Epidermal Nerve Fiber Density (ENFD) Testing

Do your patients complain of pain, numbness, tingling, or burning in their toes, feet, or legs?

Your patients could be suffering from small fiber peripheral neuropathy (SFPN).

Small fiber peripheral neuropathy (SFPN) is a progressive disease that primarily affects the terminal end-branches of peripheral nerves that result in disintegration of the nerve fiber cytoskeleton, and eventually complete nerve loss. Patients often feel pain, tingling, or numbness in their toes, feet, legs, fingers, and hands in a stocking- glove distribution.

Peripheral neuropathy affects more than 20 million people in the US, and small fiber neuropathy is often misdiagnosed with large fiber neuropathy due to its complex array of symptoms. Patients with small fiber neuropathy usually have normal reflexes, muscle strength, NCV, and EMG results.

Epidermal Nerve Fiber Density testing analysis is the best diagnostic tool for early detection and early treatment of small fiber peripheral neuropathy.

  • Metabolic (diabetes mellitus, metabolic syndrome, hyperlipidemia)
  • Inherited (Fabry’s disease, Tangier’s disease, familial amyloid polyneuropathy)
  • Toxic (chemotherapy, alcoholism, solvent exposure)
  • Autoimmune (Sjögren’s syndrome, vasculitis/polyarteritis nodosa)
  • Amyloidosis (non-inherited forms of amyloidosis, e.g. lymphoma or plasma cell dyscrasias)
  • Infectious (HIV, hepatitis C, Lyme disease)
  • Idiopathic (For a relatively large percentage of cases, there is no identifiable cause of SFPN

The Epidermal Nerve Fiber Density (ENFD) test is the best objective tool for documenting small fiber peripheral neuropathy by quantifying the terminal branches of peripheral nerves within the epidermis. ENFD analysis allows for the direct visualization of small nerve fibers. Small nerve fibers are assessed for structural integrity and counted. A diminished number of small nerve fibers are indicative of established diseases; the lower the count, the more severe the disease state. ENFD testing measures degeneration, but can also be used as a predictive tool, and to assess the effectiveness of therapy over time.

The test is highly specific and sensitive. BakoDx’s specificity of ENFD is 95%-to-97%; and the sensitivity is approximately 90%.

ENFD Specimen Collection Procedure

Processing the specimen for ENFD submission is different from a routine punch biopsy. Punches taken for ENFD cannot be placed in formalin. The specimen requires fixation in Zamboni’s fixative for 8 hours, but not more than 24 hours. If left in contact with the specimen for more than 24 hours, the ENFD test may be compromised.

NOTE: Rinse is not required if shipped same day in Zamboni’s fixative. See processing steps below.

  • Place 3mm punch biopsy in Zamboni’s fixative for no less than 8 hours (it’s best to fix overnight), but no longer than 24 hours. Refrigerate, but do not freeze.

NOTE: Rinse is not required if shipped same day in Zamboni’s fixative.

  • Immediately place specimen in yellow Zamboni’s fixative (provided in kit). Verify sample is floating in prior to sealing securely. Note: After this step, if specimen is sent same-day, proceed to label vials with appropriate patient and body site stickers from provided BakoDx Requisition form.
  • If same-day shipping is unavailable, in-office rinse is necessary. After a minimum of 8 hours in refrigerator (but no more than 24 hours), pour out Zamboni’s into secondary tray, keep specimen in vial. Refill with buffer rinse.
  • Pour out buffer rinse (into dish), again, leaving skin biopsy in its original tube.
  • Repeat buffer, using the remaining buffer rinse and pour out.
  • Refill the vial containing the biopsy specimen with cryoprotectant and screw the cap on tightly.
  • Label vials with appropriate patient and body site stickers from provided BakoDx Requisition form.
  • Ship to BakoDx in Styrofoam cooler with cool-pack (provided) using FedEx or UPS prepaid overnight shipping (prepaid shipping labels provided with kit).
  • Biopsies left in Zamboni’s fixative must be shipped Mon-Fri. Tissue sent over weekends or holidays require rinse and cryoprotection steps.
  • For help, call BakoDx at 855-422-5628.


The BakoDx Difference

BakoDx’s ENFD reporting methodology provides an assessment of small fiber peripheral neuropathy’s degree of severity. The ENFD test report also offers treatment recommendations that empower the treating clinician with evidence-based medical information. This leads to better, more timely and cost effective health care for your patients.

BakoDx ENFD report
Healthy Patient

Analyzing ENFD Results

Diagnostic Analysis Nerve Fiber Density
Normative Range 7.1mm fibers and above
Mid Nerve Degeneration 7.1mm – 3.8mm fibers
Moderate Nerve Degeneration 3.8mm – 2.0mm fibers
Severe Nerve Degeneration 2.0mm – 0.0mm fibers

Webinar: Peripheral Neuropathy Diagnosing and Treating

Case studies and procedure techniques presented by Lilly Khavari, DPM,DABPM.

We are the most experienced lab to provide Epidermal Nerve Fiber Density (ENFD) testing

Physician’s Review: BakoDx ENFD Testing

  • The most objective tool for diagnosing, documenting, and monitoring SFPN

  • Accurately assesses degree of SFPN severity (mild, moderate, severe)

  • Quick, in-office procedure with little to no post-procedure care

  • Definitive diagnosis in 5-7 days, enabling patient-centered treatment using evidence-based medicine

  • Reimbursable by most insurance companies

Get Your ENFD Kit

ENFD Kit(s) is complimentary for ordering clinicians

  • Your account manager will contact you about scheduling an in-service and shipping your kits
  • It is best to order your ENFD kit 1-2 weeks prior to the procedure date
  • When you receive kit: Place cool-pack in freezer to be ready for return shipping