What is Epidermal Nerve Fiber Density (ENFD) Testing?
ENFD testing is the clinical standard test for diagnosing small fiber peripheral neuropathy. Skin tissue is removed using the standardized punch biopsy procedure.
Once the preparation and immunohistochemical staining of the tissue specimen has occurred, it is placed under microscope for examination. Our pathologists use precise guidelines to then inspect the structural integrity of the small nerve fibers and evaluate the number of small nerve fiber endings.
What is Small Fiber Peripheral Neuropathy (SFPN)?
SFPN takes place in peripheral regions in the body - feet, legs, hands, arms - and occurs when damage to the peripheral nerves affects small somatic and autonomic fibers. These fibers are responsible for detecting and sending information to help regulate involuntary bodily functions.
Individuals could have SFPN yet test negative on electromyography and nerve conduction studies because small fiber damage can occur without large fiber involvement. SFPN can result in debilitating pain if not properly diagnosed and managed. ENFD testing looks specifically at small nerve fibers and remains the best test for diagnosing small fiber peripheral neuropathy.
WHAT DO AUTONOMIC AND SOMATIC FIBERS DO?
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Internal temperature regulation (generate or dissipate heat through blood vessel constriction or dilation, sweating, shivering)
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Feelings of sensations such as cold, hot, pain, itching, smooth, rough, pressure, tickling, and vibrations
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Sweat gland activity
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Cardiovascular (heart rate and blood pressure regulation)
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Temperature perception (detecting hot and cold)
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Gastrointestinal (digestion rate and enzyme secretion)
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Urogenital (bladder function and sexual arousal)
SYMPTOMS OF SMALL FIBER PERIPHERAL NEUROPATHY MAY INCLUDE
Common Symptoms
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Tingling or numbness in toes or feet
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Burning pain (often persistent)
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Electric shock-like pain (lasting few seconds)
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Feeling of walking on sand, pebbles, or golf balls
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Restless legs
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Bedsheet touching legs or feet is irritating or painful
Less Common Symptoms
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Dry eyes and mouth
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Abnormal sweating
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Incontinence or abnormal urination frequency
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Constipation
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Orthostatic hypotension (a quick drop in blood pressure upon standing)
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Sexual dysfunction
THE FOLLOWING CONDITIONS ARE ASSOCIATED WITH PERIPHERAL NEUROPATHY
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Diabetes
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Hyperlipidemia
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Chronic alcohol abuse
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Hypothyroidism
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Metabolic syndrome (as indicated by hyperlipidemia, hypertension, obesity, abnormal glucose metabolism with insulin resistance)
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Neurotoxic drug exposure (chemotherapy; vaccine-associated; antibiotics)
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Vitamin B12 deficiency
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Hereditary conditions (Fabry’s disease; Wilson’s disease; familial amyloidosis)
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Autoinflammatory diseases and immune-mediated conditions (celiac disease; fibromyalgia; lupus; rheumatoid arthritis; Sjogren’s syndrome; sarcoidosis)
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Infectious diseases (Hepatitis C; Lyme disease; HIV)
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Abnormal glucose metabolism or glucose intolerance (as indicated by abnormal 2-hour glucose tolerance test or abnormal fasting glucose levels)
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Copper deficiency
*A large number of cases have an unidentifiable cause
ENFD TEST DETAILS
Methodology
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3mm punch biopsy & placement in Zamboni’s fixative
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Immunohistochemical staining
Specimen​
Skin
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Patient Preparation
None
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Stability
Biopsy must fix for minimum of 8 hours & maximum of 24 hours
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Transport Temperature
​Specimen shipped overnight with freezer pack
DIAGNOSIS WITH DEGREE OF SEVERITY FOR SFPN
NERVE FIBER DENSITY MEASUREMENT
STAINING FOR VASCULITIS & AMYLOID
ENFD Test Report
Mobile access for providers & patients
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Result notifications
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EMR integration
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Colored microscopic images
