General
- PPD positive: if current infection or past exposure.
- PPD negative: if no infection and in immunocompromised patients (especially with low CD4+ cell count).
- Interferon-γ release assay (IGRA) has fewer false positives from BCG vaccination.
Pathology
- Caseating granulomas with central necrosis and Langhans giant cell (single example in figure) are characteristic of 2° tuberculosis. Do not confuse Langhans giant cell (fused macrophages) with Langerhans cell (dermal APC).
Risk factors
- TB reactivation risk highest in immunocompromised individuals (eg, HIV, organ transplant recipients, TNF-α inhibitor use). Reactivation has a predilection for the apices of the lung (due to the bacteria being highly aerobic).
Pathogenesis
Targets
Treatment
Drug | Mechanism | Adverse effects | Notes |
Rifamycins (Rifampin, rifabutin, rifapentine) | - Inhibit DNA-dependent RNA polymerase → ↓ mRNA synthesis - Rifamycin resistance arises due to mutations in gene encoding RNA polymerase | - Minor hepatotoxicity, drug interactions (CYP450 induction), red-orange discoloration of body fluids (nonhazardous adverse effect) | - Rifabutin favored over rifampin in patients with HIV infection due to less CYP450 induction - Monotherapy rapidly leads to resistance |
Isoniazid | - Inhibits mycolic acid synthesis → ↓ cell wall synthesis - Bacterial catalase-peroxidase (encoded by katG) needed to convert INH to active form - INH resistance arises due to mutations in katG | - Vitamin B6 deficiency (peripheral neuropathy, sideroblastic anemia), hepatotoxicity, drug interactions (CYP450 inhibition), drug-induced lupus - INH overdose can lead to seizures (often refractory to benzodiazepines) | - Administer with pyridoxine (vitamin B6) - INH Injures Neurons and Hepatocytes (↑ risk of hepatotoxicity with ↑ age and alcohol overuse) - Different INH half-lives in fast vs slow acetylators |
Pyrazinamide | - Mechanism uncertain | - Hepatotoxicity, hyperuricemia | - Works best at acidic pH (e.g., in host phagolysosomes) |
Ethambutol | - Inhibits arabinosyltransferase → ↓ arabinogalactan synthesis → ↓ cell wall synthesis | - Optic neuropathy (red-green color blindness or ↓ visual acuity, typically reversible) | - Pronounce "eyethambutol" |
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