GUIDANCE FOR USE
Small-Fiber Dx (SFDx) is a skin-biopsy-based test intended to provide objective assessment of the neuropathology of epidermal nerves. The central diagnostic feature of SFDx is the application of an immunofluorescent protein gene product (PGP 9.5) stain that enables quantitative measurement of intraepidermal nerve fiber density (IENFD). A reduced IENFD is indicative of a small-fiber neuropathy.
Small-Fiber Dx includes a Congo red stain for amyloid as a part of the neuropathologic assessment. The finding of amyloid deposits could indicate a potential cause for epidermal and autonomic nerve pathology, generalized peripheral neuropathy, autonomic dysfunction, and other multi-organ disorders, and should prompt an evaluation for primary and secondary causes of amyloidosis.
Small-Fiber Dx includes a hematoxylin and eosin (H&E) stain, which allows for the evaluation of dermatologic conditions that could mimic neuropathies and identify other benign and malignant skin abnormalities that may be present. The H&E results pertain only to the tissue biopsies taken for this test. Any clinically apparent lesions warrant separate analysis by a dermatologist.
Stability data is not available for tissue specimens kept in fixative for more than 120 hours. Prolonged fixative time could result in an artificial decrease in the intraepidermal nerve fiber density.
References
For additional information on the skin biopsy technique and intraepidermal nerve fiber density see:
Provitera V, Gibbons CH, Wendelschafer-Crabb G, et al. The role of skin biopsy in differentiating small-fiber neuropathy from ganglionopathy [published correction appears in Eur J Neurol. 2019 Jan;26(1):202]. Eur J Neurol. 2018;25(6):848-853. doi:10.1111/ene.13608
Provitera V, Gibbons CH, Wendelschafer-Crabb G, 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
Lauria G, Bakkers M, Schmitz C, et al. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010;15(3):202-207. doi:10.1111/j.1529-8027.2010.00271.x
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
Devigili G, Rinaldo S, Lombardi R, et al. Diagnostic criteria for small fibre neuropathy in clinical practice and research. Brain. 2019;142(12):3728-3736. doi:10.1093/brain/awz333
Freeman R, Gonzalez-Duarte A, Barroso F, et al. Cutaneous amyloid is a biomarker in early ATTRv neuropathy and progresses across disease stages. Ann Clin Transl Neurol. 2022, 9(9), 1370–1383. doi: 10.1002/acn3.51636
Immunohistochemistry and immunofluorescence tests were developed, and their performance characteristics were determined, by CND Life Sciences, Scottsdale, AZ. They have 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) and holds a Clinical Laboratory Improvement Amendments (CLIA) Certificate of Accreditation to perform high-complexity testing.
