Fiber Peripheral Neuropathy 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).

The Epidermal Nerve Fiber Density (ENFD) test is an objective method of documenting small fiber peripheral neuropathy by quantifying the terminal branches of peripheral nerves within the epidermis. The test is highly specific and sufficiently sensitive with 97% of accuracy rate. The test is recommended to perform when patients experience the following symptoms: pain and abnormal sensation (burning, prickling, shooting), as well as numbness, tightness, coldness in foot/ankle areas.

The ENFD test can also be used to predict the small nerve fiber peripheral neuropathy.

Epidermal Nerve Fiber Density (ENFD)

Collection Procedure

ENFD Results

Collection Clinical Education


Get your ENFD Kit

Requisition Form

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%.
  • 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

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.


ENFD Results

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

Clinical Resources for ENFD

ENFD Procedural Guide. Download this easy-to-follow training and reference tool for your staff.

Why ENFD Analysis Provides the Best Tool to Confirm Small Fiber Peripheral Neuropathy

For your reference, we created this ENFD Biopsy Collection Procedure Video with assistance from our BakoDx clinical consultants.

Epidermal Nerve Fiber Density Testing : An Overview

A technique for the evaluation of small fiber peripheral neuropathy


Olga Luepschen, DPM, Gentle Foot Care Center, Sebring, FL

“My patients have seen a drastic improvement in their quality of life through providing ENDF analysis and subsequent treatment. Your patients will love you for offering this test.”

Lilly Khavari, DPM DABPM, Carrollton Foot Center, Carrollton, TX

“We love BAKO because the process is so streamlined and easy to follow. The tests and reports are accurate and informative. All the people at BAKO that we have contact with are pleasant and super helpful!”

Dr. Paul Cryan, Wayne, PA

“My office, Centerock Podiatry has been using Bako for many years. The products work, the pathology services are extremely fast and accurate but above all the customer service is top notch. Overall, BAKO rocks!”

Caitlyn, Centerock Podiatry Associates, P.C.

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