Abstract Background Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have significantly improved outcomes in advanced malignancies but can cause immune-related adverse events (irAEs). Pneumonitis occurs in up to 5% of treated patients and may rarely present with diffuse alveolar hemorrhage (DAH), a potentially fatal complication. Prompt recognition and treatment are critical. Case A 66-year-old man with metastatic colon adenocarcinoma receiving pembrolizumab presented with progressive dyspnea and cough shortly after a recent hospitalization for presumed pneumonia treated with antibiotics. On arrival, he was tachypneic and speaking in two-word sentences. He required a high-flow nasal cannula (60 L/min, FiO2 100%) with PaO2 106 mm Hg. He reported scant hemoptysis but was hemodynamically stable. Laboratory studies revealed stable renal function and hemoglobin. CT chest showed bilateral ground-glass and consolidative opacities with a triple-density pattern. Broad infectious workup, including bacterial, viral, and fungal testing, was negative. Bronchoscopy with bronchoalveolar lavage (BAL) demonstrated serially bloodier aliquots, consistent with DAH. Cytology revealed hemosiderin-laden macrophages; no pathogens were identified. Given the absence of infection and the temporal relationship to pembrolizumab, a diagnosis of grade 3-4 immune-related pneumonitis complicated by DAH was made. Pembrolizumab was discontinued, and the patient received high-dose intravenous methylprednisolone (1 g × 3 days) followed by taper. His oxygenation gradually improved, and he was successfully weaned to low-flow oxygen. Repeat imaging showed partial radiographic resolution. Discussion ICI-induced DAH is a rare manifestation of pulmonary irAEs. The proposed mechanism involves immune-mediated injury to alveolar capillaries, leading to inflammation and bleeding. Presentation often mimics pneumonia or ARDS. BAL with progressively bloodier aliquots confirms DAH and differentiates it from other causes. Early discontinuation of ICI therapy and initiation of corticosteroids are essential; refractory cases may require additional immunosuppression. Conclusion Pembrolizumab can rarely induce severe pneumonitis complicated by DAH. Clinicians should maintain a high index of suspicion in patients on ICIs presenting with hypoxemia and hemoptysis unresponsive to antibiotics. Early bronchoscopy and immunosuppressive therapy are key to improving outcomes. This abstract is funded by: None
Synn et al. (2026) studied this question.