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Skin biopsy, the mainstay of the dermatologist, has become a valuable tool for neurologists to diagnose disorders that involve unmyelinated sensory nerves. A minimally invasive 3-mm punch biopsy, not requiring sutures, is usually taken from a distal skin site with minimal sensory abnormalities, fixed, cut into thick sections, and stained immunohistochemically. The epidermal nerve fibers (ENFs) may be the first detectable sign of neuropathy and perhaps can detect changes over time, as during progression of disease or therapeutic trials. ENFs are the distal terminals of small dorsal root ganglia neurons that pierce the dermal–epidermal basement membrane and penetrate the epidermis, often to stratum corneum. Their clinical use became practical with availability of immunostaining by antibody to protein gene product (PGP) 9.5.1,2 Reduced numbers of ENFs occur with diabetic neuropathy3; sensory neuropathies, including HIV4; and small fiber sensory neuropathy,5 among others.
The syndrome of painful feet from small fiber sensory neuropathy has been an enigma to practitioners because of the unexplained contrast between the severe pain in the extremities …
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