The effect of high-dose long-term therapy of intravenous immunoglobulins in autoimmune autonomic and sensory small fiber neuropathy: a retrospective open-label controlled study

Intravenous Immunoglobulins (IVIG) are used to treat autoimmune autonomic and sensory small fiber neuropathy (ASFN). The long-term effects of a high immunomodulatory dose of IVIG in ASFN remain unclear. This retrospective controlled study evaluated the long-term effects of high dose (2 g/kg/monthly) IVIG compared to usual treatment in patients with ASFN. Inclusion criteria were: Survey of Autonomic Symptoms (SAS) score ≥ 10, abnormal autonomic testing and skin biopsy, and positive inflammatory/autoimmune markers or a history of acute illness preceding autonomic symptoms. Quantitative Scale for Grading of Cardiovascular Autonomic Reflex Tests and Small Fibers from Skin Biopsies (QASAT) was used to grade tests. Patients were treated with IVIG until their condition improved and reached a plateau. Linear models controlling for baseline were used to estimate the effect of IVIG. 41 ASFN patients were treated with IVIG and compared to 66 ASFN control patients treated with usual care. Both groups had evaluations at baseline and at the end of the trial. The average time IVIG therapy improved ASFN and reached plateau was 2.25 ± 0.99 years. The adverse effects of IVIG were frequent (prevalence 93%) but tolerable in most patients. IVIG improved SAS (p < 0.001) and QASAT total (p < 0.001), cerebral blood flow (p = 0.002) and autonomic failure (p = 0.035) scores. SAS and QASAT autonomic failure scores worsened in controls. Skin biopsy improved in both arms, but improvement was greater (p = 0.017) in the IVIG arm. This study provides evidence supporting the beneficial effect of long-term high-dose IVIG therapy for ASFN. Placebo-controlled, double-blinded studies are required to confirm our findings.