Risk factors for severe anaphylaxis in the United States Megan S. Motosue, MD * ; M. Fernanda Bellolio, MD y ; Holly K. Van Houten, BA z ; Nilay D. Shah, PhD z, x, jj ; Ronna L. Campbell, MD, PhD y * Division of Allergic Diseases, Mayo Clinic, Rochester, Minnesota y Department of Emergency Medicine, Mayo Clinic, Rochester, Minnesota z Robert D. and Patricia E. Kern Center for Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota x Division of Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota jj OptumLabs, Cambridge, Massachusetts A R T IC L E IN F O Article history: Received for publication May 15, 2017. Received in revised form July 6, 2017. Accepted for publication July 11, 2017. A B ST R AC T Background: Anaphylaxis is an acute systemic allergic reaction and may be life-threatening. Objective: To assess risk factors associated with severe and near-fatal anaphylaxis in a large observational cohort study. Methods: We analyzed administrative claims data from Medicare Advantage and privately insured enrollees in the United States from 2005 to 2014. Severe anaphylaxis was defined as anaphylaxis resulting in hospital or intensive care unit (ICU) admission, requiring endotracheal intubation, or meeting criteria for near-fatal anaphylaxis. Results: Of 38,695 patients seen in the emergency department for anaphylaxis during the study period, 4,431 (11.5%) required hospitalization, 2,057 (5.3%) were admitted to the ICU, 567 (1.5%) required endotra- cheal intubation, and 174 (0.45%) were classified as having a near-fatal episode. Multivariable analysis revealed that medication-related anaphylaxis (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.38e1.63; P < .001), age of 65 years or older (OR, 3.15; 95% CI, 2.88e3.44; P < .001), and the presence of cardiac disease (OR, 1.56; 95% CI, 1.50e1.63; P < .001) or lung disease (OR, 1.23; 95% CI, 1.16e1.30; P < .001) were associated with increased odds of severe anaphylaxis requiring any hospital admission, ICU admission, or intubation or being a near-fatal reaction. Conclusion: In this large contemporary cohort study, 11.6% of patients had severe anaphylaxis. Age of 65 years or older, medication as a trigger, and presence of comorbid conditions (specifically cardiac and lung disease) were associated with significantly higher odds of severe anaphylaxis. Additional studies examining risk factors for severe anaphylaxis are needed to define risk assessment strategies and establish a framework for management. Ó 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. Introduction Anaphylaxis is an acute systemic allergic reaction and may involve life-threatening airway, breathing, or circulation problems. 1 The lifetime prevalence of anaphylaxis in the United States has been estimated at between 0.5% and 2%, 2 with a recent study suggesting a prevalence as high as 5.1%. 3 Trends in anaphylaxis- related hospitalizations appear to be increasing, not only in the United States 4,5 but also in Spain, 6 the United Kingdom, 7 and Australia. 8,9 In the United States, Ma et al 4 reported that the rate of anaphylaxis-related hospitalizations increased from 21.0 to 25.1 per million population between 1999 and 2009. The severity and out- comes of any anaphylactic episode are unpredictable 10 ; thus, risk assessment strategies are needed. An important area of anaphylaxis research has been identifying clinical markers to distinguish those likely to have more severe outcomes and even death from most patients who will have mild to moderate reactions and can safely be discharged home. The study of nonfatal but severe outcomes of anaphylaxis is important because these reactions represent key points of intervention with the potential for improving future outcomes. Our study objective was to evaluate risk factors associated with increased anaphylaxis severity by studying cases of severe Reprints: Ronna L. Campbell, MD, PhD, Department of Emergency Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; E-mail: campbell.ronna@mayo.edu. Disclosures: Dr Campbell declares personal fees from INSYS, the American College of Allergy, Asthma, and Immunology, and UpToDate (all outside this work). No other disclosures were reported. Funding Sources: This publication was made possible by funding from the Mayo Clinic Robert D. and Patricia E. Kern Center for Science of Health Care Delivery. Conflict of interest: Dr Motosue, Dr Bellolio, Ms Van Houten, and Dr Shah declare none. Previous Presentation: Portions of this article were previously published in Moto- sue MS, Bellolio MF, Van Houten HK, Shah ND, Campbell RL. Increasing emergency department visits for anaphylaxis, 2005-2014. J Allergy Clin Immunol Pract. 2017;5:171-175 (used with permission). Contents lists available at ScienceDirect http://dx.doi.org/10.1016/j.anai.2017.07.014 1081-1206/Ó 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. Ann Allergy Asthma Immunol 119 (2017) 356e361