Aspergillosis or Tuberculosis? Solving a Complex Case of Misdiagnosis

Abstract Introduction: Mycobacterium tuberculosis (TB) is a global health concern, affecting about a quarter of the world's population. Early diagnosis is crucial to prevent transmission and resistance development, but TB is often difficult to diagnose due to its slow growth and varied presentation. We present a case where conventional work-up failed to identify TB and the patient was treated for invasive aspergillosis without improvement. Ultimately the diagnosis of TB was made using robotic bronchoscopy. Case Report: A 52-year-old male with a history of homelessness, emphysema, and alcohol use disorder presented with multiple pulmonary nodules. His initial work-up, including a positive QuantiFERON-Gold test and a PET-CT scan showing hypermetabolic left upper lobe nodules, raised concern for TB. He underwent bronchoscopy with alveolar lavage (BAL), but cultures, AFB smear, and MTB-PCR were negative, with the exception of Aspergillus fumigatus and Asperigllus niger leading to a presumed diagnosis of latent TB. Treatment for latent TB was initiated but interrupted due to medication side effects. Given the patient's progressive dyspnea and worsened exercise tolerance the patient was started on isavuconazonium for invasive aspergillosis. After 6 months of therapy, the patient showed no improvement, and imaging indicated disease progression (Figure 1). Given disease progression without a clear diagnosis, a multidisciplinary team including pulmonary and infectious disease decided to discontinue antifungal treatment and pursue further diagnostics. Robotic bronchoscopy targeting the left upper lobe nodule with cryobiopsy and BAL revealed Mycobacterium tuberculosis. The patient was diagnosed with active TB and started RIPE therapy, resulting in clinical improvement. Discussion: This case highlights the challenges in diagnosing active TB, even when the pre-test probability is high. Despite negative conventional tests, the correct diagnosis was made after the failure of antifungal treatment and the use of robotic bronchoscopy. This approach, though uncommon, can be valuable in cases where TB is strongly suspected but standard diagnostics are unrevealing. This case also emphasizes the importance of considering alternative diagnoses and including multidisciplinary collaboration when clinical outcomes are not as expected.