What is the role of hydrocortisone (corticosteroid) in the treatment of patients with tuberculosis (TB), particularly those with severe forms of the disease?

Use of Hydrocortisone in Tuberculosis

Hydrocortisone and other corticosteroids should be used as adjunctive therapy in specific severe forms of TB—particularly tuberculous meningitis (where they reduce mortality by 30% in HIV-negative patients) and tuberculous pericarditis (where they reduce constriction and hospitalization)—but are NOT recommended for routine pulmonary TB. 1, 2

Established Indications for Corticosteroids in TB

Tuberculous Meningitis (Strongest Evidence)

• All patients with tuberculous meningitis should receive adjunctive dexamethasone or prednisolone tapered over 6-8 weeks (strong recommendation, moderate certainty evidence). 2
• Corticosteroids are associated with 30% lower mortality in HIV-uninfected TB meningitis patients. 1
• Dosing for adults: Dexamethasone 12 mg/day for 3 weeks, then gradually tapered over the following 3 weeks. 1, 2
• Dosing for children <25 kg: Dexamethasone 8 mg/day with the same tapering schedule. 1, 2
• Greatest benefit is seen in patients with Stage II disease (lethargic presentation); patients with decreased level of consciousness particularly benefit. 1, 2

Tuberculous Pericarditis (Conditional Use)

• Selective use of corticosteroids should be considered for patients at highest risk for inflammatory complications, including those with large pericardial effusions, high inflammatory markers in pericardial fluid, or early signs of constriction. 1, 2
• Corticosteroids reduce constriction and hospitalization but should NOT be used routinely (conditional recommendation, very low certainty evidence). 1
• When indicated, dosing: Prednisone 60 mg/day for 4 weeks, then 30 mg/day for 4 weeks, 15 mg/day for 2 weeks, and 5 mg/day for the final week. 2
• A large trial with 1400 participants did not find benefit in the combined primary endpoint, though subgroup analysis suggested benefit in preventing constrictive pericarditis. 1

TB-IRIS in HIV Patients

• Corticosteroids are beneficial for moderate to severe paradoxical TB-IRIS, with prednisone 1.25 mg/kg/day shown to reduce need for hospitalization. 2
• Corticosteroids both prevent and improve outcomes of TB-immune reconstitution inflammatory syndrome. 1

NOT Recommended for Routine Use

Pulmonary Tuberculosis

• Adjunctive corticosteroids do NOT reduce mortality, accelerate sputum conversion at 2 or 6 months, or provide major long-term benefits in pulmonary TB (low quality evidence). 3
• Short-term clinical benefits (weight gain, clinical improvement within one month) do not translate to sustained long-term outcomes. 3, 4
• Some older literature suggests possible use in severe pulmonary disease with cavitation, but modern evidence does not support routine use. 5, 6

Tuberculous Pleural Effusion

• Corticosteroids are NOT recommended routinely for tuberculous pleurisy based on four prospective, double-blind, randomized trials showing no benefit on residual pleural thickening or long-term pleural sequelae. 1, 7
• One study showed increased risk for Kaposi sarcoma with prednisolone in HIV-associated tuberculous pleurisy. 1, 8
• May be considered only for significant systemic symptoms or particularly large effusions, but not as standard therapy. 5

Other Forms of TB

• Insufficient data exist to recommend corticosteroids for peritoneal, intestinal, or genitourinary tuberculosis. 1
• No controlled trials in the modern drug era support routine use in extensive pulmonary disease. 5

Critical Safety Considerations

Drug Interactions

• Rifampin induces hepatic enzymes and may reduce corticosteroid effectiveness, requiring higher steroid doses or more frequent monitoring. 8
• Rifampin also interacts with oral contraceptives; alternative contraception should be considered. 5

HIV-Infected Patients

• Use corticosteroids with caution in HIV-infected patients due to increased risk of opportunistic infections. 8
• Despite caution, corticosteroids are generally recommended for TB meningitis and pericarditis even in HIV co-infected patients, as benefits likely outweigh risks. 9

Active vs. Latent TB

• The FDA label states that hydrocortisone use in active TB should be restricted to fulminating or disseminated tuberculosis and must be used in conjunction with appropriate antituberculous therapy. 10
• For patients with latent TB or tuberculin reactivity on corticosteroids, close observation is necessary as reactivation may occur; chemoprophylaxis should be given during prolonged corticosteroid therapy. 10

General Precautions

• Corticosteroids may mask signs of infection and decrease resistance to new infections. 10
• Monitor for hyperglycemia, hypertension, hypokalemia, and increased calcium excretion. 7, 10
• Avoid live vaccines (including smallpox) while on corticosteroid therapy. 10

Practical Implementation

When prescribing corticosteroids for TB:

1. Confirm appropriate antituberculous therapy is initiated (isoniazid, rifampicin, pyrazinamide, ethambutol for at least 6 months). 8
2. Use specific dosing protocols based on the form of TB (see above).
3. Implement gradual taper over weeks to avoid adrenal suppression. 8, 2
4. Account for rifampin-induced reduction in corticosteroid levels by considering higher doses. 8
5. Monitor closely for adverse effects and treatment response.

Common pitfall: Do not use corticosteroids routinely for pulmonary TB based on outdated literature; modern evidence does not support this practice. 3, 4