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

This is a prospective, single-center, observational diagnostic-accuracy study designed to estimate the performance of the Water-Immersion Wrinkle Test (WIWT) for identifying small-fiber neuropathy (SFN) in adults evaluated by a neuromuscular department. The composite reference standard is a specialist clinical assessment consistent with SFN together with abnormality on at least one validated clinical scale (Utah Early Neuropathy Scale [UENS] or modified Toronto Clinical Neuropathy Score [mTCNS]). Quantitative Sensory Testing (QST) and Sympathetic Skin Response (SSR) are obtained as comparator tests but do not form part of the reference standard. The study adheres to STARD principles for diagnostic-accuracy research and uses predefined operating procedures for test execution, data capture, and analysis.

Study setting and workflow Participants are evaluated in the neuromuscular clinic of a tertiary hospital. The study uses a baseline-only design: all index and comparator tests are completed on the same day whenever feasible. A separate reliability session for image scoring occurs 48 hours to 7 days later without additional patient visits. The overall workflow is: (1) confirm eligibility and obtain consent; (2) complete standardized neurological examination and clinical scales; (3) perform or verify QST and SSR (irrespective of results); (4) perform WIWT; (5) acquire standardized fingertip photographs; (6) independent scoring of images by trained raters; (7) data entry and validation; (8) statistical analysis according to the prespecified plan.

Reference standard (composite) The reference standard integrates the treating neuromuscular specialist's judgment (history and examination) with at least one abnormal clinical scale among UENS or mTCNS using their published scoring rules. The scales are administered per their manuals by personnel trained on test instructions and scoring conventions. The reference standard classification (SFN vs no SFN) is recorded in a dedicated adjudication form. Test operators for WIWT, QST, and SSR do not have access to the reference classification at the time of testing.

Index test: WIWT-technical conduct Participants are seated upright. Both hands are immersed, at least to the distal interphalangeal crease, in water for 15 minutes. Before immersion, the skin is verified to be clean and completely dry. Hands are kept relaxed (neutral finger posture) and fingertips must not press against container surfaces. Because a thermostatically controlled bath is not available, immersion begins at 43-44 °C with expected passive cooling of approximately 2 °C every 5 minutes, targeting an end temperature of about 37-38 °C. Water temperature is measured with the service thermometer at 0, 5, 10 and 15 minutes to confirm the intended range. No water is added or replaced during immersion. A calibrated stopwatch is used to time the procedure. At completion, hands are gently patted dry and standardized photographs are obtained of the palmar distal phalanges of digits 2-5 of both hands. Environmental conditions are kept stable (indoor room, typical ambient temperature, indirect lighting) and recorded on the source form.

Image acquisition and standardization Photographs are taken with the clinic's digital camera or smartphone following a fixed template: (a) distance approximately 20-25 cm from fingertips; (b) camera aligned perpendicular to the palmar surface to minimize parallax; (c) neutral, diffuse illumination avoiding hard shadows; (d) inclusion of a 1-cm scale marker within the frame; (e) focus lock on the distal pad of each fingertip. Raw images are immediately reviewed for motion blur or framing errors and repeated if necessary before the participant leaves. Images are stored as high-resolution JPEG or HEIC (≥8 MP), transferred to the secure institutional drive, and automatically renamed by a deterministic convention (StudyID_Hand_Side_Digit_Timepoint.ext). No patient identifiers appear in filenames or image content.