Health Mechanisms

Topics / Dysautonomia

What is small fiber neuropathy, and what links with POTS have been studied?

Understanding small nerve fibers, the tests used to assess them and the limits of the studies carried out in people with POTS.

  • 6 sources
  • 4 min read
  • Clinical review
  • Verified 9 November 2026

Key points

  • Small fibers include thin sensory fibers and autonomic fibers; damage to them can produce sensory and/or autonomic manifestations [1, 2].
  • Skin biopsy with measurement of intraepidermal nerve fiber density is a recognized confirmation tool; it must be interpreted together with symptoms, clinical signs and other tests [2, 1].
  • A painful symptom or isolated paresthesia is not enough to establish small fiber neuropathy; the combination of clinical signs and objective tests is important [1].
  • Specialized cohorts report abnormal small fiber test results in a subset of patients with POTS/OI, but their selection methods and samples do not allow these figures to be generalized to the whole POTS population [3, 4].
  • A small fiber abnormality in a person with POTS does not prove that it alone explains the POTS, nor that POTS causes the neuropathy.

Defining small fibers

How is SFN evaluated?

Association, mechanism and causation

Causes of SFN: do not automatically attribute it to POTS

References and level of evidence

  1. Devigili G et al. Diagnostic criteria for small fibre neuropathy in clinical practice and research. Brain, 142(12):3728–3736 2019. DOI: 10.1093/brain/awz333. PMID: 31665231.(observational study)
    Limitations: Clinical cohorts; criteria depend on the examination and the methods available. Population: reassessment and validation of diagnostic criteria. Read: full text.
    Declared conflicts of interest: The authors declare no conflicts of interest; funding: Italian Ministry of Health (Ricerca Corrente)
  2. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Journal of the Peripheral Nervous System, 15(2):79–92 2010. DOI: 10.1111/j.1529-8027.2010.00269.x. PMID: 20626771.(guideline or consensus)
    Limitations: Guideline focused on skin biopsy; older, and to be read alongside recent criteria. Population: guideline on the use of skin biopsy. Read: full text (co-publication in Eur J Neurol).
    Declared conflicts of interest: No declaration in the text read (co-publication Eur J Neurol 2010;17:903-912)
  3. Zhang R et al. Skin Biopsy and Quantitative Sudomotor Axon Reflex Testing in Patients With Postural Orthostatic Tachycardia Syndrome. Cureus, 14(11):e31021 2022. DOI: 10.7759/cureus.31021. PMID: 36349067.(observational study)
    Limitations: Retrospective; tests not performed in all patients; tertiary-center selection; mostly female and white population. Population: cohort from a specialized POTS center, with tests available in subgroups. Read: full text (Europe PMC).
    Declared conflicts of interest: The authors declare no conflicts of interest
  4. Moak JP et al. Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study. Autonomic Neuroscience, 253:103163 2024. DOI: 10.1016/j.autneu.2024.103163. PMID: 38537312.(observational study)
    Limitations: Selected cohort; does not give the prevalence across all pediatric cases. Population: young people with POTS/chronic OI and neuropathic signs referred to a specialized center. Read: abstract.
    Declared conflicts of interest: The authors declare no conflicts of interest
  5. Cortez MM, Cook G, Miglis MG, Raj SR, Robbins NM, Singer W, Sletten DM, Stino AM, Vernino S. Utility and best practices for clinical diagnostic testing of the autonomic nervous system: A Consensus Statement Endorsed by the American Autonomic Society and the American Association of Neuromuscular & Electrodiagnostic Medicine. Clinical Autonomic Research 2026. DOI: 10.1007/s10286-026-01238-9. PMID: 42766240.(guideline or consensus)
    Limitations: Expert consensus; not a comparative trial of all strategies. Population: specialist consensus on autonomic testing. Read: full text (open access, Springer).
    Declared conflicts of interest: Several authors declare consulting activities or industry funding (notably Argenx, CSL Behring, Takeda); others declare none
  6. Katzberg HD et al. Diagnostic and Screening Laboratory Tests in the Assessment of Patients With Small Fiber Neuropathy: An Evidence-Based Review-Report of the American Association of Neuromuscular and Electrodiagnostic Medicine Small Fiber Neuropathy Task Force. Muscle & Nerve, 73(6):952–960 2026. DOI: 10.1002/mus.70119. PMID: 41670166.(evidence synthesis)
    Limitations: Inconsistent search end date within the article (abstract: January 2023; methods: MEDLINE through August 2017, EMBASE through January 2023). Literature search ended in January 2023 despite publication in 2026; limited number of high-quality studies. Population: evidence-based review of diagnostic and screening tests. Read: abstract.
    Declared conflicts of interest: Not reviewed in the part of the source that was read
Written by
AI-assisted literature research (ChatGPT) and AI-assisted writing (Claude)
Editor
Jean Viry-Babel
Review status
Clinical review: Dr Françoise Charmoillaux (anesthesiologist)
Approved on
9 November 2026
Literature search
8 November 2026
Last verified
9 November 2026
Geographic scope
international, United States, France
Audience
everyone
Conflicts of interest
No known financial ties. Separately, the publisher is developing a personal approach to these conditions under the name Connected Conditions, which is not cited here (see the legal notice).
Limitations of this page
General overview: it cannot be used to interpret a skin biopsy or sudomotor test result. The proportions cited come from selected cohorts and are not prevalence figures.