Original Article Predictors of Biphasic Reactions in the Emergency Department for Patients With Anaphylaxis Sangil Lee, MD, M. Fernanda Bellolio, MD, Erik P. Hess, MD, and Ronna L. Campbell, MD, PhD Rochester, Minn What is already known about this topic? Biphasic reactions are uncommon and unpredictable, and risk factors for biphasic reactions are poorly understood. What does this article add to our knowledge? Patients with a history of prior anaphylaxis, an unknown precipitant, or who present with symptoms of diarrhea or wheezing may be at increased risk for a biphasic reaction. How does this study impact current management guidelines? This study will add additional data for possible risk factors management for biphasic reactions. BACKGROUND: A biphasic reaction is the recurrence of anaphylaxis symptoms within 72 hours of the initial anaphylactic event, without re-exposure to the trigger. Biphasic reactions are uncommon and unpredictable, and risk factors for biphasic reactions are poorly understood. OBJECTIVE: To identify predictors of biphasic anaphylactic reactions in patients with anaphylaxis in the emergency department (ED). METHODS: Patients of all ages who presented to the ED and met diagnostic criteria for anaphylaxis from April 2008 to January 2013 at an academic medical center with 73,000 annual patient visits were consecutively included. We collected data on patient characteristics, suspected triggers, signs and symptoms, ED management, and disposition. Univariate analyses were performed to estimate the association between potential predictor variables and biphasic reactions. We report associations as odds ratios (OR) and corresponding 95% CIs. RESULTS: Among 541 patients with anaphylaxis, median age was 34.6 years (interquartile range, 18-52 years), and 320 (59%) were female patients. Twenty-one patients (4%) had biphasic reactions. Two pediatric patients, ages of 5 years old and 16 years old, developed a biphasic reaction. The median time between the resolution of initial symptoms and onset of the biphasic reaction was 7 hours (range, 1-72 hours). Biphasic reactions were associated with a history of prior anaphylaxis (OR 2.6 [95% CI, 1.1-6.4]; P [ .029), unknown precipitant (OR 2.6 [95% CI, 1.1-6.2]; P [ .03), symptoms of diarrhea (OR 4.5 [95% CI, 1.4-14.0]; P [ .024), and wheezing (OR 2.6 [95% CI, 1.4-8.9]; P [ .029). CONCLUSIONS: Patients with a history of prior anaphylaxis, an unknown precipitant, or who present with symptoms of diarrhea or wheezing may be at increased risk for a biphasic reaction. Ó 2014 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2014;2:281-7) Key words: Anaphylaxis; Biphasic reactions; Risk factors; Emergency department Anaphylaxis is a systemic allergic reaction that is most commonly treated in the emergency department (ED). 1,2 Signs and symptoms can vary from relatively mild to life-threatening. 3-5 A biphasic reaction is a recurrent reaction that meets criteria for anaphylaxis and occurs after resolution of symptoms without re-exposure to the trigger. 6,7 Rates of biphasic reactions vary widely, and relatively few studies have reported risk factors for biphasic reactions. 6-10 In addition, both protective and risk factors are not consistently found among study populations. Thus, biphasic reactions are poorly understood. The objectives of this study were to determine the incidence and characteristics of biphasic reactions and to identify protective or risk factors for biphasic reactions among patients who present to the ED with anaphylaxis. METHODS Study design and setting This was an observational cohort study of consecutive patients who presented with anaphylaxis to the Saint Mary’s Hospital ED of the Mayo Clinic, a tertiary care academic ED with 73,000 annual patient visits. Selection of participants Electronic medical records of patients of all ages in the ED were queried. Records of all patients who had any ED diagnosis that contained “allerg,”“anaphy,” or “sting” were reviewed, and those who met the National Institute of Allergy and Infectious DiseaseeFood Allergy and Anaphylaxis Network diagnostic criteria 3 for anaphylaxis were included. Diagnostic criteria for anaphylaxis are summarized here. Department of Emergency Medicine, Mayo Clinic, Rochester, Minn No funding was received for this work. Conflict of interest: The authors declare that they have no relevant conflicts of interest. Received for publication October 20, 2013; revised January 1, 2014; accepted for publication January 13, 2014. Available online April 2, 2014. Corresponding author: Sangil Lee, MD, Department of Emergency Medicine, Mayo Clinic Health System, 1025 Marsh Street, Mankato, MN 56001. E-mail: Lee.Sangil@mayo.edu. 2213-2198/$36.00 Ó 2014 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2014.01.012 281