Case Presentation: This case describes a 63-year-old male who was recently diagnosed with renal cell carcinoma with metastasis to the lungs confirmed with a biopsy showing diffuse PAX-8 positivity on an immunohistochemical staining panel favoring renal origin. He was started on Nivolumab/Ipilimumab however was hospitalized in the intensive care unit for septic shock due to irAE gastroenteritis. Nivolumab/Ipilimumab was discontinued, and he was started on a prednisone taper on discharge. Unfortunately, the patient returned to the Emergency Department two weeks later with progressive shortness of breath and worsening swelling and erythema of his lower extremities. On presentation, he was noted to be febrile and hypoxic requiring BiPAP with physical exam findings revealing diffuse expiratory rales, and blood pressures with mean arterial pressure (MAP) < 65, unresponsive to fluid resuscitation and started on IV pressors. Thoracic CT imaging was negative for pulmonary embolism but did show new bilateral upper lobes ground-glass opacifications with septal pleural thickening suspicious for interstitial pneumonia and ultrasound doppler of lower extremity veins positive for deep venous thrombosis. Additional labs showed positive Fungitell. Given the patient’s history with previous irAE-causing gastroenteritis, there was a strong suspicion that the patient had developed irAE pneumonitis, and the patient was started on high-dose steroids. Throughout the hospital course, the patient responded well to treatment and was titrated off pressors and weaned down to ambient air and discharged with a long-steroid taper.
Discussion: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by their unique mechanism of actions of targeting and blocking the tumor cell’s natural anti-tumor activity including programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). ICIs are increasingly being used in a wide variety of cancers. Although these relatively novel drugs have shown promising long-term survival in patients, ICIs can also result in a wide range of immune-related adverse events (irAE) and pose a major challenge in the treatment of cancer patients. Although generally manageable, failure to recognize irAE can lead to fatal outcomes. One rare irAEs is pneumonitis with a reported incident of about 1.3% of pneumonitis of any grade and 0.3% in high-grade pneumonitis. irAE pneumonitis can present in different patterns and is diagnosed with radiological and histopathological features.
Conclusions: Pneumonitis is a rare but serious irAE and the symptoms of pneumonitis can be subtle and easily be missed due to other comorbid symptoms that could be related to underlying cancer. Those who are on ICI therapies who present with symptoms such as dyspnea, cough, and fever should have a low threshold for initiating a thorough evaluation including a consult to a pulmonologist, thoracic CT imaging, bronchoscopy with bronchoalveolar lavage to rule out infectious pneumonia. Prompt recognition and treatment of irAE pneumonitis with corticosteroids can lead to better outcomes.