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Editors' Note: Part 3: Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy

“Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy” by Geerts et al. compared the administration of IVIG with placebo for patients with idiopathic small fiber neuropathy (SFN) and found no significant difference in the Pain Intensity Numerical Rating Scale score. We summarized (1) an exchange about these findings between Wilder-Smith and Spoendlin and Faber (a coauthor on the article) in the October 19, 2021, Editors' Note and (2) an exchange between Wilder-Smith et al. and Faber et al. in the January 18, 2022, Editors' Note.1,2 Oaklander et al. now comment that while the trial used a subjective outcome (pain intensity), an objective assessment (such as autonomic function test scores) could have enhanced the methodology. They also advocate against the extrapolation of these results to all patients with SFN, noting that patients with autoimmune disorders who may benefit from IVIG may not be readily apparent, so it is beneficial to create guidelines triaging patients with SFN who may benefit from a time-limited trial of IVIG. Finally, they express concern that payors may deny treatment to some patients who could benefit, particularly those who are immune-mediated. Faber et al. respond that changes in the Pain Intensity Numerical Rating Scale score are clinically relevant and the sensitivity of autonomic function testing results in isolation to detect autonomic dysfunction in SFN is low in clinical practice. They agree that patients with immune-mediated SFN may benefit from IVIG and emphasize that their study was not intended to focus on that patient population. However, they suggest that randomized studies with valid and reliable outcome measures are needed to evaluate the role of IVIG in patients with SFN that could potentially be immune-mediated.