New Yardstick Outlines Treatment Approach for MCAS and Indolent Systemic Mastocytosis

An evidence-based expert opinion yardstick provides clinicians with a framework for treating mast cell activation syndrome (MCAS) and indolent systemic mastocytosis (ISM), 2 mast cell disorders associated with substantial morbidity and impaired quality of life.

The review reflects recent advances in mast cell biology and evolving classifications of clonal and nonclonal mast cell diseases. These distinctions have introduced different treatment paradigms, including novel therapies approved for some clonal mast cell disorders. However, the authors note that “there is some lack of guidance on how best to use these therapies.”

Because MCAS and ISM can present with broad, overlapping symptoms, the authors emphasize diagnostic confirmation before initiating a treatment plan. They note that both ISM and nonclonal mast cell activation disorders “cause morbidity and decreased quality of life in patients,” but may resemble other conditions because of their protean manifestations.

Management begins with avoidance of potential triggers and emergency preparedness for patients at risk for anaphylaxis. Pharmacologic therapy may overlap between ISM and nonclonal mast cell activation disorders, particularly when symptoms are driven by mast cell mediators.

Recommended medication categories include therapies targeting mediators, mediator release, and mediator synthesis. H1 and H2 antihistamines and leukotriene receptor antagonists are used to target mast cell mediators. Cromolyn and omalizumab may be used to address mediator release. A 5-lipoxygenase inhibitor and acetylsalicylic acid may be considered for mediator synthesis in selected patients.

For patients with ISM, cytoreductive therapy may provide significant benefit. The authors identify avapritinib as the only currently approved therapy with regulatory approval for ISM.

Reference
Akin C, Butterfield JH, Castells M, Lyons JJ. Management of indolent mastocytosis and mast cell activation syndrome: A clinical yardstick. Ann Allergy Asthma Immunol. 2025;135(4):466-477. doi:10.1016/j.anai.2025.06.032