Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

TLDR

Mast cell activation and abnormal growth are characteristic of mastocytosis, yet many patients exhibit MC activation without mastocytosis or allergic reactions, and some have clonal MCs that do not meet diagnostic criteria. The 2010 working conference aimed to establish diagnostic criteria for MC activation and to propose a unified classification of all mast cell disorders and reactions. MCA is defined by clinical symptoms, a transient rise in serum tryptase or other MC mediators, and a symptom response to agents that reduce MC mediator production or activity. The proposed classification delineates primary, secondary, and idiopathic MCAS, and the criteria aid in accurate diagnosis while preventing misinterpretation of symptoms.

Abstract

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of ‘MCA syndromes’ (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D<sub>2</sub>, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets.