Why Does MCAS Not Respond to Standard Treatment? The Four Mechanistically Distinct Patterns — The clinical pattern that defines treatment-resistant MCAS

A patient presents with the classic MCAS constellation. Flushing. Tachycardia. Bloating after eating. Skin reactions to substances they previously tolerated. New food intolerances that change week to week. Brain fog. Disturbed sleep. Sensitivity to perfumes, cleaning products, and changes in barometric pressure. The presentation is often more dramatic in the late afternoon and the perimenstrual window. The patient has been to three or four specialists. The MCAS diagnosis came last, often from an integrative practitioner, often after years of being told their tryptase was normal and their symptoms were idiopathic. The standard treatment cascade follows. Cromolyn sodium first, then often ketotifen, then montelukast for the leukotriene axis, then a low-histamine diet, then hydroxyzine for the H1 axis, then famotidine for the H2 axis, then quercetin and luteolin for the natural-product mast cell stabilizer axis. Some of these usually produce some response. Almost none of them produce durable, complete remission. The patient continues to react. The pattern of reactions shifts. The triggers multiply. New medications are added. The flare-ups continue. By the time these patients arrive at Biomelogic, they typically describe what looks like progressive escalation. Each new intervention produces a short window of relief followed by a new pattern of reactivity. The flares involve more sys