Pathogenesis and Treatment of Anaphylaxis

National Institute Of Allergy And Infectious Diseases

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Abstract

We have evaluated 116 patients referred for idiopathic anaphylaxis (IA) and antigen-specific anaphylaxis (SA) to explore pathogenesis and identify patients with clonal mast cell disease. Overall, 29% have been diagnosed with a clonal mast cell disease, 19.5% with a primary diagnosis of IA. Of the patients with SA, 54% with a primary diagnosis of venom anaphylaxis and 8.3% with a primary diagnosis of food or drug-induced anaphylaxis. In addition, 8.6% were diagnosed with alpha-gal syndrome, and 14.6% were diagnosed with hereditary alpha-tryptasemia syndrome. Among patients with antigen-induced anaphylaxis, those with venom anaphylaxis in European cohorts have been reported to have a higher prevalence of clonal mast cell disease. In our cohort of patients referred for venom anaphylaxis to date (n=13), 11 (85%) have been diagnosed with clonal mast cell disease. Of the 11 patients enrolled with food or drug-induced anaphylaxis, thus far, two (18%) have been diagnosed with clonal mast cell disease. Our patient population was instructive in highlighting that the association of hereditary alpha tryptasemia (HT) was more prevalent in patients with anaphylaxis but also the severity of the reaction was intensified when HT was coexistent with IA and SA. Thus, an important co-factor for management. In FY 2025, we closed the protocol to new patients. This protocol was instrumental in modifying the approach to a differential diagnosis and creating a predictive model to determine the probability of clonal mast cell disease. This is the first prospective data collection for idiopathic anaphylaxis, and we are currently conducting a long-term analysis and follow up to create a model for management based on the morbidity and mortality data. This manuscript is supporting a Duke Master’s program thesis for a former A/I fellow. In FY 2025, we contributed to a manuscript focused on the career of Dr. Dean Metcalfe and the contributions to mast cell research and clinical implications. Our collaboration with Dr. Jonathan Lyons has utilized proteomic data using Somascan in identifying biomarkers of mast cell activation that may proactively detect patients at risk for anaphylaxis.