Hide and Seek: The Elusiveness of Miliary Tuberculosis

Abstract We present a 59-year-old woman with a history of self-managed Sjogren's syndrome, who was admitted to our hospital with ongoing failure to thrive and progressively worsening dry cough over a 3-month period. Initial chest computed tomography (CT) revealed diffuse bilateral pulmonary miliary opacities. Given these radiological findings, tuberculosis (TB) was considered as part of the differential diagnosis. However, after a thorough clinical history, TB was deemed less likely, as the patient did not belong to a high-risk population, had no known travel to TB-endemic regions, no knowncontacts, and was not on immunosuppressive therapy. Interferon-gamma release assay was negative. Three induced sputa for acid fast bacteria (AFB) had no organisms on smear, and no growth in cultures; polymerase chain reaction (PCR) assays were negative for Mycobacteria tuberculosis. Bronchoscopy with transbronchial biopsy was performed: bronchial alveolar lavage (BAL) and lung tissue were sent for evaluation; all had negative AFB smears, TB PCRs, and no growth in AFB cultures. Histopathology of the transbronchial lung biopsy demonstrated granulomatous changes with giant cells. Special stains on BAL and lung biopsy were negative for fungal and acid-fast organisms. To this point, workup was not consistent with malignancy, bacterial, fungal, mycobacterial infections, nor any autoimmune etiology. The patient rapidly deteriorated over a two-week period, ultimately requiring mechanical ventilation. Lung transplant evaluation was initiated. Given this, an open lung biopsy was pursued. Despite negative AFB smears on multiple samples from open lung biopsy, it was decided to initiate empiric RIPE therapy due to high clinical suspicion for miliary tuberculosis. Two weeks after the biopsy, AFB cultures of lung tissue grew Mycobacterium tuberculosis, confirming the diagnosis. Historically, miliary TB was predominantly observed in infants and children. It is now most frequently encountered among immunosuppressed individuals. Miliary TB is caused by lymphohematogenous spread of Mycobacterium tuberculosis due to the immune system's inability to confine the infection within the lungs. Diagnosing miliary TB remains a significant challenge and is elusive even for experienced clinicians. In immunocompetent adults, miliary TB accounts for less than 2% of TB cases but has a high mortality rate if not identified and treated promptly. Notably, cumulative data from published studies indicate that smears and cultures yield a positive diagnosis in only 46.8% of cases. This case emphasizes the importance of maintaining clinical vigilance for miliary TB, even in the absence of typical risk factors or negative diagnostic studies, to minimize the risk of missed diagnosis.