Allergy


An allergy can refer to several kinds of immune reactions including Type I hypersensitivity in which the person’s body is hypersensitised and develops immunoglobulin E (IgE), a certain class of antibodies to typical proteins. When a person is hypersensitised, these substances are known as allergens. The word allergy derives from the Greek words allos meaning “other” and ergon meaning “work”. Type I hypersensitivity is characterised by excessive activation of mast cells and basophils by immunoglobulin E resulting in a systemic inflammatory response that can result in symptoms as benign as a runny nose, to life-threatening anaphylactic shock and death.

Allergy is a very common disorder and more than 50 million Americans suffer from allergic diseases. Allergies are the sixth leading cause of chronic disease in the United States, costing the health care system $18 billion annually.

  History

The term and concept of “allergy” was coined by a Viennese pediatrician named Clemens von Pirquet in 1906. He observed that the symptoms of some of his patients might have been a response to outside allergens such as dust, pollen, or certain foods. For a long time all hypersensitivities were thought to stem from the improper action of inflammatory immunoglobulin class IgE, however it soon became clear that several different mechanisms utilizing different effector molecules were responsible for the myriad of disorders previously classified as “allergies”. A new four-class (now five) classification scheme was designed by P. G. H. Gell and R. R. A. Coombs. Allergy has since been kept as the name for Type I Hypersensitivity, characterised by classical IgE mediation of effects.

  Signs and symptoms

Allergy is characterised by a local or systemic inflammatory response to allergens. Local symptoms are:

Systemic allergic response is also called anaphylaxis. Depending of the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma and even death.

Hay fever is one example of an exceedingly common minor allergy — large percentages of the population suffer from hayfever symptoms in response to airborne pollen. Asthmatics are often allergic to dust mites. Apart from ambient allergens, allergic reactions can be due to medications.

  Diagnosis

There are several methods for the diagnosis and assessment of allergies.

  Skin test

The typical and most simple method of diagnosis and monitoring of Type I Hypersensitivity is by skin testing, also known as prick testing due to the series of pricks made into the patient’s skin. Small amounts of suspected allergens and/or their extracts (pollen, grass, mite proteins, peanut extract, etc.) are introduced to sites on the skin marked with pen or dye (the ink/dye should be carefully selected, lest it cause an allergic response itself). The allergens are either injected intradermally or into small scratchings made into the patient’s skin, often with a lancet. Common areas for testing include the inside forearm and 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 full-blown hives in extremely sensitive patients.

After performing the skin test and receiving results, the doctor may apply a steroid cream to the test area to reduce discomfort (such as itching and inflammation).

  Problems with skin test

While the skin test is probably the most preferred means of testing because of its simplicity and economics, it is not without complications. Some people may display a delayed-type hypersensitivity (DTH) reaction which can occur as far as 6 hours after application of the allergen and last up to 24 hours. This can also cause serious long-lasting tissue damage to the affected area. These types of serious reactions are quite rare.

Additionally, the application of previously unencountered allergens can actually sensitize certain individuals to the allergen, causing the inception of a new allergy in susceptible individuals.[citation needed]

Skins tests also are not always able to pinpoint a patient’s specific allergies if the patient has an allergy but does not react to the skin test allergen.

  Total IgE count

Another method used to qualify type I hypersensitivity is measuring the amount of serum IgE contained within the patient’s serum. This can be determined through the use of radiometric and colormetric immunoassays. Even the levels the amount of IgE specific to certain allergens can be measured through use of the radioallergosorbent test (RAST).

  Treatment

There are limited mainstream medical treatments for allergies. Probably the most important factor in rehabilitation is the removal of sources of allergens from the home environment, and avoiding environments in which contact with allergens is likely.

  Immunotherapy

Hyposensitization is a form of immunotherapy where the patient is gradually vaccinated against 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 (”the blocking antibody”) production, as opposed to the excessive IgE production seen in hypersensitivity type I cases. Delivery can occur via allergy injection, or sublingual immunotherapy, allergy drops taken under the tongue. Though not commonly offered in the U.S., sublingual immunotherapy is gaining attention internationally and is very common in Europe.

A second form of immunotherapy involves the intravenous injection of monoclonal anti-IgE antibodies. These bind to free and B-cell IgE signalling such sources for 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. The first agent in this class is omalizumab.

An experimental treatment form, enzyme potentiated desensitization, has been tried with some success but is not in widespread use. EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes respond by favouring desensitization, or down-regulation, rather than sensitization. EPD is also under development for the treatment of autoimmune diseases.

  Chemotherapy

Several antagonistic drugs are used to block the action of allergic mediators, preventing activation of cells and degranulation processes. They include antihistamines, cortisone, epinephrine (adrenalin), theophylline and Cromolyn sodium. These drugs help alleviate the symptoms of allergy but play little role in chronic alleviation of the disorder. They can play an imperative role in the acute recovery of someone suffering from anaphylaxis, which is why those allergic to bee stings, peanuts, nuts, and shellfish often carry an adrenalin needle with them at all times.

  Alternative therapies

In alternative medicine, a number of treatment modalities are considered effective by its practitioners in the treatment of allergies, particularly naturopathic, herbal medicine, homeopathy, traditional Chinese medicine and kinesiology. These modalities are frequently offered as treatment for those seeking additional help when mainstream medicine has failed to provide adequate relief from allergy symptoms. However, mainstream physicians maintain that these claims lack a scientific basis and warn that the efficacy of such treatments is only supported by anecdotal evidence[citation needed].

  Pathophysiology

All hypersensitivities result from an aberration somewhere in the normal immune process. The exact cause of such malfunctions is not always apparent, however, and several arguments from genetic-basis, environmental-basis and intermediate proponents exist with varying validity and acceptance.

  Acute response

The difference between a type I hypersensitivity reaction against an allergen to the normal humoral response against a foreign body is that plasma cells secrete IgE as opposed to either IgM (against novel antigens) or IgG (against immunized antigens). IgE binds to Fc receptors on the surface of mast cells and basophils, both involved in the acute inflammatory response.

When IgE is first secreted it binds to the Fc receptors on a mast cell or basophil, and such an IgE-coated cell is said to be sensitized to the allergen in question. A later exposure by the same allergen causes reactivation of these IgE, which then signals for the degranulation of the sensitized mast cell or basophil. There is now strong evidence that mast cells and basophils require costimulatory signals for degranulation in vivo, derived from GPCRs such as chemokine receptors. These granules release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation and smooth muscle contraction. This results in the previously described symptoms of rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (calliscal anaphylaxis), or localised to particular body systems (for example, asthma to the respiratory system; eczema to the dermis).

  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 4-6 hours after the original reaction and can last from 1-2 days. Cytokines from mast cells may also play a role in the persitence of long-term effects. Late phase responses seen in asthma are slightly different from those seen in other allergic responses.

  Basis of the allergic response

  Genetic basis

There is much evidence to support the genetic basis of allergy, as allergic parents are more likely to have allergic children, and their allergies are likely to be stronger than those from non-allergic parents. However some allergies are not consistent along genealogies with parents being allergic to peanuts, but having children allergic to ragweed, or siblings not sharing the same allergens. Ethnicity has also been shown to play a role in some allergies. Interestingly, in regard to asthma, it has been suggested that different genetic loci are responsible for asthma in people of Caucasian, Hispanic, Asian, and African origins. It has also been suggested that there are both general atopy genes and tissue-specific allergy genes that target the allergic response to specific mucosal tissues. Potential disease associated alleles include both coding region variation and SNPs found in gene regulatory elements.

  Relationship with parasites

Some recent research has also begun to show that some kinds of common parasites, such as intestinal worms (e.g. hookworms), secrete immunosuppressant chemicals into the gut wall and hence the bloodstream which prevent the body from attacking the parasite. This gives rise to a new slant on the “hygiene hypothesis” — that co-evolution of man and parasites has in the past led to an immune system that only functions correctly in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive. Gutworms and similar parasites are present in untreated drinking water in undeveloped countries, and in developed countries until the routine chlorination and purification of drinking water supplies. This also coincides with the time period in which a significant rise in allergies has been observed.[citation needed] So far, there is only sporadic evidence to support this hypothesis — one scientist who suffered from seasonal allergic rhinitis (hayfever) infected himself with gutworms and was immediately ‘cured’ of his allergy with no other ill effects.[citation needed] Full clinical trials have yet to be performed however. It may be that the term ‘parasite’ could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work.[citation needed]

  Basis of increasing prevalence

There has been a notable increase in the commonness of allergies in the past decades, and there are multiple hypotheses explaining this phenomenon. This is in part because we know what they are, in contrast to earlier humans who would think that the symptoms pointed towards a non-important illness.

  The Hygiene Hypothesis

One theory that has been gaining strength is the “hygiene hypothesis“. This theory maintains that since children in more affluent countries are leading a cleaner and cleaner life (less exposure to dirt, extra use of disinfectants, etc), their immune systems have less exposure to parasites and other pathogens than children in other countries or in decades past. Their immune systems may, therefore, have many “loaded guns”, cells which might have targeted, say, the intestinal worms that no longer cause trouble in affluent neighbourhoods. Having no reasonable target, these cells inadvertently become activated by environmental antigens that might only cause minor reactions in others. It is the symptoms of this exaggerated response that is seen as the allergic reaction.

Many common allergies such as asthma have seen huge increases in the years since the second world war, and many studies appear to show a correlation between this and the increasingly affluent and clean lifestyles in the West. This is supported by studies in less developed countries that do not enjoy western levels of cleanliness, and similarly do not show western levels of incidences of asthma and other allergies. During this same period, air quality, at one time considered the “obvious” cause of asthma, has shown a considerable improvement. This has led some researchers to conclude that it is our “too clean” upbringing that is to blame for the lack of immune system stimulation in early childhood.

So far the evidence to support this theory is limited. One supporting fact is that many Chinese will develop hay fever after moving into USA for three or more years. However, contradictory examples also exist.

  Increasing use of chemicals

Another theory is the exponential use and abuse of chemicals in affluent nations since the second world war. Vast numbers of chemicals are introduced into our indoor and outdoor environments with little or no testing regarding their toxicity to living beings. Many believe that air quality is getting worse rather than better, particularly if one considers indoor air quality as well as outdoor. (Indoor air quality has become significantly worse since building codes changed in the 1970s to make buildings more air-tight to conserve energy. This affects buildings built since that time.) Adverse reactions to toxins vary considerably from one person to another, and can involve extremes in symptoms including the neurological and endocrine systems as well as the more commonly recognized allergy symptoms listed above.

In 2004, a joint Swedish-Danish research team found a very strong link between allergies in children and the phthalates DEHP and BBzP, commonly used in PVC.

Allergies are also viewed by some medical practitioners as a negative consequence of the use and abuse of antibiotics and vaccinations. This mainstream Western approach to treatment and prevention of infectious disease has been used in the more affluent world for a longer period of time than in the rest of the world, hence the much greater commonality of allergies there. It is hypothesized that use of antibiotics and vaccination affect the immune system, and that allergies are a dysfunctional immune response.

Common allergens

In addition to foreign proteins found in foreign serum (from blood transfusions) and vaccines, common allergens include:

Food allergy

A food allergy is an immunologic response to a food protein. It is estimated that up to 12 million Americans have food allergies of one type or another, and the prevalence is rising. Six to eight percent of children have food allergies and two percent of adults have them. The most common food allergies in adults are shellfish, peanuts, tree nuts, fish, and eggs, and the most common food allergies present in children are milk, eggs, and peanuts.At this time, there is no cure for food allergies. Treatment consists of avoidance diets, where the allergic person avoids any and all forms of the food that they are allergic to. For people who are extremely sensitive, this may involve the total avoidance of any exposure with the allergen, including touching or inhaling the problematic food as well as any surfaces that may have come into contact with it. Food allergy is distinct from food intolerance, which is not caused by an autoimmune reaction.

Persons diagnosed with a food allergy may carry an autoinjector of epinephrine such as an EpiPen or Twinject, wear some form of medical alert jewelry, or develop an emergency action plan, in accordance with their doctor.

  Signs and symptoms

Symptoms of food allergies include:

Angioedema is a skin reaction where the tissues swell. It can result in swelling/edema of the lips, skin tongue and airways (causing constriction, wheezing and difficulty breathing). It can also cause swelling of the face, eyes, hands, etc…

The symptoms of an IgE allergic reaction can take place within a few minutes to an hour. The process of eating and digesting food affects the timing and location of a reaction.IgG reactions build over a period of hours to days, and therefore symptoms can be difficult to notice as allergy-related.

Food allergy can lead to anaphylactic shock: A systemic reaction involving several different bodily systems including hypotension (low blood pressure) and loss of consciousness. This is a medical emergency. Allergens commonly associated with this type of reaction are peanuts, nuts, milk, egg, and seafood. [citation needed] Food anaphylaxis can also be caused by various types of fruit. Latex products can induce similar reactions.

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.

Another type of food allergy is called Gastrointestinal Food Hypersensitivity. It can be IgE or Non-IgE mediated.

In this class, IgE mediated responsese include:

  • Immediate GI Hypersensitivity
  • Oral allergy syndrome

Conditions that have been shown to have both IgE and Non-IgE causes of gastrointestinal food hypersensitity include: [citation needed]

Conditions of Non-IgE gastrointestinal food hypersensitivity include: [citation needed]

  The Big Eight

The most common food allergies are:

These are often referred to as “the big eight.” They account for over 90% of the food allergies in the United States of America. Sesame is currently the 9th most common food allergen in America according to the Food Allergy and Anaphylaxis Network.Yet virtually any food can be a food allergen. According to the website of pediatric authors Drs. Sears, berries, buckwheat, chocolate, cinnamon, citrus fruits, coconut, corn, mustard, peas, pork, seeds, sesame, sugar, tomatoes and yeast are also common allergens. The Joneja Food Allergen Scale shows the relative allergenicity of various foods.

Likelihood of allergy can increase with exposure[citation needed]. For example, rice allergy is more common in East Asia where rice forms a large part of the diet.In Central Europe, celery allergy is more common. The top allergens vary somewhat from country to country but milk, eggs, peanuts, treenuts, fish, shellfish, soy, wheat and sesame tend to be in the top 10 in many countries.

  Diagnosis

The best method for diagnosing food allergy is to be assessed by an allergist. The allergist will review the patients history and the symptoms or reactions that have been noted after food ingestion. If the allergist feels the symptoms or reactions are in keeping with a food allergy, he/she will perform allergy tests.

There are two basic types of allergy tests: Skin Prick Tests and blood tests. The skin prick is easy to do and results are available in minutes. Different allergists may use different devices for skin prick testing. Some use a “bifurcated needle” which looks like a fork with 2 prongs. Others use a “multi-test” which may look like a small board with several pins stick out of it. In these tests, a tiny amount of the suspected allergen is put onto the skin or into a testing device, and the device is placed on the skin to prick, or break through, the top layer of skin. This puts a small amount of the allergen under the skin. A hive will form at any spot where the person is allergic. This test generally yields a positive or negative result. It is good for quickly learning if a person is allergic to a particular food or not, because it detects allergic antibodies known as IgE. Skin tests cannot predict if a reaction would occur or what kind of reaction might occur if a person ingests that particular allergen. They can however confirm an allergy in light of a patient’s history of reactions to a particular food.

Blood tests, such as RAST, measure the amount of IgE antibodies, and are another useful diagnostic tool. In RAST, blood is drawn and sent to a lab for testing. Researchers have been able to determine “predictive values” for certain foods. These predictive values can be compared to the RAST blood test results. If a persons RAST score is higher than the predictive value for that food, then there is over a 95% chance the person will have an allergic reaction (limited to rash and anaphylaxis reactions) if they ingest that food.  Currently, predictive values are available for the following foods: milk, egg, peanut, fish, soy, and wheat. Blood tests allow for hundreds of allergens to be screened from a single sample, and cover food allergies as well as inhalants. However, non-IgE mediated allergies cannot be detected by this method.

Blood testing by ELISA methodologies is the only method currently available that can measure antibodies of types IgE and IgG. IgG-type anitbodies are implicated in a wide variety of food allergy reactions including rheumatoid arthritis diarrhea, and constipation, among others.

Diagnostic tools for gastrointestinal food hypersensitivity often include endoscopy, colonoscopy, and biopsy.

Important differential diagnoses are:

  • Lactose intolerance; this generally develops later in life but can present in young patients in severe cases. This is due to an enzyme deficiency (lactase) and not allergy. It occurs in many non-Western people.
  • Celiac disease; this is an autoimmune disorder triggered by specific proteins such as gliadin (present in wheat and other grains).
  • Irritable bowel syndrome (IBS); although many IBS cases might be due to food allergy, this is an important diagnosis in patients with diarrhea in whom no allergens can be identified.
  • C1 esterase inhibitor deficiency (hereditary angioedema); this rare disease generally causes attacks of angioedema, but can present solely with abdominal pain and occasional diarrhea.

  Pathophysiology

Generally, introduction of allergens through the digestive tract is thought to induce immune tolerance. In individuals who are predisposed to developing allergies (atopic syndrome), the immune system produces IgE antibodies against protein epitopes on non-pathogenic substances, including dietary components. [citation needed] The IgE molecules are coated onto mast cells, which inhabit the mucosal lining of the digestive tract.

Upon ingesting an allergen, the IgE reacts with its protein epitopes and release (degranulate) a number of chemicals (including histamine), which lead to oedema of the intestinal wall, loss of fluid and altered motility. The product is diarrhea.

Any food allergy has the potential to cause a fatal reaction.

  Causes

The immune system’s eosinophils, once activated in a histamine reaction, will register any foreign proteins they see. One theory regarding the causes of food allergies focuses on proteins presented in the blood along with vaccines, which are designed to provoke an immune response. Flu vaccines and the Yellow Fever vaccine are still egg-based, but the Measles-Mumps-Rubella vaccine stopped using eggs in 1994.There is resistance to this theory, especially as it applies to autoimmune disease.

Another theory focuses on whether an infant’s immune system is ready for complex proteins in a new food when it is first introduced.

The most popular theory at this time is the Hygiene hypothesis. Researches speculate [citation needed] that in the modern, industrialized nations, such as the United States, food allergy is more common due to the lack of early exposure to dirt and germs, in part due to the over use of antibiotics and antibiotic cleansers. This theory is based partly on studies showing less allergy in third world countries. [citation needed] Research has found [citation needed] that the body, with less dirt and germs to fight off, turns on itself and attacks food proteins as if they were foreign invaders.

  Treatment

The mainstay of treatment for food allergy is avoidance of the foods that have been identified as allergens.

If the food is accidentally ingested and a systemic reaction occurs, then epinephrine (best delivered with an autoinjector of epinephrine such as an Epipen) or Twinject should be used. It is possible that a second dose of epinephrine may be required for severe reactions. [citation needed] The patient should also seek medical care immediately.

At this time, there is no cure for food allergies.There are no allergy desensitization or allergy “shots” available for food allergy.

According to experts at the BA Festival of Science in Norwich, England, vaccines can be created using genetic engineering to cure allergies. If this can be done, food allergies could be eradicated in about ten years.

  Statistics

For reasons that are not entirely understood, the diagnosis of food allergies has become more common in Western nations in recent times. Food allergy affects as many as 6% of young children and 3% to 4% of adults.

The most common food allergens include peanuts, milk, eggs, tree nuts, fish, shellfish, soy, and wheat - these foods account for about 90% of all allergic reactions.

  Differing views

Various medical practitioners have a differing views on food allergies. Irritable Bowel Syndrome (IBS) patients have been studied with regards to food allergies. Some studies have reported on the role of food allergy in IBS; only one epidemiological study on functional dyspepsia and food allergy has been published. The mechanism by which food activates mucosal immune system is uncertain, but food specific IgE and IgG4 appeared to mediate the hypersensitivity reaction in a subgroup of IBS patients. Exclusion diets based on skin prick test, RAST for IgE or IgG4, hypoallergic diet and clinical trials with oral disodium cromoglycate have been conducted, and some success has been reported in a subset of IBS patients.

Studies comparing skin prick testing and ELISA blood testing have found that the results of skin prick testing correlate poorly with symptoms of irritable bowel syndrome demonstrated through dietary challenge.

Extensive clinical experience has demonstrated significant improvement of patients with IBS whose ELISA-based food allergy testing is positive and where treatment includes a careful exclusion diet.

In addition, many practitioners of complementary and alternative medicine ascribe symptoms to food allergy where other doctors do not. The causal relationships between these various conditions and food allergies have not been studied extensively enough to provide sufficient evidence to become authoritative. The interaction of histamine with the nervous system receptors has been demonstrated, but more study is needed. Other immune response effects are commonly known (swelling, irritation, etc.), but their relationships to some conditions has not been extensively studied. Examples are arthritis, fatigue, headaches, and hyperactivity. Nevertheless, hypoallergenic diets reportedly can be of benefit in these conditions, indicating that the current medical views on food allergy may be too narrow. Holford and Brady (2005) suggest three levels of response; classical immediate-onset allergy (IgE), delayed-onset allergy (giving a positive response on an ELISA IgG test but rarely on an IgE skin prick test), and food intolerance (non-allergic), and claim the last two to be more common.It is important to note that IgG is present in the body and is known to respond to foods. So some medical practitioners, especially allergists, state that there is no predictive value to these types of tests, despite the studies cited above.

  In children

Milk and soy allergies in children can often go undiagnosed for many months, causing much worry for parents and health risks for infants and children. Many infants with milk and soy allergies can show signs of colic, blood in the stool, reflux, rashes and other harmful medical conditions.  These conditions are often misdiagnosed as viruses or colic.

Many children who are allergic to cow’s milk protein also show a cross sensitivity to soy-based products. There are infant formulas in which the milk and soy proteins are degraded so when taken by an infant, their immune system does not recognize the allergen and they can safely consume the product.

About 50% of children with allergies to milk, egg, soy, and wheat will outgrow their allergy by the age of 6. For those that don’t, and for those that are still allergic by the age of 12 or so, have less than an 8% chance of outgrowing the allergy

Peanut and tree nut allergies are less likely to be outgrown, although evidence now shows  that about 20% of those with nut allergies do eventually outgrow the allergy. In such a case, they need to consume nuts in some regular fashion to maintain the non-allergic status.  This should be discussed with a doctor.

  Labeling laws

In response to the risk that certain foods pose to those with food allergies, countries have responded by instituting labeling laws that require food products to clearly inform consumers if their products contain major allergens or by-products of major allergens.

  United States law

Under the Food Allergen Labeling and Consumer Protection Act of 2004 (Public Law 108-282), companies are required to disclose on the label whether the product cotains a major food alergen

“Hypersensitivity which causes immune reactions can be allergy. Mostly air pollution causes respiratory allergies which can be prevented with the use of air filter. Skin allergy eczema treatment information can be taken from the net. The government agencies can handle allergy testing issues efficiently. No doubt man tries but complete allergy prevention is not possible.

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