IRAEs

Immune-related adverse events (irAEs) are adverse effects that arise from immune activation driven by immunotherapies, most notably immune checkpoint inhibitors (ICIs). ICIs target inhibitory pathways such as CTLA-4, PD-1, and PD-L1 to enhance antitumor immunity. While effective against several cancers, these therapies can also trigger inflammatory reactions in normal tissues, resembling autoimmune or inflammatory diseases.

irAEs can involve any organ system and presentations vary widely. They most commonly affect the skin (rash, pruritus), gastrointestinal tract (diarrhea, colitis), endocrine glands (thyroid dysfunction, hypophysitis, diabetes), liver (hepatitis), lungs (pneumonitis), and musculoskeletal systems (arthralgia, myositis). Less frequently, irAEs may involve the nervous system, kidneys, heart, or eyes. The onset is variable, typically within weeks to months after starting therapy, but events can occur after cessation of treatment in some cases.

Diagnosis is based on clinical presentation, exclusion of infectious causes, laboratory tests, imaging, and, when appropriate, tissue biopsy. Grading follows standard criteria (e.g., CTCAE) to guide management. Management depends on severity: mild events may be treated with symptomatic care and close monitoring; moderate (grade 2) reactions often require withholding the ICI and initiating corticosteroids; severe (grade 3–4) reactions require withholding the ICI and administering higher-dose corticosteroids, with consideration of additional immunosuppressants for refractory cases. Rarely, lifelong endocrine dysfunctions require long-term replacement therapy.

Risk factors include preexisting autoimmune disease, organ-specific autoimmunity, and combination ICI therapy, which increase incidence and severity. irAEs may necessitate temporary or permanent discontinuation of cancer therapy, though mild events often resolve with treatment and most patients retain antitumor benefit. Multidisciplinary management is recommended.