Why Does MCAS Not Respond to Standard Treatment? The Four Mechanistically Distinct Patterns — Tests that help stratify

Standard MCAS testing includes serum tryptase (often within reference range despite symptoms), 24-hour urine N-methylhistamine and prostaglandin D2 metabolites, and serum chromogranin A. These tests address whether mast cell activation is occurring. They do not address why. The pattern stratification benefits from additional testing. For Pattern A (barrier-driven): comprehensive stool panel (GI-MAP or equivalent) looking at the obligate anaerobic core (Akkermansia, Faecalibacterium), the dysbiotic markers (calprotectin, beta-glucuronidase), and the barrier markers (zonulin if reported, secretory IgA); food immunoreactivity panel if relevant to the diet pattern, recognizing the limits of these panels; LBP and CD14 if accessible; Organic Acids Test for the broader inflammatory and microbial picture. For Pattern B (neuroimmune/vagal): heart rate variability assessment, even a smartphone-based HRV assessment with a consumer wearable is informative; tilt-table or active-stand test if POTS is suspected; detailed sleep history with attention to sleep architecture and time to sleep onset; acetylcholine pathway assessment if available. For Pattern C (chemical/toxicant): mycotoxin urine panel from Mosaic Diagnostics or comparable lab; hair toxic elements panel if heavy metals are suspected; glyphosate urine if pesticide exposure is suspected; a serious assessment of the patient's living