Diagnostic Accuracy of The Water Immersion Wrinkle Test for Small Fiber Neuropathy

Plain-language summary

Small-fiber neuropathy (SFN) affects A-delta and C fibers and commonly presents with sensory symptoms and dysautonomia. Confirmation often relies on specialized tests such as quantitative sensory testing (QST) and sympathetic skin response (SSR). This prospective, single-center observational diagnostic-accuracy study will estimate the performance of the Water-Immersion Wrinkle Test (WIWT) for detecting SFN in adults evaluated by a neuromuscular service. The composite reference standard is specialist clinical assessment plus abnormality on ≥1 validated scale (Utah Early Neuropathy Scale \[UENS\] or modified Toronto Clinical Neuropathy Score \[mTCNS\]). The index procedure (WIWT) is standardized as follows: both hands immersed to at least the distal interphalangeal crease for 15 minutes; immersion begins at 43-44 °C with expected passive cooling of \~2 °C every 5 minutes; temperature measured at 0, 5, 10 and 15 minutes; no water is added or replaced during immersion. After gentle drying, standardized photographs are obtained and wrinkling grades (0-4) are recorded for digits 2-5; the bilateral summed score is classified abnormal \<24 and normal ≥24. Examiners for WIWT, QST, and SSR are mutually blinded. The primary outcome is WIWT sensitivity and specificity versus the composite reference at baseline. Secondary outcomes include ROC area under the curve (AUC), positive/negative predictive values, and inter- and intra-rater reliability (intraclass correlation coefficients). Recruitment is ongoing; anticipated primary completion: November 2025.

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