Atopy is the tendency to produce an exaggerated immunoglobulin E (IgE) immune response to otherwise harmless substances in the environment.[2]Allergic diseases are clinical manifestations of such inappropriate, atopic responses.[2]
Atopy may have a hereditary component, although contact with the allergen or irritant must occur before the hypersensitivity reaction can develop (characteristically after re-exposure).[3] Maternal psychological trauma in utero may also be a strong indicator for development of atopy.[4]
The term atopy was coined by Arthur F. Coca and Robert Cooke in 1923.[5][6] Many physicians and scientists use the term "atopy" for any IgE-mediated reaction (even those that are appropriate and proportional to the antigen), but many pediatricians reserve the word "atopy" for a genetically mediated predisposition to an excessive IgE reaction.[7] The term is from Greek ἀτοπία meaning "the state of being out of place", "absurdity".[8]
Allergic reactions can range from sneezing and rhinorrhoea to anaphylaxis and even death.[13]
Pathophysiology
In an allergic reaction, initial exposure to an otherwise harmless exogenous substance (known as an allergen) triggers the production of specific IgE antibodies by activated B cells.[13] These IgE antibodies bind to the surface of mast cells via high-affinity IgE receptors, a step that is not itself associated with a clinical response.[13] However, upon re-exposure, the allergen binds to membrane-bound IgE which activates the mast cells, releasing a variety of mediators.[13] This type I hypersensitivity reaction is the basis of the symptoms of allergic reactions, which range from sneezing and rhinorrhoea to anaphylaxis.[13] Allergens can be a number of different substances, for example pollen, dander, dust mites, and foods.
Causes
Atopic reactions are caused by localized hypersensitivity reactions to an allergen. Atopy appears to show a strong hereditary component. One study concludes that the risk of developing atopic dermatitis (3%) or atopy in general (7%) "increases by a factor of two with each first-degree family member already suffering from atopy".[14] As well, maternal stress and perinatal programming is increasingly understood as a root cause of atopy, finding that "...trauma may be a particularly robust potentiator of the cascade of biological events that increase vulnerability to atopy and may help explain the increased risk found in low-income urban populations."[4]
Environmental factors are also thought to play a role in the development of atopy, and the 'hygiene hypothesis' is one of the models that may explain the steep rise in the incidence of atopic diseases, though this hypothesis is incomplete and in some cases, contradictory to findings.[4] This hypothesis proposes that excess 'cleanliness' in an infant's or child's environment can lead to a decline in the number of infectious stimuli that are necessary for the proper development of the immune system. The decrease in exposure to infectious stimuli may result in an imbalance between the infectious-response ("protective") elements and the allergic-response ("false alarm") elements within the immune system.[15]
Some studies also suggest that the maternal diet during pregnancy may be a causal factor in atopic diseases (including asthma) in offspring, suggesting that consumption of antioxidants, certain lipids, and/or a Mediterranean diet may help to prevent atopic diseases.
A Swedish research study titled "Atopy In Children Of Families With An Anthroposophic Lifestyle" comparing the rate of bronchial asthma, allergies, dermatitis, and other atopic diseases among Steiner school pupils and pupils in public schools originally appeared in the May 1, 1999, edition of the British medical journal The Lancet. The findings indicated that Steiner school pupils were "at a significantly lower risk of atopy" than children attending public schools. The researchers investigated a variety of factors in the lives of the Steiner school pupils that might have contributed to this lower rate of atopy, which included breastfeeding, reduced immunization, avoidance of antibiotics and medications that reduce fevers, consumption of bio-dynamic and organic foods, and other physical aspects of the children's lives. [16]
The multicenter PARSIFAL study in 2006, involving 6,630 children age 5 to 13 in 5 European countries, suggested that reduced use of antibiotics and antipyretics is associated with a reduced risk of allergic disease in children.[17]
Genetics
There is a strong genetic predisposition toward atopic allergies, especially on the maternal side. Because of the strong familial evidence, investigators have tried to map susceptibility genes for atopy.[18][19] Genes for atopy (C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1/IL18R1, TLR1/TLR6/TLR10, LPP, MYC/PVT1, IL2/ADAD1, HLA-B/MICA)[20] tend to be involved in allergic responses or other components of the immune system. The gene C11orf30 seems to be the most relevant for atopy as it may increase susceptibility to poly-sensitization.[21]
Staphylococcus aureus
Bleach baths provide temporary control of eczema.[22]Ciprofloxacin is an allergen that may cause contact dermatitis, symptoms of which are indistinguishable from eczema.[23]Filaggrin mutations are associated with atopic eczema and may contribute to the excessive dryness of the skin and the loss of the barrier function of normal skin.[24] It may be possible that the filaggrin mutations and the loss of the normal skin barrier expose crevices that make it possible for Staphylococcus aureus to colonize the skin.[25] Atopic eczema is often associated with genetic defects in genes that control allergic responses. Thus, some investigators have proposed that atopic eczema is an allergic response to increased Staphylococcus aureus colonization of the skin.[26] A hallmark indicator of atopic eczema is a positive wheal and flare reaction to a skin test of S. aureus antigens. In addition, several studies have documented that an IgE-mediated response to S. aureus is present in people with atopic eczema.[27][28]
Changes in prevalence over time
In adults, the prevalence of IgE sensitization to allergens from house dust mite and cat, but not grass, seems to decrease over time as people age.[29] However, the biological reasons for these changes are not fully understood.
Treatments
Treatments for atopic disorders depend on the organ(s) involved. They can vary from local treatment options, often topical corticosteroids, to systemic treatment options with oral corticosteroids, biological treatments (e.g. omalizumab, mepolizumab) or allergen immunotherapy.[30][31][32]
^ abRalston, Stuart H., Herausgeber. Penman, Ian D., Herausgeber. Strachan, Mark W. J., Herausgeber. Hobson, Richard P., Herausgeber. Britton, Robert, Illustrator. Davidson, Leybourne S. 1894-1981 Begründer des Werks. (2018-04-23). Davidson's principles and practice of medicine. Elsevier. ISBN978-0-7020-7028-0. OCLC1040673074.{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
^Simpson, Angela; Tan, Vincent Y. F.; Winn, John; Svensén, Markus; Bishop, Christopher M.; Heckerman, David E.; Buchan, Iain; Custovic, Adnan (June 2010). "Beyond Atopy"(PDF). American Journal of Respiratory and Critical Care Medicine. 181 (11): 1200–1206. doi:10.1164/rccm.200907-1101oc. ISSN1073-449X. PMID20167852.
^Sun, Hai-Lun; Yeh, Chih-Jung; Ku, Min-Sho; Lue, Ko-Huang (2012-01-01). "Coexistence of allergic diseases: Patterns and frequencies". Allergy and Asthma Proceedings. 33 (1): e1-4. doi:10.2500/aap.2012.33.3506. ISSN1088-5412. PMID22370527.
^González-Cervera J, Arias Á, Redondo-González O, Cano-Mollinedo MM, Terreehorst I, Lucendo AJ (2017). "Association between atopic manifestations and eosinophilic esophagitis: A systematic review and meta-analysis". Ann Allergy Asthma Immunol (Systematic Review and Meta-analysis). 118 (5): 582–590.e2. doi:10.1016/j.anai.2017.02.006. PMID28366582.
^
Küster, W.; Petersen, M.; Christophers, E.; Goos, M.; Sterry, W. (December 12, 2004). "A family study of atopic dermatitis". Archives of Dermatological Research. 282 (2 / January, 1990): 98–102. doi:10.1007/BF00493466. PMID2353830. S2CID9396200.
^Nguyen, T.; Zuniga, R. (2013). "Skin conditions: New drugs for managing skin disorders". FP Essentials. 407: 11–16. PMID23600334.
^Lee, S. W.; Cheong, S. H.; Byun, J. Y.; Choi, Y. W.; Choi, H. Y. (2013). "Occupational hand eczema among nursing staffs in Korea: Self-reported hand eczema and contact sensitization of hospital nursing staffs". The Journal of Dermatology. 40 (3): 182–187. doi:10.1111/1346-8138.12036. PMID23294332. S2CID33771711.
^O'Regan GM, Sandilands A, McLean WH, Irvine AD (2008). "Filaggrin in Atopic Dermatitis". J Allergy Clin Immunol. 122 (4): 689–93. doi:10.1016/j.jaci.2008.08.002. PMID18774165.
^Abramson JS, Dahl MV, Walsh G, Blumenthal MN, Douglas SD, Quie PG (1982). "Antistaphylococcal IgE in Patients with Atopic Dermatitis". J Am Acad Dermatol. 7 (1): 105–110. doi:10.1016/s0190-9622(82)80017-0. PMID7107990.
^Parish WE, Welbourn E, Champion RH (1976). "Hypersensitivity to Bacteria in Eczema. Ii. Titre and Immunoglobulin Class of Antibodies to Staphylococci and Micrococci". Br J Dermatol. 95 (3): 285–93. doi:10.1111/j.1365-2133.1976.tb07016.x. PMID974019. S2CID5842899.
