Case Presentation: An 85-year-old female with a history of insulin-dependent diabetes, chronic kidney disease, and pemphigus vulgaris presented with four days of dyspnea and non-productive cough. History was significant for recent rituximab infusions and chronic prednisone therapy for pemphigus. On presentation to the ED, the patient was noted to be hypoxic to SpO2 84% on room air and required supplemental O2 of 4-6L via nasal canula. Inspiratory crackles were heard in the bilateral lower lung fields. Chest x-ray revealed ill-defined ground-glass opacities in the perihilar and basilar lungs. The patient received empiric treatment for community-acquired pneumonia (CAP) without improvement.Social history of prior bird ownership and persistent hypoxic respiratory failure despite CAP treatment raised suspicion for interstitial lung disease. High-resolution CT of the chest was performed and demonstrated indistinct ground-glass opacities with upper lobe predominance and areas of mosaic attenuation, raising concern for pneumocystis pneumonia (PJP). Empiric trimethoprim-sulfamethoxazole and high-dose prednisone for suspected PJP was initiated while awaiting confirmatory testing. Bronchoalveolar lavage (BAL) fungal panel initially returned positive for galactomannan antigen, and treatment was changed to liposomal amphotericin B for presumed aspergillosis or histoplasmosis. Two days later, BAL PCR analysis returned positive for Pneumocystis jirovecii, confirming diagnosis of PJP. Subsequent serum studies ruled out aspergillosis and histoplasmosis, and the BAL galactomannan result was deemed to be a false-positive. The patient was eventually discharged following resolution of hypoxia and cough on day 22 of admission to finish a 21-day course of PJP treatment.
Discussion: Pneumocystis jirovecii pneumonia has historically been associated with underlying HIV infection and CD4 cell counts < 200 cells/μL. However, improvements in anti-retroviral therapy and routine prophylaxis have led to decreased prevalence among HIV-positive individuals. Conversely, PJP incidence has risen among HIV-negative populations due to increased use of immunosuppressive agents for various conditions. Additionally, HIV-negative patients with PJP have a greater estimated mortality compared to HIV-positive patients (1,2).The reason for this discrepancy in illness severity is multifactorial. Firstly, the higher burden of organisms found in HIV-positive patients allows for easier identification of pneumocystis via microscopy. This, along with higher degree of clinical suspicion in HIV-positive patients, may prompt earlier diagnosis and treatment. Second, HIV-negative patients are found to have significantly higher levels of intra-alveolar neutrophilic infiltrates which correlate with more severe lung disease and lower arterial oxygen tension (3).
Conclusions: This case highlights the importance of maintaining a high suspicion for PJP in HIV-negative patients that may be immunocompromised from another condition or treatment. Prior exposure to prednisone and rituximab were important clinical clues as these immunosuppressants have been shown to increase susceptibility to PJP (4). Interestingly, anti-CD20 therapy alone has been shown to increase PJP risk in some cases (5). Given the presence of symptomatic hypoxia on presentation, and propensity for fulminant PJP in HIV-negative patients, empiric treatment prior to diagnostic confirmation was instrumental in averting a poor outcome in this case.
