When Immunity Backfires: Pembrolizumab-Induced Bilateral Pneumothorax in a Patient with Metastatic HPV-Associated...

Immune checkpoint inhibitors (ICIs) are standard therapy for recurrent or metastatic head and neck squamous cell carcinoma, but unleashing antitumour immunity can trigger immune-related adverse events (irAEs). Pneumothorax is a rare pulmonary complication compared with the more recognised ICI-associated pneumonitis.

A 67-year-old man with p16-positive, poorly differentiated oropharyngeal squamous cell carcinoma presented with progressive bilateral cervical lymphadenopathy and subsequently required tracheostomy and gastrostomy for upper-airway obstruction. Chemoradiation with weekly docetaxel was discontinued early due to severe mucositis. Restaging showed regression of the primary tumour but new and enlarging subpleural pulmonary nodules consistent with metastases. Pembrolizumab was initiated. Within days of the first infusion, the patient developed pleuritic chest pain and dyspnoea. Upright chest radiography demonstrated a large right pneumothorax, and a computed tomography scan revealed bilateral subpleural lesions with adjacent parenchymal abnormalities; a contralateral pneumothorax was also present. Bilateral chest tubes were placed with symptomatic improvement. In the absence of trauma, mechanical ventilation, known bullous disease, or infectious cavitation, an immune-mediated mechanism was considered most likely: rapid necrosis and cavitation of subpleural metastases creating alveolar-pleural fistulas. Given poor functional reserve and advanced disease, definitive pleurodesis was deferred and palliative care was engaged.

Acute pneumothorax-sometimes bilateral-can occur shortly after PD-1 inhibition, particularly in patients with subpleural metastatic disease. Clinicians should maintain a high index of suspicion when new respiratory symptoms arise soon after ICI initiation, obtain prompt imaging to distinguish pneumothorax from pneumonitis, and coordinate early multidisciplinary management to optimise outcomes and align treatment with patient goals.

Pneumothorax is a rare but reported pulmonary immune-related adverse event associated with PD-1/PD-L1 inhibitors; risk may be heightened by subpleural metastases undergoing immune-mediated necrosis/cavitation.New dyspnoea after checkpoint blockade warrants chest imaging for pneumothorax alongside evaluation for immune checkpoint inhibitor pneumonitis.Management should follow evidence-based pneumothorax guidelines and be individualized to performance status and goals of care.