Small fibre neuropathy and Collagen IV reduction in Postural Tachycardia Syndrome and Joint Hypermobility Syndrome

Objective. To evaluate neuropathology and autonomic and sensory function in patients with Postural Tachycardia Syndrome (PoTS) and Joint Hypermobility Syndrome (JHS). Methods. Twenty subjects with PoTS and JHS (19 Females; median age 33 years) and 11 normal controls (6 Females; median age 25 years) underwent autonomic function and sensory testing and punch skin biopsy analysis of intra-epidermal nerve fibre density (IENFD), neuropeptides (CPON/NPY, VIP, CGRP), and collagen IV. Subjects were divided into small fibre neuropathic PoTS (SFN_PoTS) and non-neuropathic PoTS (No SFN_PoTS), defining neuropathy as abnormal IENFD (reduced PGP 9.5-immunoreactive fibres). Results. A sub-group of 5 patients (20%) with PoTS and JHS had a reduction in the number of PGP 9.5 and TRPV1 -immunoreactive fibres, and impaired cool and warm perception thresholds ,and were defined as SFN_PoTS. PoTS patients with JHS also showed a reduction in Collagen IV in basement membranes and blood vessels in the skin. Heart rate during head-up tilting was significantly higher in No SFN_PoTS compared with SFN_PoTS (P < 0.01) and in both PoTS sub-groups compared to Controls. Conclusion. A sub-group of patients with PoTS and JHS has an underlying small fibre neuropathy and a reduction in Collagen IV in basement membranes and blood vessels in the skin. These findings suggest that multiple pathophysiological mechanisms could co-exist in PoTS. A combination of morphological analyses of skin biopsy and peripheral small nerve fibre function testing, can differentiate PoTS sub-types and help further understanding of underlying pathophysiology in PoTS.