Silica-Associated Tuberculosis

Silica associated tuberculosis is active tuberculosis in a person with silicosis or substantial silica exposure. Silica impairs macrophage defence, raising risk of infection, reactivation and more severe disease.

Epidemiology. Silicosis raises tuberculosis risk about threefold, and exposed workers without silicosis also have increased risk. Risk is higher with HIV, in mining populations and in high burden regions.

Presentation. It may be blunted by silicosis symptoms and often has atypical radiographic features. Non-tuberculous mycobacteria also occur.

Complications. Cavitation, haemoptysis, respiratory failure, drug resistant disease and relapse.

Pathophysiology.

Silica particles are phagocytosed by alveolar macrophages and cause macrophage dysfunction and death. Impaired phagosome maturation and altered cytokine response reduce containment of mycobacteria.

Fibrotic nodules and masses provide poor perfusion niches where bacilli persist and drug penetration is reduced.

• Cough, fever, night sweats, weight loss, increasing dyspnoea or new sputum change.
• Haemoptysis and pleuritic pain.
• Extrapulmonary disease, especially in HIV.

Red flags.

• Haemoptysis, respiratory failure, rapid weight loss.
• New cavitation or radiographic progression.
• Features of meningitis or disseminated disease.

• Sputum smear, culture and molecular testing with rifampicin resistance detection; at least 2 samples; bronchoscopy for non-productive patients.
• HIV test and CD4 count if positive.
• Chest radiograph and CT: new cavities, enlarging nodules or masses, consolidation, effusion, lymphadenopathy. Eggshell nodal calcification suggests silicosis rather than tuberculosis.
• Drug susceptibility testing on all positive cultures.
• Baseline liver function, renal function, uric acid, visual acuity and colour vision.

Differential diagnosis. Ischaemic cavitation in progressive massive fibrosis, non-tuberculous mycobacterial disease (including Mycobacterium kansasii), aspergilloma and other fungal disease, lung cancer, sarcoidosis, lung abscess.

Drug susceptible disease, adult doses:

• Isoniazid 5 mg/kg orally once daily, maximum 300 mg, for the full course, with pyridoxine 10 mg once daily (25 to 50 mg in high risk patients). Monitor liver enzymes and peripheral neuropathy. No renal adjustment; caution in liver disease.
• Rifampicin 10 mg/kg orally once daily, maximum 600 mg, for the full course, taken fasting. Monitor liver enzymes and interactions (warfarin, direct oral anticoagulants, hormonal contraception, antiretrovirals, corticosteroids). No renal adjustment; avoid in severe liver disease.
• Pyrazinamide 25 mg/kg orally once daily, maximum 2 g, for the first 2 months. Monitor liver enzymes and uric acid. If eGFR is under 30, give 25 mg/kg three times weekly; avoid in severe liver disease.
• Ethambutol 15 mg/kg orally once daily, maximum 1.6 g, for the first 2 months. Monitor visual acuity and colour vision monthly. If eGFR is under 30, give 15 to 25 mg/kg three times weekly.
• Total duration is at least 6 months. Extending the continuation phase by 2 months (8 months in total) is widely practised in silicosis, though evidence is limited.
• HIV: start antiretroviral therapy within 2 weeks if CD4 is under 50 cells/mm3, otherwise within 8 weeks; add co-trimoxazole prophylaxis. Adjust regimens for interactions.
• Stop hepatotoxic drugs for ALT over 3 times the upper limit with symptoms, or over 5 times without symptoms, and reintroduce under specialist direction.
• Drug resistant disease needs a specialist designed regimen.

Monitoring. Symptoms and weight monthly; sputum culture at 2 months and at end of treatment; liver tests at 2 and 4 weeks then as indicated; visual checks monthly on ethambutol; directly observed therapy where feasible.

Referral and escalation. Notify as required; specialist tuberculosis or respiratory care; occupational compensation; infection control measures until non-infectious.

Special groups. Pregnancy: isoniazid, rifampicin, pyrazinamide and ethambutol are used with pyridoxine. Breastfeeding is compatible. Liver and renal impairment need dose and drug selection by specialists.