Double Trouble in the Lungs: Histoplasmosis and Mycobacterium Avium Complex in an Immunocompetent Patient

Abstract Introduction: Histoplasmosis, caused by Histoplasma capsulatum, is endemic to the Ohio and Mississippi River valleys. It typically presents as an asymptomatic or self-limiting illness in immunocompetent individuals but can manifest as chronic pulmonary disease, mimicking other granulomatous infections like tuberculosis (TB) and non-tuberculous mycobacterial (NTM) infections, particularly Mycobacterium avium complex (MAC). Co-infection with histoplasmosis and MAC is rare, especially in immunocompetent hosts. Case Presentation: A 30-year-old immunocompetent woman who recently immigrated from Senegal presented with two weeks of productive cough with occasional hemoptysis, pleuritic chest pain, subjective fever, night sweats, and a 12-pound unintentional weight loss over the previous month. On exam, she had a low-grade fever (Tmax 100.4°F), and cervical and axillary lymph nodes were unremarkable. Imaging showed a 2.6 x 2.2 x 2.0 cm irregular opacity in the anterior segment of the left upper lobe and left hilar lymphadenopathy. Laboratory tests revealed elevated liver enzymes (ALK 297 U/L, ALT 265 U/L, AST 167 U/L). HIV testing was negative. Initial acid-fast bacilli (AFB) smears of sputum samples were negative, but subsequently, cultures grew MAC. Quantiferon-TB was indeterminate. Urine antigen testing was positive for histoplasmosis. Diagnostic bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed on 4L. Samples revealed budding yeast on Grocott's methenamine silver (GMS). Due to high-risk factors, including recent immigration and shelter residence, she was empirically started on RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) therapy to cover potential tuberculosis (TB). Her response to RIPE allowed the deferment of specific MAC therapy. She completed both RIPE and 6 months of itraconazole therapy, with complete resolution of symptoms and marked improvement of the left upper lobe opacity on imaging, indicating effective treatment. Conclusion: This case highlights the clinically significant co-infection of histoplasmosis and MAC in an immunocompetent patient, a rare combination that can complicate diagnosis and management. This patient's recent immigration from Senegal, a region endemic to histoplasmosis, likely heightened her exposure risk. The empiric use of RIPE therapy for suspected TB was prudent, given TB's overlapping presentation with histoplasmosis and MAC and the need for urgent treatment to mitigate potential complications. This case underscores the importance of a comprehensive diagnostic approach and consideration of co-infections in immigrant populations exposed to multiple endemic pathogens. It emphasizes the need for clinical awareness and tailored treatment strategies to optimize outcomes in complex, multi-pathogen scenarios.