Immune checkpoint inhibitor toxicity

Lymphocytic hypophysitis is a presumed autoimmune inflammation of the pituitary gland that typically presents in women during pregnancy or the postpartum period, with a sellar mass, hyperprolactinemia, or hypopituitarism. There is no specific therapy; management is hormonal replacement of any deficient axis as needed, with surgery reserved for mass effect that does not respond to observation.

Primary adrenal insufficiency (Addison disease) is destruction or dysfunction of the adrenal cortex, most often autoimmune, causing combined cortisol and aldosterone deficiency with hyperpigmentation, hyponatremia, and hyperkalemia. Lifelong glucocorticoid replacement with hydrocortisone plus mineralocorticoid replacement with fludrocortisone is required, with sick-day dose increases to prevent adrenal crisis.

Hashimoto thyroiditis is a chronic autoimmune process in which lymphocytic infiltration destroys the thyroid, and is the most common cause of hypothyroidism in iodine-sufficient regions such as the United States. Diagnosis rests on an elevated thyroid-stimulating hormone with a low or normal free thyroxine, and first-line treatment is lifelong levothyroxine replacement dosed to normalize thyroid-stimulating hormone.

Melanoma is a malignant tumor of melanocytes recognized by the ABCDE criteria (asymmetry, border irregularity, color variation, diameter greater than 6 mm, evolving) and confirmed by complete excisional biopsy that captures full lesion thickness. Treatment starts with wide local excision sized to the Breslow tumor depth, adds sentinel lymph node biopsy for deeper lesions, and escalates to BRAF/MEK-targeted therapy or checkpoint immunotherapy for metastatic disease.

Lung cancer is the leading cause of cancer death worldwide, split into non-small cell lung cancer (NSCLC, 80% of cases: adenocarcinoma, squamous cell, large cell) and small cell lung cancer (SCLC, 10-15%), both driven overwhelmingly by cigarette smoking. Diagnosis requires tissue histopathology, staging drives treatment (TNM staging for NSCLC, limited versus extensive stage for SCLC), and management ranges from lobectomy in early-stage disease through concurrent chemoradiation and consolidation immunotherapy in locally advanced disease to targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, or platinum-based chemotherapy in metastatic disease.

Myasthenia gravis is an autoimmune disorder of the postsynaptic neuromuscular junction, most often caused by acetylcholine receptor antibodies, producing fluctuating, fatigable weakness of ocular, bulbar, and limb muscles. Diagnosis rests on antibody testing and electrodiagnostics; first-line treatment is pyridostigmine, with glucocorticoids and steroid-sparing immunosuppression for generalized disease and thymectomy for eligible patients.

Myocarditis is inflammation of the myocardium, most often postviral or immune-mediated, presenting across a spectrum from a mild chest-pain syndrome mimicking myocardial infarction to fulminant heart failure and arrhythmia. Diagnosis relies on cardiac MRI (or biopsy for severe or refractory cases), and treatment is supportive heart-failure care, with cause-specific immunosuppression for giant cell, checkpoint-inhibitor, and autoimmune myocarditis.

A systemic inflammatory reaction driven by interleukin 6 and other cytokines released after chimeric antigen receptor (CAR) T-cell therapy or other T-cell engaging immunotherapy, ranging from fever alone to shock and multiorgan failure. Diagnosis is clinical and graded by fever, hypotension, and hypoxia; first-line treatment for higher-grade disease is tocilizumab, an interleukin 6 receptor blocker, with corticosteroids added for refractory or severe cases.