Abstract
Purpose of review
This review aims to describe some of the limitations in defining anaphylaxis and therefore the difficulties in studying its epidemiology. Despite these limitations we also aim to describe some of the trends observed in recent studies.
Recent findings
The epidemiological study of anaphylaxis is problematic. Although first described over 100 years ago, the definition of anaphylaxis has undergone revision in the last 2 decades, and a new international consensus definition was proposed in 2014. Clinical diagnostic criteria have been in use for little over a decade. Mast cell tryptase can be used to confirm the diagnosis, but is not always available, is of little use in determining immediate treatment and is not performed in many cases of suspected anaphylaxis. Epidemiological studies rely on clinical diagnosis and medical coding systems which have many limitations.
Summary
Recent changes adopted in the ICD-11 will aid the detection and classification of anaphylaxis cases. The absence of an objective gold standard and the difficulty in data quality at a population level mean that reliable epidemiologic data are difficult to obtain. Anaphylaxis seems to be increasing, with food-induced case in paediatrics and drug-induced cases in adults the main drivers.
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References
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Richet C, Portier P. De l’action anaphylactique de certains venins. CR Soc Biol. 1902;54:170–2.
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A, et al. Second symposium on the definition and management of anaphylaxis: summary report - second National Institute of allergy and infectious disease/Food Allergy and Anaphylaxis Network symposium. In: Journal of Allergy and Clinical Immunology. Elsevier; 2006. p. 391–7. https://doi.org/10.1016/j.jaci.2005.12.1303
Simons FER, Ardusso LRF, Bilò MB, El-Gamal YM, Ledford DK, Ring J, et al. World allergy organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13–37. https://doi.org/10.1097/WOX.0b013e318211496c.
Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010;126(3):63–76. https://doi.org/10.1016/j.jaci.2010.06.022.
Muraro A, Roberts G, Worm M, Bilò MB, Brockow K, Fernández Rivas M, et al. Anaphylaxis: guidelines from the European academy of allergy and clinical immunology. Allergy. 2014;69(8):1026–45. https://doi.org/10.1111/all.12437.
Simons FER, Ardusso LR, Bilò MB, Cardona V, Ebisawa M, El-Gamal YM, et al. International consensus on (ICON) anaphylaxis. World Allergy Organ J. 2014;7(1). https://doi.org/10.1186/1939-4551-7-9.
Johansson SGO, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: report of the nomenclature review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832–6. https://doi.org/10.1016/j.jaci.2003.12.591.
Campbell RL, Hagan JB, Manivannan V, Decker WW, Kanthala AR, Bellolio MF, et al. Evaluation of national institute of allergy and infectious diseases/food allergy and anaphylaxis network criteria for the diagnosis of anaphylaxis in emergency department patients. J Allergy Clin Immunol. 2012;129(3):748–52. https://doi.org/10.1016/j.jaci.2011.09.030.
Loprinzi Brauer CE, Motosue MS, Li JT, Hagan JB, Bellolio MF, Lee S, et al. Prospective validation of the NIAID/FAAN criteria for Emergency Department Diagnosis of Anaphylaxis. In: Journal of Allergy and Clinical Immunology: In Practice. American Academy of Allergy, Asthma and Immunology; 2016. p. 1220–6. https://doi.org/10.1016/j.jaip.2016.06.003.
Wilfox Jimenez-Rodriguez T, Garcia-Neuer M, Alenazy LA, Castells M. Anaphylaxis in the 21st century: phenotypes, endotypes, and biomarkers. J Asthma Allergy. 2018;Volume 11:11–121. https://doi.org/10.2147/JAA.S159411.
Sala-Cunill A, Guilarte M, Cardona V. Phenotypes, endotypes and biomarkers in anaphylaxis. Curr Opin allergy Clin Immunol. 2018;18(5):370–6. https://doi.org/10.1097/ACI.0000000000000472 These two articles descibe the various different mechanisms behind anaphylaxis as well as clinical and biochemical manifestations.
Isabwe GAC, Garcia Neuer M, de las Vecillas Sanchez L, Lynch DM, Marquis K, Castells M. Hypersensitivity reactions to therapeutic monoclonal antibodies: phenotypes and endotypes. J Allergy Clin Immunol. 2018;142(1):159–170.e2. https://doi.org/10.1016/j.jaci.2018.02.018.
Sala-Cunill A, Luengo O, Cardona V. Biologics and anaphylaxis. Curr Opin Allergy Clin Immunol. 2019;19(5):439–46. https://doi.org/10.1097/ACI.0000000000000550.
Castells M. Diagnosis and management of anaphylaxis in precision medicine. J Allergy Clin Immunol. 2017;140(2):321–33. https://doi.org/10.1016/j.jaci.2017.06.012.
Porebski G, Kwiecien K, Pawica M, Kwitniewski M. Mas-related G protein-coupled receptor-X2 (MRGPRX2) in drug hypersensitivity reactions. Front Immunol. 2018;9:3027. https://doi.org/10.3389/fimmu.2018.03027.
Spoerl D, Nigolian H, Czarnetzki C, Harr T. Reclassifying anaphylaxis to neuromuscular blocking agents based on the presumed patho-mechanism: IgE-mediated, pharmacological adverse reaction or “innate hypersensitivity”? Int J Mol Sci. 2017;18(6). https://doi.org/10.3390/ijms18061223.
Muñoz-Cano RM, Bartra J, Picado C, Valero A. Mechanisms of anaphylaxis beyond IgE. J Investig Allergol Clin Immunol. 2016;26(2):73–82. https://doi.org/10.18176/jiaci.0046.
Finkelman FD, Khodoun MV, Strait R. Human IgE-independent systemic anaphylaxis. J Allergy Clin Immunol. 2016;137(6):1674–80. https://doi.org/10.1016/j.jaci.2016.02.015.
Wang Y, Allen KJ, Suaini NHA, McWilliam V, Peters RL, Koplin JJ. The global incidence and prevalence of anaphylaxis in children in the general population: a systematic review. Allergy. 2019;74(6):1063–80. https://doi.org/10.1111/all.13732.
Ramsey NB, Guffey D, Anagnostou K, Coleman NE, Davis CM. Epidemiology of anaphylaxis in critically ill children in the United States and Canada. J Allergy Clin Immunol Pract. 2019;7(7):2241–9. https://doi.org/10.1016/j.jaip.2019.04.025.
Greenhawt M, Gupta RS, Meadows JA, Pistiner M, Spergel JM, Camargo CA, et al. Guiding principles for the recognition, diagnosis, and management of infants with anaphylaxis: an expert panel consensus. J Allergy Clin Immunol Pract. 2019;7(4):1148–1156.e5. https://doi.org/10.1016/j.jaip.2018.10.052.
Turner PJ, Campbell DE. Epidemiology of severe anaphylaxis: can we use population-based data to understand anaphylaxis? Curr Opin Allergy Clin Immunol. 2016;16(5):441–50. https://doi.org/10.1097/ACI.0000000000000305.
• Chaaban MR, Warren Z, Baillargeon JG, Baillargeon G, Resto V, Kuo YF. Epidemiology and trends of anaphylaxis in the United States, 2004-2016. Int forum allergy Rhinol. 2019;9(6):607–14. https://doi.org/10.1002/alr.22293 A large population based study on anaphylaxis.
Alvarez-Perea A, Ameiro B, Morales C, Zambrano G, Rodríguez A, Guzmán M, et al. Anaphylaxis in the pediatric emergency department: analysis of 133 cases after an allergy workup. J Allergy Clin Immunol Pract. 2017;5(5):1256–63. https://doi.org/10.1016/j.jaip.2017.02.011.
Grabenhenrich LB, Moneret-Vautrin A, Lange L, Spindler T, Ru F, Nemat K, et al. Anaphylaxis in children and adolescents: the European Anaphylaxis Registry. J Allergy Clin Immunol. 2016;137(4):1128–1137.e1. https://doi.org/10.1016/j.jaci.2015.11.015.
Lee S, Hess EP, Lohse C, Gilani W, Chamberlain AM, Campbell RL. Trends, characteristics, and incidence of anaphylaxis in 2001–2010: A population-based study. J Allergy Clin Immunol. 2017;139(1):182–188.e2. https://doi.org/10.1016/j.jaci.2016.04.029.
Ruiz Oropeza A, Lassen A, Halken S, Bindslev-Jensen C, Mortz CG. Anaphylaxis in an emergency care setting: a one year prospective study in children and adults. Scand J Trauma Resusc Emerg Med. 2017;25(1):111. https://doi.org/10.1186/s13049-017-0402-0.
Rudders SA, Banerji A, Clark S, Camargo CA. Age-related differences in the clinical presentation of food-induced anaphylaxis. J Pediatr. 2011;158(2):326–8. https://doi.org/10.1016/j.jpeds.2010.10.017.
Ma L, Danoff TM, Borish L. Case fatality and population mortality associated with anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(4):1075–83. https://doi.org/10.1016/j.jaci.2013.10.029.
Jerschow E, Lin RY, Scaperotti MM, McGinn AP. Fatal anaphylaxis in the United States, 1999–2010: temporal patterns and demographic associations. J Allergy Clin Immunol. 2014;134(6):1318–1328.e7. https://doi.org/10.1016/j.jaci.2014.08.018.
Mullins RJ, Wainstein BK, Barnes EH, Liew WK, Campbell DE. Increases in anaphylaxis fatalities in Australia from 1997 to 2013. Clin Exp Allergy. 2016;46(8):1099–110. https://doi.org/10.1111/cea.12748.
• Turner PJ, Gowland MH, Sharma V, Ierodiakonou D, Harper N, Garcez T, et al. Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012. J allergy Clin Immunol. 2015;135(4):956–963.e1. https://doi.org/10.1016/j.jaci.2014.10.021 A large population based study of anaphylaxis.
Michalska-Krzanowska G. Tryptase in diagnosing adverse suspected anaphylactic reaction. Adv Clin Exp Med. 2012;21(3):403–8.
Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327(6):380–4. https://doi.org/10.1056/NEJM199208063270603.
Yunginger JW, Nelson DR, Squillace DL, Jones RT, Holley KE, Hyma BA, et al. Laboratory investigation of deaths due to anaphylaxis. J Forensic Sci. 1991;36(3):857–65.
Labella M, Garcia-Neuer M, Castells M. Application of precision medicine to the treatment of anaphylaxis. Curr Opin Allergy Clin Immunol. 2018;18(3):190–7. https://doi.org/10.1097/ACI.0000000000000435.
Beck SC, Wilding T, Buka RJ, Baretto RL, Huissoon AP, Krishna MT. Biomarkers in human anaphylaxis: a critical appraisal of current evidence and perspectives. Front Immunol. 2019;10(APR). https://doi.org/10.3389/fimmu.2019.00494. This review describes current and potential future biomarkers for the diagnosis of anaphylaxis.
Krishna MT, York M, Chin T, Gnanakumaran G, Heslegrave J, Derbridge C, et al. Multi-Centre retrospective analysis of anaphylaxis during general anaesthesia in the United Kingdom: Aetiology and diagnostic performance of acute serum tryptase. Clin Exp Immunol. 2014;178(2):399–404. https://doi.org/10.1111/cei.12424.
Buka RJ, Knibb RC, Crossman RJ, Melchior CL, Huissoon AP, Hackett S, et al. Anaphylaxis and clinical utility of real-world measurement of acute serum tryptase in UK Emergency Departments. J Allergy Clin Immunol Pract. 2017;5(5):1280–1287.e2. https://doi.org/10.1016/j.jaip.2017.06.021.
De Schryver S, Halbrich M, Clarke A, La Vieille S, Eisman H, Alizadehfar R, et al. Tryptase levels in children presenting with anaphylaxis: temporal trends and associated factors. J Allergy Clin Immunol. 2016;137(4):1138–42. https://doi.org/10.1016/j.jaci.2015.09.001.
Zhou X, Whitworth HS, E-Khedr M, Brown TA, Goswami R, Eren E, et al. Mast cell Chymase: a useful serum marker in anaphylaxis. J Allergy Clin Immunol. 2011;127(2):AB143–3. https://doi.org/10.1016/j.jaci.2010.12.566.
Brown TA, Whitworth HS, Zhou XY, Lau L, Eren E, Walls AF. Mast cell Carboxypeptidase as a confirmatory and predictive marker in allergic reactions to drugs. J Allergy Clin Immunol. 2011;127(2):AB143–3. https://doi.org/10.1016/j.jaci.2010.12.567.
Zhou X, Buckley MG, Lau LC, Summers C, Pumphrey RSH, Walls AF. Mast cell carboxypeptidase as a new clinical marker for anaphylaxis. J Allergy Clin Immunol. 2006;117(2):S85. https://doi.org/10.1016/j.jaci.2005.12.342.
Abadalkareem R, Lau LCK, Abdelmotelb A, Zhou X, Eren E, Walls AF. Mast cell tryptase and carboxypeptidase A3 (CPA3) as markers for predicting susceptibility to severe allergic drug reactions. J Allergy Clin Immunol. 2017;139(2):AB39. https://doi.org/10.1016/j.jaci.2016.12.185.
Korosec P, Turner PJ, Silar M, Kopac P, Kosnik M, Gibbs BF, et al. Basophils, high-affinity IgE receptors, and CCL2 in human anaphylaxis. J Allergy Clin Immunol. 2017;140(3):750–758.e15. https://doi.org/10.1016/j.jaci.2016.12.989.
Vantur R, Koren A, Erzen M, Kosnik M, Korosec P. CCL2 and severe anaphylaxis. In: Abstracts from the European Academy of Allergy and Clinical Immunology Congress, 26–30 May 2018, Munich, Germany. 2018. p. 315.
Mochizuki A, McEuen AR, Buckley MG, Walls AF. The release of basogranulin in response to IgE-dependent and IgE-independent stimuli: validity of basogranulin measurement as an indicator of basophil activation. J Allergy Clin Immunol. 2003;112(1):102–8. https://doi.org/10.1067/mai.2003.1511.
Kivistö JE, Protudjer JLP, Karjalainen J, Wickman M, Bergström A, Mattila VM. Hospitalizations due to allergic reactions in Finnish and Swedish children during 1999-2011. Allergy. 2016;71(5):677–83. https://doi.org/10.1111/all.12837.
Jeppesen AN, Christiansen CF, Frøslev T, Sørensen HT. Hospitalization rates and prognosis of patients with anaphylactic shock in Denmark from 1995 through 2012. J Allergy Clin Immunol. 2016;137(4):1143–7. https://doi.org/10.1016/j.jaci.2015.10.027.
• Tanno LK, Chalmers R, Bierrenbach AL, Simons FER, Martin B, Molinari N, et al. Changing the history of anaphylaxis mortality statistics through the World Health Organization’s International Classification of Diseases–11. J Allergy Clin Immunol. 2019;144(3):627–33. https://doi.org/10.1016/j.jaci.2019.05.013 This paper discribes the potential effects of new ICD-11 classification on anaphylaxis mortality statistics.
Tanno LK, Demoly P. How can the World Health Organization’s international classification of diseases (ICD)-11 change the clinical management of anaphylaxis? Expert Rev Clin Immunol. 2018;14(10):783–6. https://doi.org/10.1080/1744666X.2018.1520094.
Tanno LK, Calderon MA, Goldberg BJ, Gayraud J, Bircher AJ, Casale T, et al. Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community. Allergy. 2015;70(6):609–15. https://doi.org/10.1111/all.12604.
•• Tuttle KL, Wickner P. Capturing anaphylaxis through medical records: are ICD and CPT codes sufficient? Ann allergy, asthma Immunol. 2020;124(2):150–5. https://doi.org/10.1016/j.anai.2019.11.026 This paper describes the difficulties in capturing epidemioligcal information.
Walsh KE, Cutrona SL, Foy S, Baker MA, Forrow S, Shoaibi A, et al. Validation of anaphylaxis in the Food and Drug Administration’s mini-sentinel. Pharmacoepidemiol Drug Saf. 2013;22(11):1205–13. https://doi.org/10.1002/pds.3505.
Bohlke K, Davis RL, DeStefano F, Marcy SM, Braun MM, Thompson RS. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization. J Allergy Clin Immunol. 2004;113(3):536–42. https://doi.org/10.1016/j.jaci.2003.11.033.
Harduar-Morano L, Simon MR, Watkins S, Blackmore C. Algorithm for the diagnosis of anaphylaxis and its validation using population-based data on emergency department visits for anaphylaxis in Florida. J Allergy Clin Immunol. 2010;126(1):98–104.e4. https://doi.org/10.1016/j.jaci.2010.04.017.
Choi B, Kim SH, Lee H. Missed registration of disease codes for pediatric anaphylaxis at the emergency department. Emerg Med Int. 2019;2019:1–7. https://doi.org/10.1155/2019/4198630.
Tanno LK, Ganem F, Demoly P, Toscano CM, Bierrenbach AL. Undernotification of anaphylaxis deaths in Brazil due to difficult coding under the ICD-10. Allergy. 2012;67(6):783–9. https://doi.org/10.1111/j.1398-9995.2012.02829.x.
Demoly P, Tanno LK, Akdis CA, Lau S, Calderon MA, Santos AF, et al. Global classification and coding of hypersensitivity diseases - an EAACI - WAO survey, strategic paper and review. Allergy. 2014;69(5):559–70. https://doi.org/10.1111/all.12386.
Tanno LK, Calderon MA, Demoly P. Optimization and simplification of the allergic and hypersensitivity conditions classification for the ICD-11. Allergy. 2016;71(5):671–6. https://doi.org/10.1111/all.12834.
• Tanno LK, Molinari N, Bruel S, Bourrain JL, Calderon MA, Aubas P, et al. Field-testing the new anaphylaxis’ classification for the WHO International Classification of Diseases-11 revision. Allergy. 2017;72(5):820–6. https://doi.org/10.1111/all.13093 This paper describes validation of ICD-11 coding.
Tanno LK, Bierrenbach AL, Calderon MA, Sheikh A, Simons FER, Demoly P. Decreasing the undernotification of anaphylaxis deaths in Brazil through the international classification of diseases (ICD)-11 revision. Allergy. 2017;72(1):120–5. https://doi.org/10.1111/all.13006.
Mullins RJ, Dear KBG, Tang MLK. Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012. J Allergy Clin Immunol. 2015;136(2):367–75. https://doi.org/10.1016/j.jaci.2015.05.009.
Yang MS, Kim JY, Kim BK, Park HW, Cho SH, Min KU, et al. True rise in anaphylaxis incidence. Med (United States). 2017;96(5). https://doi.org/10.1097/MD.0000000000005750.
Jeong K, Lee JD, Kang DR, Lee S. A population-based epidemiological study of anaphylaxis using national big data in Korea: trends in age-specific prevalence and epinephrine use in 2010–2014. Allergy, Asthma Clin Immunol. 2018;14(1):31. https://doi.org/10.1186/s13223-018-0251-z.
Tejedor-Alonso MA, Moro-Moro M, Mosquera González M, Rodriguez-Alvarez M, Pérez Fernández E, Latasa Zamalloa P, et al. Increased incidence of admissions for anaphylaxis in Spain 1998-2011. Allergy. 2015;70(7):880–3. https://doi.org/10.1111/all.12613.
Yao TC, Wu AC, Huang YW, Wang JY, Tsai HJ. Increasing trends of anaphylaxis-related events: an analysis of anaphylaxis using nationwide data in Taiwan, 2001-2013. World Allergy Organ J. 2018;11(1):23. https://doi.org/10.1186/s40413-018-0202-7.
Motosue MS, Bellolio MF, Van Houten HK, Shah ND, Li JT, Campbell RL. Outcomes of Emergency Department Anaphylaxis visits from 2005 to 2014. J Allergy Clin Immunol Pract. 2018;6(3):1002–1009.e2. https://doi.org/10.1016/j.jaip.2017.07.041.
Xu YS, Kastner M, Harada L, Xu A, Salter J, Waserman S. Anaphylaxis-related deaths in Ontario: a retrospective review of cases from 1986 to 2011. Allergy, Asthma Clin Immunol 2014;10(1). https://doi.org/10.1186/1710-1492-10-38.
Turner PJ, Campbell DE, Motosue MS, Campbell RL. Global trends in anaphylaxis epidemiology and clinical implications. J allergy Clin Immunol Pract. 2019. https://doi.org/10.1016/j.jaip.2019.11.027 This review summarises some of the recent trends in anaphylaxis epidemiology.
Parrish CP, Kim H. Food-induced anaphylaxis: an update. Curr Allergy Asthma Rep. 2018;18(8). https://doi.org/10.1007/s11882-018-0795-5.
Skypala IJ. Food-induced anaphylaxis: role of hidden allergens and cofactors. Front Immunol. 2019;10(APR). https://doi.org/10.3389/fimmu.2019.00673.
McGowan EC, Peng RD, Salo PM, Zeldin DC, Keet CA. Changes in food-specific IgE over time in the National Health and nutrition examination survey (NHANES). J Allergy Clin Immunol Pract. 2016;4(4):713–20. https://doi.org/10.1016/j.jaip.2016.01.017.
Dhopeshwarkar N, Sheikh A, Doan R, Topaz M, Bates DW, Blumenthal KG, et al. Drug-induced anaphylaxis documented in electronic health records. J Allergy Clin Immunol Pract. 2019;7(1):103–11. https://doi.org/10.1016/j.jaip.2018.06.010.
Park HK, Kang MG, Yang MS, Jung JW, Cho SH, Kang HR. Epidemiology of drug-induced anaphylaxis in a tertiary hospital in Korea. Allergol Int. 2017;66(4):557–62. https://doi.org/10.1016/j.alit.2017.02.008.
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Both authors contributed to the manuscript conception and literature review. Data analysis was performed by Merlin Ranald McMillan. The first draft of the manuscript was written by Merlin Ranald McMillan, and both authors commented on previous versions of the manuscript. Both authors read and approved the final manuscript.
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McMillan, M., Morais-Almeida, M. The Challenge of Establishing the Burden of Anaphylaxis: Some Recent Trends. Curr Treat Options Allergy 7, 441–456 (2020). https://doi.org/10.1007/s40521-020-00257-9
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DOI: https://doi.org/10.1007/s40521-020-00257-9