Kelley, Mary A, Oaklander, Anne Louise · Canadian journal of pain = Revue canadienne de la douleur · 2020 · DOI
This study describes two patients who developed small fiber nerve damage (affecting the smallest nerves in the body) and severe fatigue after infections. Both had immune system abnormalities and improved dramatically with immune-suppressing treatments. Genetic testing found rare changes in a gene called SCN9A that affects how nerve cells communicate. The findings suggest that genetic variations in this gene might play a role in some cases of small fiber nerve damage that respond to immune therapy.
Many ME/CFS patients report neuropathic pain and autonomic dysfunction; this study provides mechanistic evidence that small fiber nerve damage combined with immune dysregulation may underlie these symptoms in some cases. The finding that genetic variants in sodium channel genes are associated with immunotherapy-responsive neuropathy suggests potential therapeutic pathways and the importance of screening for autoimmunity in ME/CFS patients with neuropathic symptoms. Understanding the genetic and immunological basis of small fiber pathology could lead to better diagnostic and treatment approaches.
This case report cannot establish whether the identified SCN9A variants are causative, contributory, or incidental findings—this requires larger population studies. The study does not prove that all ME/CFS patients have small fiber neuropathy or that genetic SCN9A variants are common in ME/CFS. Because there are no control subjects without these variants, causation cannot be inferred from the genetic data alone.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Kelley, Mary A & Oaklander, Anne Louise (2020). Association of small-fiber polyneuropathy with three previously unassociated rare missense SCN9A variants.. Canadian journal of pain = Revue canadienne de la douleur. https://doi.org/10.1080/24740527.2020.1712652
BibTeX
@article{mecfsatlas-kelley-2020-association-small,
author = {Kelley, Mary A and Oaklander, Anne Louise},
title = {Association of small-fiber polyneuropathy with three previously unassociated rare missense SCN9A variants.},
journal = {Canadian journal of pain = Revue canadienne de la douleur},
year = {2020},
doi = {10.1080/24740527.2020.1712652},
note = {PubMed: 32719824},
url = {https://www.mecfsatlas.com/evidence/kelley-2020-association-small},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/kelley-2020-association-small
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