Progress in mast cell activation syndrome: the global consensus-2 diagnostic criteria at six years

Since establishment in 2020 of the global consensus-2 diagnostic criteria for mast cell activation syndrome (MCAS), recognition of this prevalent disease, existing alongside rare cutaneous or systemic mastocytosis, has grown significantly. Despite this progress, some have continued using more restrictive criteria, significantly underdiagnosing this complex but treatable disorder. Consensus-2 has brought diagnosis and effective treatment in many MCAS patients previously labeled with unexplained (mostly inflammatory) syndromes or misdiagnosed as somatization or other primary psychiatric disorders. Fears that consensus-2 diagnostic criteria might bring overdiagnosis have not been realized. Appropriate therapy for MCAS can dramatically improve quality of life, sometimes after decades of morbidity and disability despite extensive past unhelpful workups and treatment. Appreciating the breadth and heterogeneity of MCAS, and achieving good management outcomes, requires understanding the complexity of mast cell biology and pathophysiology as well as the range of comorbidities the disease can drive and which can aggravate the disease. The spectrum of diseases thought possibly rooted in variants of MCAS (or to which MCAS is significantly contributing) continues expanding, calling for more research. New therapeutic options have emerged, and clinicians have gained better appreciation for use of existing treatments and mitigation of impediments to treatment. MCAS research remains in early stages, hampered by many factors including limited awareness of the disease and challenges in objective assessment of treatment response. This review examines developments in awareness, education, clinical care, and research since consensus-2 emerged, while discussing challenges and opportunities for accelerating progress.