Gastrointestinal Dysautonomia After Immune Checkpoint Inhibitor Therapy: A Case Series and Systematic Review

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are associated with gastrointestinal (GI) immune-related adverse events (IrAEs). GI dysautonomia is a rare IrAE due to enteric nervous system dysfunction with/without generalized autonomic failure. Here, we present a case series of GI dysautonomia following ICI therapy and conduct a systematic review of the literature.

We present three patients with ICI-induced GI dysautonomia referred to our tertiary ICI-neurotoxicity service. A systematic review was conducted in OVID, Cochrane, and Scopus until December 2024 for studies evaluating ICI-induced GI dysautonomia, including clinical presentation, treatment choice, and mortality.

Three male patients were treated with ICIs for melanoma (n = 2) and chondrosarcoma. Severe GI symptoms developed at seven years, two months, and three weeks from treatment initiation at ages 77, 60, and 57 years old, respectively. All three had panenteric involvement with additional autonomic dysfunction. Two patients had poor outcomes with enteral and parenteral nutrition dependence, respectively, and died from GI complications. The third case responded well to prolonged high-dose corticosteroids and mycophenolate maintenance. On systematic review, 18 individual cases were reported in 15 publications, with the onset of GI dysautonomia at a mean time of 13.6 weeks (SD 14.3) from ICI exposure. Corticosteroids were the primary treatment in 72% (n = 13), with a limited duration and low (< 1 mg/kg/day prednisolone equivalent) dose used in 46.2% (n = 6/13). There was GI recovery in 38.5% (n = 5) and mortality in 47.0% (n = 8; 1 missing).

ICI-induced GI dysautonomia is a potentially life-threatening IrAE requiring early recognition and effective immunosuppression to optimize outcome.