Diagnosis and Management of Patients With Mast Cell Activation Syndromes: Status 2026.

Abstract

Over the past 15 years, the number of patients referred to specialized centers because of a suspected or known mast cell activation disorder (MCAD) has increased substantially in various countries. MCAD is an umbrella term encompassing a heterogeneous group of conditions in which inappropriate or excessive mast cell activation plays a central role. These include IgE-mediated allergic diseases, clonal mast cell disorders such as systemic mastocytosis, and mast cell activation syndrome (MCAS), a distinct clinical entity characterized by systemic symptoms, objective biochemical evidence of mast cell mediator release, and a response to targeted therapy. The increased referral rate is due to an increased awareness of MCAD, a high prevalence of IgE-dependent allergies where mast cell activation is a pathognomonic feature, and the growing access to internet and social media with unverified medical information resources, which may lead to incorrect self- or health care provider-suggested diagnoses. An additional challenge is that solid criteria for MCAS and other MCADs have been proposed but are not known, not applied, or not accepted by all providers. However, to confirm mast cell involvement with certainty in such disorders, which is an ultimate diagnostic prerequisite, stringent diagnostic criteria of MCAS or other MCADs have to be fulfilled. In this article, we provide an overview of available diagnostic standards, assays, and criteria used to diagnose MCAS and other forms of MCADs. In addition, we provide a state-of-the-art overview of therapeutic options. Finally, we review differential diagnoses that must be considered before MCAS is diagnosed.