Mast cell activation syndrome: Global perspectives from a World Allergy Organization survey on knowledge, diagnosis, and access to care.

Background: Mast Cell Activation Syndrome (MCAS) has emerged as a highly debated and increasingly recognized condition in allergy and clinical immunology. Despite established AIM/ECNM consensus criteria, major uncertainties persist regarding its diagnosis, implementation in real-world practice, and equitable access to diagnostic resources worldwide. Objective: To evaluate global knowledge, diagnostic practices, clinical exposure, and access to care related to MCAS among allergists and clinical immunologists, and to identify critical unmet needs contributing to diagnostic uncertainty. Methods: We conducted a cross-sectional international survey primarily involving allergists and clinical immunologists affiliated with the World Allergy Organization (WAO). The survey instrument was developed by international experts in mast cell disorders, including contributors to the conceptual framework and consensus diagnostic criteria for MCAS. The questionnaire assessed knowledge of consensus diagnostic criteria, clinical experience with suspected and confirmed MCAS, access to validated laboratory testing, diagnostic confidence, and treatment strategies. Regional comparisons were performed to identify disparities in practice patterns and resource availability. Results: Marked global heterogeneity was observed in knowledge of MCAS diagnostic criteria, application of consensus frameworks, and access to essential laboratory testing. Across all regions, clinicians reported a substantial and consistent gap between the number of patients suspected of having MCAS and those who ultimately fulfilled all diagnostic criteria. Objective biomarker confirmation-particularly documentation of dynamic serum tryptase changes and access to urinary mast cell mediator metabolites-emerged as the principal diagnostic bottleneck worldwide. However, the imbalance between suspected and confirmed cases persisted even in regions with relatively greater laboratory access, suggesting that structural limitations coexist with potential diagnostic overextension and inconsistent clinical phenotyping. Management approaches were predominantly empiric and symptom-driven, often implemented in the absence of complete diagnostic confirmation. Respondents highlighted the need for clearer guidance, improved biomarker accessibility, and refinement of definitions to reduce diagnostic ambiguity. Conclusions: MCAS represents a condition in which both under-recognition and diagnostic uncertainty remain important challenges in contemporary practice. Significant unmet needs include strengthening clinician knowledge and application of the AIM/ECNM diagnostic framework, expanding global access to validated biomarkers, improving diagnostic precision, and harmonizing clinical approaches. At the same time, the findings of this survey suggest a need for continued evaluation and refinement of the current diagnostic framework to improve its applicability across the heterogeneous clinical spectrum of patients with suspected MCAS. Coordinated international efforts are urgently required to reduce diagnostic uncertainty, minimize inequities in care, and support the continued evolution toward a more accurate, consistent, and clinically applicable diagnostic approach worldwide.