Reviews and feature article
Mast cell activation syndromes

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Mast cell activation is common and possibly necessary for maintenance of survival. Disordered mast cell activation occurs when mast cells are pathologically overproduced or if their activation is out of proportion to the perceived threat to homeostasis. Mast cell activation syndrome refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release. Despite introduction of diagnostic criteria and some advances in treatment in the last decade, many areas of mast cell activation syndrome are in need of research. This article reviews our current knowledge about the various types of mast cell activation disorders, their treatment, and areas of uncertainty in need of future investigation.

Section snippets

Validated markers of mast cell activation

Clinically available and validated markers of mast cell activation are shown in Table III. The most specific marker of mast cell burden and activation is tryptase.8 The normal median tryptase level is approximately 5 ng/mL. A serum or plasma level of greater than 11.4 ng/mL is considered increased. Although basophils and early myeloid cells produce trace amounts of tryptase, the great majority of the serum or plasma tryptase is derived from mast cells. Tryptases detectable in serum at baseline

Clinical variety of mast cell activation syndromes

Mast cell activation syndromes can be divided into primary, secondary, and idiopathic.5, 6 Primary disorders of mast cell activation result from a defect in the mast cell progenitor, leading to abnormal qualitative or quantitative production of mast cells. These include 2 major subgroups: mastocytosis and MMAS.

Mastocytosis is a disorder characterized by abnormal proliferation and accumulation of mast cells deriving from a clonal progenitor carrying a gain-of-function mutation in KIT.4, 18 The

Management of mast cell activation syndromes

General principles of the management of mast cell activation syndromes include avoidance of triggers, pharmacologic management of the actions of mast cell mediators, treatment of the associated conditions, and consideration of mast cell cytoreduction in those with primary (clonal) mast cell disorders.32

Areas of uncertainty and opportunities for research

In clinical practice some patients with a variety of multisystem symptoms who do not have an identifiable central cause for their complaints are referred for investigation of mast cell activation syndrome. These symptoms can include chronic fatigue; intolerances to various environmental factors, foods, and medications; and neuropsychiatric findings, including memory problems and headaches. These complaints can be present on a chronic basis without well-defined attacks or episodes of mast cell

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    Disclosure of potential conflict of interest: C. Akin serves as a consultant for Novartis, Patara, and Deciphera; has a patent with LAD2 cell line; and receives royalties from UpToDate.

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