AAAAI Mast Cell Disorders Committee Work Group Report: Mast Cell Activation Syndrome (MCAS) Diagnosis and Management.

Our current recommendations for diagnosing and treating primary MCAS make use of the latest studies and consensus guidelines for clinically recognizing systemic anaphylaxis in real time, regardless whether allergen-triggered an allergen-triggered IgE:FcεRI-mediated pathway or to ligands of G protein receptor pathways, or to intrinsic dysregulation of mast cells; our current understanding of the biomarkers secreted by activated mast cells that best discriminate this disorder from other conditions; and the therapeutic drugs that may selectively affect those mediators or mast cells themselves. Finding familial or somatic mutations of genes that cause mast cells to be hyper-activatable would extend our diagnostic tools and potentially indicate new therapeutic interventions, targeting either the mutated gene product or the associated molecular pathway. In conclusion, we trust that the clinical, laboratory and therapeutic criteria for primary MCAS(s) described herein will provide clinicians with practical criteria of sufficient sensitivity and specificity to diagnose most cases, without over-diagnosing the disorder in patients who likely have other conditions.