Nerve Fiber Density

Epidermal nerve fiber density (ENFD) is a test which allows for the diagnosis of small fiber peripheral neuropathy in an objective manner based on the analysis of a common punch biopsy of skin.

This test has proven to be highly specific and sufficiently sensitive in the diagnosis of small fiber neuropathy, and an ideal method for monitoring the disease process in patients. Through ENFD physicians are able to objectively monitor both disease progression as well as regression, helping them to refine treatment methods for their patients.

An estimated 15 to 20 million people in the United States over age 40 have some type of peripheral neuropathy.

In many, the impairment is purely or predominantly in small nerve fibers (small fiber peripheral neuropathy, SFPN) and the clinical presentation consists of pain, burning, tingling, and numbness starting in the foot/ankle area. The common causes of SFPN include Types I & II diabetes, HIV, vibratory trauma, amyloidosis/monoclonal gammopathy, alcohol abuse, pharmacologic toxins (metronidazole), solvent exposure, and idiopathic neuropathy. Early and accurate diagnosis of SFPN is key, as aggressive cause-specific treatment, lifestyle modification, and pain control are essential for patient treatment and the halt to disease and symptom progression.

At Warrior Diagnostics, we offer the Epidermal Nerve Fiber Density (ENFD) test, an objective method of documenting small fiber peripheral neuropathy (SFPN) by quantifying the terminal branches of peripheral nerves within the epidermis. The test is highly specific and sensitive in diagnosing SFPN, with an accuracy rate of 97% (as compared to 54% for the clinical examination, and 49% for quantitative sensory testing, QST). A simple 3×3 mm skin biopsy is all we need to provide diagnostic information on small nerve fibers.

Warrior Diagnostics novel method for processing ENFD samples allows our providers to submit case samples into standard formalin. This new approach simplifies your handling of these cases and stabilizes your patient’s sample for analysis as compared to traditional methods. Punch biopsies taken for ENFD testing are taken from specific anatomic locations but in a manner similar to those obtained to assess other conditions of skin (please see our requisition form for details).

Small Fiber Peripheral Neuropathy

Damage to or loss of small somatic nerve fibers results in pain, burning, tingling, or numbness that typically affects the limbs in a distal-to-proximal gradient. In rare cases, small fiber neuropathy follows a non-length-dependent distribution in which symptoms may be manifested predominantly in the arms, face, or trunk. Symptoms may be mild initially, with some patients complaining of vague discomfort in one or both feet similar to the sensation of a sock gathering at the end of a shoe. Others report a wooden quality in their feet, numbness in their toes, or a feeling as if they are walking on pebbles, sand, or golf balls. The most bothersome and fairly typical symptom is burning pain in the feet that extends proximally in a stocking-glove distribution and is often accompanied by stabbing or aching pains, electric shock-like or pins-and-needles sensations, or cramping of the feet and calves. Symptoms are usually worse at night and often affect sleep. Some patients say that their feet have become so exquisitely tender that they cannot bear having the bed sheets touch them, and so they sleep with their feet uncovered. A small number of patients do not have pain but report a feeling of tightness and swelling in their feet (even though the feet appear normal).


Small Fiber Neuropathy Affects Sensory Nerves

Small fiber neuropathy is a major cause of pain in the hands and feet, especially in the elderly. Diabetes mellitus is the most common identifiable cause, but there are many others. The affected nerve fibers are the small-diameter myelinated A-delta fibers and unmyelinated C fibers, which mediate pain, thermal sensation, and autonomic function. Large fibers that innervate muscles are not affected. Skin biopsy may show a paucity of nerve fibers. Quantitative sudomotor axon reflex testing may show a lack of sweating in response to acetylcholine.