Contemporary Challenges in Mastocytosis

Mastocytosis denotes a wide range of disorders characterized by having abnormal growth and accumulation of mast cells. Mast cells contain histamine and other inflammatory mediators, which have diverse actions within the body, and play crucial roles in acquired and innate immunity. The diverse actions of these inflammatory mediators can lead to puzzling symptoms in individuals with mastocytosis. These symptoms can include flushing, pruritis, nausea, vomiting, abdominal pain, diarrhea, vascular instability, and headache. These clinical features generally divide into cutaneous and systemic manifestations, giving rise to the two divisions of mastocytosis: cutaneous mastocytosis (CM) and systemic mastocytosis. CM has a highly favorable clinical prognosis. Systemic mastocytosis has a range of severity, with the milder forms often remaining chronic conditions, while the severe forms have rapid complex courses with poor prognoses. Generally, treatment is aimed at avoiding mast cell degranulation, inhibiting the actions of the constitutive mediators released by mast cells and, in severe cases, cytoreductive and polychemotherapeutic agents. Behavioral intervention includes avoidance of triggers, such as heat, cold, pressure, exercise, sunlight, and strong emotions. Treatment for released histamine and other inflammatory mediators includes H1 antihistamines, H2 antihistamines, proton pump inhibitors, anti-leukotriene agents, and injectible epinephrine (for possible anaphylaxis). For severe cases, treatment includes cytoreductive agents (interferon alpha, glucocorticoids, and cladribine) and polychemotherapeutic agents (daunomycin, etoposide, and 6-mercaptopurine). For very specific and severe cases, tyrosine kinase inhibitors, imatinib and midostaurine, have shown promise.