Case Presentation: We present the case of a 77-year-old man admitted with failure to thrive and progressive dyspnea. He had a 6-year history of lung squamous cell carcinoma and a recent history of immune checkpoint inhibitor (ICI) toxicity (myocarditis, pneumonitis, and hepatitis), currently on week 27 of a prednisone taper (35 mg daily). He was maintained on inhaled pentamidine for pneumocystis jirovecii prophylaxis. Prior to presentation, his recent history had been complicated by multiple recent exacerbations of cough, dyspnea, and new opacities on chest x-ray. His symptoms had not improved after two courses of antibiotics for community acquired pneumonia in the last month. An ICI-pneumonitis flare was also considered due to ongoing tapering of steroids. Due to the lack of improvement, a broader workup was conducted. A CT chest demonstrated nodular and consolidative densities throughout both lungs, progressed from prior. Blood cultures were ultimately positive for Cryptococcus neoformans at 85 hours, consistent with disseminated cryptococcus with pulmonary involvement. On further focused history, he reported blurry vision and headaches. Lumbar puncture studies were notable for elevated opening pressure, elevated protein, and cultures positive for Cryptococcus neoformans. He was initiated on amphotericin B and flucytosine for treatment of disseminated cryptococcus and his prednisone dose was cautiously reduced while monitoring for recurrent ICI-related symptoms. Regrettably, he experienced progressive respiratory failure, elected to transition to comfort-care, and passed away peacefully.
Discussion: The incidence of ICI-related toxicities and the need for high-dose steroid treatment has increased with the widespread use of ICIs in cancer therapy. Hospitalists play a crucial role in recognizing opportunistic infections in this population, especially when symptoms fail to improve with standard treatments. Cryptococcal infections are often diagnosed late, with one study showing a median delay of 9 days, which is linked to worse neurologic outcomes 1. Pulmonary involvement can manifest as a pneumonia-like illness while disseminated infection may present with neurologic symptoms including headache, altered mental status, nuchal rigidity, and photophobia. A thorough history and physical should be followed by cryptococcal antigen testing, lumbar puncture, chest and brain imaging, fungal cultures, and histopathology. Accurate identification of the cryptococcosis syndrome, categorized as CNS, disseminated, isolated pulmonary, or direct skin inoculation, is essential for guiding antifungal treatment type and duration. Early treatment with liposomal amphotericin B and flucytosine induction therapy, followed by consolidation therapy with fluconazole, is crucial for reducing CNS fungal burden and preventing relapse.
Conclusions: As long-term corticosteroids remain the primary treatment for ICI toxicity, opportunistic infections are likely to become more common. Hospitalists must possess the ability to promptly recognize and treat these infections to mitigate avoidable sequelae.