Selecting the right criteria and proper classification to diagnose mast cell activation syndromes: a critical review

In recent years, our knowledge about mechanisms underlying mast cell activation (MCA) and accumulation in various pathologic conditions increased substantially. In addition, criteria and a classification of MCA syndromes (MCAS) have been set forth. MCAS is defined by typical clinical symptoms, a substantial increase in serum tryptase level during an attack over the patient´s baseline tryptase, and a response of the symptoms to drugs targeting mast cells, mediator production and/or mediator effects. Alternative diagnostic criteria of MCAS have also been suggested, but these alternative criteria often lack specificity and validation. In the current document, we critically review the contemporary literature relating to MCAS and compare the specificity, sensitivity, and strength of MCAS-related parameters within proposals to diagnose and classify MCAS and its variants. Furthermore, we highlight the necessity to apply specific consensus criteria in the evaluation and classification of MCAS in individual patients. This is an urgent and important medical need, as an increasing number of patients are being misdiagnosed with MCAS based on non-specific criteria which contributes to confusion and frustration by patients and caregivers and may sometimes delay recognition and treatment of the correct medical conditions which often turns out to be unrelated to MCA.