GUIDANCE FOR USE
Small-Fiber Dx® (SFDx) is an anatomical pathology test to aid in the evaluation of patients with signs or symptoms suggestive of small fiber neuropathy. The test utilizes immunofluorescence techniques with protein gene product 9.5 (PGP 9.5) staining to quantify intraepidermal nerve fiber density (INEFD) as a marker of small fiber neuropathy. Histopathologic evaluation with hematoxylin and eosin (H&E) is performed to diagnose dermatologic conditions. Congo red staining is ordered to diagnose amyloidosis. Results should be interpreted in conjunction with the patient’s medical history and clinical presentation.
Stability of tissue specimens in fixative beyond 120 hours has not been established. Prolonged fixation may affect detection of phosphorylated alpha-synuclein and measurement of intraepidermal nerve fiber density.
This test was developed and its performance characteristics determined by CND Life Sciences, Inc. It has not been cleared or approved by the U.S. Food and Drug Administration. CND Life Sciences, Inc. is accredited by the College of American Pathologists (CAP), holds a CLIA Certificate of Accreditation to perform high-complexity testing, and holds a Clinical Laboratory Evaluation Program (CLEP) permit from New York.
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References
For additional information on the skin biopsy technique and intraepidermal nerve fiber density see:
Lauria G, Hsieh ST, Johansson O, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010;17(7):903-12, e44-9. doi:10.1111/j.1468-1331.2010.03023.x
Provitera V, Gibbons CH, et al. A multi-center, multinational age- and gender-adjusted normative dataset for immunofluorescent intraepidermal nerve fiber density at the distal leg. Eur J Neurol. 2016;23(2):333-338. doi:10.1111/ene.12842
Boruchow SA, Gibbons CH. Utility of skin biopsy in management of small fiber neuropathy. Muscle Nerve. 2013 Dec;48(6):877-82. doi: 10.1002/mus.23859. Epub 2013 Sep 11. PMID: 23553795.
Samolis A, Troupis T, et al. Intraepidermal Nerve Fiber Density as an Indicator of Neuropathy Predisposition: A Systematic Review with Meta-Analysis. Diagnostics (Basel). 2025 May 23;15(11):1311. doi: 10.3390/diagnostics15111311. PMID: 40506883; PMCID: PMC12154223.
Devigili G, Lombardi R, Lauria G, Cazzato D. The Evolving Landscape of Small Fiber Neuropathy. Semin Neurol. 2025 Feb;45(1):132-144. doi: 10.1055/s-0044-1791823. Epub 2024 Oct 21. PMID: 39433284.
