The Other Side of the Checkpoint: An Emergency Physician's Guide to Immune-Related Adverse Events of Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) have reshaped prognosis across more than twenty malignancies, yet their mechanism of action carries the cost of a heterogeneous and potentially life-threatening spectrum of immune-related adverse events (irAEs) that may involve virtually every organ system. As indications expand and survival lengthens, a growing share of these patients reach emergency departments (EDs) before reaching their oncology team, where toxicity often masquerades as common acute pathology. This narrative review synthesises current epidemiology, pathophysiology, and management of clinically relevant irAEs from the perspective of acute care, drawing on guidelines from the American Society of Clinical Oncology, the European Society for Medical Oncology, the National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Cardiology, supplemented by recent observational data and pharmacovigilance series. Organ-specific syndromes (cardiac, endocrine, pulmonary, gastrointestinal, hepatic, neurological, renal, haematological, and dermatologic) are described with diagnostic pearls, time-from-exposure patterns, key differential considerations, and graded treatment pathways. Particular attention is given to fulminant myocarditis, adrenal crisis, hyponatraemia of mixed pathogenesis, and neuromuscular emergencies, which carry disproportionate mortality. Early recognition, methodical exclusion of infection, and judicious use of high-dose corticosteroids form the backbone of emergency management of irAEs. Familiarity with this class of adverse events has become a competency of acute care, alongside sepsis recognition and stroke pathway activation.