Skin biopsy for small fiber neuropathy

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Skin biopsy for small fiber neuropathy

Small fiber neuropathy is a type of peripheral neuropathy, or condition which affects the nerve endings, characterized by nerve pain.  This discomfort tends to affect the feet or hands initially.  However, some people may experience thigh pain, pain in other body areas or a more generalized, whole-body pain. The pain in small fiber neuropathy is often described as stabbing or burning, or it may involve abnormal skin sensations such as tingling, electrical sensations or itchiness. In some individuals, the pain is more severe during times of rest or at night.  Individuals with small fiber neuropathy may not be able to feel pain that is concentrated in a very small area, such as the prick of a pin.  However, they also tend to be bothered by increased sensitivity to pain.  People affected with this condition may also have a reduced ability to differentiate between hot and cold.

In contrast to large fiber neuropathy, small fiber neuropathy occurs from damage to the small unmyelinated peripheral nerve fibers, also called C fibers.  These nerves provide nerve supply to the skin and autonomic nervous system.  The most common causes of small fiber neuropathy is diabetes or glucose intolerance. Other possible causes include alcohol abuse, hypothyroid, autoimmunse disease such as Sjogren’s syndrome, Lupus or vasculitis, sarcoid or nutritional deficiency. Uncommon causes include Celiac disease, amyloid or Lyme disease. Approximately 30-40% of cases occur for undetermined reasons.

Also in contrast to large fiber neuropathy, EMG/NCS tend to be normal in cases of small fiber neuropathy.  A skin biopsy with measurement of the intraepidermal nerve fiber density has emerged as the best test for direct visualization of the unmyelinated small nerve fibers. The finding of reduced Epidermal Nerve Fiber Density (ENFD) on punch skin biopsy is a highly sensitive and specific test for Small Fiber Neuropathy (SFN).

In this minor procedure, skin samples are obtained at standard sites by punch biopsy distally at the distal leg (calf), and proximally at the thigh. Northwest Neurology sends these specimens to Therapath Labs in New York, New York.  This laboratory is used by leading academic centers nationwide and specializes in skin biopsies for small fiber neuropathy.  Please visit the frequently asked questions on Therapath’s webpage at


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