No abstract

Mastocytosis is a term used to denote a heterogeneous group of conditions defined by expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis (CM), systemic mastocytosis (SM), and localized mast cell tumors. Based on histomorphologic criteria, clinical parameters, and organ involvement, SM is further divided into indolent SM (ISM) and advanced SM variants, including aggressive SM (ASM) and mast cell leukemia (MCL). The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis (ECNM). In addition, new treatment options are available for patients with advanced SM, including allogeneic hematopoietic stem cell transplantation and multi-kinase inhibitors directed against KIT D816V and other key signalling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced SM.

The local effects of intracutaneous injections into humans of 1-3 nmol of five products of arachidonic acid metabolism, leukotrienes (LT) C4, D4, E4, and B4 from the 5-lipoxygenase pathways and prostaglandin (PG) D2 from the cyclooxygenase pathway, were assessed clinically and histologically. In equimolar concentrations, LTC4, LTD4, and LTE4, elicited erythema and wheal formation, in which a wheal with central pallor was present up to 2 hr, and the erythema persisted as long as 6 hr. PGD2 elicited a wheal that lasted up to 1 hr and erythema that lasted up to 2 hr. The dermal vascular sites affected by LTD4 and PGD2 included capillaries, superficial and deep venules, and arterioles. LTB4 elicited a transient wheal and flare, followed in 3-4 hr by induration that was characterized by a dermal infiltrate comprised predominantly of neutrophils. The combination of LTB4 and PGD2 elicited tenderness and increased induration associated with a more intense neutrophil infiltration. Thus, the products of the 5-lipoxygenase pathway of arachidonic acid metabolism in nanomole amounts can induce cutaneous vasodilation with edema formation and a neutrophil infiltrate, and these responses are enhanced by a cyclooxygenase pathway product, PGD2.