Clinical, genetic, and therapeutic insights into systemic mast cell disease

Mast cell disease is markedly heterogeneous in its underlying molecular pathogenesis, clinical presentation, natural history, and specific treatment. Skin-only disease (cutaneous mastocytosis) is infrequent in adults and systemic mastocytosis may be broadly classified as an indolent or aggressive variant based on the absence or presence of impaired organ function. Urticaria pigmentosa and mast cell mediator release symptoms can occur in all categories of mast cell disease and may not be prognostically detrimental. The purpose of this review is to summarize current concepts and recent advances in the pathogenesis and treatment of adult mast cell disease.

A series of laboratory investigations has revealed that mast cell disease is a clonal stem cell disorder, and at least two genes (c-kit and PDGFRA) with pathogenetically relevant mutations have been identified. FIP1L1-PDGFRA+ mast cell disease responds completely to imatinib mesylate. Both Asp816Val c-kit+ and molecularly undefined cases have been shown to respond to 2-chlorodeoxyadenosine therapy after failing treatment with interferon-alpha.

A partial molecular classification of mast cell disease is now possible; Asp816Val c-kit+, FIP1L1-PDGFRA+, and molecularly undefined cases. Such molecular classification is therapeutically relevant.