Extrapulmonary Tuberculosis

Extrapulmonary tuberculosis is disease at sites outside the lung parenchyma: lymph nodes, pleura, pericardium, peritoneum, meninges and brain, bone and joints, spine, genitourinary tract, adrenals, skin and disseminated (miliary) disease. It accounts for 15 to 20 percent of cases, and over 50 percent in advanced HIV.

• Often paucibacillary, so diagnosis is difficult and delayed.
• Concurrent pulmonary disease is common.

Site specific features plus systemic symptoms of fever, night sweats, weight loss and malaise.

• Lymph nodes: painless, matted cervical nodes with cold abscess and sinus; pleura: pleuritic pain and dyspnoea; pericardium: dyspnoea, raised venous pressure, pulsus paradoxus; meninges: subacute headache, vomiting, cranial nerve palsies, confusion; bone and spine: back pain, deformity (gibbus), paraplegia; abdomen: ascites, pain, masses; genitourinary: sterile pyuria, haematuria, epididymitis, infertility.
• Differential diagnosis: lymphoma, malignancy, bacterial and fungal infection, brucellosis, sarcoidosis, Crohn disease, cryptococcal meningitis, pyogenic spine infection, non tuberculous mycobacteria.
• Complications: organ dysfunction (tamponade, constriction, spinal cord compression, hydrocephalus), disability, dissemination, relapse, death, paradoxical reactions on treatment.

Obtain tissue or fluid from the affected site.

• Fine needle aspirate or biopsy with Xpert MTB/RIF Ultra, culture, acid fast stain and histology (caseating granuloma); fluid analysis: lymphocytic exudate with high adenosine deaminase (pleural over 40 U/L, ascitic over 39 U/L, pericardial over 40 U/L); CSF (lymphocytes, protein over 1 g/L, glucose under 2.2 mmol/L or under half of blood glucose, Xpert).
• Urine lipoarabinomannan and chest radiograph in HIV; HIV test and CD4; imaging: ultrasound, CT, MRI, echocardiography.
• Always screen sputum for concurrent lung disease.

Prolonged multi drug therapy, adjunctive steroids at critical sites and intervention for complications.

• Supportive: nutrition, pain control, adherence support, physiotherapy and bracing in spinal disease, contact screening, HIV care.
• Pharmacological: 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol then 4 months of isoniazid and rifampicin for lymph node, pleural, peritoneal, genitourinary and most other sites (daily doses isoniazid 5 mg/kg, rifampicin 10 mg/kg, pyrazinamide 25 mg/kg, ethambutol 15 mg/kg). Tuberculous meningitis and bone or joint disease: 2 months of the four drug phase then 10 months of isoniazid and rifampicin (12 months total). Pyridoxine 25 to 50 mg daily. Dexamethasone for meningitis (0.4 mg/kg/day IV, tapered over 6 to 8 weeks) and prednisolone for pericarditis. Antiretroviral therapy within 2 weeks if CD4 is under 50 and within 8 weeks otherwise; dolutegravir 50 mg twice daily while on rifampicin. Cotrimoxazole 960 mg daily.
• Procedures: drainage of abscess or effusion, pericardiocentesis, ventriculoperitoneal shunt for hydrocephalus, spinal decompression and stabilisation for cord compression or instability, nephrectomy or ureteric stenting.
• Special groups: pregnancy, first line drugs with pyridoxine; children, weight band dosing (isoniazid 10 mg/kg, rifampicin 15 mg/kg, pyrazinamide 35 mg/kg, ethambutol 20 mg/kg); liver disease, modified regimens; HIV, close monitoring for immune reconstitution inflammatory syndrome.
• Red flags: neurological deficits, altered consciousness, tamponade, spinal cord compression, severe anaemia, paradoxical worsening, drug resistance, hepatitis.
• Follow-up: clinical review monthly; imaging at 2 and 6 months for deep sites; extend therapy when response is slow; long term follow-up for constrictive pericarditis, spinal deformity and hydrocephalus.