Miliary Tuberculosis

Miliary tuberculosis is haematogenous dissemination of Mycobacterium tuberculosis to multiple organs, producing numerous 1 to 3 mm granulomas (millet seed pattern) on chest imaging. It affects infants, the elderly, people with HIV, malnutrition, diabetes, alcohol use and those on immunosuppressants.

• Seeding sites: lungs, liver, spleen, bone marrow, meninges, adrenals, eyes.
• High mortality when diagnosis is delayed.

Prolonged fever, night sweats, weight loss, anorexia, cough, dyspnoea, hepatosplenomegaly; some present as fever of unknown origin or with respiratory failure.

• Choroidal tubercles on fundoscopy, meningism or headache, lymphadenopathy, skin lesions (tuberculids).
• Cryptic miliary disease in the elderly lacks classic findings; HIV positive patients have lower zone disease with negative skin tests.
• Differential diagnosis: disseminated fungal infection (histoplasmosis, cryptococcosis, talaromycosis), sarcoidosis, lymphoma, metastatic malignancy, pneumocystis pneumonia, typhoid, brucellosis, infective endocarditis, viral pneumonitis, drug reaction.
• Complications: tuberculous meningitis, acute respiratory distress syndrome, adrenal insufficiency, pancytopenia and haemophagocytosis, hyponatraemia (SIADH), liver failure, sepsis like state, death.

Combine imaging, microbiology and tissue.

• Chest radiograph (fine nodular pattern, may be normal early) or CT; sputum, gastric aspirate or bronchoalveolar lavage with Xpert MTB/RIF Ultra and culture; urine lipoarabinomannan test in HIV; blood and bone marrow culture for mycobacteria.
• Fundoscopy for choroidal tubercles; lumbar puncture if headache, confusion or meningism.
• Liver, lymph node or bone marrow biopsy; full blood count (pancytopenia), liver enzymes, sodium, calcium, cortisol, HIV test and CD4, cryptococcal antigen.

Start treatment on clinical suspicion in a sick patient.

• Supportive: oxygen and ventilatory support for hypoxia, nutrition, correct sodium and fluids, transfuse for severe anaemia, infection control, adherence support.
• Pharmacological: 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol followed by 4 months of isoniazid and rifampicin (daily doses isoniazid 5 mg/kg, rifampicin 10 mg/kg, pyrazinamide 25 mg/kg, ethambutol 15 mg/kg), with pyridoxine 25 to 50 mg daily; extend to 12 months (2 plus 10) if meningitis. Dexamethasone 0.4 mg/kg/day IV tapered over 6 to 8 weeks for meningitis; prednisolone 1 mg/kg daily for 4 to 8 weeks with taper for severe hypoxia, adrenal insufficiency or acute respiratory distress syndrome. Hydrocortisone 100 mg IV every 8 hours for adrenal crisis. HIV: antiretroviral therapy within 2 weeks if CD4 is under 50 and by 8 weeks otherwise; in meningitis, delay to 4 to 8 weeks with specialist input; dolutegravir 50 mg twice daily during rifampicin; cotrimoxazole 960 mg daily.
• Procedures: mechanical ventilation, lumbar puncture, bone marrow aspirate, biopsy.
• Special groups: pregnancy, first line regimen with pyridoxine; children, weight band dosing and steroids for meningitis; liver failure, specialist regimen with ethambutol, fluoroquinolone and an injectable or alternative agents; elderly, low threshold for empirical therapy.
• Red flags: headache or altered consciousness, hypoxia, hypotension, jaundice, haemophagocytosis, no defervescence within 2 to 3 weeks.
• Follow-up: weekly review in the first month; chest imaging at 2 and 6 months; liver tests at 2 and 4 weeks; screen for drug resistance.