Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility

• Published in: Neurogastroenterology and motility Vol. 26; no. 9; pp. 1285 - 1297
• Main Authors: Flanagan, E. P., Saito, Y. A., Lennon, V. A., McKeon, A., Fealey, R. D., Szarka, L. A., Murray, J. A., Foxx‐Orenstein, A. E., Fox, J. C., Pittock, S. J.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2014
• Subjects: Adolescent; Adult; Aged; Autoimmune Diseases; autonomic nervous system; Autonomic Nervous System Diseases - complications; Autonomic Nervous System Diseases - diagnosis; Autonomic Nervous System Diseases - drug therapy; autonomic neuropathy; celiac disease; Gastrointestinal Diseases - complications; Gastrointestinal Diseases - diagnosis; Gastrointestinal Diseases - drug therapy; Gastrointestinal Diseases - immunology; Gastrointestinal Transit; Humans; immunoglobulin; Immunoglobulins, Intravenous - therapeutic use; Immunotherapy; Male; Manometry; Methylprednisolone - therapeutic use; Middle Aged; Retrospective Studies; scintigraphy; thyroid disease; transit study; Treatment Outcome; Young Adult; thyroid disease; autonomic nervous system; immunoglobulin; scintigraphy; celiac disease; autonomic neuropathy; transit study
• ISSN: 1350-1925; 1365-2982; 1365-2982
• DOI: 10.1111/nmo.12391

Background Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under‐recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID). Methods Twenty‐three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006–February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy–manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6–12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). Key Results Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra‐intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re‐evaluated had scintigraphic evidence of improvement. The majority of responders who were re‐evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). Conclusions & Inferences This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy. In this article, we report 23 patients seen by members of this study group with suspected AGID in whom an immunotherapy trial (with intravenous immune globulin or methylprednisolone) was undertaken. The 17 responders described in this study provide the first objective evidence that immunotherapy may reverse autoimmune gastrointestinal dysmotility and illustrate the practical importance of considering an autoimmune basis for acquired idiopathic gastrointestinal motility disorders. Symptomatic improvements were generally accompanied by objective evidence of improved gastrointestinal motility and autonomic function on repeated scintigraphic, manometric, and autonomic function tests. These supportive tests offer useful surrogate markers of improvement for future randomized controlled clinical trials.