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

Arch Neurol. 2005 Oct;62(10):1574-8. doi: 10.1001/archneur.62.10.1574.


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.

MeSH terms

  • Celiac Disease / complications*
  • Celiac Disease / pathology
  • Epidermis / innervation*
  • Female
  • Gliadin / blood
  • Humans
  • Male
  • Neural Conduction
  • Neurons / pathology
  • Peripheral Nervous System Diseases / etiology*
  • Peripheral Nervous System Diseases / pathology
  • Transglutaminases / blood


  • Gliadin
  • Transglutaminases