Pathogenesis and Treatment of Anaphylaxis

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We have evaluated 102 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, 15% had clonal mast cell disease, 8.5% were diagnosed with alpha-gal syndrome, and 12.8% were diagnosed with hereditary alpha-tryptasemia. 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=8), six have been diagnosed with clonal mast cell disease. Of the five patients enrolled with food or drug-induced anaphylaxis, thus far, none have been diagnosed with clonal mast cell disease. In FY 2020, we continued to admit patients with anaphylaxis prior to the Clinical Center COVID restrictions. Most patients are admitted to the inpatient unit and undergo a bone marrow procedure in an attempt 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. We will resume protocol enrollment as allowed by the CC guidelines. It is challenging to identify a therapeutic regimen for patients with IA. Omalizumab is approved for the treatment of severe asthma and in part 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. We recruited patients from our anaphylaxis protocol that met criteria for frequent events to enroll in a DBPC trial to evaluate the efficacy of omalizumab in this patient population. In FY 2020, we completed the manuscript and will submit for publication. There were no serious adverse events attributed to the study drug, in particular drug-induced anaphylaxis. In FY 2020, we contributed to a manuscript by Lyons et al with our idiopathic anaphylaxis patient population. Patients with idiopathic anaphylaxis were found to a have higher prevalence of hereditary alpha tryptasemia(HaTS) when compared to controls without anaphylaxis and patients with clonal mast cell disease and anaphylaxis. HaTS also was associated with an elevated baseline serum tryptase and was possibly associated with an increased risk of severe anaphylaxis. Insights gained from the anaphylaxis study were considerd in the creation of a practical guide to the management of patients with idiopathic anaphylaxis published in Allergy and an AAAAI Work Group report on mast cell activation syndrome in the Journal of Allergy and Clinical Immunology.