Small-fiber neuropathy/neuronopathy associated with celiac disease - Skin biopsy findings

Background: Celiac disease (CD) is increasingly recognized in North America and is associated with a peripheral neuropathy. Objective: To report the clinical characteristics and skin biopsy results in patients with CD and small-fiber neuropathy symptoms. Design: Case series. Setting: Academic peripheral neuropathy clinic. Patients: Eight patients with CD and neuropathy symptoms. Intervention: Three-millimeter punch biopsy using the panaxonal marker protein gene product 9.5 to assess epidermal nerve fiber (ENF) density and a gluten-free diet. Main Outcome Measure: Clinical data and ENF density. Results: All patients had asymmetric numbness and paresthesias. Three had more prominent involvement of hands than feet, and 3 had facial numbness. Celiac disease was diagnosed in 5 after their neuropathy began. The following serum antibody levels were elevated: tissue transglutaminase (n=6), IgA gliadin (n=4), and IgG gliadin (n = 7). Results of nerve conduction studies were normal in 7 patients. One patient had mildly reduced sural amplitudes. The ENF density was reduced in 5 patients. The ENF density was at the low limit of the normal range in 3 additional patients, 2 of whom had morphologic changes in axons. Three patients had decreased ENF density at the thigh or forearm, which was more severe than at the distal leg, compatible with a non-length-dependent process. Four reported improvement with a gluten-free diet. One had no improvement after 4 months. Symptoms developed in 2 while receiving a gluten-free diet. Conclusions: Patients with CD may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non-length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study.