Objective:

To demonstrate efficacy of Intravenous Immunoglobulin (IVIG) in pure small fiber neuropathy (SFN) patients who had trisulfated heparin disaccharide (TS-HDS), fibroblast growth factor-3 (FGFR-3), or Plexin D1 antibodies (seropositive).

Background:

SFN has an increasing prevalence and over 30% of cases may be immune-mediated. TS-HDS, FGFR-3, and Plexin D1 autoantibodies have been shown to be present in 44-55% of cryptogenic SFN cases, suggesting an immune-mechanism. Some reports have shown IVIG to be an effective treatment.

Design/Methods:

In a retrospective review, all pure SFN cases tested for the 3 antibodies from January 2021-May 2022 were tabulated, and cases who underwent IVIG treatment were separated and analyzed for changes in length-dependent (LD)-, non-length dependent (NLD)-, and composite-epidermal nerve fiber density (ENFD) on skin biopsy (composite is an average of all sites), as well as SFN-specific questionnaire and pain scores.

Results:

92 patients with pure SFN had antibody testing (68% seropositive, 32% seronegative). 17 seropositive patients underwent IVIG treatment. Of these, 2 patients stopped treatment due to side effects (severe headaches or allergic reaction), and the remaining 15 completed at least 6 months of IVIG. Of these, 12 had a post-IVIG skin biopsy, and of these, 11 (92%) had a 55.1% mean improved composite ENFD (p=0.01). NLD-ENFD specimens improved by 42.3% (p=0.02) and LD-ENFD specimens improved by 99.7% (p=0.01). Composite ENFD in Plexin D1-SFN patients improved by 139% (p=0.04). Also, 14 patients had questionnaires pre-/post-IVIG and average pain decreased by 2.7 (p=0.002).

Conclusions:

IVIG shows disease-modifying effect in immune SFN with novel antibodies, especially Plexin D1-SFN, as well as significantly improved pain. NLD-ENFD should be examined as well as LD-ENFD to see this effect. Further randomized controlled trials looking at NLD- as well as LD-ENFD improvement, along with pain and SFN-specific questionnaires, are needed to confirm these findings.