Identifying Predictors of Idiopathic Small‐Fiber Neuropathy in Adolescent Patients With Chronic Pain

Introduction Small‐fiber neuropathy (SFN) affects thinly myelinated and unmyelinated nerve fibers and often presents with pain. While this condition is observed in pediatric chronic pain settings, it is unclear which patients are most appropriate for SFN testing, particularly for idiopathic cases. Skin biopsy is the most accurate diagnostic tool, but guidelines for its use are lacking. This study aimed to identify clinical and laboratory variables predictive of a positive skin biopsy for SFN in adolescents with chronic pain. Methods This retrospective study analyzed clinical, demographic, and laboratory characteristics of 104 adolescents with chronic pain who had undergone PGP9.5‐immunolabeled distal‐leg skin biopsy to assess for SFN. Fisher's exact tests, ANOVA, and logistic regression were used to identify predictive factors. Results Patient mean age was 15 years old and 51.9% had positive diagnostic skin biopsies. Results indicated adolescents with positive biopsies were more likely to have Juvenile Idiopathic Arthritis (JIA) compared to those without (33.3% vs. 14.3%, p = 0.02) and had higher median angiotensin‐converting enzyme (ACE) levels ( p < 0.01) and thyroid free T4 levels ( p = 0.02). Logistic regression only showed increased odds of positive skin biopsies with JIA (OR = 3.27, p = 0.02). No clinical symptoms were predictive of positive skin biopsies. Discussion Findings suggest that common clinical observations and laboratory tests used to guide referrals for skin biopsies were not predictive of SFN diagnosis. Clinicians should consider the risks and benefits of skin biopsies for adolescents with chronic pain. Additional research is warranted to validate potentially predictive markers and improve diagnostic pathways for SFN in pediatric chronic pain settings.