The Spectrum of Mast Cell Activation Syndromes

1 Introduction

Mast cells play an essential role in the allergic inflammatory response. They are prevalent in many tissues, especially in the skin, gastrointestinal tract and respiratory  systems. Mast cells develop in the bone marrow and mature in the tissue. The protein KIT (also known as CD117) and its ligand (also known as stem cell factor, SCF) are  critical for the regulation of mast cell homeostasis – specifically the development, survival, and effector functions of mast cells [1-4].

Mast cells play a fundamental role in IgE-mediated allergic reactions. Mast cells express high-affinity FcεRI receptors, which allergen-specific IgE antibodies can bind to  and elicit an allergic reaction. The IgE receptor cross-linking on mast cells results in mast cell degranulation and the robust mediator release, including several preformed substances and cytokines, along with stimulating the synthesis of lipid-derived molecules. These mediators include histamine, tryptase, chymase, cysteinyl leukotrienes, platelet activating factor, prostaglandins D2 and E2, heparin, and TNF-α [2, 5-7]. Clinically, this strong rapid release of mediators into the systemic circulation can manifest with classic signs and symptoms (Table 1, Figure 1) and lead to severe hypersensitivity reactions, such as anaphylaxis [7, 8]. While allergens commonly trigger mast cell activation, mast cell activation can also be triggered by bacteria, viruses, drugs, venoms, alcohol, and physical stimuli (such as heat and pressure) [2, 7].  

There are both physiologic and pathologic conditions that can lead to abnormal, recurrent and severe mast cell activation and/or proliferation of mast cells. This chapter reviews the spectrum of mast cell activation syndromes (MCAS), including their pathophysiology, diagnosis, and management.