Anaphylaxis pathophysiology
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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 is usually caused by food, particularly peanuts, drugs, and insect venoms. [3] [4] There have also been cases of idiopathic anaphylaxis. [5] [6] 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]
Specifically, histamine causes vasodilation and increased heart rate and permeability which ultimately leads to the hypoperfusion of various tissues. Prostaglandin D2 causes bronchoconstriction of both cardiac and pulmonary systems culminating in peripheral vasodilation and further hypoperfusion of tissues. Leukotrienes and platelet activation factor also contribute to vascular permeability, along with bronchoconstriction and airway remodeling. Finally, TNF-alpha activate neutrophils which increases the synthesis of chemokines. [7] [1]
Anaphylaxis can be divided into IgE-dependent and IgE-independent mechanisms. 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. [8] IgE levels are even used during the diagnosis of allergies to determine what allergens a patient is susceptible to. [9] Meanwhile, in IgE-independent reactions, IgG mechanisms were also found to lead to anaphylaxis, which has largely been studied in mice. A single episode of anaphylaxis may also be caused by simultaneous IgG and IgE-mediated pathways. [10]
Genetics
Genes involved in the pathogenesis of anaphylaxis include:[11] [12] [13] [14] [15] [16] [17] [18] [19]
- Polymorphisms in IL-10, IL-13, IL-4Rα are 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: [20] [21]
- 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. [22]
References
- ↑ 1.0 1.1 1.2 1.3 "StatPearls". 2021. PMID 29489197.
- ↑ 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.
- ↑ Sampson HA, Muñoz-Furlong A, Bock SA, Schmitt C, Bass R, Chowdhury BA; et al. (2005). "Symposium on the definition and management of anaphylaxis: summary report". J Allergy Clin Immunol. 115 (3): 584–91. doi:10.1016/j.jaci.2005.01.009. PMID 15753908.
- ↑ Kemp SF, Lockey RF (2002). "Anaphylaxis: a review of causes and mechanisms". J Allergy Clin Immunol. 110 (3): 341–8. doi:10.1067/mai.2002.126811. PMID 12209078.
- ↑ Lenchner K, Grammer LC (2003). "A current review of idiopathic anaphylaxis". Curr Opin Allergy Clin Immunol. 3 (4): 305–11. doi:10.1097/00130832-200308000-00012. PMID 12865776.
- ↑ Ring J, Darsow U (2002). "Idiopathic anaphylaxis". Curr Allergy Asthma Rep. 2 (1): 40–5. doi:10.1007/s11882-002-0036-8. PMID 11895624.
- ↑ Peavy RD, Metcalfe DD (2008). "Understanding the mechanisms of anaphylaxis". Curr Opin Allergy Clin Immunol. 8 (4): 310–5. doi:10.1097/ACI.0b013e3283036a90. PMC 2683407. PMID 18596587.
- ↑ 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.
- ↑ Finkelman FD, Khodoun MV, Strait R (2016). "Human IgE-independent systemic anaphylaxis". J Allergy Clin Immunol. 137 (6): 1674–1680. doi:10.1016/j.jaci.2016.02.015. PMC 7607869 Check
|pmc=value (help). PMID 27130857. - ↑ 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).