🎯 Pathology

• infection caused by Mycobacterium tuberculosis

• spread from person to person through air

• initial infection usually results in latent TB

• active TB tends to occur following the reactivation of latent TB

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💡 Cause

• latent TB

  • asymptomatic as the infection is “walled off” by the Ghon focus which is formed by the immune system

• active TB

  • the initial infection becomes reactivated if the host becomes immunocompromised

• types:

  • pulmonary TB (most common)

  • extra-pulmonary TB

  • miliary TB (haematogenous dissemination of TB)

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🧐 What organs does TB affect?

• any organ!

  • lungs (most common)

  • pleura —> “tuberculous pleurisy”

  • lymph nodes —> “tuberculous cervical lymphadenitis” or “scrofuloderma”

  • GI tract

  • spine (Pott’s disease of the spine)

  • genitourinary system

  • kidneys

  • skin —> “lupus vulgaris” or “cutaneous tuberculosis”

  • CNS —> “tuberculous meningitis”

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😢 Risk factors of reactivation

• HIV

• organ transplantation

• immunosuppression

• drugs: corticosteroids

• silicosis

• malnutrition

• high-risk settings (homelessness, prison

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📌 Pathophysiology of the formation of the Ghon focus

• Type IV hypersensitivity reaction (cell-mediated):

  1. Inhaled mycobacteria enter the lungs (usually the middle zones)

  2. Neutrophils will migrate to areas of infection in the lungs

  3. Neutrophils will release cytokines and die to form the “caseous necrosis”

  4. Cytokines will attract macrophages and T-lymphocytes

  5. Macrophages phagocytose mycobacteria and surround the caseous necrosis to trap mycobacteria

  6. Lymphocytes surround macrophages

  7. Fibroblasts surround lymphocytes

  8. Deposition of collagen and calcium on fibroblasts

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• Note: Ghon complex = Ghon focus + hypertrophied lymph nodes

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🩺 Clinical features of active tuberculosis​

• prolonged symptom duration (> 3 weeks)

• systemic symptoms

• fever, night sweats, weight loss, anorexia, lymphadenopathy

• pulmonary symptoms

• cough, dyspnoea, haemoptysis

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💆‍♂️ Investigations​

• latent TB

  • Mantoux test

    • a positive result —> presence of a hard bump at the site where the tuberculous protein was injected

      • skin induration >5mm: positive in individuals at high risk for TB infection

      • skin induration >15mm: positive in individuals with no known risk factors

    • negative result —> no reaction to tuberculin protein

  • Interferon-gamma release assays (IGRAs)

  • Note: these tests cannot diagnose active TB

• active TB

  • initial tests

    • sputum smear (3 specimens needed including an early-morning sample) + add Ziehl-Neelsen stain

    • nucleic acid amplification tests (NAAT) —> more sensitive than smear

  • best test

    • sputum culture —> more sensitive than smear and NAAT

  • chest x-ray —> cavitation, calcification, lymphadenopathy

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💆‍♂️ Management​

• latent TB

  • 3 months isoniazid + rifampicin, OR

  • 6 months isoniazid alone

• active TB

  • first 2 months: RIPE (Rifampicin, Isoniazid, Pyrizinamide, Ethambutol)

  • next 4 months: RI (not PE)

• CNS disease

  • treatment may be extended up to 10 months with the addition of steroids

• multi-drug resistant TB

  • resistant to rifampicin and isoniazid

  • seek expert advice

• extensively drug-resistant TB

  • resistant to rifampicin, isoniazid, one injectable agent (e.g. amikacin, capreomycin, kanamycin) and one fluoroquinolone

  • seek expert advice

• note: isoniazid must be given with pyridoxine to prevent peripheral neuropathy and sideroblastic anaemia

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😢 Complications of treatment​

• rifampicin

  • liver enzyme inducer

  • orange-red secretions

  • hepatitis

• isoniazid

  • liver enzyme inhibitor

  • peripheral neuropathy

  • sideroblastic anaemia

• pyrizinamide

  • hyperuricaemia —> gout

  • arthralgia

  • hepatitis

• ethambutol

  • optic neuritis

  • reduced visual acuity