EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy

Giuseppe Lauria, David Cornblath, O. Johansson, Justin Charles McArthur, S. I. Mellgren, M. Nolano, N. Rosenberg, C. Sommer

Research output: Contribution to journalArticle

Abstract

Skin biopsy has become a widely used tool to investigate small calibre sensory nerves including somatic unmyelinated intraepidermal nerve fibres (IENF), dermal myelinated nerve fibres, and autonomic nerve fibres in peripheral neuropathies and other conditions. Different techniques for tissue processing and nerve fibre evaluation have been used. In March 2004, a Task Force was set up under the auspices of the European Federation of Neurological Societies (EFNS) with the aim of developing guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathies. We searched the Medline database from 1989, the year of the first publication describing the innervation of human skin using immunostaining with anti-protein-gene-product 9.5 (PGP 9.5) antibodies, to 31 March 2005. All pertinent papers were rated according to the EFNS guidance. The final version of the guidelines was elaborated after consensus amongst members of the Task Force was reached. For diagnostic purposes in peripheral neuropathies, we recommend performing a 3-mm punch skin biopsy at the distal leg and quantifying the linear density of IENF in at least three 50-μm thick sections per biopsy, fixed in 2% PLP or Zamboni's solution, by bright-field immunohistochemistry or immunofluorescence with anti-PGP 9.5 antibodies (level A recommendation). Quantification of IENF density closely correlated with warm and heat-pain threshold, and appeared more sensitive than sensory nerve conduction study and sural nerve biopsy in diagnosing small-fibre sensory neuropathy. Diagnostic efficiency and predictive values of this technique were very high (level A recommendation). Confocal microscopy may be particularly useful to investigate myelinated nerve fibres, dermal receptors and dermal annex innervation. In future, the diagnostic yield of dermal myelinated nerve fibre quantification and of sweat gland innervation should be addressed. Longitudinal studies of IENF density and regeneration rate are warranted to correlate neuropathological changes with progression of neuropathy and to assess the potential usefulness of skin biopsy as an outcome measure in peripheral neuropathy trials (level B recommendation). In conclusion, punch skin biopsy is a safe and reliable technique (level A recommendation). Training in an established cutaneous nerve laboratory is recommended before using skin biopsy as a diagnostic tool in peripheral neuropathies. Quality control at all levels is mandatory.

Original languageEnglish (US)
Pages (from-to)747-758
Number of pages12
JournalEuropean Journal of Neurology
Volume12
Issue number10
DOIs
StatePublished - Oct 2005

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Peripheral Nervous System Diseases
Guidelines
Biopsy
Skin
Nerve Fibers
Myelinated Nerve Fibers
Advisory Committees
Autonomic Pathways
Sweat Glands
Sural Nerve
Unmyelinated Nerve Fibers
Nerve Regeneration
Pain Threshold
Antibodies
Neural Conduction
Confocal Microscopy
Quality Control
Fluorescent Antibody Technique
Longitudinal Studies
Publications

Keywords

  • Immunostaining
  • Intra-epidermal
  • Nerve fibres
  • Painful neuropathy
  • Peripheral neuropathy
  • Skin biopsy
  • Small fibre neuropathy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. / Lauria, Giuseppe; Cornblath, David; Johansson, O.; McArthur, Justin Charles; Mellgren, S. I.; Nolano, M.; Rosenberg, N.; Sommer, C.

In: European Journal of Neurology, Vol. 12, No. 10, 10.2005, p. 747-758.

Research output: Contribution to journalArticle

Lauria, Giuseppe ; Cornblath, David ; Johansson, O. ; McArthur, Justin Charles ; Mellgren, S. I. ; Nolano, M. ; Rosenberg, N. ; Sommer, C. / EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. In: European Journal of Neurology. 2005 ; Vol. 12, No. 10. pp. 747-758.
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AU - Rosenberg, N.

AU - Sommer, C.

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