Any site in the body can be involved, but the most commonly affected sites are (in order of frequency) the lymph nodes, pleura, genitourinary tract, bones and joints, meninges, peritoneum, and pericardium. Up to two-thirds of HIV-infected pts with TB have extrapulmonary disease.

• Lymphadenitis occurs in 35% of extrapulmonary TB cases, especially among children and HIV-infected pts. Painless swelling of cervical and supraclavicular nodes (scrofula) is typical.
  • - Nodes are discrete early on but can develop into a matted nontender mass with a fistulous tract.
  • - Fine-needle aspiration or surgical-excision biopsy of the node is required for diagnosis. Cultures are positive in 70-80% of cases.
• Pleural involvement is common (~20% of extrapulmonary cases) and results from a hypersensitivity response to mycobacterial antigens or contiguous spread of parenchymal inflammation.
  • - Pleural fluid is straw-colored and exudative, with protein levels >50% of those in serum, normal to low glucose levels, a usual pH of ~7.3 (occasionally <7.2), and pleocytosis (500-6000 cells/µL). The pleural concentration of adenosine deaminase, if low, virtually excludes TB.
  • - Pleural biopsy is often required for diagnosis, with up to 80% of biopsy cultures and 75% of PCR tests positive. Direct smears, cultures, and PCR of pleural fluid are less sensitive.
  • - Empyema is an uncommon complication of pulmonary TB and results from rupture of a cavity with many bacilli into the pleural space. In these cases, direct smears and cultures are often positive, and surgical drainage is usually required in addition to chemotherapy.
• In genitourinary disease, local symptoms predominate (e.g., urinary frequency, dysuria, hematuria, abdominal or flank pain), and up to 75% of pts have a CXR demonstrating previous or concomitant pulmonary disease. Disease is occasionally identified only after severe destructive lesions of the kidneys have developed.
  • - In 90% of cases, urinalysis shows pyuria and hematuria with negative bacterial cultures.
  • - Mycobacterial culture of three morning urine specimens is diagnostic in 90% of cases.
• Weight-bearing joints (spine, hips, and knees) are the most common sites of skeletal disease.
  • - Spinal TB (Pott's disease) often involves two or more adjacent vertebral bodies; in adults, lower thoracic/upper lumbar vertebrae are usually affected. Disease spreads to adjacent vertebral bodies, later affecting the intervertebral disk and causing collapse of vertebral bodies in advanced disease (kyphosis, gibbus). Paravertebral cold abscesses may form.
• Meningitis occurs most often in young children and HIV-seropositive pts. Disease typically evolves over 1-2 weeks and often involves paresis of cranial nerves (particularly of ocular nerves). The ultimate evolution is toward coma, with hydrocephalus and intracranial hypertension.
  • - CSF can have a high lymphocyte count, an elevated protein level, and a low glucose concentration. Cultures are positive in 80% of cases. PCR is ~80% sensitive and is the preferred initial diagnostic option.
  • - Neurologic sequelae are seen in ~25% of treated pts; adjunctive glucocorticoids enhance survival among pts >14 years of age but do not reduce the frequency of neurologic sequelae.
• Gastrointestinal disease can affect any portion of the GI tract (with the terminal ileum and cecum most commonly involved), causing abdominal pain, obstruction, hematochezia, and often a palpable mass. TB peritonitis can follow spread of the organism from ruptured lymph nodes and intraabdominal organs; peritoneal biopsy is usually required for diagnosis.
• Pericarditis is characterized by an acute or subacute onset of fever, dull retrosternal pain, and sometimes a friction rub. Effusion is common. Chronic constrictive pericarditis is a potentially fatal complication, even in treated pts. Adjunctive glucocorticoids remain controversial; no conclusive data demonstrate a benefit.
• Miliary disease arises from hematogenous spread of M. tuberculosis throughout the body. Symptoms are nonspecific, and small (1- to 2-mm) granulomas may develop in many organs. Hepatomegaly, splenomegaly, lymphadenopathy, and choroidal tubercles of the eye may occur.