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Title: Allergies  
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Classification and external resources
10 9 DiseasesDB MedlinePlus eMedicine MeSH D006967



A variety of tests exist to diagnose allergic conditions. If done they should be ordered and interpreted in light of a person's history of exposure as many positive test results do not mean a clinically significant allergy.[3] Tests include placing possible allergens on the skin and looking for a reaction such as swelling and blood tests to look for an allergen-specific IgE.


Signs and symptoms

Common symptoms
Affected organ Symptom
Nose swelling of the nasal mucosa (allergic rhinitis)
Sinuses allergic sinusitis
Eyes redness and itching of the conjunctiva (allergic conjunctivitis)
Skin rashes, such as eczema and hives (urticaria)
Gastrointestinal tract abdominal pain, bloating, vomiting, diarrhea



Substances that come into contact with the skin, such as latex, are also common causes of allergic reactions, known as contact dermatitis or eczema.[10] Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a "wheal and flare" reaction characteristic of hives and angioedema.[11]


Risk factors for allergy can be placed in two general categories, namely host and environmental factors.[12] 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.[13]


Main article: 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, peanut, tree nuts, fish and shellfish.[14] Other food allergies, affecting less than 1 person per 10,000 population, may be considered "rare".[15]

The most common food allergy in the US population is a sensitivity to crustacea.[15] Although peanut allergies are notorious for their severity, peanut allergies are not the most common food allergy in adults or children. Severe or life-threatening reactions may be triggered by other allergens and are more common when combined with asthma.[14]

Rates of allergies differ between adults and children. Peanut allergies can sometimes be outgrown by children. Egg allergies affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5.[16] The sensitivity is usually to proteins in the white rather than the yolk.[17]

Milk-protein allergies are not Immunoglobulin E reactions, and are usually attributable to proctocolitis. They are most prevalent in children.[18] Some people are unable to tolerate milk from goats or sheep as well as cows, and many are also unable to tolerate dairy products such as cheese. A small portion of children with a milk allergy, roughly ten percent, will have a reaction to beef. Beef contains a small amount of protein that is present in cow's milk.[19] Lactose intolerance, a common reaction to milk, is not a form of allergy at all, but rather due to the absence of an enzyme in the digestive tract.

Those with tree nut allergies may be allergic to one or many tree nuts, including pecans, pistachios, pine nuts, and walnuts.[17] Also seeds, including sesame seeds and poppy seeds, contain oils where protein is present, which may elicit an allergic reaction.[17]

Non-food proteins



Latex and banana sensitivity may cross-react; furthermore, those with latex allergy may also have sensitivities to avocado, kiwifruit, and chestnut.[21] 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.[20]

Toxins interacting with proteins

Another non-food protein reaction, urushiol-induced contact dermatitis, originates after contact with poison ivy, eastern poison oak, western poison oak, or poison sumac. Urushiol, which is not itself a protein, acts as a hapten and chemically reacts with, binds to, and changes the shape of integral membrane proteins on exposed skin cells. The immune system does not recognize the affected cells as normal parts of the body, causing a T-cell-mediated immune response.[22] Of these poisonous plants, sumac is the most virulent.[23] The resulting dermatological response to the reaction between urushiol and membrane proteins includes redness, swelling, papules, vesicles, blisters, and streaking.[24]


Genetic basis

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.[26] Allergic parents are more likely to have allergic children,[27] 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.[27]

The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk.[28] Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years.[28] The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.[29] Overall, boys have a higher risk of developing allergies than girls,[27] although for some diseases, namely asthma in young adults, females are more likely to be affected.[30] Sex differences tend to decrease in adulthood.[27] Ethnicity may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to migration.[27] It has been suggested that different genetic loci are responsible for asthma, to be specific, in people of European, Hispanic, Asian, and African origins.[31]

Hygiene hypothesis

Main article: Hygiene hypothesis



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.[34] Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner.[35] The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.[36] 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.[37][38]

Other environmental factors


Exposure to allergens, especially in early life, is an important risk factor for allergy. Alterations in exposure to microorganisms is another plausible explanation, at present, for the increase in atopic allergy.[13] Endotoxin exposure reduces release of inflammatory cytokines such as TNF-α, IFNγ, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood.[40] Certain microbe-sensing proteins, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes.[41]

Gutworms and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine chlorination and purification of drinking water supplies.[42] 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.[43] 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.[44] In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in infants.[45] 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.[39] Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies.[46] It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work.[46] For more information on this topic, see Helminthic therapy.


Acute response



Late-phase response



Effective management of allergic diseases relies on the ability to make an accurate diagnosis.[49] Allergy testing can help confirm or rule out allergies.[50][51] 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.[50] 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.[51][52]

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.[50] Also, earlier and more accurate diagnoses save cost due to reduced consultations, referrals to secondary care, misdiagnosis and emergency admissions.[53]


Skin testing



Blood testing


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.






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.


Unreliable tests: There are other types of allergy testing methods that the that are unreliable including applied kinesiology (allergy testing through muscle relaxation), cytotoxicity testing, urine autoinjection, skin titration (Rinkel method), and provocative and neutralization (subcutaneous) testing or sublingual provocation.[60]

Differential diagnosis

Before a diagnosis of allergic disease can be confirmed, other possible causes of the presenting symptoms should be considered.[61] Vasomotor rhinitis, for example, is one of many maladies that shares symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis.[62] 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.




New technology approaches to decreasing IgE overproduction, and regulating histamine release in allergic individuals have demonstrated statistically significant reduction on Total Nasal Symptom Scores.[64][65]




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.[66] 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.[67] Meta-analyses have also confirmed efficacy of the treatment in allergic rhinitis in children[68] and in asthma.[69] 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.[70] 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.[71]


A third type, 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.[72]






The consumption of various foods during pregnancy has been linked to eczema; these include celery, citrus fruit, raw pepper, margarine, and vegetable oil.[75] A high intake of antioxidants, zinc, and selenium during pregnancy may help prevent allergies. This is linked to a reduced risk for childhood-onset asthma, wheezing, and eczema.[76] Further research needs to be conducted. Probiotic supplements taken during pregnancy or infancy may help to prevent atopic dermatitis. [77] After birth, an early introduction of solid food and high diversity before week 17 could increase a child's risk for allergies. Studies suggest that introduction of solid food and avoidance of highly allergenic food such as peanuts during the first year does not help in allergy prevention.[75]


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.[78] 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,[79] although some suggest that a steady rise in sensitization has been occurring since the 1920s.[80] The incidence of atopy in developing countries has, in general, remained much lower.[79]

Allergic conditions: Statistics and Epidemiology
Allergy type United States United Kingdom[81]
Allergic rhinitis 35.9 million[82] (about 11% of the population[83]) 3.3 million (about 5.5% of the population[84])
Atopic eczema About 9% of the population. Between 1960 and 1990 prevalence has increased from 3% to 10% in children.[86] 5.8 million (about 1% severe).
Anaphylaxis At least 40 deaths per year due to insect venom. About 400 deaths due to penicillin anaphylaxis. About 220 cases of anaphylaxis and 3 deaths per year are due to latex allergy.[87] An estimated 150 people die annually from anaphylaxis due to food allergy.[88] Between 1999 and 2006, 48 deaths occurred in people ranging from five months to 85 years old.
Food allergies About 6% of US children under age 3 and 3.5-4% of the overall US population. Peanut and/or tree nut (e.g. walnut) allergy affects about three million Americans, or 1.1% of the population.[88] 5-7% of infants and 1-2% of adults. A 117.3% increase in peanut allergies was observed from 2001 to 2005, an estimated 25,700 people in England are affected.

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.[79] 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.[78] The hygiene hypothesis maintains[91] that high living standards and hygienic conditions exposes 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.[44][92]

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%,[93] and an increased prevalence of parasitic infections has been associated with a decreased prevalence of asthma.[94] It is speculated that these infections exert their effect by critically altering TH1/TH2 regulation.[95] Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm.[95]


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.[96] Pirquet called this phenomenon "allergy" from the Ancient Greek words ἄλλος allos meaning "other" and ἔργον ergon meaning "work".[97] 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.[98] With this new classification, the word "allergy" was restricted to type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions.



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.[100] Other newer methods use colorimetric or fluorescence-labeled technology in the place of radioactive isotopes.



Medical specialty


In the United Kingdom, allergy is a subspecialty of general medicine or pediatrics. After obtaining postgraduate exams (MRCP or MRCPCH respectively), a doctor works for several years as a specialist registrar before qualifying for the General Medical Council specialist register. Allergy services may also be delivered by immunologists. A 2003 Royal College of Physicians report presented a case for improvement of what were felt to be inadequate allergy services in the UK.[104] In 2006, the House of Lords convened a subcommittee that reported in 2007. It concluded likewise that allergy services were insufficient to deal with what the Lords referred to as an "allergy epidemic" and its social cost; it made several other recommendations.[105]

See also


External links

  • American Academy of Allergy, Asthma & Immunology

