Intraepidermal nerve fiber densities in chronic inflammatory autoimmune diseases

Arch Neurol. 2006 Oct;63(10):1410-3. doi: 10.1001/archneur.63.10.1410.


Background: Some patients with systemic lupus erythematosus have selective loss of small-diameter nerve fibers, while larger nerve fibers are unaffected.

Objective: To determine intraepidermal nerve fiber densities in patients with different chronic inflammatory autoimmune diseases.

Design: Cross-sectional study.

Setting: Stavanger University Hospital, Stavanger, and Haukeland University Hospital, Haukeland, Norway.

Patients: Sixty patients with systemic lupus erythematosus (SLE) (mean +/- SD age, 43.2 +/- 13.5 years), 61 patients with primary Sjögren syndrome (age, 57.1 +/- 14.7 years), and 52 patients with rheumatoid arthritis (age, 57.4 +/- 12.3 years) were compared with 106 healthy subjects (age, 49.0 +/- 19.6 years).

Interventions: Skin biopsy specimens.

Main outcome measures: To evaluate small-diameter nerve fiber loss, intraepidermal nerve fiber densities were measured in skin punch biopsy specimens obtained from the distal part of the leg.

Results: The mean +/- SD densities were 7.5 +/- 3.8 fibers/mm in patients with SLE, 9.2 +/- 3.8 fibers/mm in primary Sjögren syndrome, and 10.9 +/- 5.4 fibers/mm in rheumatoid arthritis vs 12.4 +/- 4.6 fibers/mm in healthy subjects. Densities were significantly less in patients with SLE vs patients with rheumatoid arthritis and vs healthy subjects (P<.001 for both), as well as in patients with primary Sjögren syndrome vs healthy subjects (P<.001). Eight patients (13%) with SLE, 2 patients (3%) with primary Sjögren syndrome, and 2 patients (4%) with rheumatoid arthritis had densities below the lower reference limit of 3.4 fibers/mm, consistent with small-diameter nerve fiber neuropathy.

Conclusion: The degree of loss of small-diameter nerve fibers differs among patients with these chronic inflammatory autoimmune diseases, likely reflecting differences in pathogenesis and organ affinity of the individual disease entities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / pathology
  • Autoimmune Diseases / diagnosis*
  • Autoimmune Diseases / pathology*
  • Axons / pathology
  • Chronic Disease
  • Cross-Sectional Studies
  • Disease Progression
  • Epidermis / innervation
  • Epidermis / pathology*
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / pathology
  • Male
  • Middle Aged
  • Nerve Fibers, Unmyelinated / pathology
  • Sensory Receptor Cells / pathology*
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / pathology