We have assembled the data from the idiopathic anaphylaxis (IA) patient cohort and a manuscript titled A distinct biomolecular profile identifies monoclonal mast cell disorders in patients with idiopathic anaphylaxis is in press. Seventeen per cent of the patients with IA in our study cohort were diagnosed with a monoclonal mast cell activation syndrome (MMAS) or indolent systemic mastocytosis. Allele-specific qPCR to detect the D816V mutation in KIT was used to strengthen our ability to predict which patients would benefit from a bone marrow biopsy to rule out a clonal mast cell disorder. This assay is sensitive enough to detect the mutation in circulating progenitor cells and when used with other markers of severity such as serum tryptase levels, is useful in identifying patients needing closer observation for progression of disease. Additionally, we have used allele-specific qPCR to expand the current published scoring system to increase its sensitivity and thus provide a tool to prevent unnecessary bone marrow procedures. The expression of in vivo activation markers by bone marrow mast cells was only seen in patients with a clonal mast cell disorder, but not in those with IA. Mast cells cultured from patients with IA did not exhibit a hyper-responsive mast cell. No specific signaling abnormalities were identified from genetic analysis from peripheral blood-derived mast cells. A sub-group of patients with IA were found to have multiple copies of the alpha-tryptase gene in a familial distribution. These patients are under study. As of the date of this report, patients with either idiopathic or antigen-induced anaphylaxis continue to be admitted for study (08-I-0184). 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 the patient bone marrow aspirates and biopsies obtained based on the 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 including asthma, food allergy and chronic urticaria. Similarly, we have reported that omalizumab prevented episodes of spontaneous anaphylaxis in two patients with mastocytosis that have been followed for 10 years. In FY 2017, we will complete enrollment for the omalizumab treatment protocol for IA and will report our findings after unblinding of the data.There have been no serious adverse events related to study drug, in particular drug-induced anaphylaxis.
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