Anaphylaxis pathophysiology: Difference between revisions
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Anaphylactic shock, the most severe type of anaphylaxis, occurs when an allergic response triggers a quick release from [[mast cell]]s of large quantities of [[immunology|immunological]] mediators ([[histamine]]s, [[prostaglandin]]s, [[leukotriene]]s) leading to systemic [[vasodilation]] (associated with a sudden drop in blood pressure) and [[edema]] of [[bronchial]] [[mucosa]] (resulting in [[bronchoconstriction]] and difficulty breathing). Anaphylactic shock can lead to death in a matter of minutes if left untreated. <ref name="pmid28800865">{{cite journal| author=LoVerde D, Iweala OI, Eginli A, Krishnaswamy G| title=Anaphylaxis. | journal=Chest | year= 2018 | volume= 153 | issue= 2 | pages= 528-543 | pmid=28800865 | doi=10.1016/j.chest.2017.07.033 | pmc=6026262 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28800865 }} </ref> | Anaphylactic shock, the most severe type of anaphylaxis, occurs when an allergic response triggers a quick release from [[mast cell]]s of large quantities of [[immunology|immunological]] mediators ([[histamine]]s, [[prostaglandin]]s, [[leukotriene]]s) leading to systemic [[vasodilation]] (associated with a sudden drop in blood pressure) and [[edema]] of [[bronchial]] [[mucosa]] (resulting in [[bronchoconstriction]] and difficulty breathing). Anaphylactic shock can lead to death in a matter of minutes if left untreated. <ref name="pmid28800865">{{cite journal| author=LoVerde D, Iweala OI, Eginli A, Krishnaswamy G| title=Anaphylaxis. | journal=Chest | year= 2018 | volume= 153 | issue= 2 | pages= 528-543 | pmid=28800865 | doi=10.1016/j.chest.2017.07.033 | pmc=6026262 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28800865 }} </ref> | ||
Anaphylaxis can be divided into IgE-dependent and IgE-independent. IgE levels are higher in those patients that have allergies. Once IgE binds to FcεRI on mast cells and basophils this releases histamine and other inflammatory mediators. On repeat exposure to the antigen, these IgE aggregates lead to anaphylaxis. <ref name="pmid17438574">{{cite journal| author=Kraft S, Kinet JP| title=New developments in FcepsilonRI regulation, function and inhibition. | journal=Nat Rev Immunol | year= 2007 | volume= 7 | issue= 5 | pages= 365-78 | pmid=17438574 | doi=10.1038/nri2072 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17438574 }} </ref> IgE levels are even used during the diagnosis of allergies to determine what allergens a patient is susceptible to. <ref name="pmid20066506">{{cite journal| author=Hamilton RG, MacGlashan DW, Saini SS| title=IgE antibody-specific activity in human allergic disease. | journal=Immunol Res | year= 2010 | volume= 47 | issue= 1-3 | pages= 273-84 | pmid=20066506 | doi=10.1007/s12026-009-8160-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20066506 }} </ref> | |||
==Genetics== | ==Genetics== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Dushka Riaz, MD
Overview
The progression to anaphylaxis usually involves an IgE-mediated or non IgE-mediated response. It is a medical emergency that involves multiple systems. [1] The condition involves pulmonary, gastrointestinal, cardiovascular and integumentary systems and can lead to cardiorespiratory arrest. [2]
Pathophysiology
Anaphylaxis arises from mast cell and basophil degranulation after repeated exposure to an antigen. This results in a type 1 hypersensitivity reaction. The IgE then crosslinks and aggregates with receptors resulting in the release of histamine, proteoglycans, and tryptase. This results in arachidonic acid metabolites being released with further consequences. The reaction as a whole leads to vasodilation, increase heart rate, bronchoconstriction, and hypoperfusion of vital organs. [1]
Anaphylactic shock, the most severe type of anaphylaxis, occurs when an allergic response triggers a quick release from mast cells of large quantities of immunological mediators (histamines, prostaglandins, leukotrienes) leading to systemic vasodilation (associated with a sudden drop in blood pressure) and edema of bronchial mucosa (resulting in bronchoconstriction and difficulty breathing). Anaphylactic shock can lead to death in a matter of minutes if left untreated. [2]
Anaphylaxis can be divided into IgE-dependent and IgE-independent. IgE levels are higher in those patients that have allergies. Once IgE binds to FcεRI on mast cells and basophils this releases histamine and other inflammatory mediators. On repeat exposure to the antigen, these IgE aggregates lead to anaphylaxis. [3] IgE levels are even used during the diagnosis of allergies to determine what allergens a patient is susceptible to. [4]
Genetics
Genes involved in the pathogenesis of anaphylaxis include:[5] [6] [7] [8] [9] [10] [11] [12] [13]
- Polymorphisms in IL-10, IL-13, IL-4Rα linked to anaphylaxis to drugs and latex.
- PAF-AH activity levels are correlated inversely with the severity of anaphylaxis.
- Variations in angiotensinogen MM genotype with low levels of angiotensin are linked with high rates of hymenoptera venom allergy.
- Patients with peanut allergies and low serum ACE levels are linked with high rates of pharyngeal edema.
- Activating mutation in c-KIT and D816V are associated with mastocytosis and hyperresponsivity of their mast cells with resulting increasing severity of anaphylaxis rates.
- Anaphylaxis occurs more commonly in women though the mechanism is not clear.
Associated Conditions
Conditions associated with anaphylaxis include the following and are associated with poor prognosis: [14] [15]
- Asthma
- Cardiovascular disease
- Antihypertensive medication use
Gross Pathology
On gross pathology, basophil and mast cell degranulation are characteristic findings of anaphylaxis. [1]
Microscopic Pathology
On microscopic histopathological analysis, upper airways showing eosinophils due to edema are characteristic findings of anaphylaxis. Tissue sections can also show tryptase, which is an enzyme specific to mast cells. [16]
References
- ↑ 1.0 1.1 1.2 "StatPearls". 2021. PMID 29489197.
- ↑ 2.0 2.1 LoVerde D, Iweala OI, Eginli A, Krishnaswamy G (2018). "Anaphylaxis". Chest. 153 (2): 528–543. doi:10.1016/j.chest.2017.07.033. PMC 6026262. PMID 28800865.
- ↑ Kraft S, Kinet JP (2007). "New developments in FcepsilonRI regulation, function and inhibition". Nat Rev Immunol. 7 (5): 365–78. doi:10.1038/nri2072. PMID 17438574.
- ↑ Hamilton RG, MacGlashan DW, Saini SS (2010). "IgE antibody-specific activity in human allergic disease". Immunol Res. 47 (1–3): 273–84. doi:10.1007/s12026-009-8160-3. PMID 20066506.
- ↑ Reber LL, Hernandez JD, Galli SJ (2017). "The pathophysiology of anaphylaxis". J Allergy Clin Immunol. 140 (2): 335–348. doi:10.1016/j.jaci.2017.06.003. PMC 5657389. PMID 28780941.
- ↑ Apter AJ, Schelleman H, Walker A, Addya K, Rebbeck T (2008). "Clinical and genetic risk factors of self-reported penicillin allergy". J Allergy Clin Immunol. 122 (1): 152–8. doi:10.1016/j.jaci.2008.03.037. PMID 18538381.
- ↑ Brown RH, Hamilton RG, Mintz M, Jedlicka AE, Scott AL, Kleeberger SR (2005). "Genetic predisposition to latex allergy: role of interleukin 13 and interleukin 18". Anesthesiology. 102 (3): 496–502. doi:10.1097/00000542-200503000-00004. PMID 15731584.
- ↑ Niedoszytko M, Ratajska M, Chełmińska M, Makowiecki M, Malek E, Siemińska A; et al. (2010). "The angiotensinogen AGT p.M235T gene polymorphism may be responsible for the development of severe anaphylactic reactions to insect venom allergens". Int Arch Allergy Immunol. 153 (2): 166–72. doi:10.1159/000312634. PMID 20413984.
- ↑ Summers CW, Pumphrey RS, Woods CN, McDowell G, Pemberton PW, Arkwright PD (2008). "Factors predicting anaphylaxis to peanuts and tree nuts in patients referred to a specialist center". J Allergy Clin Immunol. 121 (3): 632–638.e2. doi:10.1016/j.jaci.2007.12.003. PMID 18207562.
- ↑ Nagata H, Worobec AS, Oh CK, Chowdhury BA, Tannenbaum S, Suzuki Y; et al. (1995). "Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder". Proc Natl Acad Sci U S A. 92 (23): 10560–4. doi:10.1073/pnas.92.23.10560. PMC 40651. PMID 7479840.
- ↑ Gülen T, Ljung C, Nilsson G, Akin C (2017). "Risk Factor Analysis of Anaphylactic Reactions in Patients With Systemic Mastocytosis". J Allergy Clin Immunol Pract. 5 (5): 1248–1255. doi:10.1016/j.jaip.2017.02.008. PMID 28351784.
- ↑ Webb LM, Lieberman P (2006). "Anaphylaxis: a review of 601 cases". Ann Allergy Asthma Immunol. 97 (1): 39–43. doi:10.1016/S1081-1206(10)61367-1. PMID 16892779.
- ↑ Worm M, Edenharter G, Ruëff F, Scherer K, Pföhler C, Mahler V; et al. (2012). "Symptom profile and risk factors of anaphylaxis in Central Europe". Allergy. 67 (5): 691–8. doi:10.1111/j.1398-9995.2012.02795.x. PMID 22335765.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.1186/s13223-018-0283-4 Check
|pmid=value (help). - ↑ Lee S, Hess EP, Nestler DM, Bellamkonda Athmaram VR, Bellolio MF, Decker WW; et al. (2013). "Antihypertensive medication use is associated with increased organ system involvement and hospitalization in emergency department patients with anaphylaxis". J Allergy Clin Immunol. 131 (4): 1103–8. doi:10.1016/j.jaci.2013.01.011. PMID 23453138.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.1007/s12024-016-9799-4 Check
|pmid=value (help).