BACKGROUND: Hereditary α-tryptasemia, a genetic trait caused by increased α-tryptase copy number, is associated with idiopathic and venom anaphylaxis. OBJECTIVE: We aimed to determine the impact of tryptase genotypes on drug-induced anaphylaxis. METHODS: A prospective discovery cohort of 99 patients from a referral center in Slovenia with acute anaphylaxis to drugs underwent tryptase genotyping by droplet digital PCR. For validation, we included a cohort of 26 patients from the Czech Republic. Associated inciting agents and the severity of the reactions were subsequently examined. RESULTS: Hereditary α-tryptasemia was associated with drug-induced anaphylaxis with a prevalence of 13% (n = 13 of 99) in the discovery cohort and 15% in the validation cohort (n = 4 of 26). Hereditary α-tryptasemia was identified in every individual with elevated basal serum tryptase levels (11.6-21.9 ng/mL; n = 14) within both cohorts of patients. Hereditary α-tryptasemia was more prevalent in individuals with antibiotic- or mAb-induced anaphylaxis in both the discovery and validation cohorts (n = 13 of 51; 26%) compared to those with anaphylaxis resulting from neuromuscular blocking agents, nonsteroidal anti-inflammatory drugs, contrast, chlorhexidine, or other drugs (n = 5 of 74; 7%; P = .02; odds ratio = 4.1; 95% CI, 1.3-11.1). Overall, we found fewer individuals with no ⍺-tryptase than in the general population, and there was a trend for subjects with more ⍺-tryptase copies to have more severe reactions. Thus, among subjects with three ⍺-tryptase copies, the prevalence of severe anaphylaxis was 73%, compared with 59% with one to two ⍺-tryptase copies and 58% for subjects without ⍺-tryptase. CONCLUSIONS: Risk for anaphylaxis to antibiotics and biologics is associated with inherited differences in α-tryptase-encoding copies at Tryptase α/β1.

Division of Allergy and Immunology Department of Medicine University of California San Diego La Jolla Calif; Veterans Affairs San Diego Healthcare System La Jolla Calif

GENNET s r o Department of Allergy and Clinical Immunology Prague Czech Republic

GNTlabs by GENNET Centre of Medical Genetics and Reproductive Medicine GENNET Prague Czech Republic

University Clinic of Respiratory and Allergic Diseases Golnik Slovenia; Biotechnical Faculty University of Ljubljana Ljubljana Slovenia

University Clinic of Respiratory and Allergic Diseases Golnik Slovenia; Faculty of Pharmacy University of Ljubljana Ljubljana Slovenia

University Clinic of Respiratory and Allergic Diseases Golnik Slovenia; Medical Faculty Department of Internal Medicine University of Ljubljana Ljubljana Slovenia

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