Evidence of autoimmune etiology in children with small fiber neuropathy

Objective Small fiber neuropathy (SFN) is becoming increasingly recognized as a cause of autonomic dysfunction, sensory disturbances, and neuropathic pain. While SFN was previously considered predominantly idiopathic, cases of autoimmune SFN are now well described in adults but remain underexplored in children. Methods In this retrospective chart review, we identified pediatric patients diagnosed with SFN of suspected autoimmune etiology. SFN was diagnosed based on epidermal nerve fiber density (ENFD) and/or sweat gland nerve fiber density (SGNFD) values from skin biopsy and/or quantitative sudomotor axon reflex testing (QSART). Autoantibodies were assessed using the Mayo Clinic Dysautonomia Panel and the Washington University in St. Louis (WUSTL) Sensory Neuropathy Panel. Results Twenty patients with SFN of suspected autoimmune etiology were identified. Seventy-five percent were females, with mean ages at symptom onset and diagnosis of 11.158 and 14.038 years, respectively. Presenting symptoms included gastrointestinal (GI) symptoms (60%, n = 12), neurological/sensory (40%, n = 8), and postural orthostatic tachycardic syndrome (POTS) (40%, n = 8); 35% ( n = 7) presented with a combination of symptoms. IgM TS-HDS antibodies were identified in 45% ( n = 9), IgG FGFR3 antibodies in 25% ( n = 5), both antibodies in 5% ( n = 1), and ganglionic acetylcholine receptor antibodies in 5% ( n = 1). Comorbid autoimmune conditions included Crohn’s disease ( n = 1), and Sjögren’s syndrome ( n = 3). Abnormal findings were recorded on QSART in 5 of 6 patients and GI motility studies in 10 of 11 patients. Twelve patients received IVIG therapy for more than 3 months, of whom 10 (83%) reported improvement in symptom burden or complete resolution of symptoms. Conclusion Pediatric SFN typically presents with a combination of POTS, neurologic, and GI symptoms. Our study demonstrates a potential autoimmune etiology, supported by the presence of identifiable autoantibodies and observed clinical improvement after a minimum of 3 months of IVIG therapy.