Introduction/Aims Small fiber neuropathies (SFN) have been associated with two autoantibodies, trisulfated heparin disaccharide (TS‐HDS) and fibroblast growth factor receptor 3 (FGFR‐3), and intravenous immune globulin (IVIG) has been suggested as a potential therapy. The study objective is to determine the efficacy of IVIG on nerve density, pain and neurologic examinations in patients with SFN associated with TS‐HDS and FGFR‐3 autoantibodies. Methods This was a double‐blind placebo‐controlled pilot study. Subjects with SFN confirmed by history, examination, and skin biopsy with elevated autoantibodies to TS‐HDS and/or FGFR‐3 received IVIG (or blinded placebo) 2 grams/kg followed by 1 gram/kg every 3 wk for a total of 6 treatments. All subjects had Utah Early Neuropathy Scores (UENS), questionnaires and skin biopsies with quantitation of intra‐epidermal nerve fiber density (IENFD) taken from adjacent sites at the distal leg at baseline and 6 mo later. The primary outcome was the change in IENFD over 6 mo. Results Twenty subjects were enrolled; 17 completed treatment (8 IVIG, 9 placebo). Three did not have final data due to coronavirus disease 2019 (COVID‐19). Skin biopsy IENFD improved by 0.5 ± 0.8 fibers/mm in the placebo group and improved by 0.6 ± 0.6 fibers/mm in the IVIG‐treated group (p = NS).Over 24 wk the change in pain scores (11 point pain scale) was −1.9 ± 2.6 in the placebo group, and − 1.7 ± 0.9 in the IVIG group (p = NS), the UENS improved by 3.0 ± 5.8 in the placebo group and improved by 1.8 ± 3.9 in the IVIG group (p = NS). Discussion This pilot study did not detect a benefit of treatment with IVIG in patients with SFN and autoantibodies to TS‐HDS and FGFR‐3.

E26LETTERS TO THE EDITOR immunoglobulin, at a cost of tens of thousands of dollars per patient, provides less benefit in nerve density recovery than has been reported with 12 months of simple lifestyle modifications, 7 then perhaps debate on the use of intravenous immunoglobulin in SFN should end. AUTHOR CONTRIBUTIONSChristopher Gibbons H: Writingoriginal draft; writingreview and editing. Sharika Rajan: Writingreview and editing.Katherine Senechal: Writingreview and editing. Erin Hendry:Writingreview and editing. Brady McCallister: Writingreview and editing. Todd D. Levine: Writingreview and editing. FUNDING INFORMATION Grifols CONFLICT OF INTEREST STATEMENTC.H.G. and T.D.L. have received institutional research support from Grifols to conduct this study. The remaining authors declare no potential conflicts of interest. ETHICAL PUBLICATION STATEMENTWe confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.