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ENFD Testing Now Available

Jon Wilson, MD neuropathologist at arkana laboratories
By Jon Wilson, MD

Jul 14, 2021

ENFD testing at Arkana Laboratories Neuropathology services

Arkana Laboratories is very pleased to offer epidermal nerve fiber density (ENFD) testing as an addition to our growing Neuropathology service offerings.

What is small fiber neuropathy (SFN)?

SFN is a sensory neuropathy that preferentially involves thinly myelinated A-delta and unmyelinated C sensory fibers involved in the perception of pain and temperature. They are typically length-dependent and symmetrical.  Less commonly, patients may have non-length-dependent, focal, or multifocal symptoms. As SFN does not involve large motor and sensory fibers, patients typically present with burning pain and paresthesias beginning in the feet and progressing upwards, with normal EMG and NCS, and abnormal Quantitative Sensory Testing (QST).

What does ENFD testing evaluate?

ENFD testing quantitatively evaluates the degree of small nerve fiber loss in 3mm punch biopsies of skin. The nerve fibers are made visible by PGP9.5 antibody staining performed on 50um thick frozen sections of Zamboni-fixed biopsy tissue. Samples from the ankle (10cm proximal to the lateral malleolus) and at least one more proximal site (proximal thigh and/or distal thigh) are typically taken to demonstrate the length-dependent nature that is characteristic of most small fiber neuropathies (SFN). The number of nerve fibers that cross the dermo-epidermal junction per millimeter is compared to normative data.

Why perform skin punch biopsy for ENFD:

1) Evaluate possible cause(s) of painful neuropathy
2) Establish the diagnosis of SFN
3) Monitor response to treatment

Causes of small fiber neuropathy include: 

Idiopathic/unknown (up to 50% of cases)

Diabetes Mellitus, pre-diabetes/impaired glucose intolerance

Amyloidosis, paraproteinopathy/monoclonal gammopathy, and vasculitis

Connective tissue disorders

Sjögren syndrome (often seronegative), celiac disease, lupus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, mixed connective tissue disease (MCTD), nutritional deficiencies, and vitamin B1 deficiency

Vitamin B12 deficiency

Copper deficiency, an endocrine disorder, hypothyroidism, infection, HIV, Lyme disease, hepatitis C, Toxic/drug, Alcohol abuse


Vitamin B6 toxicity, metronidazole (Flagyl), solvent exposure, genetic, pathogenic variants in genes encoding voltage-gated sodium channels (VGSC), SCN9A, SCN10A, and SCN11A, fabry disease (pathogenic variants involving GLA gene), hereditary transthyretin amyloidosis hATTR (pathogenic variants involving TTR gene), Ehllers-Danlos syndrome


Visit ENFD Testing for more information or to download our requisition form. 

If you have questions regarding ENFD testing or any of our other Neuropathology services, please do not hesitate to contact us.





Quick note: This post is to be used for informational purposes only and does not constitute medical or health advice. Each person should consult their own doctor with respect to matters referenced. Arkana Laboratories assumes no liability for actions taken in reliance upon the information contained herein.