Screening Value of the I‐Douleur Neuropathique 4 Questionnaire for Small Fibre Neuropathy in Patients With Painful Syndromes: Insights From 872 Skin Biopsies

BACKGROUND: Small-fibre neuropathy (SFN), which is defined by the sole involvement of small sensory fibres, often leads to neuropathic pain. The diagnosis of SFN relies on clinical, neurophysiologic, and morphologic abnormalities. A decrease in intraepidermal nerve fibre density (IENFD) on a skin biopsy specimen is considered useful in the diagnosis of SFN in the appropriate clinical context. The self-administered Douleur Neuropathique 4 (I-DN4) questionnaire, designed to differentiate neuropathic from somatic pain, shows high sensitivity and specificity but has not been specifically investigated with regard to SFN. METHODS: This retrospective study examined the diagnostic accuracy of I-DN4 for SFN in 872 patients who were systematically assessed at the time of skin biopsy according to local standards of routine care, after excluding central nervous system diseases and other peripheral nerve disorders by careful clinical examination and medical history. RESULTS: An I-DN4 score of ≥ 3 had a sensitivity of 93% and a specificity of 18.13% for diagnosing SFN. ROC analysis revealed an AUC of 0.53, indicating no discriminative ability for this condition. There were no correlations between the I-DN4 scores and the adjusted IENFD or proximo-distal IENFD ratio. Only the sensation of burning was a moderate predictor of SFN risk (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.04-2.68; p = 0.038). Hypoesthesia to pinprick was also associated with a moderate risk of a reduced IENFD at the distal leg (OR = 1.52; 95% CI, 1.03-2.25; p = 0.040). CONCLUSIONS: I-DN4 is not an effective standalone tool for screening SFN in patients with painful syndromes.