Pulmonary Co-Infection with Pneumocystis jirovecii and Histoplasma capsulatum. Hickam’s Dictum or Occam’s Razor

Introduction: Co-infection with Histoplasma capsulatum and Pneumocystis jirovecii is rarely documented in HIV-negative immunocompromised patients and poses significant diagnostic challenges due to overlapping radiological patterns and limited access to advanced mycological testing. Case report: A 58-year-old woman with systemic lupus erythematosus and lupus nephritis, under treatment with corticosteroids and cyclophosphamide, presented with fever and hypoxemia. Chest computed tomography demonstrated bilateral micronodules, ground-glass opacities, and mediastinal lymphadenopathy. HIV testing and initial cultures were negative. Bronchoalveolar lavage revealed P. jirovecii, prompting the initiation of trimethoprim-sulfamethoxazole. Despite targeted therapy, the patient developed progressive respiratory failure, requiring intensive care. Transbronchial biopsy later confirmed coinfection with H. capsulatum. Antifungal therapy with liposomal amphotericin B and itraconazole was initiated; however, the clinical course was marked by progressive deterioration, culminating in death. Conclusions: This case highlights the need for high clinical suspicion of dual opportunistic infections in non-HIV immunocompromised patients. Diagnostic delays, particularly in resource-limited settings without fungal PCR, may adversely affect outcomes. In such complex hosts, early invasive diagnostics and broader access to rapid molecular testing are critical to improving prognosis in this vulnerable population.