View source for Medicine:Allergy

{{short description|Immune system response to a substance that most people tolerate well}}
{{Infobox medical condition (new)
| name            = Allergy
| synonyms        =
| image           = Hives2010.JPG
| caption         = [[Medicine:Hives|Hives]] are a common allergic symptom.
| field           = [[Biology:Immunology|Immunology]]
| symptoms        = Red eyes, itchy rash, vomiting, runny nose, shortness of breath, swelling, sneezing, and cough.
| complications   =
| onset           =
| duration        =
| types           = [[Medicine:Allergic rhinitis|Hay fever]], [[Medicine:Food allergy|food allergies]], [[Medicine:Atopic dermatitis|atopic dermatitis]], allergic asthma, [[Medicine:Anaphylaxis|anaphylaxis]]<ref name=NIH2015Types/>
| causes          = [[Biology:Genetics|Genetic]] and environmental factors<ref name=Kay2000/>
| risks           =
| diagnosis       = Based on symptoms, skin prick test, [[Medicine:Blood test|blood test]]<ref name=NIH2012pdf/>
| differential    = Food intolerances, food poisoning<ref name=Bah2012/>
| prevention      = Early exposure to potential allergens<ref name=Sic2014/>
| treatment       = Avoiding known allergens, medications, allergen immunotherapy<ref name=NIH2015Imm/>
| medication      = [[Biology:Corticosteroid|Steroids]], antihistamines, [[Chemistry:Epinephrine (medication)|epinephrine]], mast cell stabilizers, antileukotrienes<ref name=NIH2015Imm/><ref name=Review09/><ref>{{cite journal | vauthors = Finn DF, Walsh JJ | title = Twenty-first century mast cell stabilizers | journal = British Journal of Pharmacology | volume = 170 | issue = 1 | pages = 23–37 | date = September 2013 | pmid = 23441583 | pmc = 3764846 | doi = 10.1111/bph.12138 }}</ref><ref>{{cite journal | vauthors = May JR, Dolen WK | title = Management of Allergic Rhinitis: A Review for the Community Pharmacist | journal = Clinical Therapeutics | volume = 39 | issue = 12 | pages = 2410–2419 | date = December 2017 | pmid = 29079387 | doi = 10.1016/j.clinthera.2017.10.006 | doi-access = free }}</ref>
| prognosis       =
| frequency       = Common<ref name=NIH2015Epi/>
| deaths          =
}}

<!-- Definition and symptoms -->
'''Allergies''', also known as '''allergic diseases''', are various conditions caused by [[Medicine:Hypersensitivity|hypersensitivity]] of the [[Biology:Immune system|immune system]] to typically harmless substances in the environment.<ref name=Con2007>{{cite book| vauthors = McConnell TH |title=The Nature of Disease: Pathology for the Health Professions|date=2007|publisher=Lippincott Williams & Wilkins|location=Baltimore, MD|isbn=978-0-7817-5317-3|page=159|url=https://books.google.com/books?id=chs_lilPFLwC&pg=PA159}}</ref> These diseases include [[Medicine:Allergic rhinitis|hay fever]], [[Medicine:Food allergy|food allergies]], [[Medicine:Atopic dermatitis|atopic dermatitis]], allergic asthma, and [[Medicine:Anaphylaxis|anaphylaxis]].<ref name=NIH2015Types>{{cite web|title=Types of Allergic Diseases |url=https://www.niaid.nih.gov/topics/allergicdiseases/Pages/allergic-diseases-types.aspx |website=NIAID |access-date=17 June 2015 |date=29 May 2015 |archive-url=https://web.archive.org/web/20150617123632/http://www.niaid.nih.gov/topics/allergicdiseases/Pages/allergic-diseases-types.aspx |archive-date=17 June 2015 }}</ref> Symptoms may include red eyes, an itchy rash, [[Biology:Sneeze|sneezing]], coughing, a runny nose, shortness of breath, or swelling.<ref name=NIH2015Sym>{{cite web|title=Environmental Allergies: Symptoms |url=https://www.niaid.nih.gov/topics/environmental-allergies/Pages/symptoms.aspx |website=NIAID |access-date=19 June 2015 |date=22 April 2015 |archive-url=https://web.archive.org/web/20150618023408/http://www.niaid.nih.gov/topics/environmental-allergies/Pages/symptoms.aspx |archive-date=18 June 2015 }}</ref> Note that food intolerances and food poisoning are separate conditions.<ref name=NIH2012pdf/><ref name=Bah2012>{{cite journal | vauthors = Bahna SL | title = Cow's milk allergy versus cow milk intolerance | journal = Annals of Allergy, Asthma & Immunology | volume = 89 | issue = 6 Suppl 1 | pages = 56–60 | date = December 2002 | pmid = 12487206 | doi = 10.1016/S1081-1206(10)62124-2 }}</ref>

<!-- Causes and diagnosis-->
Common [[Biology:Allergen|allergen]]s include [[Biology:Pollen|pollen]] and certain foods.<ref name=Con2007/> Metals and other substances may also cause such problems.<ref name=Con2007/> Food, insect stings, and medications are common causes of severe reactions.<ref name=Kay2000/> Their development is due to both genetic and environmental factors.<ref name=Kay2000>{{cite journal | vauthors = Kay AB | title = Overview of 'allergy and allergic diseases: with a view to the future' | journal = British Medical Bulletin | volume = 56 | issue = 4 | pages = 843–64 | year = 2000 | pmid = 11359624 | doi = 10.1258/0007142001903481 | doi-access = free }}</ref> The underlying mechanism involves immunoglobulin E antibodies (IgE), part of the body's immune system, binding to an allergen and then to a receptor on [[Biology:Mast cell|mast cell]]s or [[Biology:Basophil|basophil]]s where it triggers the release of inflammatory chemicals such as [[Chemistry:Histamine|histamine]].<ref>{{cite web|title=How Does an Allergic Response Work? |url=https://www.niaid.nih.gov/topics/allergicdiseases/Pages/allergic-Response.aspx |website=NIAID |access-date=20 June 2015 |date=21 April 2015 |archive-url=https://web.archive.org/web/20150618023413/http://www.niaid.nih.gov/topics/allergicdiseases/Pages/allergic-Response.aspx |archive-date=18 June 2015 }}</ref> Diagnosis is typically based on a person's [[Medicine:Medical history|medical history]].<ref name=NIH2012pdf/> Further testing of the skin or blood may be useful in certain cases.<ref name=NIH2012pdf/> Positive tests, however, may not necessarily mean there is a significant allergy to the substance in question.<ref name=Cox2008>{{cite journal | vauthors = Cox L, Williams B, Sicherer S, Oppenheimer J, Sher L, Hamilton R, Golden D | title = Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force | journal = Annals of Allergy, Asthma & Immunology | volume = 101 | issue = 6 | pages = 580–92 | date = December 2008 | pmid = 19119701 | doi = 10.1016/S1081-1206(10)60220-7 }}</ref>

<!-- Prevention and treatment -->
Early exposure of children to potential allergens may be protective.<ref name=Sic2014>{{cite journal | vauthors = Sicherer SH, Sampson HA | title = Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment | journal = The Journal of Allergy and Clinical Immunology | volume = 133 | issue = 2 | pages = 291–307; quiz 308 | date = February 2014 | pmid = 24388012 | doi = 10.1016/j.jaci.2013.11.020 }}</ref> Treatments for allergies include avoidance of known allergens and the use of medications such as [[Biology:Corticosteroid|steroids]] and antihistamines.<ref name=NIH2015Imm/> In severe reactions, injectable [[Biology:Adrenaline|adrenaline]] (epinephrine) is recommended.<ref name=Review09/> Allergen immunotherapy, which gradually exposes people to larger and larger amounts of allergen, is useful for some types of allergies such as hay fever and reactions to insect bites.<ref name=NIH2015Imm/> Its use in food allergies is unclear.<ref name=NIH2015Imm>{{cite web|title=Allergen Immunotherapy |url=https://www.niaid.nih.gov/topics/allergicdiseases/Pages/allergen-immunotherapy.aspx |access-date=15 June 2015 |date=22 April 2015 |archive-url=https://web.archive.org/web/20150617122922/http://www.niaid.nih.gov/topics/allergicdiseases/Pages/allergen-immunotherapy.aspx |archive-date=17 June 2015 }}</ref>

<!-- Epidemiology and history -->
Allergies are common.<ref name=NIH2015Epi>{{cite web|title=Allergic Diseases |url=https://www.niaid.nih.gov/topics/allergicdiseases/Pages/default.aspx |website=NIAID |access-date=20 June 2015 |date=21 May 2015 |archive-url=https://web.archive.org/web/20150618023404/http://www.niaid.nih.gov/topics/allergicdiseases/pages/default.aspx |archive-date=18 June 2015 }}</ref> In the developed world, about 20% of people are affected by allergic rhinitis,<ref name=NEJM2015>{{cite journal | vauthors = Wheatley LM, Togias A | title = Clinical practice. Allergic rhinitis | journal = The New England Journal of Medicine | volume = 372 | issue = 5 | pages = 456–63 | date = January 2015 | pmid = 25629743 | pmc = 4324099 | doi = 10.1056/NEJMcp1412282 }}</ref> about 6% of people have at least one food allergy,<ref name=NIH2012pdf>{{cite web|author1=National Institute of Allergy and Infectious Diseases |title=Food Allergy An Overview |url=https://www.niaid.nih.gov/topics/foodAllergy/Documents/foodallergy.pdf |date=July 2012 |archive-url=https://web.archive.org/web/20160305145206/http://www.niaid.nih.gov/topics/foodallergy/documents/foodallergy.pdf |archive-date=5 March 2016 }}</ref><ref name="Sic2014"/> and about 20% have or have had atopic dermatitis at some point in time.<ref>{{cite journal | vauthors = Thomsen SF | title = Atopic dermatitis: natural history, diagnosis, and treatment | journal = ISRN Allergy | volume = 2014 | pages = 354250 | date = 2014 | pmid = 25006501 | pmc = 4004110 | doi = 10.1155/2014/354250 | doi-access = free }}</ref> Depending on the country, about 1–18% of people have asthma.<ref name=GINA2015p2>{{cite web|url=http://www.ginasthma.org/local/uploads/files/GINA_Report_2015_Aug11.pdf |title=Global Strategy for Asthma Management and Prevention: Updated 2015 |publisher=Global Initiative for Asthma |year=2015 |page=2 |archive-url=https://web.archive.org/web/20151017163339/http://www.ginasthma.org/local/uploads/files/GINA_Report_2015_Aug11.pdf |archive-date=2015-10-17}}</ref><ref name=GINA2011p2>{{cite web |url=http://www.ginasthma.org/uploads/users/files/GINA_Report2011_May4.pdf |title=Global Strategy for Asthma Management and Prevention |publisher=Global Initiative for Asthma |year=2011|pages=2–5|archive-url=https://web.archive.org/web/20121120205023/http://www.ginasthma.org/uploads/users/files/GINA_Report2011_May4.pdf |archive-date=2012-11-20}}</ref> Anaphylaxis occurs in between 0.05–2% of people.<ref>{{cite book|author1=Leslie C. Grammer|title=Patterson's Allergic Diseases|date=2012|publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-4863-3|edition=7|url=https://books.google.com/books?id=MWdT7W4_N8sC&pg=PA199}}</ref> Rates of many allergic diseases appear to be increasing.<ref name=Review09>{{cite journal | vauthors = Simons FE | title = Anaphylaxis: Recent advances in assessment and treatment | journal = The Journal of Allergy and Clinical Immunology | volume = 124 | issue = 4 | pages = 625–36; quiz 637–38 | date = October 2009 | pmid = 19815109 | doi = 10.1016/j.jaci.2009.08.025 | url = https://secure.muhealth.org/~ed/students/articles/JAClinImmun_124_p0625.pdf | archive-url = https://web.archive.org/web/20130627084618/https://secure.muhealth.org/~ed/students/articles/JAClinImmun_124_p0625.pdf | archive-date = 27 June 2013 }}</ref><ref>{{cite journal | vauthors = Anandan C, Nurmatov U, van Schayck OC, Sheikh A | title = Is the prevalence of asthma declining? Systematic review of epidemiological studies | journal = Allergy | volume = 65 | issue = 2 | pages = 152–67 | date = February 2010 | pmid = 19912154 | doi = 10.1111/j.1398-9995.2009.02244.x | s2cid = 19525219 | doi-access = free }}</ref><ref>{{Cite web|url=https://www.aaaai.org/conditions-and-treatments/library/allergy-library/prevalence-of-allergies-and-asthma|title=Increasing Rates of Allergies and Asthma| vauthors = Pongdee T |website=American Academy of Allergy, Asthma & Immunology}}</ref> The word "allergy" was first used by Clemens von Pirquet in 1906.<ref name="Kay2000" />

==Signs and symptoms==

{| class = "wikitable" style = "width:50%; float:right; font-size:90%; margin-left:15px"
! Affected organ || Common signs and symptoms
|-
| Nose || Swelling of the nasal [[Biology:Mucous membrane|mucosa]] ([[Medicine:Rhinitis#Allergic|allergic rhinitis]]) runny nose, sneezing
|-
| Sinuses || Allergic [[Medicine:Sinusitis|sinusitis]]
|-
| [[Biology:Human eye|Eyes]] || Redness and itching of the [[Medicine:Conjunctiva|conjunctiva]] (allergic conjunctivitis, watery)
|-
| Airways || Sneezing, coughing, [[Medicine:Bronchoconstriction|bronchoconstriction]], wheezing and dyspnea, sometimes outright attacks of [[Medicine:Asthma|asthma]], in severe cases the airway constricts due to swelling known as laryngeal edema
|-
| Ears || Feeling of fullness, possibly pain, and impaired hearing due to the lack of [[Medicine:Eustachian tube|eustachian tube]] drainage.
|-
| Skin || Rashes, such as eczema and hives (urticaria)
|-
| Gastrointestinal tract || [[Medicine:Abdominal pain|Abdominal pain]], [[Medicine:Bloating|bloating]], vomiting, [[Medicine:Diarrhea|diarrhea]]
|}

Many allergens such as dust or pollen are airborne particles. In these cases, symptoms arise in areas in contact with air, such as the eyes, nose, and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, itching, and redness of the eyes.<ref name="Conn's Current Therapy 2005"/> Inhaled allergens can also lead to increased production of [[Biology:Mucus|mucus]] in the [[Medicine:Lung|lung]]s, shortness of breath, coughing, and wheezing.<ref name="holgate98"/>

Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications like [[Chemistry:Aspirin|aspirin]] and [[Chemistry:Antibiotic|antibiotic]]s such as [[Chemistry:Penicillin|penicillin]]. Symptoms of food allergy include abdominal pain, [[Medicine:Bloating|bloating]], vomiting, [[Medicine:Diarrhea|diarrhea]], itchy skin, and [[Medicine:Angioedema|hives]]. Food allergies rarely cause [[Medicine:Respiratory tract|respiratory]] (asthmatic) reactions, or [[Medicine:Rhinitis|rhinitis]].<ref name="rusznak98"/> Insect stings, food, [[Chemistry:Antibiotic|antibiotic]]s, and certain medicines may produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including the digestive system, the respiratory system, and the [[Biology:Circulatory system|circulatory system]].<ref name="Insect sting anaphylaxis"/><ref name="Penicillin allergy skin testing: what do we do now?"/><ref name="tang03"/> Depending on the severity, anaphylaxis can include skin reactions, bronchoconstriction, [[Medicine:Edema|swelling]], [[Medicine:Hypotension|low blood pressure]], coma, and death. This type of reaction can be triggered suddenly, or the onset can be delayed. The nature of anaphylaxis is such that the reaction can seem to be subsiding but may recur throughout a period of time.<ref name=tang03/>

===Skin===
Substances that come into contact with the skin, such as [[Chemistry:Latex|latex]], are also common causes of allergic reactions, known as contact dermatitis or eczema.<ref name="Natural rubber latex allergy: a problem of interdisciplinary concern in medicine"/> Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a "weal and flare" reaction characteristic of hives and [[Medicine:Angioedema|angioedema]].<ref name="Urticaria and angioedema: a practical approach"/>

With insect stings, a large local reaction may occur in the form of an area of skin redness greater than 10&nbsp;cm in size that can last one to two days.<ref name=Lud2015>{{cite journal | vauthors = Ludman SW, Boyle RJ | title = Stinging insect allergy: current perspectives on venom immunotherapy | journal = Journal of Asthma and Allergy | volume = 8 | pages = 75–86 | date = 2015 | pmid = 26229493 | pmc = 4517515 | doi = 10.2147/JAA.S62288 | doi-access = free }}</ref> This reaction may also occur after [[Medicine:Immunotherapy|immunotherapy]].<ref>{{cite book| veditors = Slavin RG, Reisman RE |title=Expert guide to allergy and immunology|date=1999|publisher=American College of Physicians|location=Philadelphia|isbn=978-0-943126-73-9|page=222|url=https://books.google.com/books?id=QhNRrAeXdbAC&pg=PA222}}</ref>

==Cause==
Risk factors for allergies can be placed in two broad categories, namely [[Biology:Host|host]] and [[Earth:Natural environment|environmental]] factors.<ref name="The genetic and environmental basis of atopic diseases"/> Host factors include [[Biology:Heredity|heredity]], sex, race, and age, with heredity being by far the most significant. However, there has been a recent increase in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to [[Medicine:Infectious disease|infectious disease]]s during early childhood, environmental pollution, allergen levels, and dietary changes.<ref name="Janeway"/>

===Dust mites===

[[Biology:House dust mite|Dust mite]] allergy, also known as house dust allergy, is a [[Biology:Sensitization (immunology)|sensitization]] and allergic reaction to the droppings of [[Biology:House dust mite|house dust mite]]s. The allergy is common<ref>{{Cite news| vauthors = Alderman L |date=4 March 2011|title=Who Should Worry About Dust Mites (and Who Shouldn't)|language=en-US|work=The New York Times|url=https://www.nytimes.com/2011/03/05/health/05patient.html|access-date=23 July 2020|issn=0362-4331}}</ref><ref>{{Cite journal|title=Dust Mite Allergy|url=https://www.thh.nhs.uk/documents/_Patients/PatientLeaflets/paediatrics/allergies/PI018-Dust_Mite_Allergy_A4_May13.pdf|journal=NHS|access-date=27 July 2021|archive-date=26 April 2020|archive-url=https://web.archive.org/web/20200426125759/https://www.thh.nhs.uk/documents/_Patients/PatientLeaflets/paediatrics/allergies/PI018-Dust_Mite_Allergy_A4_May13.pdf|url-status=dead}}</ref> and can trigger allergic reactions such as asthma, [[Medicine:Dermatitis|eczema]], or itching. It is the manifestation of [[Medicine:Parasitic disease|parasitosis]]. The mite's gut contains potent digestive enzymes (notably [[Biology:Peptidase 1 (mite)|peptidase 1]]) that persist in their feces and are major inducers of allergic reactions such as wheezing. The mite's exoskeleton can also contribute to allergic reactions. Unlike [[Medicine:Scabies|scabies]] mites or skin follicle mites, house dust mites do not burrow under the skin and are not parasitic.<ref name="unl">{{cite web| vauthors = Ogg B |title=Managing House Dust Mites|url=https://lancaster.unl.edu/pest/resources/311dusmi.pdf|access-date=24 January 2019|publisher=Extension, Institute of Agriculture and Natural Resources, University of Nebraska–Lincoln}}</ref>

===Foods===
{{main|Medicine: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 [[Biology:Crustacea|shellfish]].<ref name="aafa.org">{{cite web |url= http://www.aafa.org/display.cfm?id=9&sub=20&cont=286 |title= Asthma and Allergy Foundation of America |access-date= 23 December 2012 |archive-url= https://web.archive.org/web/20121006052320/http://aafa.org/display.cfm?id=9&sub=20&cont=286 |archive-date= 6 October 2012 |df= dmy-all }}</ref> Other [[Medicine:Food allergy|food allergies]], affecting less than 1 person per 10,000 population, may be considered "rare".<ref name=Maleki/> The use of hydrolyzed milk baby formula versus standard milk baby formula does not appear to affect the risk.<ref>{{cite journal | vauthors = Boyle RJ, Ierodiakonou D, Khan T, Chivinge J, Robinson Z, Geoghegan N, Jarrold K, Afxentiou T, Reeves T, Cunha S, Trivella M, Garcia-Larsen V, Leonardi-Bee J | title = Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis | journal = BMJ | volume = 352 | pages = i974 | date = March 2016 | pmid = 26956579 | doi = 10.1136/bmj.i974 | pmc=4783517}}</ref>

The most common food allergy in the US population is a sensitivity to [[Biology:Crustacea|crustacea]].<ref name=Maleki>{{cite book | vauthors = Maleki SJ, Burks AW, Helm RM |title=Food Allergy |year=2006 |publisher=Blackwell Publishing |pages=39–41 |isbn=978-1-55581-375-8}}</ref> Although [[Biology:Peanut|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.<ref name="aafa.org"/>

Rates of allergies differ between adults and children. Children can sometimes outgrow peanut allergies. Egg allergies affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5.<ref>{{cite journal | vauthors = Järvinen KM, Beyer K, Vila L, Bardina L, Mishoe M, Sampson HA | title = Specificity of IgE antibodies to sequential epitopes of hen's egg ovomucoid as a marker for persistence of egg allergy | journal = Allergy | volume = 62 | issue = 7 | pages = 758–65 | date = July 2007 | pmid = 17573723 | doi = 10.1111/j.1398-9995.2007.01332.x | s2cid = 23540584 }}</ref> The sensitivity is usually to proteins in the white, rather than the yolk.<ref name="Sicherer 63"/>

Milk-protein allergies are most common in children.<ref>{{harvnb|Maleki|Burks|Helm|2006|pp=41}}</ref> Approximately 60% of milk-protein reactions are [[Biology:Immunoglobulin E|immunoglobulin E]]-mediated, with the remaining usually attributable to inflammation of the colon.<ref>{{cite web |url=http://www.worldallergy.org/professional/allergic_diseases_center/foodallergy/ |title=World Allergy Organization |access-date=13 April 2015 |url-status=live |archive-url=https://web.archive.org/web/20150414054458/http://www.worldallergy.org/professional/allergic_diseases_center/foodallergy/ |archive-date=14 April 2015 }}</ref> Some people are unable to tolerate milk from goats or sheep as well as from cows, and many are also unable to tolerate dairy products such as cheese. Roughly 10% of children with a milk allergy will have a reaction to beef. Beef contains small amounts of proteins that are present in greater abundance in cow's milk.<ref>Sicherer 64</ref> [[Medicine:Lactose intolerance|Lactose intolerance]], a common reaction to milk, is not a form of allergy at all, but due to the absence of an [[Biology:Enzyme|enzyme]] in the digestive tract.{{citation needed|date=July 2022}}

Those with [[Biology:Nut (fruit)|tree nut]] allergies may be allergic to one or to many tree nuts, including [[Biology:Pecan|pecan]]s, pistachios, [[Biology:Pine nut|pine nut]]s, and [[Biology:Walnut|walnut]]s.<ref name="Sicherer 63"/> In addition, seeds, including sesame seeds and poppy seeds, contain oils in which protein is present, which may elicit an allergic reaction.<ref name="Sicherer 63"/>

Allergens can be transferred from one food to another through [[Biology:Genetic engineering|genetic engineering]]; however genetic modification can also remove allergens. Little research has been done on the natural variation of allergen concentrations in unmodified crops.<ref>{{cite journal | vauthors = Herman EM | title = Genetically modified soybeans and food allergies | journal = Journal of Experimental Botany | volume = 54 | issue = 386 | pages = 1317–19 | date = May 2003 | pmid = 12709477 | doi = 10.1093/jxb/erg164 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Panda R, Ariyarathna H, Amnuaycheewa P, Tetteh A, Pramod SN, Taylor SL, Ballmer-Weber BK, Goodman RE | title = Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety | journal = Allergy | volume = 68 | issue = 2 | pages = 142–51 | date = February 2013 | pmid = 23205714 | doi = 10.1111/all.12076 | s2cid = 13814194 | url = https://digitalcommons.unl.edu/foodsciefacpub/165 | doi-access = free }}</ref>

===Latex===
[[Chemistry:Latex|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, 1 in 800 surgical patients (0.125 percent) reported 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.<ref name="Sussman"/>

The most prevalent response to latex is an allergic contact dermatitis, a delayed hypersensitive reaction appearing as dry, crusted lesions. This reaction usually lasts 48–96 hours. Sweating or rubbing the area under the glove aggravates the lesions, possibly leading to ulcerations.<ref name=Sussman/> Anaphylactic reactions occur most often in sensitive patients who have been exposed to a surgeon's latex gloves during abdominal surgery, but other [[Biology:Mucous membrane|mucosal]] exposures, such as dental procedures, can also produce systemic reactions.<ref name=Sussman/>

Latex and banana sensitivity may cross-react.  Furthermore, those with latex allergy may also have sensitivities to [[Biology:Avocado|avocado]], kiwifruit, and chestnut.<ref>{{cite journal | vauthors = Fernández de Corres L, Moneo I, Muñoz D, Bernaola G, Fernández E, Audicana M, Urrutia I | title = Sensitization from chestnuts and bananas in patients with urticaria and anaphylaxis from contact with latex | journal = Annals of Allergy | volume = 70 | issue = 1 | pages = 35–39 | date = January 1993 | pmid = 7678724 }}</ref> These people 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, [[Biology:Avocado|avocado]], [[Biology:Kiwifruit|kiwifruit]], and [[Biology:Chestnut|chestnut]] occurs because latex proteins are structurally [[Biology:Homology|homologous]] with some other plant proteins.<ref name=Sussman/>

===Medications===
{{main|Medicine:Drug allergy}}
About 10% of people report that they are allergic to [[Chemistry:Penicillin|penicillin]]; however, of that 10%, 90% turn out not to be.<ref name=Al2015/> Serious allergies only occur in about 0.03%.<ref name=Al2015>{{cite journal | vauthors = Gonzalez-Estrada A, Radojicic C | title = Penicillin allergy: A practical guide for clinicians | journal = Cleveland Clinic Journal of Medicine | volume = 82 | issue = 5 | pages = 295–300 | date = May 2015 | pmid = 25973877 | doi = 10.3949/ccjm.82a.14111 | s2cid = 6717270 | doi-access = free }}</ref>

===Insect stings===
Typically, insects which generate allergic responses are either stinging insects (wasps, bees, hornets and ants) or biting insects (mosquitoes, ticks). Stinging insects inject venom into their victims, whilst biting insects normally introduce anti-coagulants.{{citation needed|date=July 2022}}

===Toxins interacting with proteins===
Another non-food protein reaction, urushiol-induced contact dermatitis, originates after contact with [[Biology:Poison ivy|poison ivy]], [[Biology:Toxicodendron pubescens|eastern poison oak]], [[Biology:Toxicodendron diversilobum|western poison oak]], or poison sumac. [[Chemistry:Urushiol|Urushiol]], which is not itself a protein, acts as a [[Biology:Hapten|hapten]] and chemically reacts with, binds to, and changes the shape of [[Biology:Integral membrane protein|integral membrane protein]]s on exposed skin cells. The immune system does not recognize the affected cells as normal parts of the body, causing a T-cell<nowiki>-</nowiki>mediated [[Biology:Immune response|immune response]].<ref>{{cite web | vauthors = Hogan CM | url = http://globaltwitcher.auderis.se/artspec_information.asp?thingid=82914 | title = Western poison-oak: Toxicodendron diversilobum | archive-url = https://web.archive.org/web/20090721044257/http://globaltwitcher.auderis.se/artspec_information.asp?thingid=82914 | archive-date = 21 July 2009 | work = GlobalTwitcher | veditors = Stromberg N | date = 2008 | access-date = 30 April 2010 }}</ref> Of these poisonous plants, sumac is the most virulent.<ref>{{cite book | vauthors = Keeler HL | date = 1900 | title = Our Native Trees and How to Identify Them | location = New York | publisher = Charles Scribner's Sons | pages = 94–96 }}</ref><ref>{{cite book | vauthors = Frankel E | title = Poison Ivy, Poison Oak, Poison Sumac and Their Relatives; Pistachios, Mangoes and Cashews | publisher = The Boxwood Press | location = Pacific Grove, CA | date = 1991 | isbn = 978-0-940168-18-3}}</ref> The resulting dermatological response to the reaction between urushiol and membrane proteins includes redness, swelling, papules, vesicles, [[Medicine:Blister|blister]]s, and streaking.<ref name="Dermatlas" >{{DermAtlas|-1892628434}}</ref>

Estimates vary on the population fraction that will have an immune system response. Approximately 25% of the population will have a strong allergic response to urushiol. In general, approximately 80–90% of adults will develop a rash if they are exposed to {{cvt|0.0050|mg}} of purified urushiol, but some people are so sensitive that it takes only a molecular trace on the skin to initiate an allergic reaction.<ref>{{cite journal |author1=Armstrong W.P. |author2=Epstein W.L. |title=Poison oak: more than just scratching the surface |journal=Herbalgram |volume=34 |pages=36–42 |year=1995 }} cited in {{cite web |url=http://waynesword.palomar.edu/ww0802.htm |title=Poison Oak |access-date=6 October 2015 |url-status=live |archive-url=https://web.archive.org/web/20151006212234/http://waynesword.palomar.edu/ww0802.htm |archive-date=6 October 2015 }}</ref>

===Genetics===
Allergic diseases are strongly [[Social:Family|familial]]: [[Biology:Twin#Monozygotic twins|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 [[Biology:Twin#Dizygotic twins|non-identical twins]].<ref name="Allergy"/> Allergic parents are more likely to have allergic children,<ref name="DeSwert"/> 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 [[Social:Genealogy|genealogies]]; parents who are allergic to peanuts may have children who are allergic to [[Biology:Ragweed|ragweed]]. The likelihood of developing allergies is [[Biology:Heredity|inherited]] and related to an irregularity in the immune system, but the specific [[Biology:Allergen|allergen]] is not.<ref name=DeSwert/>

The risk of allergic [[Biology:Sensitization (immunology)|sensitization]] and the development of allergies varies with age, with young children most at risk.<ref name="Croner"/> Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years.<ref name=Croner/> The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.<ref>{{cite book |vauthors=Jarvis D, Burney P |chapter=Epidemiology of atopy and atopic disease | veditors = Kay AB |title=Allergy and allergic diseases |publisher=Blackwell Science |location=London |year=1997 |pages=1208–24 |volume=2 }}</ref>

[[Social:Ethnic group|Ethnicity]] may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to [[Biology:Human migration|migration]].<ref name=DeSwert/> It has been suggested that different [[Biology:Locus (genetics)|genetic loci]] are responsible for asthma, to be specific, in people of [[Biology:Caucasian race|European]], Hispanic, [[Biography:Asian people|Asian]], and African origins.<ref name="African Americans with asthma: genetic insights"/>

===Hygiene hypothesis===
{{Main|Unsolved:Hygiene hypothesis}}
Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a [[Biology:T helper cell|TH2]]-mediated immune response. Many bacteria and viruses elicit a [[Biology:T helper cell|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.<ref>{{cite journal | vauthors = Folkerts G, Walzl G, Openshaw PJ | title = Do common childhood infections 'teach' the immune system not to be allergic? | journal = Immunology Today | volume = 21 | issue = 3 | pages = 118–20 | date = March 2000 | pmid = 10777250 | doi = 10.1016/S0167-5699(00)01582-6 }}</ref> 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.<ref>{{cite web |url=http://edwardwillett.com/2000/05/the-hygiene-hypothesis/ |title=The Hygiene Hypothesis |publisher=Edward Willett |date=30 January 2013 |access-date=30 May 2013 |url-status=live |archive-url=https://web.archive.org/web/20130430180522/http://edwardwillett.com/2000/05/the-hygiene-hypothesis/ |archive-date=30 April 2013 }}</ref>

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 [[Biology:Immunology|immunologists]] and [[Social:Epidemiology|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.{{citation needed|date=July 2022}}

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.<ref name="pmid12910582"/> Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner.<ref name="pmid17326711"/> The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.<ref name="Does antibiotic exposure during infancy lead to development of asthma?: a systematic review and metaanalysis"/> The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by [[Medicine:Caesarean section|Caesarean section]] rather than vaginal birth.<ref name="A meta-analysis of the association between Caesarean section and childhood asthma"/><ref name="The use of household cleaning sprays and adult asthma: an international longitudinal study"/>

===Stress===
Chronic stress can aggravate allergic conditions. This has been attributed to a T helper 2 (TH2)-predominant response driven by suppression of interleukin 12 by both the autonomic nervous system and the [[Medicine:Hypothalamic–pituitary–adrenal axis|hypothalamic–pituitary–adrenal axis]]. Stress management in highly susceptible individuals may improve symptoms.<ref>{{cite journal | vauthors = Dave ND, Xiang L, Rehm KE, Marshall GD | title = Stress and allergic diseases | journal = Immunology and Allergy Clinics of North America | volume = 31 | issue = 1 | pages = 55–68 | date = February 2011 | pmid = 21094923 | pmc = 3264048 | doi = 10.1016/j.iac.2010.09.009 }}</ref>

===Other environmental factors===
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.<ref name=cooper04>{{cite journal | vauthors = Cooper PJ | title = Intestinal worms and human allergy | journal = Parasite Immunology | volume = 26 | issue = 11–12 | pages = 455–67 | year = 2004 | pmid = 15771681 | doi = 10.1111/j.0141-9838.2004.00728.x | s2cid = 23348293 }}</ref> Historically, the trees planted in urban areas were predominantly male to prevent litter from seeds and fruits, but the high ratio of male trees causes high pollen counts, a phenomenon that horticulturist Tom Ogren has called "botanical sexism".<ref>{{cite web | vauthors = Ogren TL |title=Botanical Sexism Cultivates Home-Grown Allergies |url=https://blogs.scientificamerican.com/guest-blog/botanical-sexism-cultivates-home-grown-allergies/ |website=Scientific American |date=29 April 2015 |access-date=18 January 2020}}</ref>

Alterations in exposure to [[Biology:Microorganism|microorganism]]s is another plausible explanation, at present, for the increase in atopic allergy.<ref name= Janeway/> Endotoxin exposure reduces release of inflammatory [[Biology:Cytokine|cytokine]]s such as [[Biology:Tumor necrosis factor alpha|TNF-α]], IFNγ, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood.<ref name="pmid12239255"/> Certain microbe-sensing [[Biology:Protein|protein]]s, known as [[Biology:Toll-like receptor|Toll-like receptor]]s, found on the surface of cells in the body are also thought to be involved in these processes.<ref name="Epidemiological and immunological evidence for the hygiene hypothesis"/>

[[Biology:Parasitic worm|Parasitic worms]] and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine [[Chemistry:Water chlorination|chlorination]] and purification of drinking water supplies.<ref name="Parasitic food-borne and water-borne zoonoses"/> Recent research has shown that some common parasites, such as intestinal worms (e.g., [[Biology:Hookworm|hookworm]]s), secrete chemicals into the gut wall (and, hence, the bloodstream) that [[Chemistry:Immunosuppressant|suppress]] the immune system and prevent the body from attacking the parasite.<ref name="Worms and allergy"/> This gives rise to a new slant on the hygiene hypothesis theory—that co-evolution of humans 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.<ref name=Yazdanbakhsh02>{{cite journal | vauthors = Yazdanbakhsh M, Kremsner PG, van Ree R | title = Allergy, parasites, and the hygiene hypothesis | journal = Science | volume = 296 | issue = 5567 | pages = 490–94 | date = April 2002 | pmid = 11964470 | doi = 10.1126/science.296.5567.490 | bibcode = 2002Sci...296..490Y | citeseerx = 10.1.1.570.9502 }}</ref> In particular, research suggests that allergies may coincide with the delayed establishment of [[Biology:Gut flora|gut flora]] in infants.<ref name="pmid17382394"/> 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.<ref name=cooper04/> Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies.<ref name=falcone05>{{cite journal | vauthors = Falcone FH, Pritchard DI | title = Parasite role reversal: worms on trial | journal = Trends in Parasitology | volume = 21 | issue = 4 | pages = 157–60 | date = April 2005 | pmid = 15780835 | doi = 10.1016/j.pt.2005.02.002 }}</ref> It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected [[Biology:Mutualism|symbiosis]] is at work.<ref name=falcone05/> For more information on this topic, see [[Biology:Helminthic therapy|Helminthic therapy]].

==Pathophysiology==
[[File:The Allergy Pathway.jpg|thumb|A summary diagram that explains how allergy develops]]
[[File:Tissues Affected In Allergic Inflammation.jpg|thumb|Tissues affected in allergic inflammation]]

===Acute response===
[[File:Allergy degranulation processes 01.svg|thumb|Degranulation process in allergy. Second exposure to allergen. '''1''' – antigen; '''2''' – IgE antibody; '''3''' – FcεRI receptor; '''4''' – preformed mediators (histamine, proteases, chemokines, heparin); '''5''' – granules; '''6''' – mast cell; '''7''' – newly formed mediators (prostaglandins, leukotrienes, thromboxanes, PAF).]]
In the initial 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 [[Biology:T helper cell|T<sub>H</sub>2 lymphocyte]], a subset of [[Biology:T cell|T cell]]s that produce a [[Biology:Cytokine|cytokine]] called interleukin-4 (IL-4). These T<sub>H</sub>2 cells interact with other lymphocytes called [[Biology:B cell|B cell]]s, 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 [[Biology:Fc receptor|Fc receptor]] called FcεRI) on the surface of other kinds of immune cells called [[Biology:Mast cell|mast cell]]s and [[Biology:Basophil|basophil]]s, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage, are sensitized to the allergen.<ref name=Janeway/>

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 [[Biology:Degranulation|degranulation]], during which they release [[Chemistry:Histamine|histamine]] and other inflammatory chemical mediators ([[Biology:Cytokine|cytokine]]s, [[Biology:Interleukin|interleukin]]s, [[Biology:Leukotriene|leukotriene]]s, and prostaglandins) from their [[Biology:Granule (cell biology)|granules]] into the surrounding tissue causing several systemic effects, such as [[Medicine:Vasodilation|vasodilation]], [[Biology:Mucus|mucous]] secretion, [[Biology:Nerve|nerve]] stimulation, and [[Biology:Smooth muscle|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 specific body systems. Asthma is localized to the respiratory system and eczema is localized to the [[Biology:Dermis|dermis]].<ref name=Janeway/>

===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 [[Biology:Neutrophil|neutrophil]]s, [[Biology:Lymphocyte|lymphocyte]]s, [[Biology:Eosinophil|eosinophil]]s, and [[Biology:Macrophage|macrophage]]s to the initial site. The reaction is usually seen 2–24 hours after the original reaction.<ref name="Effector and potential immunoregulatory roles of mast cells in IgE-associated acquired immune responses"/> Cytokines from mast cells may 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 T<sub>H</sub>2 cells.<ref name="Th2 cytokines in the asthma late-phase response"/>

===Allergic contact dermatitis===
Although allergic contact dermatitis is termed an "allergic" reaction (which usually refers to type I hypersensitivity), its pathophysiology involves a reaction that more correctly corresponds to a type IV hypersensitivity reaction.<ref>{{cite journal | vauthors = Martín A, Gallino N, Gagliardi J, Ortiz S, Lascano AR, Diller A, Daraio MC, Kahn A, Mariani AL, Serra HM | title = Early inflammatory markers in elicitation of allergic contact dermatitis | journal = BMC Dermatology | volume = 2 | pages = 9 | date = August 2002 | pmid = 12167174 | pmc = 122084 | doi = 10.1186/1471-5945-2-9 | doi-access = free }}</ref> In type IV hypersensitivity, there is activation of certain types of T cells (CD8+) that destroy target cells on contact, as well as activated [[Biology:Macrophage|macrophage]]s that produce hydrolytic [[Biology:Enzyme|enzyme]]s.{{citation needed|date=July 2022}}

==Diagnosis==
[[File:Allergy testing machine.jpg|left|thumb|An allergy testing machine being operated in a diagnostic immunology lab]]
Effective management of allergic diseases relies on the ability to make an accurate diagnosis.<ref>{{cite journal |author=Portnoy JM |year=2006 |title=Evidence-based Allergy Diagnostic Tests |journal=Current Allergy and Asthma Reports |volume=6 |issue=6|pages=455–61 |doi=10.1007/s11882-006-0021-8|pmid=17026871 |s2cid=33406344 |display-authors=0}}</ref> Allergy testing can help confirm or rule out allergies.<ref name="ReferenceA">NICE Diagnosis and assessment of food allergy in children and young people in primary care and community settings, 2011</ref><ref name="ReferenceB">{{cite journal | vauthors = Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Camargo CA, Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, Levy BD, Lieberman P, Luccioli S, McCall KM, Schneider LC, Simon RA, Simons FE, Teach SJ, Yawn BP, Schwaninger JM | display-authors = 6 | title = Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel | journal = The Journal of Allergy and Clinical Immunology | volume = 126 | issue = 6 Suppl | pages = S1–58 | date = December 2010 | pmid = 21134576 | pmc = 4241964 | doi = 10.1016/j.jaci.2010.10.007 }}</ref> Correct diagnosis, counseling, and avoidance advice based on valid allergy test results reduce the incidence of symptoms and need for medications, and improve quality of life.<ref name="ReferenceA"/> To assess the presence of allergen-specific IgE antibodies, two different methods can be used: a skin prick test, or an allergy [[Medicine:Blood test|blood test]]. Both methods are recommended, and they have similar diagnostic value.<ref name="ReferenceB"/><ref>{{cite journal | vauthors=Cox L | year=2011 | title=Overview of Serological-Specific IgE Antibody Testing in Children | journal=Pediatric Allergy and Immunology | volume=11 | issue=6 | pages=447–53 | doi=10.1007/s11882-011-0226-3 | pmid=21947715 | s2cid=207323701 }}</ref>

Skin prick tests and blood tests are equally cost-effective, and health economic evidence shows that both tests were cost-effective compared with no test.<ref name="ReferenceA"/> Early and more accurate diagnoses save cost due to reduced consultations, referrals to secondary care, misdiagnosis, and emergency admissions.<ref>{{cite web|title = CG116 Food allergy in children and young people: costing report|date =  23 February 2011 |url=http://guidance.nice.org.uk/CG116/CostingReport/pdf/English |archive-url=https://web.archive.org/web/20120117230445/http://guidance.nice.org.uk/CG116/CostingReport/pdf/English |archive-date=17 January 2012 |website = National Institute for Health and Clinical Excellence}}</ref>

Allergy undergoes dynamic changes over time. Regular allergy testing of relevant allergens provides information on if and how patient management can be changed to improve health and quality of life. Annual testing is often the practice for determining whether allergy to milk, egg, soy, and wheat have been outgrown, and the testing interval is extended to 2–3 years for allergy to peanut, tree nuts, fish, and crustacean shellfish.<ref name="ReferenceB"/> Results of follow-up testing can guide decision-making regarding whether and when it is safe to introduce or re-introduce allergenic food into the diet.<ref name="United States 2010">{{cite web|publisher = NIH|title = Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report|date = 2010|id = 11-7700|url = https://www.foodallergy.org/sites/default/files/migrated-files/file/niaid-clinician-summary.pdf|access-date = 1 April 2019|archive-date = 1 April 2019|archive-url = https://web.archive.org/web/20190401215258/https://www.foodallergy.org/sites/default/files/migrated-files/file/niaid-clinician-summary.pdf}}</ref>

===Skin prick testing===
<!-- Hidden text, as this links back to the same page, restore when main article is created - {{Main|Skin Test|l1=Skin testing}}-->
[[File:Allergy skin testing.JPG|thumb|right|Skin testing on arm]]
[[File:Skintest2.jpg|thumb|right|Skin testing on back]]
Skin testing is also known as "puncture testing" and "prick testing" due to the series of tiny punctures or pricks made into the patient's skin. Tiny amounts of suspected allergens and/or their extracts (''e.g.'', pollen, grass, mite proteins, peanut extract) 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). A small plastic or metal device is used to puncture or prick the skin. Sometimes, the allergens are injected "intradermally" into the patient's skin, with a needle and syringe. 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&nbsp;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.<ref name="pmid16164451"/> 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.<ref name="pmid11101180"/>

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 in the last several days.

===Patch testing===
[[File:Epikutanni-test.jpg|thumb|Patch test]]
Patch testing is a method used to determine if a specific substance causes allergic inflammation of the skin. It tests for delayed reactions. It is used to help ascertain the cause of skin contact allergy or contact dermatitis. Adhesive patches, usually treated with several common allergic chemicals or skin sensitizers, are applied to the back. The skin is then examined for possible local reactions at least twice, usually at 48 hours after application of the patch, and again two or three days later.

===Blood testing===
An allergy [[Medicine:Blood test|blood test]] is quick and simple and can be ordered by a licensed health care provider (''e.g.'', an allergy specialist) or general practitioner. 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 get an allergy blood test. For babies and very young children, a single needle stick for allergy blood testing is often gentler than several skin pricks.

An allergy blood test is available through most [[Medicine:Medical laboratory|laboratories]]. 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. [[Chemistry:Quantitative analysis|Quantitative]] IgE test results increase the possibility of ranking how different substances may affect symptoms. A 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 cannot 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 [[Biology:Cross-reactivity|cross-reactivity]].<ref>{{cite journal | vauthors = Yunginger JW, Ahlstedt S, Eggleston PA, Homburger HA, Nelson HS, Ownby DR, Platts-Mills TA, Sampson HA, Sicherer SH, Weinstein AM, Williams PB | display-authors = 6 |title=Quantitative IgE antibody assays in allergic diseases |journal=Journal of Allergy and Clinical Immunology |date=June 2000 |volume=105 |issue=6 |pages=1077–84 |doi=10.1067/mai.2000.107041| pmid = 10856139 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Sampson HA | title = Utility of food-specific IgE concentrations in predicting symptomatic food allergy | journal = The Journal of Allergy and Clinical Immunology | volume = 107 | issue = 5 | pages = 891–96 | date = May 2001 | pmid = 11344358 | doi = 10.1067/mai.2001.114708 }}</ref>

A low total IgE level is not adequate to rule out [[Biology:Sensitization (immunology)|sensitization]] to commonly inhaled allergens.<ref name="pmid12911420"/> [[Statistics|Statistical methods]], such as ROC curves, predictive value calculations, and likelihood ratios have been used to examine the relationship of various testing methods to each other. These methods have shown that patients with a high total IgE have a high probability of allergic sensitization, but further investigation with allergy tests for specific IgE antibodies for a carefully chosen of allergens is often warranted.

Laboratory methods to measure specific IgE antibodies for allergy testing include enzyme-linked immunosorbent assay (ELISA, or EIA),<ref name=webmd>{{cite web|url=http://www.webmd.com/allergies/guide/blood-test|title=Blood Testing for Allergies|access-date=5 June 2016|website=[[Company:WebMD|WebMD]]|url-status=live|archive-url=https://web.archive.org/web/20160604101105/http://www.webmd.com/allergies/guide/blood-test|archive-date=4 June 2016}}</ref> [[Medicine:Radioallergosorbent test|radioallergosorbent test]] (RAST)<ref name=webmd/> and fluorescent enzyme [[Biology:Immunoassay|immunoassay]] (FEIA).<ref name="KhanUeno-Yamanouchi2012">{{cite journal | vauthors = Khan FM, Ueno-Yamanouchi A, Serushago B, Bowen T, Lyon AW, Lu C, Storek J | title = Basophil activation test compared to skin prick test and fluorescence enzyme immunoassay for aeroallergen-specific Immunoglobulin-E | journal = Allergy, Asthma, and Clinical Immunology | volume = 8 | issue = 1 | pages = 1 | date = January 2012 | pmid = 22264407 | doi = 10.1186/1710-1492-8-1 | pmc=3398323 | doi-access = free }}</ref>

===Other testing===
'''Challenge testing:''' Challenge testing is when tiny amounts of a suspected allergen are introduced to the body orally, through inhalation, or via 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.

'''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 diet to totally avoid that allergen for a set time. If the patient experiences significant improvement, he may then be "challenged" by reintroducing the allergen, to see if symptoms are reproduced.

'''Unreliable tests:''' There are other types of allergy testing methods that are unreliable, including [[Unsolved:Applied kinesiology|applied kinesiology]] (allergy testing through muscle relaxation), [[Biology:Cytotoxicity|cytotoxicity]] testing, urine autoinjection, skin [[Chemistry:Titration|titration]] (Rinkel method), and provocative and neutralization (subcutaneous) testing or sublingual provocation.<ref name="Allergy Diagnosis"/>

===Differential diagnosis===
Before a diagnosis of allergic disease can be confirmed, other plausible causes of the presenting symptoms should be considered.<ref>{{EMedicine|med|3390|Allergic and Environmental Asthma}} –
Includes discussion of differentials</ref> Vasomotor rhinitis, for example, is one of many illnesses that share symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis.<ref name="pmid16190503"/> Once a diagnosis of [[Medicine:Asthma|asthma]], rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy.

==Prevention==
{{See|Allergy prevention in children}}
Giving peanut products early may decrease the risk of allergies while only [[Social:Breastfeeding|breastfeeding]] during at least the first few months of life may decrease the risk of [[Medicine:Dermatitis|dermatitis]].<ref name=Gre2019>{{cite journal | vauthors = Greer FR, Sicherer SH, Burks AW | title = The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods | journal = Pediatrics | volume = 143 | issue = 4 | pages = e20190281 | date = April 2019 | pmid = 30886111 | doi = 10.1542/peds.2019-0281 | doi-access = free }}</ref><ref name=Gar2018/> There is no good evidence that a mother's diet during pregnancy or breastfeeding affects the risk of allergies,<ref name=Gre2019/> nor is there evidence that delayed introduction of certain foods is useful.<ref name=Gre2019/> Early exposure to potential allergens may actually be protective.<ref name="Sic2014" />

Fish oil supplementation during pregnancy is associated with a lower risk.<ref name=Gar2018>{{cite journal | vauthors = Garcia-Larsen V, Ierodiakonou D, Jarrold K, Cunha S, Chivinge J, Robinson Z, Geoghegan N, Ruparelia A, Devani P, Trivella M, Leonardi-Bee J, Boyle RJ | title = Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis | journal = PLOS Medicine | volume = 15 | issue = 2 | pages = e1002507 | date = February 2018 | pmid = 29489823 | doi = 10.1371/journal.pmed.1002507 | pmc=5830033 | doi-access = free }}</ref> Probiotic supplements during pregnancy or infancy may help to prevent atopic dermatitis.<ref>{{cite journal | vauthors = Pelucchi C, Chatenoud L, Turati F, Galeone C, Moja L, Bach JF, La Vecchia C | title = Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: a meta-analysis | journal = Epidemiology | volume = 23 | issue = 3 | pages = 402–14 | date = May 2012 | pmid = 22441545 | doi = 10.1097/EDE.0b013e31824d5da2 | s2cid = 40634979 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Osborn DA, Sinn JK | title = Prebiotics in infants for prevention of allergy | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD006474 | date = March 2013 | pmid = 23543544 | doi = 10.1002/14651858.CD006474 | veditors = Osborn D }}</ref>

==Management==
Management of allergies typically involves avoiding the allergy trigger and taking medications to improve the symptoms.<ref name=NIH2015Imm/> Allergen immunotherapy may be useful for some types of allergies.<ref name=NIH2015Imm/>

===Medication===
Several medications may be used to block the action of allergic mediators, or to prevent activation of cells and [[Biology:Degranulation|degranulation]] processes. These include [[Chemistry:Antihistamine|antihistamine]]s, [[Chemistry:Glucocorticoid|glucocorticoid]]s, [[Chemistry:Epinephrine (medication)|epinephrine]] (adrenaline), mast cell stabilizers, and antileukotriene agents are common treatments of allergic diseases.<ref name="MCAS">{{cite journal | vauthors = Frieri M | title = Mast Cell Activation Syndrome | journal = Clinical Reviews in Allergy & Immunology | volume = 54 | issue = 3 | pages = 353–65 | date = June 2018 | pmid = 25944644 | doi = 10.1007/s12016-015-8487-6 | s2cid = 5723622 }}</ref> [[Medicine:Anticholinergic|Anticholinergic]]s, [[Chemistry:Decongestant|decongestant]]s, and other compounds thought to impair [[Biology:Eosinophil|eosinophil]] [[Physics:Chemotaxis|chemotaxis]] are also commonly used. Although rare, the severity of anaphylaxis often requires [[Chemistry:Epinephrine (medication)|epinephrine]] injection, and where medical care is unavailable, a device known as an [[Medicine:Epinephrine autoinjector|epinephrine autoinjector]] may be used.<ref name=tang03/>

===Immunotherapy===
[[File:Anti-Allergy Immunotherapy.jpg|thumb|Anti-allergy immunotherapy]]
Allergen [[Medicine:Immunotherapy|immunotherapy]] is useful for environmental allergies, allergies to insect bites, and asthma.<ref name=NIH2015Imm/><ref name=Abra2010/> Its benefit for food allergies is unclear and thus not recommended.<ref name=NIH2015Imm/> Immunotherapy involves exposing people to larger and larger amounts of allergen in an effort to change the immune system's response.<ref name=NIH2015Imm/>

Meta-analyses have found that injections of allergens under the skin is effective in the treatment in allergic rhinitis in children<ref name="Penagos06">{{cite journal | vauthors = Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G, Canonica GW | title = Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials | journal = Annals of Allergy, Asthma & Immunology | volume = 97 | issue = 2 | pages = 141–48 | date = August 2006 | pmid = 16937742 | doi = 10.1016/S1081-1206(10)60004-X }}</ref><ref>{{cite journal | vauthors = Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S | title = Allergen injection immunotherapy for seasonal allergic rhinitis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD001936 | date = January 2007 | volume = 2007 | pmid = 17253469 | doi = 10.1002/14651858.CD001936.pub2 | pmc = 7017974 }}</ref> and in asthma.<ref name=Abra2010>{{cite journal | vauthors = Abramson MJ, Puy RM, Weiner JM | title = Injection allergen immunotherapy for asthma | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD001186 | date = August 2010 | pmid = 20687065 | doi = 10.1002/14651858.CD001186.pub2 }}</ref> The benefits may last for years after treatment is stopped.<ref name=Canonica09/> It is generally safe and effective for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insects.<ref name="pmid17803880"/>

To a lesser extent, the evidence also supports the use of sublingual immunotherapy for rhinitis and asthma.<ref name=Canonica09>{{cite journal | vauthors = Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, Potter PC, Bousquet PJ, Cox LS, Durham SR, Nelson HS, Passalacqua G, Ryan DP, Brozek JL, Compalati E, Dahl R, Delgado L, van Wijk RG, Gower RG, Ledford DK, Filho NR, Valovirta EJ, Yusuf OM, Zuberbier T, Akhanda W, Almarales RC, Ansotegui I, Bonifazi F, Ceuppens J, Chivato T, Dimova D, Dumitrascu D, Fontana L, Katelaris CH, Kaulsay R, Kuna P, Larenas-Linnemann D, Manoussakis M, Nekam K, Nunes C, O'Hehir R, Olaguibel JM, Onder NB, Park JW, Priftanji A, Puy R, Sarmiento L, Scadding G, Schmid-Grendelmeier P, Seberova E, Sepiashvili R, Solé D, Togias A, Tomino C, Toskala E, Van Beever H, Vieths S | display-authors = 6 | title = Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009 | journal = Allergy | volume = 64 | issue = Suppl 91 | pages = 1–59 | date = December 2009 | pmid = 20041860 | doi = 10.1111/j.1398-9995.2009.02309.x | s2cid = 10420738 | url = http://www.worldallergy.org/publications/slit-wao-pp_final.pdf | archive-url = https://web.archive.org/web/20111112132041/http://www.worldallergy.org/publications/slit-wao-pp_final.pdf | archive-date = 12 November 2011 }}</ref> For seasonal allergies the benefit is small.<ref>{{cite journal | vauthors = Di Bona D, Plaia A, Leto-Barone MS, La Piana S, Di Lorenzo G | title = Efficacy of Grass Pollen Allergen Sublingual Immunotherapy Tablets for Seasonal Allergic Rhinoconjunctivitis: A Systematic Review and Meta-analysis | journal = JAMA Internal Medicine | volume = 175 | issue = 8 | pages = 1301–09 | date = August 2015 | pmid = 26120825 | doi = 10.1001/jamainternmed.2015.2840 | doi-access = free }}</ref> In this form the allergen is given under the tongue and people often prefer it to injections.<ref name=Canonica09/> Immunotherapy is not recommended as a stand-alone treatment for asthma.<ref name=Canonica09/>

===Alternative medicine===
An experimental treatment, [[Biology:Enzyme potentiated desensitization|enzyme potentiated desensitization]] (EPD), has been tried for decades but is not generally accepted as effective.<ref name="pmid15042943"/> EPD uses dilutions of allergen and an enzyme, [[Biology:Beta-glucuronidase|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 evidence does not show effectiveness.<ref name="pmid15042943" />

A review found no effectiveness of homeopathic treatments and no difference compared with [[Medicine:Placebo|placebo]]. The authors concluded that based on rigorous clinical trials of all types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of homeopathic treatments.<ref name="pmid17285788"/>

According to the [[Organization:National Center for Complementary and Integrative Health|National Center for Complementary and Integrative Health]], U.S., the evidence is relatively strong that saline nasal irrigation and butterbur are effective, when compared to other [[Medicine:Alternative medicine|alternative medicine]] treatments, for which the scientific evidence is weak, negative, or nonexistent, such as honey, acupuncture, omega 3's, probiotics, astragalus, capsaicin, grape seed extract, Pycnogenol, quercetin, spirulina, stinging nettle, tinospora, or guduchi.
<ref>{{cite web |url=http://www.webmd.com/allergies/ss/slideshow-natural-relief |title=12 Natural Ways to Defeat Allergies |access-date=3 July 2016 |url-status=live |archive-url=https://web.archive.org/web/20160702011133/http://www.webmd.com/allergies/ss/slideshow-natural-relief |archive-date=2 July 2016 }}</ref><ref>{{cite web |url=https://nccih.nih.gov/health/providers/digest/allergies-science |title=Seasonal Allergies and Complementary Health Approaches: What the Science Says |access-date=3 July 2016 |url-status=live |archive-url=https://web.archive.org/web/20160705152320/https://nccih.nih.gov/health/providers/digest/allergies-science |archive-date=5 July 2016 |date=11 April 2013 }}</ref>

==Epidemiology==
The allergic diseases—hay fever and asthma—have increased in the Western world over the past 2–3 decades.<ref name="Platts"/> 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,<ref name=" Bloomfield"/> although some suggest that a steady rise in sensitization has been occurring since the 1920s.<ref name="The allergy epidemic extends beyond the past few decades"/> The number of new cases per year of atopy in developing countries has, in general, remained much lower.<ref name=" Bloomfield"/>

{| class = "wikitable" style = "width:70%; float:center; font-size:90%; margin-left:15px"
|+ Allergic conditions: Statistics and epidemiology
|-
! Allergy&nbsp;type || United States || United Kingdom<ref name="Chapter 4: The Extent and Burden of Allergy in the United Kingdom"/>
|-
| Allergic&nbsp;rhinitis ||35.9&nbsp;million<ref name="AAAAI - rhinitis, sinusitis, hay fever, stuffy nose, watery eyes, sinus infection"/> (about 11% of the population<ref>Based on an estimated population of 303 million in 2007 {{cite web | url = https://www.census.gov/population/www/popclockus.html | title = U.S. POPClock Projection | archive-url = https://web.archive.org/web/20120516231727/http://www.census.gov/population/www/popclockus.html | archive-date=16 May 2012 | work = U.S. Census Bureau }}</ref>)||3.3 million (about 5.5% of the population<ref>Based on an estimated population of 60.6 million {{cite web | url = http://www.statistics.gov.uk/cci/nugget.asp?id=6 | title = UK population grows to 60.6 million | work = National Statistics | publisher = UK Web Archive | archive-url = http://webarchive.nationalarchives.gov.uk/20021202165044/http://www.statistics.gov.uk/CCI/nugget.asp?ID=6 | archive-date=2 December 2002 }}</ref>)
|-
| Asthma ||10&nbsp;million have allergic asthma (about 3% of the population). The prevalence of asthma increased 75% from 1980 to 1994. Asthma prevalence is 39% higher in African Americans than in Europeans.<ref name="AAAAI - asthma, allergy, allergies, prevention of allergies and asthma, treatment for allergies and asthma"/> || 5.7&nbsp;million (about 9.4%). In six- and seven-year-olds asthma increased from 18.4% to 20.9% over five years, during the same time the rate decreased from 31% to 24.7% in 13- to 14-year-olds.
|-
| Atopic eczema ||About 9% of the population. Between 1960 and 1990, prevalence has increased from 3% to 10% in children.<ref name="AAAAI - skin condition, itchy skin, bumps, red irritated skin, allergic reaction, treating skin condition"/>|| 5.8&nbsp;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.<ref name="AAAAI - anaphylaxis, cause of anaphylaxis, prevention, allergist, anaphylaxis statistics"/> An estimated 150 people die annually from anaphylaxis due to food allergy.<ref name=Food/>|| Between 1999 and 2006, 48 deaths occurred in people ranging from five months to 85 years old.
|-
| Insect venom ||Around 15% of adults have mild, localized allergic reactions. Systemic reactions occur in 3% of adults and less than 1% of children.<ref name="AAAAI - stinging insect, allergic reaction to bug bite, treatment for insect bite"/>|| Unknown
|-
| Drug allergies || Anaphylactic reactions to penicillin cause 400 deaths per year. || Unknown
|-
| Food allergies ||7.6% of children and 10.8% of adults.<ref>{{Cite web |title=Allergy Facts {{!}} AAFA.org |url=https://www.aafa.org/allergy-facts/ |access-date=24 June 2022 |website=www.aafa.org |language=en}}</ref> Peanut and/or tree nut (e.g. [[Biology:Walnut|walnut]]) allergy affects about three million Americans, or 1.1% of the population.<ref name="Food"/> ||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.
|-
| Multiple&nbsp;allergies (Asthma, eczema and allergic rhinitis together) ||Unknown ||2.3&nbsp;million (about 3.7%), prevalence has increased by 48.9% between 2001 and 2005.<ref name="Incidence and prevalence of multiple allergic disorders recorded in a national primary care database"/>
|}

===Changing frequency===
Although genetic factors govern susceptibility to atopic disease, increases in atopy have occurred within too short a period to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes.<ref name=" Bloomfield"/> Several hypotheses have been identified to explain this increased rate. Increased exposure to perennial allergens may be due to housing changes and increased time spent indoors, and a decreased activation of a common immune control mechanism may be caused by changes in cleanliness or hygiene, and exacerbated by dietary changes, obesity, and decline in physical exercise.<ref name=Platts/> The [[Unsolved:Hygiene hypothesis|hygiene hypothesis]] maintains<ref name="Hay fever, hygiene, and household size"/> 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 [[Biology:T helper cell|T<sub>H</sub>]]1 type responses, leading to unrestrained T<sub>H</sub>2 responses that allow for an increase in allergy.<ref name=Yazdanbakhsh02/><ref name="Renz"/>

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 [[Biology:Gut flora|gastrointestinal microbial environment]]. Evidence has shown that exposure to food and fecal-oral pathogens, such as [[Medicine:Hepatitis A|hepatitis A]], ''[[Biology:Toxoplasma gondii|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%,<ref name="Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study"/> and an increased rate of parasitic infections has been associated with a decreased prevalence of asthma.<ref name="Parasites and asthma--predictive or protective?"/> It is speculated that these infections exert their effect by critically altering T<sub>H</sub>1/T<sub>H</sub>2 regulation.<ref name=" Sheikh" /> Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm.<ref name=" Sheikh"/>

==History==
Some symptoms attributable to allergic diseases are mentioned in ancient sources.<ref name="aai">{{Cite journal | url =https://aai.org.tr/index.php/aai/article/download/406/321 |title=Were Allergic Diseases Prevalent in Antiquity?|author1=Kürşat Epöztürk |author2=Şefik Görkey|journal=Asthma Allergy Immunol| doi=10.21911/aai.406|date=2018| access-date =22 September 2018|doi-access=free}}</ref> Particularly, three members of the Roman Julio-Claudian dynasty (Augustus, [[Biography:Claudius|Claudius]] and [[Biology:Britannicus|Britannicus]]) are suspected to have a family history of atopy.<ref name="aai"/><ref>{{cite journal |title=1st description of an "atopic family anamnesis" in the Julio-Claudian imperial house: Augustus, Claudius, Britannicus|author=Ring J.|pmid=3899999| date=August 1985| volume=36|issue = 8| journal=Hautarzt| pages=470–71}}</ref> The concept of "allergy" was originally introduced in 1906 by the Viennese pediatrician Clemens von Pirquet, after he noticed that patients who had received injections of horse serum or smallpox vaccine usually had quicker, more severe reactions to second injections.<ref>{{WhoNamedIt|Doctor|2382|Clemens Peter Pirquet von Cesenatico}}</ref> Pirquet called this phenomenon "allergy" from the Ancient Greek words ἄλλος ''allos'' meaning "other" and ἔργον ''ergon'' meaning "work".<ref name="Allergie"/>

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 a 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.<ref name="GellCoombs"/> With this new classification, the word ''allergy'', sometimes clarified as a ''true allergy'', was restricted to type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions involving IgE antibodies.<ref>{{Cite book|url=https://books.google.com/books?id=sXagBwAAQBAJ&pg=PA361|title=The Complement System: Novel Roles in Health and Disease| vauthors = Szebeni J |date=8 May 2007|publisher=Springer Science & Business Media|isbn=978-1-4020-8056-2|pages=361|language=en}}</ref>

A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled [[Biology:Immunoglobulin E|immunoglobulin E]] (IgE). IgE was simultaneously discovered in 1966–67 by two independent groups:<ref>{{cite journal | vauthors = Stanworth DR | title = The discovery of IgE | journal = Allergy | volume = 48 | issue = 2 | pages = 67–71 | date = February 1993 | pmid = 8457034 | doi = 10.1111/j.1398-9995.1993.tb00687.x | s2cid = 36262710 | doi-access = free }}</ref> Ishizaka's team at the Children's Asthma Research Institute and Hospital in Denver, USA,<ref name="Ishizaka K"/> and by Gunnar Johansson and Hans Bennich in Uppsala, Sweden.<ref>Johansson SG, Bennich H. Immunological studies of an atypical (myeloma) immunoglobulin" ''Immunology'' 1967; 13:381–94.</ref> Their joint paper was published in April 1969.<ref name="Joint paper 1969">{{cite journal | vauthors = Ishizaka T, Ishizaka K, Johansson SG, Bennich H | title = Histamine release from human leukocytes by anti-gamma E antibodies | journal = Journal of Immunology | volume = 102 | issue = 4 | pages = 884–892 | date = April 1969 | pmid = 4181251 | doi = 10.4049/jimmunol.102.4.884 | s2cid = 255338552 | doi-access = free }}</ref>

===Diagnosis===
Radiometric assays include the [[Medicine:Radioallergosorbent test|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.<ref name="pmid7630219">{{cite journal | vauthors = Ten RM, Klein JS, Frigas E | title = Allergy skin testing | journal = Mayo Clinic Proceedings | volume = 70 | issue = 8 | pages = 783–84 | date = August 1995 | pmid = 7630219 | doi = 10.4065/70.8.783 | url = http://www.mayoclinicproceedings.org/article/S0025-6196(11)64353-X/abstract }}</ref> Other, newer methods use colorimetric or fluorescence-labeled technology in the place of radioactive isotopes.{{citation needed|date=April 2014}}

The RAST methodology was invented and marketed in 1974 by Pharmacia Diagnostics AB, Uppsala, Sweden, and the acronym RAST is actually a brand name. In 1989, Pharmacia Diagnostics AB replaced it with a superior test named the ImmunoCAP Specific IgE blood test, which uses the newer fluorescence-labeled technology.{{citation needed|date=April 2014}}

[[Organization:American College of Allergy, Asthma and Immunology|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:

{{blockquote|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 be abandoned.<ref name="Cox2008" />}}

The updated version, the ImmunoCAP Specific IgE blood test, is the only specific IgE assay to receive [[Organization:Food and Drug Administration|Food and Drug Administration]] approval to quantitatively report to its detection limit of 0.1kU/L.{{citation needed|date=April 2014}}

==Medical specialty==
{{Infobox Occupation
| name= Allergist/Immunologist
| image=
| caption=
| official_names=
* Physician
| type= Specialty
| activity_sector= Medicine
| competencies=
| formation=
* [[Medicine:Doctor of Medicine|Doctor of Medicine]] (M.D.)
* Doctor of Osteopathic medicine (D.O.)
* Bachelor of Medicine, Bachelor of Surgery (M.B.B.S.)
* Bachelor of Medicine, Bachelor of Surgery (MBChB)
| employment_field= Hospitals, Clinics
| related_occupation=
}}
An allergist is a physician specially trained to manage and treat allergies, asthma, and the other allergic diseases.
In the United States physicians holding certification by the American Board of Allergy and Immunology (ABAI) have successfully completed an accredited educational program and evaluation process, including a proctored examination to demonstrate knowledge, skills, and experience in patient care in allergy and immunology.<ref name="ABAI: American Board of Allergy and Immunology"/> Becoming an allergist/immunologist requires completion of at least nine years of training. After completing medical school and graduating with a medical degree, a physician will undergo three years of training in internal medicine (to become an internist) or [[Medicine:Pediatrics|pediatrics]] (to become a pediatrician). Once physicians have finished training in one of these specialties, they must pass the exam of either the American Board of Pediatrics (ABP), the American Osteopathic Board of Pediatrics (AOBP), the American Board of Internal Medicine (ABIM), or the American Osteopathic Board of Internal Medicine (AOBIM). Internists or pediatricians wishing to focus on the sub-specialty of allergy-immunology then complete at least an additional two years of study, called a fellowship, in an allergy/immunology training program. Allergist/immunologists listed as ABAI-certified have successfully passed the certifying examination of the ABAI following their fellowship.<ref name="AAAAI - What is an Allergist?"/>

In the United Kingdom, allergy is a subspecialty of general medicine or [[Medicine:Pediatrics|pediatrics]]. After obtaining postgraduate exams (MRCP or MRCPCH), 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.<ref>{{cite book | publisher = Royal College of Physicians | date = 2003 | title =Allergy: the unmet need | location = London | isbn = 978-1-86016-183-4 | url = http://www.rcplondon.ac.uk/pubs/contents/81e384d6-0328-4653-9cc2-2aa7baa3c56a.pdf | archive-url = https://web.archive.org/web/20071128175524/http://www.rcplondon.ac.uk/pubs/contents/81e384d6-0328-4653-9cc2-2aa7baa3c56a.pdf | archive-date=28 November 2007 | quote = (1.03&nbsp;MB) }}</ref> In 2006, the House of Lords convened a subcommittee. It concluded likewise in 2007 that allergy services were insufficient to deal with what the Lords referred to as an "allergy epidemic" and its social cost; it made several recommendations.<ref name="Allergy - HL 166-I, 6th Report of Session 2006-07 - Volume 1: Report"/>

==Research==
Low-allergen foods are being developed, as are improvements in skin prick test predictions; evaluation of the atopy patch test, wasp sting outcomes predictions, a rapidly disintegrating epinephrine tablet, and anti-IL-5 for eosinophilic diseases.<ref name="Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects"/>

== See also ==
* [[Medicine:Allergic shiner|Allergic shiner]]
* GWAS in allergy
* Histamine intolerance
* [[Medicine:List of allergens|List of allergens]]
* [[Medicine:Oral allergy syndrome|Oral allergy syndrome]]

== References ==
{{reflist|32em|refs=
<ref name=" Bloomfield">{{cite journal | vauthors = Bloomfield SF, Stanwell-Smith R, Crevel RW, Pickup J | title = Too clean, or not too clean: the hygiene hypothesis and home hygiene | journal = Clinical and Experimental Allergy | volume = 36 | issue = 4 | pages = 402–25 | date = April 2006 | pmid = 16630145 | pmc = 1448690 | doi = 10.1111/j.1365-2222.2006.02463.x }}</ref>

<ref name=" Sheikh">{{cite journal | vauthors = Sheikh A, Strachan DP | title = The hygiene theory: fact or fiction? | journal = Current Opinion in Otolaryngology & Head and Neck Surgery | volume = 12 | issue = 3 | pages = 232–36 | date = June 2004 | pmid = 15167035 | doi = 10.1097/01.moo.0000122311.13359.30 | s2cid = 37297207 }}</ref>

<ref name="AAAAI - anaphylaxis, cause of anaphylaxis, prevention, allergist, anaphylaxis statistics">{{cite web |url=http://www.aaaai.org/patients/gallery/anaphylaxis.asp?item=1a |title=AAAAI – anaphylaxis, cause of anaphylaxis, prevention, allergist, anaphylaxis statistics |access-date=3 December 2007 |archive-url=https://web.archive.org/web/20101130155003/http://www.aaaai.org/patients/gallery/anaphylaxis.asp?item=1a |archive-date=30 November 2010 }}</ref>

<ref name="A meta-analysis of the association between Caesarean section and childhood asthma">{{cite journal | vauthors = Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR | title = A meta-analysis of the association between Caesarean section and childhood asthma | journal = Clinical and Experimental Allergy | volume = 38 | issue = 4 | pages = 629–33 | date = April 2008 | pmid = 18352976 | doi = 10.1111/j.1365-2222.2007.02780.x | s2cid = 23077809 }}</ref>

<ref name="AAAAI - What is an Allergist?">{{cite web|url=http://www.aaaai.org/media/resources/allergist.asp |title=AAAAI – What is an Allergist? |access-date=5 August 2007 |archive-url=https://web.archive.org/web/20101130000642/http://www.aaaai.org/media/resources/allergist.asp |archive-date=30 November 2010 |url-status=live  }}</ref>

<ref name="AAAAI - asthma, allergy, allergies, prevention of allergies and asthma, treatment for allergies and asthma">{{cite web |url=http://www.aaaai.org/patients/gallery/prevention.asp?item=1a |title=AAAAI – asthma, allergy, allergies, prevention of allergies and asthma, treatment for allergies and asthma |access-date=3 December 2007 |archive-url=https://web.archive.org/web/20110718174927/http://www.aaaai.org/patients/gallery/prevention.asp?item=1a |archive-date=18 July 2011 }}</ref>

<ref name="AAAAI - rhinitis, sinusitis, hay fever, stuffy nose, watery eyes, sinus infection">{{cite web |url=http://www.aaaai.org/patients/gallery/rhinitissinusitis.asp?item=1a |title=AAAAI – rhinitis, sinusitis, hay fever, stuffy nose, watery eyes, sinus infection |access-date=3 December 2007 |archive-url=https://web.archive.org/web/20110718174853/http://www.aaaai.org/patients/gallery/rhinitissinusitis.asp?item=1a |archive-date=18 July 2011 }}</ref>

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<ref name="Sicherer 63">Sicherer 63</ref>

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<ref name="pmid12910582">{{cite journal | vauthors = Gibson PG, Henry RL, Shah S, Powell H, Wang H | title = Migration to a western country increases asthma symptoms but not eosinophilic airway inflammation | journal = Pediatric Pulmonology | volume = 36 | issue = 3 | pages = 209–15 | date = September 2003 | pmid = 12910582 | doi = 10.1002/ppul.10323 | s2cid = 29589706 }}. Retrieved 6 July 2008.</ref>

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}}

== External links ==
* {{Wikivoyage-inline}}
* {{cite web | url = https://medlineplus.gov/allergy.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Allergy }}
* {{curlie|Health/Conditions_and_Diseases/Allergies/}}

{{Medical resources
|  DiseasesDB = 33481
|  ICD10 = {{ICD10|T|78|4|t|66}}
|  ICD9 = {{ICD9|995.3}}
|  MedlinePlus = 000812
|  eMedicineSubj = med
|  eMedicineTopic = 1101
|  MeshID = D006967
}}

{{Hypersensitivity and autoimmune diseases}}
{{medicine}}


[[Category:Effects of external causes]]
[[Category:Immunology]]
[[Category:Respiratory diseases]]
[[Category:Immune system]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Allergy}}