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Key Points

  • Disease summary:

    • Tuberculosis (TB) is an infectious disease that is caused by Mycobacterium tuberculosis (Mtb). Most individuals are able to control infection in an asymptomatic or latent stage (>90%), while only 3% to 10% of those infected will progress to develop active TB disease during their lifetime. Host susceptibility is dependent on multiple interacting genetic loci and environmental factors, such as coinfections (HIV), malnutrition, and immunosuppressive medication. Around 1.7 million people die from TB, and 9 million develop active TB disease each year.

    • TB most often presents as pulmonary TB (75%). Extrapulmonary TB can present as meningeal TB, TB lymphadenopathy, bone TB, spinal TB, skin TB, disseminated (miliary) TB, and in principle can affect any organ or tissue. Extrapulmonary TB is more commonly found in individuals with an acquired (HIV, tumor necrosis factor [TNF]-blocking medication) or primary immunodeficiency (PID).

    • Clinical systemic features of TB are mostly nonspecific, and include fever, night sweats, weight loss or cachexia, anemia, tachycardia, and fatigue. Local clinical features depend on the specific site of disease: persistent and productive cough and possibly hemoptysis in pulmonary TB, enlarged lymph nodes in TB lymphadenopathy, headache, and nuchal rigidity in meningeal TB, etc.

  • Differential diagnosis:

    • For pulmonary TB bronchitis, bacterial pneumonia including pneumonia caused by nontuberculous mycobacteria (NTM) such as Mycobacterium kansasii, chronic obstructive pulmonary disease, sarcoidosis, lung cancer. For extrapulmonary TB disseminated infection with nontuberculous mycobacteria related to HIV or Mendelian susceptibility to mycobacterial disease, other disseminated granulomatous infections.

  • Monogenic forms:

    • No single genetic cause of TB has been identified. TB is however occasionally found in patients with certain primary immunodeficiencies, such as genetic deficiencies in the interleukin-12 or -23/interferon-gamma axis or chronic granulomatous disease.

  • Family history:

    • An affected first-degree relative confers a relative risk of 2.1 for TB.

  • Twin studies:

    • Monozygotic twins have a 32% concordance rate, dizygotic twins have a 14% concordance rate for clinical TB, although environmental factors play a large role in these concordance rates.

  • Environmental factors:

    • Mycobacterium tuberculosis, Mycobacterium bovis (the cause of bovine TB but also pathogenic in humans), or, less commonly and mostly in West Africa, Mycobacterium africanum infection is causative.

  • Genome-wide associations:

    • TB susceptibility-associated genetic variants (Table 82-1) have been identified mainly through candidate gene studies. Most variants confer only a small additional risk for TB, and testing for genetic variants is therefore of no diagnostic value in TB. Genetic variants have provided insight into disease pathogenesis.

  • Pharmacogenomics:

    • Testing for genetic variants to guide treatment of TB (Table 82-2) is not yet clinically validated.

Table 82-1Tuberculosis Disease-Associated Susceptibility Variants

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