and soy formulas. A review of trials found that in infants at high risk of allergy who are unable to completely breastfeed, there is no reduction in allergies in later infancy and childhood associated with feeding soy formula compared to a cow’s milk formula. No eligible studies were found that compared a soy with a hydrolysed protein formula.

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CD23: An overlooked regulator of allergic disease: 

Given the importance of immunoglobulin (Ig) E in mediating type I hypersensitivity, inhibiting IgE production would be a general way of controlling allergic disease. The low-affinity IgE receptor (FceRI or CD23) has long been proposed to be a natural regulator of IgE synthesis. In vivo research supporting this concept includes the observation that mice lacking CD23 have increased IgE production whereas mice overexpressing CD23 show strongly suppressed IgE responses. In addition, the finding that mice injected with monoclonal antibody directed against the coiled-coil stalk of CD23 have enhanced soluble CD23 release and increased IgE production demonstrates that full-length, trimeric CD23 is responsible for initiating an IgE inhibitory signal. The recent identification of ADAM10 (a disintegrin and metalloprotease) as the CD23 metalloprotease provides an alternative approach for designing therapies to combat allergic disease. Current data suggest that stabilizing cell-surface CD23 would be a natural means to decrease IgE synthesis and thus control type I hypersensitivity. 

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C-Section Babies 5 times more likely to develop Allergies:

C-section babies are five times more likely to develop allergies by age two than those born naturally. The finding came from a new study conducted by researchers from Henry Ford Hospital and was presented at the American Academy of Allergy, Asthma, and Immunology yearly meeting in San Antonio. The findings coincide with previous research which demonstrated that babies born by c-section are more likely to have asthma than babies delivered naturally. A different report showed that caesarean section babies have an increased risk of food allergies and diarrhea during their first year of life. The new report indicated that c-section (cesarean section) babies are more vulnerable to allergies. They found that the chance of developing allergies for c-section babies is five times greater than for those born naturally when exposed to high levels of common allergens in the home, including those from cats, dogs, and dust mites. Leading author Christine Cole Johnson, Ph.D., MPH, chair of Henry Ford Department of Health Sciences, said: “This further advances the hygiene hypothesis that early childhood exposure to microorganisms affects the immune system’s development and onset of allergies. We believe a baby’s exposure to bacteria in the birth canal is a major influencer on their immune system.” In the gastrointestinal tract of babies born by c-section, there is a pattern of “at risk” microorganisms that may cause them to be more vulnerable to developing the antibody Immunoglobulin E, or IgE, when in contact with allergens, according to Dr. Johnson.  It is known that IgE is associated with the development of asthma and allergies. 

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Mast cells and stress:

Mast cells are well known for their involvement in allergic and anaphylactic reactions, but recent findings implicate them in a variety of inflammatory diseases affecting different organs, including the heart, joints, lungs, and skin. In these cases, mast cells appear to be activated by triggers other than aggregation of their IgE receptors (FcRI), such as anaphylatoxins, immunoglobulin-free light chains, superantigens, neuropeptides, and cytokines leading to selective release of mediators without degranulation. These findings could explain inflammatory diseases, such as asthma, atopic dermatitis, coronary inflammation, and inflammatory arthritis, all of which worsen by stress. It is proposed that the pathogenesis of these diseases involve mast cell activation by local release of corticotropin-releasing hormone (CRH) or related peptides. Combination of CRH receptor antagonists and mast cell inhibitors may present novel therapeutic interventions. Mast cells have emerged as unique immune cells that can be activated by many immune and nonimmune triggers, including acute stress through CRH; it is, therefore, proposed that CRH be renamed SRH (Stress Response Hormone) to reflect its versatile role in stress. Mast cells are critical in the development of inflammatory diseases, especially dermatoses, asthma, arthritis, and CAD. Inhibition of mast cell activation by CRH receptor antagonist therefore is a novel mechanism for the development of new treatments for inflammatory and autoimmune disorders. Certain dietary supplements have recently been shown to be effective in this regard because they combine the proteoglycan chondroitin sulfate and the flavonoid quercetin, both of which have mast cell inhibitory and anti-inflammatory actions.

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What is leaky gut syndrome?

Intestinal permeability or “leaky gut syndrome” is receiving increasing attention as the hard-to-deal factor in patients being treated for food allergies. Hyper- permeability is also associated with Celiac disease, alcoholism, Crohn’s disease, atopic eczema, chronic giardiasis and intestinal candida, lupus, fibromyalgia, M.S. arthritis, and a myriad of chronic inflammatory diseases. In a healthy gut the larger proteins “bounce off” until they are either fully digested or they pass into the stool and out of the body through bowel elimination while in leaky gut syndrome, larger proteins can “leak” across the gut walls and enter the bloodstream. Leaky gut is a condition that occurs due to the development of gaps between the cells (enterocytes) that make up the membrane lining your intestinal wall. These tiny gaps allow substances such as undigested food, bacteria and metabolic wastes that should be confined to your digestive tract to escape into your bloodstream — hence the term leaky gut syndrome. Once the integrity of your intestinal lining is compromised, and there is a flow of toxic substances “leaking out” into your bloodstream, your body experiences significant increases in inflammation. Besides being associated with inflammatory bowel diseases like Crohn’s and ulcerative colitis, or celiac disease, leaky gut can also be a contributing factor to allergies. These large complex substances are antigenic and allergenic, meaning they stimulate your immune system to produce antibodies against them. This is what sets the stage for the occurrence of allergies and other autoimmune disorders. It was quickly linked to many of the problems experienced in patients with severe yeast overgrowth, since it was known that candida, in its fungal form, can put down “roots” into the gut wall, allowing comparatively large molecules to pass through into the bloodstream. Whether these are food molecules, bacteria or chemical toxins, the result would be the same: an immune response by the body, an attack by antibodies and the start of a cycle of immune response, inflammation and antibody-antigen reactions.

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Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice:

IgE-mediated hypersensitivity is central to the pathogenesis of asthma and other allergic diseases. Although neutralization of serum IgE with IgE-specific antibodies is an efficacious treatment for allergic asthma, one limitation of this approach is its lack of effect on IgE production. Here, researchers have developed a strategy to disrupt IgE production by generating monoclonal antibodies that target a segment of membrane IgE on human IgE-switched B cells that is not present in serum IgE. This segment is known as the M1′ domain, and using genetically modified mice that contain the human M1′ domain inserted into the mouse IgE locus, they demonstrated that M1′-specific antibodies reduced serum IgE and IgE-producing plasma cells in vivo, without affecting other immunoglobulin isotypes. M1′-specific antibodies were effective when delivered prophylactically and therapeutically in mouse models of immunization, allergic asthma, and Nippostrongylus brasiliensis infection, likely by inducing apoptosis of IgE-producing B cells. In addition, researchers generated a humanized M1′-specific antibody that was active on primary human cells in vivo, as determined by its reduction of serum IgE levels and IgE plasma cell numbers in a human PBMC-SCID mouse model. Thus, targeting of human IgE-producing B cells with apoptosis-inducing M1′-specific antibodies may be a novel treatment for  asthma and allergy.  

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Assembling complete panels of hypoallergenic allergen derivatives for prophylactic vaccination against allergy:

Allergen-specific immunotherapy, unlike anti-allergic drugs, promises to attenuate symptoms for several years after discontinuation of the therapy. However, the safety of this treatment, particularly the threat of anaphylaxis, and the use of relatively crude allergen extracts limit its usefulness. Naturally occurring allergen isoforms from plants and trees have been shown to have a reduced capacity to bind IgE due to amino acid substitutions or deletions. These hypo-allergenic isoforms may minimize the risk of anaphylaxis. The use of recombinant allergens should circumvent the problem of standardization of crude extracts by allowing production and purification of many of the major allergens in ways that eliminate batch variation and yield uniform products. Recombinant allergens that contain most of the relevant epitopes that are present in various allergen sources have been produced by molecular cloning. The recombinant allergen molecules can be used to establish multi-allergen test systems (for example, allergen microarrays) that facilitate the determination of the reactivity profile of an allergic patient. On the basis of this information, it is possible to discriminate between those allergic patients who are sensitized against a few allergen components (oligosensitized patients) and those who react against many allergen components (polysensitized patients). Antigen-targeted immunotherapy of established allergy in oligosensitized patients can be carried out according to their reactivity profiles, whereas polysensitized patients might benefit more from symptomatic treatment. At present, hypoallergenic allergen derivatives are being developed for most of the important allergens, which can then be used for patient-tailored immunotherapy of oligosensitized patients with a reduced risk of inducing anaphylactic side effects. If hypoallergenic derivatives can be developed that comprise most of the relevant allergen sources, it will be possible to assemble prophylactic allergy vaccines.

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Allergy bullying: When food is a weapon:

It’s hard for parents of food-allergic children to keep them safe at school when there are so many opportunities to eat snacks and meals with unsafe ingredients. For some kids, just touching a certain food or inhaling particles of it could cause a reaction. But on top of the safety question is a social one. A study released suggests that almost half of children who have food allergies have been bullied — sometimes by having food thrown at them. “Clearly, it’s an issue for these school-aged children in terms of how they interact with their peers,” said Dr. Clifford Bassett, director of Allergy & Asthma Care of New York. “Immediately, when there’s a diagnosis of food allergy, there’s a little bit of a stigma.” The new study furthers the mounting evidence that many kids with food allergies may endure social ostracism while also trying to eat safely. A 2010 study in the journal Annals of Allergy, Asthma & Immunology said that 35% of kids over age 5 with food allergies have endured bullying, teasing or harassment. Parents of children with food allergies reported in the study that these incidents — both physical and verbal — happened because of food allergies. Communication with teachers, administrators, coaches, and the school nurse is a key to ensuring that a food-allergic child does well, in terms of staying safe from allergens and psychologically speaking. It’s also important to talk to a child about bullying, which can have serious psychological consequences, such as anxiety. It’s harder to get teenagers to not take risks when it comes to avoiding problem foods and always carrying the epinephrine auto-injector.

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Allergy myths:

1. Myth: If you suffer from dust allergies at home, that means your house is not clean.

Fact: While it’s true that an unclean house can aggravate a dust allergy, keeping your house clean does not guarantee that you’ll be free of symptoms. That’s because normal cleaning routines such as dusting, vacuuming or mopping won’t completely rid your linens or carpets of dust mites. Try eliminating dust-catching curtains and carpets from the bedroom of an allergy sufferer. A damp mop run across a hard floor each day does the best job of minimizing dust mite numbers.

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2. Myth: If you haven’t developed allergies as a child, you’re not going to get them as an adult.

Fact: This misconception often stands in the way of adults figuring out that their itchy throat and sneezing isn’t a cold. While the vast majority of allergies develop before age 30, it’s not uncommon for people to get them later in life. Plus, some young people’s allergies go away but then they crop up again later. If you had eczema (atopic dermatitis) as a child or if allergies or asthma run in your family, you’re on notice; you could develop an allergy to anything, anytime. People do develop allergies as adults. The older you are, though, the better your chances of staying allergy-free. Generally, as people get older, their allergic response changes. As they reach their 50s, it tends to die down. It’s fairly uncommon for someone over 50 to develop new allergies.

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3. Myth: Children outgrow allergies.

Fact: Children are ten times more likely than adults to have food allergies. Some researchers believe that as a person’s gastrointestinal system develops, it gets better at blocking the absorption of components that trigger food allergies. Over time, children typically outgrow allergies to cow’s milk, eggs, wheat, and soybean products. However, allergies to peanuts, tree nuts, fish, and shellfish can be lifelong. And some children will outgrow one allergy only to develop another. A hospital in Sweden tracked 82 patients with allergic rhinitis. The patients reported that 99% still suffered from allergic rhinitis 12 years later, although 39% reported improvement. Researchers have now shown that, contrary to popular belief, milk and egg allergies are outgrown much more slowly than previously thought and that a great number of children never outgrow these allergies.  

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4. Myth: There are short-haired breeds of dogs that do not cause allergies.

Fact: The substances in dogs that cause allergy and asthma symptoms are found in both hair and saliva. While different breeds may produce different amounts of allergens, all can trigger symptoms in vulnerable people. However, since short-haired pets have less hair to shed, they send less dander into the air, so are preferable for those with pet allergies.

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5. Myth: Allergy shots must be continued for the rest of your life.

Fact: Many people who receive allergy shots are able to eventually stop them. Studies have shown that people who have become immune to the substances that provoke their allergies are still benefiting from the shots eight years after they have been stopped.  

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6. Myth: Allergies are psychosomatic.

Fact: Allergies are a very real medical condition. Allergies are very real – in some cases, potentially life-threatening – rooted in heredity and the environment. That said, emotional stress can help cause an allergic reaction and relaxation is a good way to help with an outbreak. A person who is strongly allergic to roses, for example, may react to the sight of a plastic rose, demonstrating the involvement of the mind.

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7. Myth: Allergy shots do not work.

Fact: Allergy shots have anywhere from an 85-95 percent rate of effectiveness. That said, everyone is different and sometimes the procedure does not yield the desired results.

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8. Myth: Allergies aren’t Life-threatening

Fact: Although it rarely happens, allergies can kill. Some people have such an extreme sensitivity to a particular substance that the allergen can trigger an episode known as an anaphylactic shock. A sudden, potentially fatal reaction, anaphylactic shock lowers blood pressure, swells the tongue or throat, and constricts the airways of the lungs, making it difficult to breathe. Such a reaction requires immediate medical attention. Anaphylactic shock is most often triggered by a food or drug, but it can also result from an insect sting or even, rarely, from immunotherapy for an allergy. People with a history of severe allergic reactions should always carry a pre-loaded syringe of epinephrine, which can be administered in an emergency.

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9. Myth: Wearing gloves will protect you from Poison Ivy.

Fact: The chemical that gives these plants their poisonous reputation is an oily resin called urushiol. And what makes it truly diabolical is that it can get a ride on clothing, dog’s fur and even garden tools. If you come into contact with poison ivy, wash the oil off (preferably with brown soap and water) within 20 to 30 minutes, before it soaks into the skin. Since the residue can remain potent for a year or more, scrub tainted items as well.

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10. Myth: People who are allergic to fish are actually allergic to the Iodine.

Fact: Some people who are allergic to seafood avoid certain skin medications and diagnostic medical tests that use iodine because they fear an allergic reaction. But there is no connection between allergies to fish and allergies to iodine. Allergies to fish are caused by the protein in them, not the iodine.

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11. Myth: Natural (Organic) foods are Non-allergenic.

Fact: Typically, organic products are those that are grown without the use of synthetic fertilizers, pesticides and genetically modified organisms (GMO). Limiting your diet to organic food is no guarantee that you’ll avoid food allergies. In fact, some of the most allergenic foods are “natural,” unprocessed foods: cow’s milk, eggs, peanuts, wheat, soybeans, fish and shellfish and tree nuts. Combined, these foods account for up to 90 percent of all allergic reactions. Allergies are caused not by chemicals (pesticides) & fertilizers related to growing the food (crop), but by proteins in the food. If you are specifically allergic to GMO (genetically engineered food), you can prevent allergic reaction by eating organic foods. Current USDA regulations allow food products that contain 95-100% certified organic ingredients to use the USDA Organic seal. These regulations prohibit the use of chemical fertilizers, various synthetic substances, irradiation, sewage sludge, or genetically modified organisms (GMOs) in organic production, prohibit antibiotic and synthetic hormone use in organic meat and poultry and require 100% organic feed for organic livestock. The United States and Canadian governments do not allow companies to label products “100% Certified Organic” if they contain genetically modified foods. However, when products are labeled as “made with organic ingredients”, it only requires 70% of the ingredients to be organic and therefore may still contain GMO.   

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12. Myth: Desert climates cure Allergies.

Fact: Don’t pick up and move to escape your allergies. Changing climates can affect your reaction to allergy-triggering substances called allergens — but only to a limited extent. Some Eastern and Midwestern plants are rare out West, but grass and ragweed pollens are found nearly everywhere. Also, once you move, you may simply start reacting to different allergens.

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13. Myth: Flowers commonly trigger Allergies.

Fact: Some florists with prolonged exposure to flowers can have allergy symptoms. But very few people suffer allergic reactions from a bouquet of beautiful blossoms. The culprit is usually the pollen produced by trees, grasses, and weeds (and yes, occasionally flowers) that’s picked up by breezes and carried through the air. 

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14. Myth: Rain washes away pollen.

Fact: There are two sides to almost any story, and it’s the same for rain and allergies. Rain is great on the one hand as it can really wash pollen away, whether in the spring or fall. On the other hand, things bloom when it rains. So not only do plants grow more and produce more pollen, but rain can increase mold counts which many people are allergic to along with pollen. So though it does wash the pollen away for a day or two, soon more will be take its place. Also heavy rains tend to break pollen into small particles, allowing the smaller pieces to be inhaled deeper into the lungs and causing more significant symptoms. The bad news does not stop there for allergy sufferers. In addition, rainfall is only known to eliminate tree pollen, not grass pollen. For those that are allergic to the latter irritant, rainfall does not afford them much of reprieve. Also, rain is frequently associated with storm. An updraft effect occurs before a significant storm, as a warm air mass quickly rises and creates thunderclouds. This upward surge of air instigates pollen and other particles, increasing airborne mold spore counts to levels 100 times more than normal. Pollen and spores can also be stirred up after a storm, when wind patterns are just as volatile.

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15. Myth: Hay Fever comes from Hay.

Fact: Hay fever isn’t a fever, and it doesn’t come from hay. Hay fever is allergic rhinitis is caused by pollens especially grass pollens.

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16. Myth: Eating local honey will combat spring allergies.

Fact: While the benefit of honey over refined sugars is evident, many people also believe eating local honey can cure their allergies through repeated exposure to their allergen. Local honey is made from the pollen of local flowers, so it might seem logical that eating it would increase your allergy tolerance. However, the pollens that cause spring allergies are produced by trees, grasses and weeds, not the showy flowers that bees buzz around. Occasionally raw honey can contain contaminating pollen from ragweed which could cause severe reactions, including shock.

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17. Myth: Pollen allergy won’t lead to food allergy.

Fact: Actually, about one-third of people with pollen allergies also may react to certain food. The reaction is called oral allergy syndrome.

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18. Myth: A blood test is the best test to diagnose allergies.

Fact: Actually, skin tests are more sensitive than blood tests.

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19. Myth: Only take medication when showing symptoms of an allergy attack.

Fact: Experts say most allergy medications work best if they are already in the person’s system or immediately after exposure, even if the person has shown no allergic symptoms. For patients with asthma and allergic rhinitis, allergic inflammation in the nose & airways can be present even if the person can’t feel it. Even though a person might suffer from low levels of symptoms, as the season progresses, a person can experience complete obstruction of the nasal passage if it goes untreated.  By that time, it’s almost too late to take a medication.

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20. Myth: Allergy shots only work in children.

Fact: Experts say allergy shots or immunotherapy, have nothing to do with age and can offer relief at any time. The shots contain just enough of an allergen to stimulate the immune system, but not enough to cause an allergic reaction.

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21. Myth: An allergy to one thing means you’ll react only to that thing.

Fact: Having certain allergies makes you more prone to developing others. For example, people who are sensitive to certain pollens can also react to plant-based foods and beverages with similar proteins. So if you’re allergic to birch tree pollen, eating raw apples, peaches, pears, cherries, carrots, hazelnuts or almonds could cause itching in your mouth or throat, particularly during pollen season. Similarly, if you’re allergic to ragweed, having cantaloupe, bananas, cucumber, zucchini, sunflower seeds or chamomile tea could trigger these symptoms. Not everyone will have this kind of cross-reaction, so there’s no need to go out of your way to avoid these foods if you haven’t had a problem before, but keep it in mind. Peeling the fruit or vegetable (proteins are often in the skin) or cooking it (which can change the proteins) can also help.

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22. Myth: Food allergies cause hyperactivity.

Fact: Food allergies can’t trigger hyperactivity. Children with attention deficit hyperactivity disorder (ADHD) may become more active after consuming sweets and junk foods, but this is caused by a sugar surge rather than an allergy.

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23. Myth: Allergy testing is a waste of time because you’ll probably react to everything.

Fact: Allergy testing is accurate and testing should be done after carefully discussing the person’s symptoms and medical history. Most allergic people will react to a few allergens, which once identified can then be avoided.

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24. Myth: Allergic reactions get worse with each subsequent exposure.

Fact:Allergic reactions are unpredictable. When they occur, they can be the same, less severe than, or more severe than previous reactions. You may also experience different allergic symptoms to the same allergen, making a connection even more difficult to establish. The nature of a reaction depends on your level of allergy and how much of the allergen you ingested.  However, if your allergic reaction is an anaphylactic reaction to an allergen, then they can worsen with each exposure and can lead to death.    

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25. Myth: Antihistamines lose their effect if taken continuously.

Fact: Antihistamines can be taken safely for prolonged periods and don’t become less effective. People do feel antihistamine losing effects but that is due to exacerbation of allergic inflammation.

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26. Myth: Steroid creams for eczema cause skin thinning and shouldn’t be used on children.

Fact: Steroid creams are the only effective treatment for eczema and have no adverse effect if used for short periods of up to a week at a time. Once clear of eczema, the skin should be continuously protected with a moisturizing ointment.

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27. Myth: Building dust and sand cause allergic rhinitis.

Fact: The powdered faeces of house dust mites cause allergies, not dust particles or sand grains.

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28. Myth: Tobacco smoke causes allergy.

Fact: No one really is allergic to smoke. Smoke technically is not an allergen, but an irritant. This explains why most people feel no relief when they take antihistamine after exposure to smoke. Smoke does aggravate other allergic disorders of nose and airways due to its irritant effects. Children exposed to environmental tobacco smoke are at an increased risk for a variety of health problems including asthma, allergic diseases, and recurrent respiratory infections.

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29. Myth: A food can be made less allergenic by cooking it.

Fact: Unlike microbiological risks, heating does not necessarily destroy food allergens and may actually increase their potency. There are no general rules regarding the consequences of heating on allergenicity. The main proteins in peanut that trigger allergic reactions are very robust during heating and processing and therefore there is no reduction in allergenicity. Low-heat treatment like pasteurisation ensures the bacteriological safety of milk but does not cause significant reduction in the allergenicity. Strong-heat treatment (121° C for 20 minutes) largely destroys the allergenicity of whey proteins (alpha-lactalbumin, beta-lactoglobulin, and lactoferrin), but only reduces that of casein and serum albumin. Anyone allergic to casein is likely to react to milk that has undergone strong-heat treatment. Cooking can destroy some of the allergens in egg, but not all of them. In egg white, ovomucoid is heat resistant, whereas ovalbumin is heat labile. This means that some people react to raw eggs but not cooked eggs.

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30. Myth: Alternative medicines are equally effective as prescription medications.

Reality: Alternative medications should never substitute for scientifically proven medical treatments for allergic rhinitis or asthma. Most alternative medications have only recently been subject to scientific scrutiny and their safety and effectiveness remain largely unknown. I have seen many patients of asthma improved by ayurvedic medicine but when analysis of ayurvedic medicine was done, it contained steroids. I have seen some patients of asthma coming to me with status asthmaticus, a life threatening condition, caused by persistent homeopathic treatment of allergic asthma. Some anecdotal studies have shown that allergy improved by acupuncture therapy. In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins. Research also found that histamine is secreted by mast cells under influence of endorphins. Then, how can acupuncture relieve allergy? Even today, medical science is neither exact nor perfect but acupuncture is definitely a pseudoscience.    

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The moral of the story:

1. Allergies are an overreaction of the body’s immune system to specific substances that it misidentifies as harmful. Allergy is the result of mistaken identity. An allergen enters the body and is wrongly identified by the immune system as a dangerous substance. Allergic reactions are unpredictable.  

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2. In its most narrow usage, the term allergy refers to immediate hypersensitive immune responses in which IgE antibodies play an important part. The term allergy however can be used quite broadly to include any hypersensitivity reaction mediated by immunological mechanisms. The term immediate hypersensitivity is somewhat of a misnomer because it does not account for the late-phase reaction or for the chronic allergic inflammation that often occurs with these types of reactions.

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3. Studies suggest that when clinicians use the history and physical examination alone in evaluating possible allergic disease, the accuracy of their diagnoses rarely exceeds 50%.

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4. Neither allergy blood testing nor skin testing should be used for screening: they may be most useful as confirmatory tests when the patient’s history is compatible with an IgE-mediated reaction.

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5. Evidence of sensitization to a particular allergen (i.e., a positive blood/skin test result) is not synonymous with clinically relevant disease (i.e., clinical sensitivity). Venom- and food-specific IgE has been reported in up to 25 and 60 percent of the general population, respectively. Less commonly, patients who react to an allergen may not have any allergen-specific IgE that is detectable with routine testing.   

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6. One study showed that in 103 out of 111 children who were avoiding foods based on allergy test results had no reaction to the food when they ate it during a carefully conducted food challenge. Such false diagnoses are disruptive. Special diets can be difficult to follow and restrictive diets can be more expensive.

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7. Allergy is an immune response, while intolerance is a chemical reaction due to lack of substances necessary to process something.

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8. There is abundant confusion between cold, sinus and allergy symptoms. This means that often these conditions get mistreated or go untreated. 

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9.Breast milk is best to prevent allergy in babies but in case not available, extensively hydrolyzed protein based infant formula [it contains a milk protein that is broken down into tiny pieces to virtually eliminate allergic reactions] containing probiotic and prebiotic may help prevent eczema and improve tolerance to cow’s milk in allergy-prone babies.  

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10. Penicillin skin testing has the potential to identify patients at high risk for a severe reaction. A skin test for allergy to penicillin must be done before giving IV/IM penicillin although in 3 % cases, skin test may be negative but patient is allergic to penicillin all the same mildly allergic. A positive test indicates that the person is truly allergic and must avoid penicillin because penicillin anaphylaxis is rapidly fatal and it would be unwise to consider false positive test. One must never forget that rarely oral penicillin administration may also induce anaphylaxis. Also, if you’re allergic to one type of penicillin, you’re at risk of being allergic to all penicillin-related antibiotics.

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11. The only apparent cure of allergy as on today is by use of allergen-specific immunotherapy (allergy shots or allergy drops) which is effective in 90 % of cases and which attenuate symptoms for several years even after discontinuation of the therapy; by down-regulating Th2 cells, up-regulating Th1 cells and induction of T (reg) cells. 

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12. An epinephrine (adrenaline) will prevent death if it’s used within 20 minutes of exposure, but after that window, the anaphylactic reaction cannot always be halted. 

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13. I hypothesize from experiments on mice that it is worthwhile to do serum B-12 levels in allergic patients and those deficient may be given vitamin B-12 as it may help restore Th1/ Th2 balance. I am also tempted to recommend vitamin D for similar purpose but evidence is conflicting.

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14. Autoimmune diseases occur as a result of an exaggerated Th1 associated immune system response. Allergies, on the other hand, occur as a result of an exaggerated Th2 associated immune system response.  If the Th1 / Th2 balance was restored, autoimmune diseases and allergies would cease, or at least alleviated to great extent. Restoration of Th1 / Th2 balance, in fact, has been shown to benefit both allergy and autoimmune disorder. There is a unique and fascinating genetic mechanism at the crux of allergy, immune defense (combat infection) and self-tolerance (prevent autoimmunity). 

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15. It is the co-evolution of man and microorganisms (pathogenic and non-pathogenic) that has led to an immune system that functions correctly only in the presence of the microorganisms. Without them, the immune system becomes unbalanced and oversensitive. Studies do show that stimulation of immunity by microorganisms does reduce allergy and autoimmune diseases. However, in my view, pollution would make hygiene hypothesis hollow.

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16. From an evolutionary point of view, IgE is conserved and can be found in all mammalia. It therefore originated at least 160 million years ago, possibly even more than 300 million years ago, from a gene duplication of IgY, in which the anaphylactic and opsonic activities of IgY were separated, giving rise to IgE and IgG, respectively. IgG now represented the opsonic activities, which are needed to label antigens with antibodies and complement factors to enable scavenger cells to recognizes and destroy the enemy. IgE was responsible for anaphylactic activities, which represent another way of immune defense, which may involve the whole body. Apparently, in an evolutionary sense, anaphylactic defense mechanisms are needed, but at a potentially high price to the organism. In my view, no defense mechanism bearing such a high cost would be perpetuated evolutionarily unless that defense mechanism is necessary to neutralize a vicious offending agent which can harm the defending organism instantly. Our immune systems evolved in a dirty environment with infections and pathogens threatening us all the time. Until about 100 years ago, everyone would have grown up exposed to dirt, human waste, animals, parasites, and all sorts of unsanitary influences. In those conditions, having a strong immune system capable of reacting to many threats at once and able to repel parasites would have been a very good thing, something evolution would strongly select for. Some allergic responses, for instance, seem to degrade and detoxify snake and bee venom, while others seem to prevent pests from biting or stinging again. It makes sense that such a response should be preferential evolutionarily. Allergies are mediated by a unique immune response that also evolved to fight parasitic infections. Parasites have an advantage if they can suppress the immune system and keep it from killing them off. If these immunosuppressive parasites are common, hosts with an overly aggressive immune system will have an advantage, since once the parasite mellows it out, it will be at just the right level of aggressiveness. Take away the parasites, and you have lots of formerly fit hosts with hyper-aggressive immune systems that flip out over pollen and cat hair. So evolutionary logic is correct but what has gone wrong is the identification of vicious offending agent by markedly hypersensitive defense mechanism. It seems evolutionarily advantageous for our immune systems to be aggressive in the defense of our bodies from foreign items. It also seems to me that people with permissive immune systems are more likely to die out than those will aggressive immune systems. Therefore it is unlikely that evolution will act to select against allergies if it means decreasing the overall robustness of the immune system.    

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17. Researchers assert that the cross-reactivity of latex with banana, avocado, kiwifruit, and chestnut occurs because latex proteins are structurally homologous with some plant proteins. This extensive cross-reactivity of latex-allergic patients is due to the fact that major latex allergens are defense-related proteins of a rubber tree. Higher plants universally induce such protective proteins under certain conditions, and their structures are relatively conserved during the course of evolution. Please note similar antigenic cross-reactivity between pollen and fruits, vegetable & nuts. Allergenic proteins responsible for extensive cross-reactivity are often called ‘pan-allergens’. Profilin is a representative pan-allergen. It has an actin-binding property, and every eukaryotic cell contains structurally related profilin. Because of its structural conservatism, profilin can provide common epitopes that are at the root of the extensive cross-reactivity. One of the reasons for the marked cross-reactivity of pollen-allergic patients to various vegetable foods is the profilin present both in the pollen and in the offensive foods. Most plant food allergens belong to only 4 structural families, indicating that conserved structures and biological activities may play a role in determining or promoting allergenic properties. The most widespread groups of plant proteins that contain allergens are the cupin and prolamin superfamilies and the protein families of the plant defense system. The cupin superfamily includes allergenic seed storage proteins of the vicilin and legumin type present in soybeans, peanuts, and tree nuts. The prolamin superfamily includes several important types of allergens of legumes, tree nuts, cereals, fruits, and vegetables, such as the 2S albumin seed storage proteins, the nonspecific lipid transfer proteins, and the cereal α-amylase and protease inhibitors. Plant food allergens are also found among the various groups of defense proteins that enable plants to resist biotic and abiotic stress, such as the pathogenesis-related proteins, certain proteases, and protease inhibitors. Some of the defense-related proteins strengthen the cell walls to protect the plant, and others are necessary for the biosynthesis of a low-molecular-weight antibiotic called phytoalexin. It is becoming more and more evident that plant defense related proteins form novel families of cross-reactive plant allergens. 

These protective proteins of plants are also meant for their survival against animals as mammals including human ancestors would regularly destroy (eat) plants for their living. This protective plant protein system has taken advantage of faulty identification by immediate hypersensitivity mechanisms of mammals including human ancestors. So harmless plant protein antigens evoke severe allergic reaction in mammals including humans to prevent animal kingdom to destroy plant kingdom. Therefore evolutionary basis for existence of allergenic plant proteins is survival of plant kingdom.        

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18. Non-IgE-mediated immediate hypersensitive reactions [anaphylactoid, pseudoallergic or idiosyncratic] may represent as high as 77% of all immune-mediated immediate hypersensitive reactions, implying hundreds of thousands of reactions and numerous fatalities every year. These cannot be diagnosed by allergic skin/blood tests. Pseudoallergies do not have a sensitization phase. Symptoms occur even at the first exposure. It is deplorable that medical fraternity and lay people are obsessed by allergy overlooking more common and more harmful pseudoallergy.  

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Dr. Rajiv Desai. MD.

May 1, 2013

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Postscript:

Who would have thought that son of Marilyn Monroe could be allergic to perfume as his mom loved and used perfume throughout her life. Also, after living in India and suffering from infectious diseases like trachoma, typhoid, chicken pox, viral hepatitis and tuberculosis, my immune system is predominantly Th1 type and not pro-allergy Th2 type. So we have a missing link between genes and environment and that is individuality. You need not conform to either your DNA or to your environment as you are a unique individual.   

 

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