Mast Cell Disorders and Hymenoptera Venom-Triggered Anaphylaxis: Evaluation and Management

Abstract

Patients with Hymenoptera venom allergy (HVA), especially those with severe anaphylaxis, frequently have concomitant clonal mast cell disease (MCD) in the form of systemic mastocytosis or monoclonal mast cell activation syndrome. Detection of clonal MCD is important since it will have significant consequences for management of HVA. Therefore, we recommend patients with HVA be systematically screened for clonal MCD. The pre-test probability of clonal MCD can be assessed in a stepwise fashion starting with examination of the skin for typical monomorphic maculopapular cutaneous mastocytosis (MPCM) lesions; measurement of the baseline serum tryptase (BST) and tryptase genotyping for patients with BST>11 ng/mL; followed by the REMA score which is calculated by utilizing anaphylaxis clinical features, BST, and patient sex. A bone marrow biopsy should be performed in patients with monomorphic MPCM, a REMA score ≥2, or an elevated BST based upon tryptase genotype. Patients with HVA and a clonal MCD should be treated with immunotherapy directed against the Hymenoptera venom for which they are sensitized. For this high-risk subgroup of HVA patients, it is recommended to continue immunotherapy for more than 5 years or indefinitely and to carry at least three epinephrine autoinjectors. Future studies should determine whether KIT D816V-selective tyrosine kinase inhibitors are effective at preventing or reducing severity of Hymenoptera-venom triggered anaphylaxis in patients with clonal MCD.