Why hEDS, POTS, and MCAS Almost Always Come Together: The Mechanistic Triad and the Upstream Lesion Standard Medicine Doesn't Treat — What hEDS, POTS, and MCAS Each Actually Are

Before I describe the integration, a brief and accurate description of each condition is necessary. The descriptions in patient communities are often imprecise, and the precision matters for the mechanistic argument. Hypermobile Ehlers Danlos Syndrome and the Hypermobility Spectrum Ehlers Danlos Syndrome refers to a group of heritable connective tissue disorders. Classical EDS, vascular EDS, and several other subtypes have identified genetic causes (COL5A1 and COL5A2 for classical, COL3A1 for vascular, and others for the remaining subtypes). Hypermobile EDS, the most common form by far, does not yet have a single identified genetic cause that explains the majority of cases. The 2017 international diagnostic criteria are clinical, based on joint hypermobility, skin features, systemic manifestations, family history, and exclusion of other conditions. The connective tissue in hEDS is more flexible and less mechanically robust than in unaffected individuals. The principal molecule involved is collagen, the protein that provides tensile strength to connective tissue throughout the body. Collagen is everywhere that mechanical support is needed: skin, joints, blood vessel walls, the gut wall, the dura mater that surrounds the brain and spinal cord, fascia, ligaments, tendons, and the structural framework of every organ. In hEDS, the collagen network is qualitatively or quantitatively