Rituximab treatment in seronegative autoimmune autonomic neuropathy and autoimmune autonomic ganglionopathy: Case-report and literature review

Background and purpose: Autoimmune autonomic ganglionopathy (AAG) is a rare disease with no well-established treatment. Until recently, AAG could be seropositive (50 to 60% of patients) or seronegative for ganglionic (alpha 3-type) nicotinic acetylcholine receptor (G alpha 3NAChR) antibodies. In early 2018, the two forms of the disease were distinguished, separating seropositive from seronegative ones, designating this latter form "seronegative autoimmune autonomic neuropathy" (SAAN). Most described treatments are plasma exchange (PE) and intravenous immunoglobulin (IVIG). However in some cases with no or small benefit, other immunomodulatory therapies, such as rituximab have been reported. We report the case of a 24-year-old female patient successfully treated for SAAN with rituximab and steroids after IVIG and PE failure. We also provide a review of case-reports reporting rituximab treatment for both SAAN and AAG. Methods: To identify articles reporting SAAN and AAG treatment with rituximab, we searched the PubMed database using the terms "autoimmune autonomic ganglionopathy", "autoimmune autonomic neuropathy" or "seronegative autoimmune autonomic neuropathy" and "rituximab". Results: Including our patient, nine cases have been described in the literature (4 SAAN and 5 AAG). Rituximab had a significant positive effect in 2 out of 4 SAAN and all 5 AAG cases, used alone or in association with other etiologic treatments. Conclusion: Our study suggests rituximab (alone or in association with other treatments) could provide efficacy in both SAAN and AAG when PE and/or IVIG are not effective enough.