Clinical Approach to MCAS Diagnosis and Cutaneous Mastocytosis

Mast cells primarily reside in the tissues of the mucocutaneous, respiratory, gastrointestinal, and  cardiovascular systems, with local effects of their biochemical mediators primarily impacting these organs. Receptors (FcƐRI) on the surface of MCs bind IgE, and when an allergen is recognized by and binds IgE, there is cross-linking of these receptors and generation of a  signaling cascade that in turn causes a release of mediators from preformed granules within the MC as well as stimulating the synthesis of new mediators (Figure 1.) Histamine is the prototypical MC mediator which, along with tryptase and other mediators, causes vasodilation  and pruritus. These mediators affect the skin (hives, swelling), mucosa (rhinorrhea, pruritus), gastrointestinal system (abdominal pain, diarrhea), respiratory system (wheezing, shortness of breath), and cardiovascular system (hypotension, tachycardia) (Figure 1). Non-specific neurological symptoms, such as irritability or fatigue, and other issues like uterine cramping, bone pain, or headaches, may also occur, especially with chronic mediator elevation.

Figure 1: Mast cell mediators and symptoms