Pathogenesis and Treatment of Anaphylaxis

National Institute Of Allergy And Infectious Diseases

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Abstract

We have evaluated 107 patients referred for idiopathic anaphylaxis (IA) and antigen-specific anaphylaxis (SA) to explore pathogenesis and identify patients with clonal mast cell disease. Within the patient group with IA, 14% had clonal mast cell disease, 9.3% were diagnosed with alpha-gal syndrome, and 14% 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=9), seven (78%) have been diagnosed with clonal mast cell disease. Of the eight patients enrolled with food or drug-induced anaphylaxis, thus far, one has been diagnosed with clonal mast cell disease. In FY 2021, we continue to admit patients with IA and antigen-specific anaphylaxis (SA) as allowed by the Clinical Center COVID restrictions. Most patients are admitted to the inpatient unit and undergo a bone marrow procedure as part of the effort to elucidate the etiology and evaluate the pathogenesis of their disease. In collaboration with the NIH Clinical Center's myeloid core facility, we assess all patient bone marrow aspirates and biopsies obtained based on the current WHO criteria to diagnose systemic mastocytosis. Omalizumab is approved for the treatment of severe asthma and acts through a mechanism that down regulates the IgE receptor on the surface of basophils, mast cells, and dendritic cells. Omalizumab has been reported to be useful as adjunct therapy in the treatment of diseases other than asthma including food allergy and chronic urticaria. In FY 2021, we published a study in the Journal of Allergy and Clinical Immunology that consisted of a randomized double-blinded, placebo-controlled study of omalizumab for idiopathic anaphylaxis in which no statistically significant difference was demonstrated between the placebo and treated groups when administered omalizumab. However, there was a trend for efficacy in the treatment group, particularly after 60 days. Overall, the safety profile was favorable and there were no serious adverse events attributed to the study drug, in particular drug-induced anaphylaxis. In FY 2021, we contributed to a manuscript by Lyons et al with our IA patient population. Patients with IA and patients with mastocytosis were found to have a higher prevalence of hereditary alpha tryptasemia (HAT) when compared to healthy volunteers or non-atopic disease controls. Among patients with mastocytosis, concomitant HAT was associated with increased risk for systemic anaphylaxis. Insights gained from this anaphylaxis study were important in the creation of a practical guide to the management of patients with IA to include the creation of an algorithm and calculator to enhance accuracy to predict a significant rise in serum tryptase typical of an anaphylactic event.