Small Fiber Neuropathy Small fiber neuropathy results from damage to the small unmyelinated nerve fibers that connect the pain receptors in the skin to the spinal cord and brain. Causes are many, and they are similar to large fiber neuropathy, as diabetes, autoimmune, toxic, and nutritional. The condition is diagnosed by demonstrating every reduction in the epidermal nerve fiber density (ENFD) in a skin punch biopsy. Unlike large fiber neuropathy, the diagnosis is easy to miss, as the sensory examination and EMG and nerve conduction studies are usually normal. The ENFD is reported as the average number of nerve fibers that approach the basement membrane of the dermal epidermal junction. Making the correct diagnosis explains the symptoms, guides the evaluation for the underlying cause, and helps decide treatment. Reason for performing a skin biopsy: 1 – To diagnose small fiber neuropathy. 2 – To follow up progression of the neuropathy in response to therapy. 3 – To provide documentation, for purposes of insurance coverage, to support recommended treatments. 4 – To confirm the diagnosis of sensory neuropathy in a patient with a compatible clinical presentation but normal electrodiagnostic studies. 5- To diagnose vasculitis neuropathy that also involve the skin. 6 – To diagnose amyloid neuropathy. 7 – Indicated for patients with "a diagnosis of" fibromyalgia" without specific underlying etiology. 8 – Indicated for patients with unexplained muscle pain and cramps. 9- Help in establishing cause of dysautonomia, as POTS. Skin Biopsy Procedure: skin biopsies performed in an office setting. This can usually cleaned with alcohol with anesthetic agent and then a small piece of skin is removed with a small tool and about 3 mm in diameter and 2 mm deep. Biopsy sites usually done 10 cm proximal to the lateral ankle and lateral knee. Complication of skin biopsy procedure: It is a simple procedure with minimal to no complication is performed in the right setting. Reported complications are mainly but not limited to bleeding and infection. Post biopsy instruction: The biopsy site may continue to bleed for the rest of the day. It may or may not form a scab in a few days. Keep the area clean and dry. Do not soak in water like a swimming, hot tops or baths for a few days. Showers are okay. Change the Band-Aid at least once a day and whenever it's become wet or damp. Once a scab Has formed or new skin began to grow over the area and the bleeding has stopped a bandage is no longer necessary. The biopsy site may form a small pump or small indent and may be slightly discolored. In the long term while minimal scaring may occur, in most cases the biopsy site is indistinguishable within a few months.