Nonclonal Mast Cell Activation Syndrome

Abstract

Patients who present with typical features of mast cell activation with laboratory confirmation and without evidence of a clonal mast cell disorder or other medical condition should be initiated on medical treatment to block mast cells and their mediators. If a major response is achieved, a diagnosis of nonclonal mast cell activation syndrome (NC-MCAS) is likely and treatment should be optimized, including management of any associated conditions. In this review, the latest evidence with regard to the diagnosis and treatment of NC-MCAS is presented.

Mast Cell Biology and Linkages for Non-clonal Mast Cell Activation and Autoimmune/Inflammatory Syndrome Induced by Adjuvants

“…Distributed throughout the body, mast cells are unified by their functions and their hematopoietic origin. With presence in the gastrointestinal tract, in the airways, and in the skin, mast cells function in host defense and have various modulatory activities in other immune and non-immune functions [1]. There are very few body compartments, however, in which mast cells are absent.…”

“…Secondary and idiopathic definitions were united by nonclonal proliferations of mast cell activation, but was there sufficient to clearly differentiate the two despite a defined putative causation for the former? This rational and important approach towards the understanding of NC-MCAD must nevertheless be placed in the more contemporary reality as expressed by Hamilton-there are no yet reliable subclassifications of NC-MCAD, and there is even less consensus with the diagnostic criteria for NC-MCAD [1]. The call to collaboration in this regard and a next-order proposal to exact more science for the creation of diagnostic algorithms point towards some well-needed consistencies [42,43].…”

“…Non-clonal mast cell activation disorder (syndrome) (NC-MCAD) and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) have garnered attention over the last decade albeit with much debate and indeed some skepticism [1,2]. While initially capturing the attention of allergists, immunologists, and rheumatologists, the discussion is clearly entering the mainstream of medicine, and the public especially, given the broad definitions of such disorders and their potentially considerable application to the general populace.…”

Comparing histamine intolerance and non-clonal mast cell activation syndrome

“…The clinical symptomatology of HI, although diverse and hence confusing, has a remarkable similarity to non-clonal mast cell activation syndrome (NC-MCAS) which is gathering increasing attention, but especially in North America. [4][5][6][7] Whereas patients with severe NC-MCAS are a more definitive subset, the majority of patients with the NC-MCAS diagnosis are difficult to understand, and the entity is considerably heterogeneous from a clinical perspective. 8 NC-MCAS can be relapsing or indolent, but not as severe as more aggressive forms of mastocytosis.…”

Systemic mastocytosis: variable manifestations can lead to a challenging diagnostic process

“…This syndrome presents with typical features of mast cell activation but without evidence of a clonal mast cell disorder. No consensus diagnostic criteria exist for MCAS but proposed criteria have been published incorporating symptoms, measurement of a mast cell mediator such as mast cell tryptase and response of symptoms to antagonists of mast cells or their mediators 5…”