Skin biopsy and small fibre neuropathies: facts and thoughts 30 years later

Origins

Between 1989 and 1990, two independent research groups of anatomists and histologists at the Karolinska Institute of Stockholm, Sweden, showed that antibodies against the cytoplasmic protein gene product 9.5 (PGP9.5) could visualise in bright-field immunohistochemistry the rich cutaneous innervation much better than neuropeptides and other antibodies previously did1 2 (figure 1). Their publications would soon widen the interests of neurology to the human skin.

This novel pathological technique was then used to understand the symptoms in a group of patients who had distal neuropathic limb pain, primarily in the feet, but in whom standard neurological examinations, aside from reduced pinprick sensation, standard nerve conduction studies3 and even nerve biopsy findings4 were normal. The findings of reduced or absent intraepidermal nerve fibres (IENF), either distally alone or in a length-dependent fashion, strongly suggested that the complaints of distal neuropathic limb pain…

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