Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy

Neurology. 2021 May 18;96(20):e2534-e2545. doi: 10.1212/WNL.0000000000011919. Epub 2021 Mar 25.


Objective: This is the first double-blind randomized controlled trial evaluating the efficacy and safety of IV immunoglobulin (IVIG) vs placebo in patients with idiopathic small fiber neuropathy (I-SFN).

Methods: Between July 2016 and November 2018, 60 Dutch patients with skin biopsy-proven I-SFN randomly received a starting dose of IVIG (2 g/kg body weight) or matching placebo (0.9% saline). Subsequently, 3 additional infusions of IVIG (1 g/kg) or placebo were administered at 3-week intervals. The primary outcome was a 1-point change in Pain Intensity Numerical Rating Scale score at 12 weeks compared to baseline.

Results: Thirty patients received IVIG, and 30 received placebo. In both groups, 29 patients completed the trial. In 40% of patients receiving IVIG, the mean average pain was decreased by at least 1 point compared to 30% of the patients receiving placebo (p = 0.588, odds ratio 1.56, 95% confidence interval 0.53-4.53). No significant differences were found on any of the other prespecified outcomes, including general well-being, autonomic symptoms, and overall functioning and disability.

Conclusions: This randomized controlled trial showed that IVIG treatment had no significant effect on pain in patients with painful I-SFN.

Trial registration information: Identifier: NCT02637700, EudraCT 2015-002624-31.

Classification of evidence: This study provides Class I evidence that for patients with painful I-SFN, IVIG did not significantly reduce pain compared to placebo.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Neuralgia / drug therapy*
  • Neuralgia / physiopathology
  • Pain Measurement
  • Small Fiber Neuropathy / drug therapy*
  • Small Fiber Neuropathy / physiopathology
  • Treatment Outcome


  • Immunoglobulins, Intravenous
  • Immunologic Factors

Associated data

  • EudraCT/2015-002624-31