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

Area of Science:

• Oncology
• Immunology
• Gastroenterology
• Neurology

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but can induce immune-related adverse events (IrAEs).
• Gastrointestinal (GI) dysautonomia is a rare but severe IrAE resulting from dysfunction of the enteric nervous system, potentially with generalized autonomic failure.
• This study investigates GI dysautonomia following ICI treatment through a case series and systematic literature review.

Purpose of the Study:

• To describe the clinical characteristics, treatment strategies, and outcomes of patients experiencing GI dysautonomia after ICI therapy.
• To systematically review existing literature on ICI-induced GI dysautonomia to identify trends in presentation, management, and mortality.
• To emphasize the importance of early diagnosis and intervention for this potentially life-threatening condition.

Main Methods:

• A case series of three patients with ICI-induced GI dysautonomia treated at a specialized neurotoxicity service.
• A systematic literature search was conducted using OVID, Cochrane, and Scopus databases up to December 2024.
• The review focused on clinical presentation, treatment choices, and mortality associated with ICI-induced GI dysautonomia.

Main Results:

• Three male patients developed severe GI dysautonomia after ICI treatment for melanoma or chondrosarcoma, with panenteric and autonomic involvement.
• Two patients experienced poor outcomes, including dependence on nutritional support and death from GI complications; one patient responded to corticosteroids and mycophenolate.
• The systematic review identified 18 cases, with a mean onset of 13.6 weeks post-ICI exposure. Corticosteroids were used in 72%, but often at low doses or for limited durations. Recovery occurred in 38.5%, while mortality was 47%.

Conclusions:

• Immune checkpoint inhibitor-induced GI dysautonomia is a serious and potentially fatal immune-related adverse event.
• Early recognition and prompt, effective immunosuppressive therapy are essential to improve patient outcomes.
• Further research is needed to optimize treatment strategies for this rare but devastating condition.