Tuberculosis

Background/Microbiology/Epidemiology

  • Caused by Mycobacterium tuberculosis
    • spread by aerosolised droplets from other patients.
  • Worldwide it is extremely common but in the UK, cases are not common (4/100,000)
  • It is thought that around one third of the world’s population has latent (carrier) TB

Risk factors

  • Age (children> young adults > elderly)
  • First generation immigrants from high from high prevalence countries
  • Close contact with patients with smear-positive pulmonary TB; or a personal history of TB (particularly if only partly treated)
  • Overcrowded social circumstances/homelessness, alcoholism
  • Immunosuppression (including HIV, patients on immunosuppressing drugs including corticosteroids- particularly biological agents)

Pathophysiology

  • Organisms lodge in the alveoli and cause an inflammatory response, involving Langhans cells which can aggregate with lyphocytes to form granulomas
    • Granulomas can aggregate to form a primary lesions (‘Ghon focus’- pale yellow, caseous nodule, usually on a few mm long; usually at the lung periphery)

Clinical Presentation

  • Primary pulmonary TB
    • Patients will normally report a history of flu-like illness (fever, myalgia, nausea/vomiting, cough etc)
      • Represents initial infection
    • Progressive primary disease may present after a latent period of weeks/months
      • Lymphadenopathy (often central i.e. hilar (commonly unilateral), paratracheal or mediastinal)
      • Lung collapse or consolidation (especially right middle lobe)
  • Miliary TB (Blood-borne dissemination)
    • 2-3 weeks of fever, night sweats, anorexia, weight loss and dry cough
  • Post-primary pulmonary TB (occurs in patients previously sensitised to TB from earlier exposure)
    • Fever, night sweats, weight loss, loss of appetite
    • Pulmonary symptoms
      • Chronic productive cough, often with haemoptysis
      • Shortness of breath
  • Extra-pulmonary disease (more frequent in patients with HIV but can occur in patients without HIV (20%))
    • Lymphadenitis (cervical lymph node enlargement)
    • GI
      • Abdominal pain, bloating, obstruction (can present with acute abdomen)
    • Cardiac
      • Pericardial effusion
      • Constrictive pericarditis
    • Central nervous system
    • Bone/Joint
      • Classically presents with back pain (lower thoracic/lumbar spine involvement) but can present in hip/knee joints also

Investigations

  • Sputum microscopy/culture (at least 3, with one early morning sample)
    • Acid-fast bacilli (Ziehl-Neelson)(smear positive) may be detected (however they may be dead so culture is still considered gold standard)
    • If the patient can’t produce a sputum sample, consider bronchoalveolar lavage
    • Nucleic acid amplification can also be used
  • CXR
    • Features include
      • Consolidation/collapse of the right middle lobe (loss of right heart border)
      • Cavitation (often apical)
      • Pleural effusion/empyema
      • Miliary shadowing (diffuse nodular shadowing)
  • Tuberculin skin tests can be used in patients with negative smear and CXR to help support a diagnosis of active TB (particularly in people who have not received the BCG)
  • In non-pulmonary TB, consider FNA/Biopsy

Management

  • Notify Public Health
    • Contact tracing and BCG vaccination (note not prophylactic antibiotics unless children or HIV positive patients
  • Chemotherapy for active TB- start prior to culture results
    • Usually 6 months of isoniazid and rifampicin
      • supplemented by 2 months of pyrazinamide and ethambutol
  • fff
  • Latent TB can be treated with 6 months of isoniazid or 3 months of isoniazid + rifampicin

Drugs and Side effects

  • Rifampicin
    • Mechanism: Inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
    • Potent liver enzyme inducer
    • Hepatitis; orange secretions; flu-like symptoms
  • Isoniazide
    • Mechanism: inhibits mycolic acid synthesis
    • Peripheral neuropathy: prevent with pyridoxine (vit B6)
    • Hepatitis; agranulocytosis
    • Liver enzyme inhibitor
  • Pyrazinamide
    • Mechanism: inhibits fatty acid synthase
    • Hyperuricaemia (gout); arthralgia; myalgia; hepatitis
  • Ethambutol
    • Mechanism: Inhibits arabinosyl transferase
    • Optic neuritis (check visual acuity before treatment (baseline) as well as during)
    • Caution: renal impairment
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