Why Does MCAS Not Respond to Standard Treatment? The Four Mechanistically Distinct Patterns — The four mechanistically distinct patterns of MCAS

In the cases I have worked through, four patterns appear repeatedly. Most cases are dominated by one pattern. Some cases have two patterns running in parallel. A few cases shift between patterns over time. The framework below is a working stratification, not a final taxonomy. It has held up across the case work I have done. It accounts for the clinical heterogeneity better than any single-mechanism model. It also points to different interventions for different patterns, which is what a stratification needs to do to be useful. Pattern A: Barrier-driven MCAS In Pattern A, the proximate driver of mast cell activation is the trafficking of luminal contents across a compromised gut barrier into the lamina propria, where mucosal mast cells are densely concentrated. The barrier is leaking. The mast cells are responding to what is leaking. The mast cell activation is appropriate to the signal it is receiving. The lesion is in the barrier, not in the cell. The signal includes food antigens that should have been processed and excluded, microbial fragments (LPS, peptidoglycan, flagellin) that should have remained luminal, and metabolic products of the dysbiotic community that signal mast cells directly. Each of these binds receptors on mucosal mast cells. The cells degranulate because they have been told to. This is the pattern that travels with recurrent SIBO, with the chronic gut dysfun