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-lm 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.

Objective-(1) To evaluate a clinical guideline for the diagnostic investigation of patients presenting with signs and symptoms (present for longer than 6 weeks) suggesting a chronic polyneuropathy. (2) To investigate the contribution of electrophysiological studies to a focused search for aetiology in these patients. Methods-A chart review was carried out of a consecutive group of outpatients in 1993-7 at a university department of neurology, with signs and symptoms suggesting a polyneuropathy in whom the diagnostic investigation had been carried out according to a recently introduced guideline. Diagnostic tests were performed and final diagnoses were made. Results-Unnecessary investigations were carried out in 108 (51%) of 213 patients and too few tests in 23 (11%) of these patients. In 82 (48%) of the 172 patients who fulfilled the inclusion criteria neurophysiological tests did not contribute to the final diagnosis. Neurophysiological criteria for demyelination were fulfilled in only 13 (8%) of the 172 patients. Conclusion-In patients presenting with signs and symptoms of chronic polyneuropathy the number of tests in the diagnostic investigation can be considerably reduced. In patients with signs and symptoms of polyneuropathy, providing the clinical phenotype is typical, in the presence of diabetes mellitus, renal failure, HIV infection, alcoholism, or use of potentially neurotoxic drugs further investigations are non-contributory. The significance of electrophysiological studies in the investigation of patients with polyneuropathy is rather to separate sensorimotor neuropathies from pure sensory neuropathies than to distinguish between demyelinating and axonal neuropathies. (J Neurol Neurosurg Psychiatry 2001;71:205-209)

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In half of the patients with the diagnosis CIAP, this diagnosis was changed after revision, including the family history of neuropathies. Therefore, in patients with the diagnosis CIAP, this diagnosis should be reconsidered. In addition the question should be whether the hereditary neuropathies have been excluded.