Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains one of the leading infectious causes of Pyrexia of Unknown Origin worldwide. While pulmonary TB is frequently recognized, extrapulmonary and disseminated (miliary) TB present insidiously, often evading routine radiological and microbiological detection.
Clinical Patterns in PUO
Extrapulmonary TB accounts for a significant proportion of TB-related PUO:
Miliary Tuberculosis: Hematogenous dissemination leading to micronodular lesions throughout the lungs, liver, spleen, and bone marrow. Chest X-rays may initially appear normal in early disease.
Tuberculous Lymphadenitis: Cervical or abdominal lymph nodes showing caseating granulomatous inflammation.
Genitourinary & Abdominal TB: Peritoneal thickening, ascites, and renal parenchymal lesions presenting without classical cough.
Diagnostic Workup for Occult TB
Immunological Tests: Tuberculin Skin Test (TST / Mantoux) and Interferon-Gamma Release Assays (IGRAs like QuantiFERON-TB Gold). Note: False negatives occur in severe disease or immunocompromised states.
Molecular Testing: GeneXpert MTB/RIF assay for rapid DNA identification and rifampicin resistance screening.
Advanced Imaging: High-Resolution CT (HRCT) of chest for subtle miliary nodules; Abdominal CT for necrotic lymph nodes or peritoneal stranding.
Histopathology & Culture: Fine Needle Aspiration Cytology (FNAC) or biopsy of involved tissue demonstrating caseating granulomas and Acid-Fast Bacilli (AFB) on Ziehl-Neelsen staining; Lowenstein-Jensen (LJ) medium or liquid culture (MGIT).
Diagnostic Comparison: Pulmonary vs. Extrapulmonary TB in PUO
| Parameter | Pulmonary TB | Extrapulmonary / Miliary TB |
| Primary Symptom | Chronic Cough, Hemoptysis | Unexplained Fever, Night Sweats, Weight Loss |
| Chest X-Ray | Apical Infiltrates / Cavitations | Normal or Miliary "Millet Seed" Pattern |
| Sputum Smear | Frequently Positive | Often Negative / Not Applicable |
| Biopsy Target | Sputum / Bronchial Washings | Lymph Node, Bone Marrow, Liver, Peritoneum |
Treatment Guidelines
Standard anti-tubercular therapy (ATT) consists of a 2-month intensive phase followed by a continuation phase:
Intensive Phase (2 Months): Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E).
Continuation Phase (4–7 Months): Isoniazid (H) and Rifampicin (R).