Combined Immunomodulatory Therapy in Autoimmune Autonomic Ganglionopathy

BACKGROUND: Autoimmune autonomic ganglionopathy is a disorder defined by antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. Patients present with symptoms of autonomic failure, including syncope, orthostatic hypotension, bowel and bladder hypomotility, pupillary dysfunction, and dry mouth and eyes. Symptomatic and immunomodulatory therapy has provided limited clinical benefit in small uncontrolled studies. OBJECTIVE: To investigate the effects of combined immunosuppressive therapy and plasmapheresis in autoimmune autonomic ganglionopathy. DESIGN: Prospective case series. SETTING: Academic medical center. PATIENTS: Three patients with autoimmune autonomic ganglionopathy who had a limited response to symptomatic therapy, such as midodrine, fludrocortisone, vasopressin, and erythropoietin. Additional treatment with plasmapheresis alone and intravenous immunoglobulin alone provided no additional clinical benefit. Patients underwent 6 months of treatment with prednisone and mycophenolate mofetil followed by 5 cycles of plasma exchange. RESULTS: Immunosuppressive therapy (prednisone and mycophenolate mofetil) combined with plasmapheresis resulted in substantial improvements in bowel control, pupillary function, dry mouth, and dry eyes. Mean (SD) blood pressure during immunosuppressive therapy was 162/83 (16/12) mm Hg supine and 76/45 (22/11) mm Hg standing (3 minutes). After 5 cycles of plasmapheresis, mean blood pressure was 132/82 (7/4) mm Hg supine and 127/81 (5/1) mm Hg standing (3 minutes; P < .01). Mean antibody level was 7.92 nmol/L on combined immunosuppressive therapy alone and dropped to 0.5 nmol/L after plasmapheresis. CONCLUSIONS: In patients with autoimmune autonomic ganglionopathy, combining immunosuppressive medications prednisone and mycophenolate mofetil with plasmapheresis provides substantial and sustained clinical improvement that was not seen using either treatment alone. Multi-agent immunomodulatory therapies may be necessary to satisfactorily treat this immune-mediated disorder.