Why hEDS, POTS, and MCAS Almost Always Come Together: The Mechanistic Triad and the Upstream Lesion Standard Medicine Doesn't Treat — Why Single Diagnosis Treatment Fails

If the integration described above is correct, the failure profile of standard treatment becomes predictable. Treatment of hEDS in isolation focuses on physical therapy, joint stabilization, pain management, and lifestyle adaptation. None of these interventions addresses the bioenergetic layer that determines how much capacity the patient has to sustain the structural vulnerability. The interventions help with specific symptoms (joint instability, pain) but do not move the floor of the integrated illness. Treatment of POTS in isolation focuses on volume expansion (salt, fluids, fludrocortisone), heart rate management (beta blockers, ivabradine), vasoconstriction (midodrine), and exercise reconditioning. Each of these targets a downstream variable. Volume expansion compensates for the venous pooling without addressing why the venous pooling is occurring. Beta blockers blunt the heart rate response without addressing the driver. Midodrine raises peripheral resistance without addressing the autonomic dysregulation upstream. Exercise reconditioning is helpful for some POTS patients but counterproductive in patients with significant mast cell or post exertional components, in whom exercise drives further mast cell activation and bioenergetic depletion. Treatment of MCAS in isolation focuses on H1 and H2 antihistamines, mast cell stabilizers (cromolyn, ketotifen, quercetin, luteolin)