Patient are being asked to undergo punch skin biopsy epidermal nerve fiber analysis to aid in the diagnosis of peripheral neuropathy and autonomic disorders. Epidermal or more correctly termed “intraepidermal” nerve fibers are thinly myelinated A-d and unmyelinated C fibers that transmit neuropathic pain and autonomic symptoms. The prevalence of small fiber neuropathy is increasing because of better techniques to diagnose the disorder. Moreover, the manifestations of small fiber neuropathy may accompany or precede development of large fiber peripheral neuropathy.  In a cohort of 265 patients with abnormal epidermal nerve fiber findings, investigators (PDF) discovered that one-third of patients had evidence of a connective tissue disorder such as lupus, Sjögren syndrome, or sarcoidosis. One-third of patients had a metabolic disturbance due to diabetes, vitamin levels, paraproteinemia, Lyme disease, alcohol and medication related side effects, thyroid disease and Celiac disease and rarely cancer. The diagnosis in the remaining one-third was not ascertained calling them idiopathic small fiber neuropathy. The commonest symptoms associated with small fiber involvement were neuropathic pain manifested as sensitive skin, burning feet, sheet intolerance and restless legs. Other associated complaints included sweating pattern changes, diarrhea or constipation, urinary disturbances, dry eyes or mouth, dizziness or orthostatic hypotension, palpitations, and hot flashes due to concomitant dysautonomia. Quality of life (QoL) can be seriously impaired in symptomatic small and large fiber neuropathy and autonomic neuropathies, so undergoing the procedure can be a useful first step toward finding the correct treatment and cure. Learn about the procedure if you are to undergo it sometime soon.