Trial Report Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and POTS: A retrospective study, 2024, Moak

https://www.sciencedirect.com/science/article/abs/pii/S1566070224000171

Autonomic Neuroscience
Available online 8 March 2024, 103163
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Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study
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Jeffrey P. Moak a, Carolyn B. Ramwell a, Heather Gordish-Dressman b, Sangeeta D. Sule c, Elizabeth Bettini a
a
Division of Cardiology, Children's National Hospital, Washington, DC, United States of America
b
Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, United States of America
c
Division of Rheumatology, Children's National Hospital, Washington, DC, United States of America
Received 19 July 2023, Revised 11 February 2024, Accepted 7 March 2024, Available online 8 March 2024.


https://doi.org/10.1016/j.autneu.2024.103163Get rights and content

Abstract
Purpose
To determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state.

Methods
A cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests.

Results
In CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process.

Conclusion
Our data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.