Mast cell activation syndrome: The overdiagnosis problems

The incidence of mast cell activation syndrome (MCAS) has increased since first definition as a mastocytosis-like phenotype. Despite well-described criteria developed by the MCAS consortium, its growing rates have occurred in the context of multiple alternative criteria for MCAS diagnostics. The Vienna Consensus has defined clear diagnostic criteria for MCAS, which include, first of all, a clinical criterion characterized by severe recurrent symptoms involving two or more organs and meeting the criteria for anaphylactic response. Secondly, a laboratory criterion, has been established where the most specific and golden standard marker is a significant increase in tryptase levels, determined in blood serum for several hours (up to 4 h) after the event, being calculated as 120% of the basal tryptase level plus 2 ng/mL. Determination of other biomarkers is currently not recommended due to their lower specificity and lack of clearly set cut-off values. Third, the therapeutic response criterion, which implies that the drugs targeting mast cells, should reduce the frequency and severity of MCAS episodes. There is a classification of MCAS, which discriminates primary (clonal) and secondary (non-clonal) response from idiopathic MCAS. Primary MCAS is defined by clonal expansion of mast cells and proceeds in confirmed systemic mastocytosis, or two minor criteria for mastocytosis. Secondary MCAS is diagnosed when the mast cells are activated by known triggers. Most often, it is associated with IgE-mediated or other hypersensitivity reactions (e.g., drug-, food-, or insect-induced anaphylaxis). If neither clonal expansion, nor a trigger event for mast cell activation can be identified, the condition is classified as idiopathic MCAS. Consensus 2 clinical criteria are not specific enough to diagnose MCAS, and the use of less specific (or non-specific) laboratory tests may lead to overdiagnosis of this condition. Recent studies confirm that MCAS is quite rare. However, patients with unspecified MCAS exhibit non-specific symptoms without a clear pathogenic significance, do not respond to standard mast cell-targeted therapy, thus leading to a reduced quality of life, as well as to social stigmatization. However, it is important to understand that false diagnostics of MCAS may lead to missing the diagnosis of underlying disease not associated with mast cell activation, and appropriate treatment will be not administered to the patient.