To introduce a potential novel treatment for autoimmune autonomic ganglionopathy (AAG).

AAG is a rare disorder characterized by subacute, generalized sympathetic and parasympathetic failure. Pathogenesis is attributed to an underlying autoimmune etiology, evidenced by detection of ganglionic nicotinic acetylcholine receptor serum antibodies (α3-nAChR). Treatment guidelines are not established, and typically include a combination of immunomodulatory therapies.

We report a case of a 57-year-old man who presented with worsening orthostatic hypotension over 12 months on a background of seronegative polyarthritis for 15 years. At his initial presentation in 2003, he had symptoms of syncope, sicca, chronic constipation, incomplete bladder emptying, decreased sweating, and weight loss. He was found to have generalized autonomic dysfunction associated with nAChR of 14.3 nmol/L (normal <0.02nmol/L). Paraneoplastic work up including imaging of abdomen and chest was negative for malignancy. Symptomatic management, plasma fluid expanders and IVIG therapy failed to offer a salutary response.

Etanercept, a tumor necrosis factor-alpha inhibitor was started in 2005 at an outside hospital for treatment of his polyarthritis. The patient experienced symptomatic improvement in AAG with etanercept, with subsequent improvement in autonomic function testing (AFT). He now presents with clinical deterioration in the setting of nAChR of 98.5 nmol/L. Quantitative autonomic testing revealed abnormal parasympathetic (abnormal heart rate variability to deep breathing and Valsalva maneuver) and sympathetic function (abnormal blood pressure response during a Valsalva maneuver and a >100 mmHg drop in systolic blood pressure). 

This case highlights the inadvertent treatment of AAG for >10 years using etanercept in a patient being treated for seronegative polyarthritis.  These findings suggest etanercept may be a novel treatment option for patients with AAG - a disorder that may require two or more immunomodulatory interventions - although the recent resurgent symptoms and increase in antibody titer suggest a limited durability of treatment.