Reviews and feature articleMast cell activation syndrome: Proposed diagnostic criteria
Section snippets
Historical perspective
In the late 1980s, the existence of “mast cell activation disorders” apparently associated with sudden synchronous mediator release in the absence of evidence of mast cell proliferation began to be discussed in the literature.3 The possibility of such disorders, which would have as their basis activated mast cells, was considered at a consensus conference to classify variants of systemic mastocytosis. To quote, “There also may be unknown diseases of mast cell activation, in which mast cells
Mast cells and mediators
Mast cells are derived from hematopoietic stem cells and undergo terminal differentiation in tissues.16 They are found concentrated in locations, such as the mucosal and endothelial surfaces, where tissues interface with the external environment. This is consistent with the current understanding of mast cells as sentinels of innate and adaptive immune systems. Although the exact role of mast cells in maintaining a healthy homeostatic state is yet to be understood, mast cells most often come to
Classification of diseases associated with mast cell proliferation/activation
Mast cells play a critical role in the genesis or perpetuation of a number of clinical diseases ranging from those associated with an intrinsic or primary defect in mast cells, such as occurs in mastocytosis, to diseases in which mast cells are recruited through a non–mast cell–dependent, extrinsic mechanism, resulting in a disease associated with “secondary” mast cell activation (Table I).
Proposed criteria for the diagnosis of idiopathic MCAS
The presence of a distinct idiopathic MCAS (Table I), when MMAS has been eliminated, has not been universally accepted. Despite the absence of a consensus for objective guidelines for diagnosis, this syndrome is assigned to some patients with a variable number of unexplained signs and symptoms (see Table E1) and with an otherwise negative diagnostic workup result.
We therefore propose that the diagnosis of MCAS is appropriate when primary and secondary diseases associated with mast cell
Summary
We believe that these recommendations for the diagnosis and management of MCAS form a starting point toward a global classification of mast cell disorders in general and MCAS in specific. To be generally acceptable, this classification scheme must be validated and modified by findings from prospective multicenter clinical studies.
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Supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and grants #P21173-B13 and #SFB-F01820 of the Fonds zur Förderung der Wissenschaftlichen Forschung in Österreich (FWF).
Disclosure of potential conflict of interest: C. Akin receives research support from the Food Allergy Initiative, has provided legal consultation/expert witness testimony in cases related to anaphylaxis, and is on the Medical Advisory Board for the Mastocytosis Society. P. Valent receives research support from Novartis and Bristol-Myers Squibb. D. D. Metcalfe receives research support from the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and is a member of the Editorial Board for the World Allergy Organization.
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Dr Akin is currently affiliated with the Department of Medicine, Division of Rheumatology, Allergy and Immunology, Brigham and Women’s Hospital, Boston, Mass.