Snapshot A 33-year-old man presents to his primary care physician for a cough and generalized malaise. His symptoms are associated with 2 episodes of mild hemoptysis and night sweats. He denies any sick contacts or recent travels; however, he states he was released from prison 4 months ago. Physical examination is unremarkable. A chest radiograph is obtained, which demonstrates pulmonary infiltrates and cavitations in the upper lobe. Introduction Classification acid-fast, rod-shaped, obligate aerobic, intracellular bacteria Epidemiology risk factors traveling to endemic areas (e.g., Angola and the Central African Republic) close contact (e.g., prisons, nursing homes, homeless shelters, and hospitals) immunocompromised (e.g., HIV, immunosuppressive medications, and diabetes) Transmission airborne spread of droplet nuclei from patients with infectious tuberculosis (TB) Microbiology acid-fast on Ziehl-Neelsen staining immune system itself causes damage TB contains no endotoxins or exotoxins cord factor inhibits leukocyte migration causes characteristic serpentine growth pattern induces TNF-α release tuberculin triggers cell-mediated immunity → caseation and granulomas triggers delayed hypersensitivity reaction a surface protein sulfatides prevent phagosome-lysosome fusion Pathogenesis the infected person coughs up small droplets containing the bacteria that reaches the terminal alveoli of the uninfected person alveolar macrophages are recruited, which eventually become infected, transporting the microbe to deeper tissues more alveolar macrophages are recruited, leading to granuloma formation granulomas are formed to "wall off" TB, where it lies dormant secondary TB occurs when the patient's immune system is weakened (e.g., newly acquired HIV infection, being on immunosuppressant medications, malignancy, and poor nutrition) macrophages' ability to maintain their barrier decreases, facilitating possible dissemination TB infection typically manifests in the apical/posterior segments of the lung due to its increased oxygen tension Presentation TB can lead to pulmonary and extrapulmonary manifestations lymph nodes (tuberculous lymphadenitis) pleura genitourinary skeleton (can lead to Pott disease with spinal involvement) meninges gastrointestinal system pericardium (tuberculous pericarditis) Symptoms typically asymptomatic in primary TB cough hemoptysis fever night sweats malaise Physical exam weight loss lymphadenopathy dullness to percussion or decreased/absent breath sounds if there is a pleural effusion back pain in spinal TB (Pott disease) Imaging Chest radiograph indication initial imaging study in the evaluation of TB findings middle or lower lung infiltrate (suggestive of primary infection) upper lobe infiltrate (suggestive of latent TB reactivation) apices have higher oxygen tension and reduced perfusion/lymph clearance compared to the base cavitary lesions Ghon complex (lobar or perihilar lymph node involvement) Studies Sputum acid-fast testing demonstrates acid-fast bacilli Real-time nucleic acid amplification rapidly confirms TB and is considered the first-line diagnostic study Tuberculin skin test (TST) most widely used to screen for latent TB infection a delayed-type hypersensitivity reaction against purified protein derivative (PPD) is induced the size of the induration is assessed after 48-72 hours note, patients who received the Bacille Calmette-Guerin (BCG) vaccination will have false positive results a false negative result can be seen in immunocompromised patients interpretation (positive results) ≥ 15 mm in patients with no risk factors ≥ 10 mm in patients with risk factors (e.g., healthcare worker, traveling to endemic areas, and being in prison) ≥ 5 mm in immunocompromised patients (e.g., HIV, on immunosuppressants, and organ transplant recipients) positive tests require a chest radiograph Interferon-γ release assay measures interferon levels released by the patient's immune system in response to TB antigens the results are not affected by previous BCG vaccination Differential Lung cancer differentiating factor patients will not have positive TB studies Treatment Medical rifampin, isoniazid, pyrazinamide, and ethambutol therapy indication first-line treatment for active pulmonary TB infection for 4 months after 4 months, treatment involves isoniazid and rifampin comments isoniazid can cause peripheral neuropathy as well as sideroblastic anemia due to vitamin B6 deficiency, thus warranting pyridoxine in hopes to prevent this development from occurring can also cause hepatitis ethambutol can cause optic neuropathy mutations in RNA polymerase lead to rifampin resistance isoniazid monotherapy indication prophylactic treatment for latent primary TB after active TB has been excluded Complications Pott disease Miliary or disseminated TB Meningitis Pericarditis Lymphadenitis Adrenal insufficiency