Systemic mastocytosis is a rare disorder that causes the body to produce too many mast cells. A mast cell, or mastocyte, is a type of blood cell that is found throughout your body that helps your immune system protect your body from disease and assists in wound healing. In systemic mastocytosis, excess mast cells (that are abnormal in both shape and function) build up in your skin, bone marrow, digestive tract, and other body organs. These abnormal mast cells may be easily triggered to activate. When mast cells are triggered, they release substances (mediators including histamine, tryptase, prostaglandins, etc) are responsible for causing signs and symptoms similar to those of an allergic reaction and sometimes severe inflammation that may result in organ damage. When there are too many of these mast cells, they can create a response that overwhelms the body.
The majority of cases of systemic mastocytosis are caused by a mutation in a gene called KIT. This gene is responsible for assisting in mast cell development, and mastocytosis can occur when mutations in KIT lead to the overproduction and accumulation of mast cells. The KIT D816V mutation occurs in the majority (>90%) of people living with systemic mastocytosis.
Systemic mastocytosis is further divided into 5 categories: smoldering systemic mastocytosis (SMM), indolent mastocytosis (ISM), aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). Advanced Systemic Mastocytosis (AdvSM) has three subtypes: ASM, SM-AHN, and MCL.