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How To... Order SFN Skin Biopsy - A Guide for Practitioners

04 July 2022

Practitioners Guide - How to Order a Small Fiber Neuropathy (SFN) Skin Biopsy

“SFN occurs when damage to the peripheral nerves predominantly or entirely affects the small myelinated (Aδ) fibers or unmyelinated C fibers. The specific fiber types involved in this process include both small somatic and autonomic fibers.”  Diagnosis and Treatment of Pain in Small Fiber Neuropathy Diagnosis and Treatment of Refractory Autoimmune Dysautonomia (SFN Testing)


Skin Biopsy Specimen Collection:

Skin biopsy kit: The package contains a 3-mm biopsy punch, scalpel, forceps, ice packs, specimen tubes filled with Zamboni’s fix solution and labeled distal leg, distal thigh, and proximal thigh. Zamboni’s fix solution is stable at room temperature for up to a year. Expiration date is labeled on tubes. Skin biopsy specimen collection:

  • Place the patient in a lateral position.
  • Identify 3 standard biopsy sites on one leg: distal leg (10 cm above the lateral malleolus), distal thigh (7 cm above the knee, lateral), and proximal thigh (7 cm below the hip, lateral). ** Recent studies have shown compelling findings with sweat gland biopsies. Adding this biopsy to the order is recommended.
  • Clean the biopsy sites with alcohol swabs and numb the areas with local anesthesia (1% lidocaine or 1% lidocaine with Epinephrine to reduce bleeding)
  • Perform the skin biopsy using a 3-mm punch going down 2/3 of the punch in depth.
  • Remove biopsy specimens using a surgical blades and forceps technique (do not pinch epidermis).
  • Put each specimen into a tube containing Zamboni’s fix solution immediately after removing it and tighten lids. The tube should be labeled with patient’s name, DOB, and biopsy side and site (e.g. left distal leg).
  • Seal specimen tubes in plastic specimen bag with absorbent material.
  • Refrigerate specimens until ready to ship. Use ice packs when shipping specimens.
  • Licensed Independent Provider must sign and date the enclosed Skin Biopsy Referral Form. You can also download the Referral Form from the website.

Skin biopsy specimen shipping:

  • Please ship specimens using enclosed ice packs via overnight delivery either by UPS or FedEx the same day as the biopsy is performed in the original kit box.
  • Please include the signed and completed Skin Biopsy Referral Form. · Please apply enclosed “Perishable” and “Human Specimen” stickers to shipping box.
  • Please contact the lab via phone or email with the Tracking Number and shipping date and include patient’s name and date of birth in the subject line.
  • Please do not ship specimens on Friday, weekends, or holidays.
The positive predictive value of skin biopsy in diagnosing Small Fiber Neuropathy is estimated at 93%; specificity is 97% and sensitivity ranges from 69% to 82%.



  • Consider an additional skin biopsy site in the area that the patient complains of the most sensory symptoms (if the standard biopsy sites does not already include this).
  • Two biopsy sites are the minimum obtained for diagnosis, with the distal leg (10 cm above the lateral malleolus) routinely considered standard as one of these two sites to allow for consideration of length versus non-length dependent Small Fiber Neuropathy diagnosis.
  • Before performing this procedure, ensure that you have established a laboratory that will accept this sample for interpretation.


Columbia University tests for intraepidermal nerve fiber swelling and branching pattern changes which make the results more conclusive. Biopsies may be run by Therapath **Therapath does not test for qualitative alterations including intraepidermal nerve fiber swelling and branching pattern changes.  Therapath Requisition Skin Biopsy Test Selection:


*Confirm that you have checked off each of these 3 tests:

  1. Epidermal Nerve Fiber Density (ENFD). This test measures the density of the small sensory nerve fibers in the skin.
  2. Sweat Gland Nerve Fiber Density (SGNFD) test. This test measures the density of the small autonomic nerve fibers in the sweat glands. *This test is available but is not typically ordered by the physician, but this option is available and relevant.
  3.   Amyloidosis and Vasculitis test. These are usually run with every test, but your doctor can also check this box. If these conditions are not seen, it does not rule them out.
Everything presented on this site is for informational and educational purposes only.
Look, read the research, talk with your doctor, make informed decisions.