IVIg for apparently autoimmune small-fiber polyneuropathy: first analysis of efficacy and safety

Abstract

Objectives:Small-fiber polyneuropathy (SFPN) has various underlying causes, including associations with systemic autoimmune conditions. We have proposed a new cause; small-fiber-targeting autoimmune diseases akin to Guillain-Barré and chronic inflammatory demyelinating polyneuropathy (CIDP). There are no treatment studies yet for this ‘apparently autoimmune SFPN’ (aaSFPN), but intravenous immunoglobulin (IVIg), first-line for Guillain-Barré and CIDP, is prescribed off-label for aaSFPN despite very high cost. This project aimed to conduct the first systematic evaluation of IVIg’s effectiveness for aaSFPN.Methods:With IRB approval, we extracted all available paper and electronic medical records of qualifying patients. Inclusion required having objectively confirmed SFPN, autoimmune attribution and other potential causes excluded. IVIg needed to have been dosed at ⩾1 g/kg/4 weeks for ⩾3 months. We chose two primary outcomes – changes in composite autonomic function testing (AFT) reports of SFPN and in ratings of pain severity – to capture objective as well as patient-prioritized outcomes.Results:Among all 55 eligible patients, SFPN had been confirmed by 3/3 nerve biopsies, 62% of skin biopsies, and 89% of composite AFT. Evidence of autoimmunity included 27% of patients having systemic autoimmune disorders, 20% having prior organ-specific autoimmune illnesses and 80% having ⩾1/5 abnormal blood-test markers associated with autoimmunity. A total of 73% had apparent small-fiber-restricted autoimmunity. IVIg treatment duration averaged 28 ± 25 months. The proportion of AFTs interpreted as indicating SFPN dropped from 89% at baseline to 55% (p ⩽ 0.001). Sweat production normalized (p = 0.039) and the other four domains all trended toward improvement. Among patients with pre-treatment pain ⩾3/10, severity averaging 6.3 ± 1.7 dropped to 5.2 ± 2.1 (p = 0.007). Overall, 74% of patients rated themselves ‘improved’ and their neurologists labeled 77% as ‘IVIg responders’; 16% entered remissions that were sustained after IVIg withdrawal. All adverse events were expected; most were typical infusion reactions. The two moderate complications (3.6%) were vein thromboses not requiring discontinuation. The one severe event (1.8%), hemolytic anemia, remitted after IVIg discontinuation.Conclusion:These results provide Class IV, real-world, proof-of-concept evidence suggesting that IVIg is safe and effective for rigorously selected SFPN patients with apparent autoimmune causality. They provide rationale for prospective trials, inform trial design and indirectly support the discovery of small-fiber-targeting autoimmune/inflammatory illnesses.

Diagnosis and management of sensory polyneuropathy

“…Some experts have proposed an additional category of “apparently autoimmune” SFN that could account for some forms of otherwise idiopathic SFN 80. Patients in this category, who have evidence of systemic autoimmune disorders and blood markers of autoimmunity, have been described as having an atypical, painful SFN that responds to corticosteroids and intravenous immunoglobulins 55818283.…”

How We Treat Autoimmune Small Fiber Polyneuropathy with Immunoglobulin Therapy

“…For all of these patients, however, the duration of treatment was less than 1 year. Dr. Liu, however, has reported 16% of their patients were eventually able to stop IVIg [22]. Dependence on IVIg can be assessed by gradually reducing the dosing interval, for example, from every 4 weeks to every 5 weeks to every 6 weeks and so on.…”

“…Seventeen of 23 patients (74%) improved subjectively and most also demonstrated objective improvement in autonomic testing. Most recently, Liu and Schofield separately reported 2 large retrospective case series in the use of IVIg in patients with autoimmune or "apparently autoimmune" SFPN with similar response rates of approximately 80% [2,22].…”

Fibromyalgia and small‐fiber polyneuropathy: What's in a name?

“…Unlike syndromes (also known as symptom complexes ), diseases can be objectively diagnosed, such as with the distal‐leg skin biopsies recommended for SFPN . Their biological causes can be identified, tracked, and sometimes prevented or cured . Cough caused by pneumonia is not treated in the same manner as an asthma cough, even if the coughing sounds the same.…”

“…18,19 Their biological causes can be identified, tracked, and sometimes prevented or cured. 20 Cough caused by pneumonia is not treated in the same manner as an asthma cough, even if the coughing sounds the same. Now, in this issue of Muscle & Nerve, Lawson et al 21 further document that neuropathy is one of the diseases underlying the fibromyalgia label.…”