Miliary tuberculosis (TB) occurs following systemic dissemination of the Mycobacterium tubercle (M.Tb). Though common worldwide, it is infrequently seen in the United States. Delays in diagnosis contribute to poor outcome. We present a case of miliary TB in which an unusual presentation and empiric community-acquired pneumonia (CAP) therapy contributed to a late diagnosis and fatal result.
An 83-year old female presented with 5 weeks of dry cough, dyspnea, weakness and weight loss. There was no history for immune compromise or tuberculosis exposure. The physical examination revealed an afebrile, tachypneic woman with diffuse inspiratory crackles, without jugular venous distension or peripheral edema. Laboratory studies confirmed severe hypoxemia (PaO2/FiO2 ratio 169), and a transaminitis. Chest radiograph (CXR) revealed bilateral symmetric infiltrates, consistent with acute respiratory distress syndrome (ARDS). Levofloxacin was started for presumed CAP. An echocardiogram demonstrated normal cardiac function. The patient clinically and radiographically improved except for a lingering reticulonodular infiltrate. All routine cultures were negative, but an angiotensin converting enzyme level was elevated. Fiberoptic bronchoscopy was performed 7 days into the hospital antibiotic course. Transbronchial biopsies revealed non-caseating granulomas, with negative acid-fast bacillus (AFB) stains of lung tissue and bronchoscopy wash. Prednisone was started for presumed sarcoidosis, and she was discharged with outpatient follow-up. Four weeks later she returned with confusion and fever. CXR was unchanged. A lumbar puncture revealed a cerebrospinal fluid (CSF) pleocytosis (total white blood cell count 476 cells/mm2, 48% lymphocytes), elevated protein (617 mg/dl) and depressed glucose (18 mg/dl). The CSF gram stain, AFB smear, fungal stain, bacterial antigens, fungal and bacterial cultures were all negative. Antituberculous medications were started empirically, but the patient died four days later. CSF acid-fast cultures ultimately revealed M. Tb growth.DISCUSSION: Worldwide, tuberculosis occurs frequently in its miliary form and is among the most common causes of death by infectious disease. In the United States however, the incidence of miliary TB is low, resulting in a reduced vigilance for this disease. Unlike cavitary tuberculosis, miliary disease is less easily diagnosed by sputum analysis, and carries a broader differential diagnosis including sarcoidosis, hypersensitivity pneumonitis, and other granulomatous infections. This case highlights several difficulties in establishing an accurate diagnosis. First the patient presented with ARDS. In developing nations miliary TB is a reported trigger for ARDS, possibly from activation of an inflammatory cascade due to hematogenous dissemination of the organism. In the United States however, TB is rarely encountered as a cause of acute lung injury. That the patient improved early in the hospital course probably reflects a partial response to levofloxacin. Fluoroquinolones have proven activity against M. Tb. However the expanding use of fluoroquinolones as empiric treatment for CAP may limit the diagnostic yield of acid-fast cultures. Though respiratory cultures are positive in miliary TB in 55 - 75 % of cases, this patient’s bronchoscopy culture was negative, perhaps due to levofloxacin pretreatment. Finally, unlike cavitary tuberculosis the granulomas of miliary disease are more frequently smear-negative and non-caseating. In such instances, PCR amplification on formalin-fixed tissue with subsequent DNA probe-hybridization has recently been shown to provide an accurate early diagnosis of tuberculosis, and may have proved useful in this case.
This case represents an unusual presentation of miliary TB with ARDS, and a misleadingly negative AFB culture possibly due to treatment with levofloxacin. Given their proven activity against M. Tb. and their wide usage as empiric CAP treatment, fluoroquinolones may delay the diagnosis of tuberculosis. In cases where fluoroquinolones have been given, negative respiratory cultures do not exclude TB, and further diagnostic work-up such as PCR amplification may be warranted.
E.A. Kseibi, None.