From mechanism to management: CEREMAST perspectives on the intersection of HαT and clonal mast cell disorders

Laura Polivka^1,2,3Olivier Hermine^1,2,4*Julien Rossignol^1,2,4

• ¹French Reference Center for Mastocytosis (CEREMAST), Paris Cité University, Necker - Enfants Malades University Hospital, AP-HP, Paris, France, Paris, France
• ²Laboratory of physiopathology and treatment of hematological disorders, Imagine Institute, INSERM U1163, Paris, France., Paris, France
• ³Department of Dermatology and Pediatric, Necker Enfants malades, Assistance Publique (AP-HP), Paris Cité University, Paris, France, Paris, France
• ⁴Department of Hematology Cochin-Necker, Assistance Publique (AP-HP), Paris Cité University, Paris, France, Paris, France

Since its initial description ten years ago, numerous studies have contributed to a better understanding of the role of hereditary alpha-tryptasemia (HαT) in the diagnosis and management of patients with clonal mast cell activation disorders (cMCADs). These studies have highlighted the high prevalence of HαT among cMCADs patients, the associated elevation in baseline serum tryptase levels—which can influence both diagnosis and disease monitoring—and distinct clinical features, notably an increased risk of severe anaphylaxis. As a result, screening for HαT has become an integral part of the diagnostic work-up in patients with cMCADs. However, several key questions remain unresolved: Why is HαT more prevalent among cMCADs patients? How can we accurately distinguish between HαT and cMCADs during the diagnostic process? And how does the presence of this genetic trait influence the clinical management of cMCADs? In this article, we present the position and clinical approach of the French National Reference Center for Mastocytosis (CEREMAST).