Mast cell activation syndrome (MCAS) is a condition characterized by episodic, excessive release of mast cell mediators causing multisystem symptoms without evidence of clonal mast cell proliferation (which would indicate systemic mastocytosis). Mast cells are tissue-resident immune cells derived from CD34+ hematopoietic progenitors that mature in tissues under the influence of stem cell factor (SCF) binding to the KIT receptor (CD117). They are strategically located at host-environment interfaces (skin, GI mucosa, respiratory mucosa, perivascular spaces) and contain cytoplasmic granules loaded with preformed mediators including histamine, tryptase, heparin, proteases (chymase, carboxypeptidase), and cytokines (TNF-alpha). Upon activation, mast cells undergo degranulation (immediate release of preformed mediators within seconds) and de novo synthesis of lipid mediators (prostaglandin D2, leukotrienes C4/D4/E4) and cytokines (IL-4, IL-5, IL-6, IL-13). The diagnostic consensus criteria for MCAS require: (1) episodic symptoms consistent with mast cell mediator release affecting two or more organ systems, (2) biochemical evidence of mast cell activation (elevated serum tryptase >20% above baseline + 2 ng/mL during or within 4 hours of a symptomatic episode, or elevated 24-hour urinary metabolites of histamine [N-methylhistamine] or prostaglandin...