Use of skin biopsy and skin blister in neurologic practice

Recently developed immunohistochemical methods permit the visualization of intraepiderma! nerve fibers (ENFs) in punch skin biopsies and skin blisters. ENF density has been shown to be diminished in diabetic neuropathy as well as other focal and generalized sensory-predominant neuropathies, including the neuropathy associated with anti-retroviral therapy, idiopathic small-fiber sensory neuropathy, Fabry disease, and diabetic truncal radiculopathy. ENF depletion is often found prior to the development of clinical or eleo trodiagnostic abnormalities, making this procedure arguably the most sensitive diagnostic test for sensory neuropathies, particularly those with predominant involvement of unmyelinated fibers. Characteristic morphologic changes of epidermal nerves and the subepidermal neural plexus are often seen in these conditions as well. The fibers visualized by this technique are thought to be polymodal heat and mechanical nociceptors. We review the history, clinical applications, and methodology of this exciting technique.