Expanding Spectrum of Mast Cell Activation Disorders: Monoclonal and Idiopathic Mast Cell Activation Syndromes

Abstract

BackgroundIn recent years, 2 new syndromes of mast cell activation have been described in patients with episodes of mast cell mediator release that range from flushing and abdominal cramping to anaphylaxis: monoclonal mast cell activation syndrome (MMAS) and idiopathic mast cell activation syndrome (MCAS). ObjectiveThis review will discuss these 2 new syndromes in the larger context of mast cell activation disorders as well as the diagnostic and treatment approaches for these conditions. MethodsPubMed was searched using the following terms: mast cell activation disorder, mast cell activation syndrome, and clonal mast cell. Only English-language articles published up until February 27, 2013, were considered. ResultsMMAS has been diagnosed in patients with systemic reactions to hymenoptera stings and elevated baseline serum tryptase as well as in patients with unexplained episodes of anaphylaxis. A bone marrow biopsy establishes the diagnosis by revealing the presence of monoclonal mast cells that carry the D816V KIT mutation and/or express CD25 while the diagnostic requirements for systemic mastocytosis are not met. MCAS affects predominantly women in whom no mast cell abnormality or external triggers account for their episodes of mast cell activation. MCAS is a diagnosis of exclusion, and primary and secondary mast cell activation disorders as well as idiopathic anaphylaxis have to be ruled out before making the diagnosis. Patients with MCAS and MMAS are treated in a stepwise fashion with drugs that block the effects of mediators released by mast cells on activation. One third of MCAS patients experience complete resolution of symptoms with treatment, while one third have a major response and one third a minor response to treatment. A combination of drugs is usually necessary to achieve symptom control. No drug trial has been performed in patients with MMAS and MCAS. ConclusionsMMAS and MCAS are 2 newly described, rare syndromes of mast cell activation. Further studies will be necessary to better understand the cause of these conditions and their natural evolution and to validate and improve the treatment approach. Research should also focus on developing drugs with the potential to cure these debilitating disorders. To achieve these goals, centers with expertise in mast cell activation disorders are essential as they allow for a critical mass of these patients to be enrolled in studies while providing those patients with the most up-to-date diagnostic procedures and treatment strategies.