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Updated: Jul 19, 2026

Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies
Published on: April 29, 2013
Intraepidermal nerve fiber densities in chronic inflammatory autoimmune diseases
Lasse G Gøransson1, Johan G Brun, Erna Harboe
1Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway. gola@sus.no
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.
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