TB by kanok


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TB by kanok

  1. 1. Tuberculosis
  2. 2. Pathophysiology• Mycobacterium tuberculosis (obligate aerobe)• Inhalation of droplet nuclei suspended in air ---host defenses---> some survive and be transported to the regional LN >> Granulomas (tubercles) ---may progress to caseation necrosis and calcification (= Ghon foci)
  3. 3. Pathophysiology• If fails to contain the infection --> hematogenous/ lymphatic/ direct mechanical spreading• Immunocompromised: spread rapidly, early active dz• Immunocompetent: survive in areas of high O2/blood – apical and posterior segments of the upper lobe – superior segment of the lower lobe – renal cortex – meninges – epiphyses of long bones – vertebrae => Latent infection --- as the host defense system weakens ---> progress to active tuberculosis
  4. 4. From Mason: Murray and Nadels Textbook of Respiratory Medicine
  5. 5. Risk for Reactivation of TB
  6. 6. Clinical FeaturesPrimary Tuberculosis• Usually asymptomatic & PPD-positive• Symptoms: fever, malaise, weight loss, chest pain• Pneumonitis ≈ a viral or bacterial infection• Hilar adenopathy• Some (esp. immunocompromised) rapidly progressive and fatal
  7. 7. Clinical FeaturesReactivation Tuberculosis• Symptom: fever, night sweats, malaise, fatigue, weight loss, productive cough, hemoptysis, dyspnea, pleuritic chest pain• PE - unremarkable, +/- rales• 20% extrapulmonary – LN, adrenal glands, bones and joints, GI, GU, meninges, pericardium, peritoneum, pleura
  8. 8. Tuberculin Skin Test (TST)• Most common method to detect exposure• Mantoux test: PPD 0.1 mL ID  read induration at 48-72 h• If PPD positive or recent conversion  treatment of latent TB
  9. 9. Tuberculin Skin Test (TST)• False positive: – exposure to nontuberculosis mycobacteria – receive BCG• False negative: – improper administration technique – abnormal immune systems• Unreliable in acute stages of the disease (>20% of active TB pts = false-negative results)
  10. 10. Chest Radiograph• Most useful study for making a presumptive diagnosis of pulmonary TB• Normal CXR - high NPV  screening ED pts for active pulmonary TB• No specific abnormalities - not exclude active TB
  11. 11. CXR – Primary TB• Infiltrates – Homogeneous – any lobe, most = single lobe• Enlarged hilar/mediastinal LN (most common) – hallmark in children, less common in adults – usually unilateral and assoc/w infiltrate  atelectasis (esp. < 2 y/o)• Normal CXR (common)
  12. 12. CXR – Primary TB• Other findings: – moderate to large pleural effusion – miliary TB – tuberculoma• Calcified 1o focus = Ghon focus• Ghon focus + calcified hilar LN = Ranke complex• Calcified 2o foci = Simon’s foci
  13. 13. CXR – Primary TB• Progressive primary TB – progressive parenchymal consolidation often including secondary foci in the upper lobes – multiple cavitary lesions – single large abscess
  14. 14. CXR – Reactivation TB• Upper lung infiltrate/consolidation – usually apical/posterior segment of the upper lobe, superior segment of the lower lobe +/-cavitation • high infectivity • assoc/w bronchogenic spread
  15. 15. CXR – Reactivation TB Alveolar opacity (exudative) ↓ Reticulonodular opacity (fibroproductive) ↓ Fibrotic scar ?Infectivity?Only serial CXR can reliably differentiate active from inactive disease
  16. 16. CXR – Reactivation TB• Atypical radiographic patterns: – Hilar adenopathy +/- RML collapse – Infiltrates or cavities in the middle or lower lung – Bronchogenic spread  multiple lobes – Pleural effusion – Solitary nodule• Normal CXR
  17. 17. AFB Sputum Microscopy• Most rapid test to support diagnosis• Sensitivity 20-80% (Fluorochrome > Ziehl- Neelsen or Kinyoun), Specificity 90-100%• For pts unable to expectorate sputum: – nebulized induction of sputum – gastric aspiration – fiberoptic bronchoscopy with bronchial washings, brushings, and BAL or transbronchial biopsy may be necessary
  18. 18. Culture• “gold standard”• (solid C/S) available in ≈ 4-8 wk• (liquid C/S) available in ≈ 1-2 wk – BACTEC, MGIT (mycobacteria growth indicator tube) – detect 10 - 100 bacilli/mL
  19. 19. Other Methods• Nucleic Acid Amplification Tests• The Ligase Chain Reaction• Interferon-γ Release Assay (IGRA)• Serology
  20. 20. Case Definition• Tuberculosis suspect: symptoms or signs suggestive of TB – most common = productive cough >2 wks – +/- dyspnea, chest pains, hemoptysis – +/- constitutional symptoms (loss of appetite, weight loss, fever, night sweats, fatigue)• Case of tuberculosis – definite case of TB or – one in which a health worker has diagnosed TB and has decided to treat with a full course of TB treatment. Note. Incomplete “trial” TB treatment should not be given as a method for diagnosis.
  21. 21. Case Definition• Definite case of tuberculosis – M. tuberculosis complex identified from a clinical specimen (culture or newer method) – In countries that lack the laboratory capacity, a pulmonary case with one or more initial AFB-positive sputum is also considered to be a “definite” case, provided that there is a functional external quality assurance (EQA) system with blind rechecking
  22. 22. Case Definition• Pulmonary TB (PTB): TB involving lung parenchyma or both pulmonary and extrapulmonary TB• Extrapulmonary TB (EPTB): TB involving organs other than lung parenchyma, e.g. pleura, LN, abdomen, etc.• Smear positive case: only one sputum specimen smear positive AFB• Smear negative case: 2 specimens are smear negative AFB (at least one early-morning specimen) in a well functional EQA system (take sputum culture in all settings with an HIV prevalence of >1% in pregnant women or ≥5% in TB pts)• Smear not done
  23. 23. Management• Suspected TB pts should be placed in separate waiting areas, wear surgical masks, and be instructed to cover the mouth and nose when coughing.• Immunocompromised pts with respiratory symptoms should be isolated until TB can be excluded.
  24. 24. Treatment• New pts – “new patient regimen” containing 6 mo of rifampicin: 2HRZE/4HR• Previously treated pts – culture – drug susceptibility testing (DST) for at least H & R – Rapid DST (1-2 d) >> wait for result – Conventional DST/unavailable • Tx failure/high risk MDR >> “MDR regimen” • Default/Relapse >> “retreatment regimen with first- line drugs”: 2HRZES/1HRZE/5HRE
  25. 25. Drug-induced Hepatitis• Stop all drugs• If severely ill with TB and unsafe to stop TB treatment  streptomycin, ethambutol and a fluoroquinolone should be started
  26. 26. INH-induced Peripheral Neuropathy• Numbness/tingling/burning sensation of the hands or feet• Common in – pregnant women - HIV infection – alcohol dependency - malnutrition – DM - chronic liver disease – renal failure• Prevention: pyridoxine 10 mg/day
  27. 27. Paradoxical Reaction or Immune Reconstitution Disease• clinically worsen after the initiation of anti-TBs• common in HIV pts• ↑ fever, radiographic infiltrates, lymphadenopathy, worsening sign/symptom• dDx: treatment failure, drug resistance, noncompliance• Tx: supportive, systemic steroids often added
  28. 28. Special Situations• Pregnancy: streptomycin should not be used (ototoxic to the fetus )• Contraception: Rifampicin >> ↓T½ of pills• Renal failure: ethambutol and pyrazinamide doses = 3 times per week (significant renal excretion)• Advanced liver disease: LFT at the start >> if ↑ALT > 3X  different regimen
  29. 29. Miliary TB= wide hematogenous spread (primary inf.) or= secondary seeding of multiple organs in the young or immunocompromised host• Dx by 1) diffuse miliary nodules on CXR (1-3 mm) or 2) demonstration of mycobacteria in multiple organs• Choroidal tubercles on ocular exam are pathognomonic
  30. 30. Miliary TB
  31. 31. Multidrug-resistant Tuberculosis (MDR-TB)• resistance to at least H & R• Risks: – prior TB treatment – contact with a proven MDR case – AFB positive at month 2 or 3 of treatment – exposed in institutions with an MDR outbreak or a high prevalence of MDR (such as certain prisons or mines) – co-morbid conditions assoc/w malabsorption or rapid- transit diarrhea – HIV infection (in some settings) – DM type 2
  32. 32. Extensive Drug-resistant Tuberculosis (XDR-TB)• resistance to H & R plus• resistance to any fluoroquinolone and• resistance to at least one injectable second- line drug (kanamycin, amikacin , capreomycin, strepyomycin)
  33. 33. Disposition• Outpatient: – D/C instructions = home isolation and follow-up – Antituberculosis medications should not be instituted in the ED unless physicians are directed to do so by health care professionals who will coordinate the treatment and monitor adverse effects
  34. 34. Disposition• Admission: I/C – clinically toxic, hypoxic, or dyspneic – uncertain diagnosis – noncompliant – difficult to obtain a proper Dx and institute Tx – active drug-resistant TB• Hospitalized pts require respiratory isolation
  35. 35. TB & HIV• HIV >> ↑ risk of latent disease (≈ 10X) ↑ initial inf => active disease ↑ extrapulmonary TB ↑ sputum smear-negative TB• CXR: ↑ typical of primary inf / atypical findings• “provider-initiated” HIV testing for suspected/ confirmed-TB pts of all ages  early Dx & Tx
  36. 36. Latent TB Infection (LTBI)• Asymptomatic + Positive TST + No active dz• Tx. considered for pts with 1. recent conversion to PPD-positive status 2. close contact with an individual with active TB 3. anergic individuals with known TB contact• > 20 million Thais have LTBI >> impossible to treat all• Tx. INH 9 mo or Rifampicin 4 mo
  38. 38. Extrapulmonary TB1. Lymphatic 42%2. Pleural 18%3. Bone/joint 12%4. Genitourinary 6%5. Meningeal 6%6. Peritoneal 5%7. Other sites 11% CXR for ALL (exclude pulmonary TB)
  39. 39. Tuberculous Lymphadenitis• “Scrofula”• Common site: cervical > supraclavicular• Other sites: inguinal, axillary, mesenteric, mediastinal, intramammary• enlarging, painless, mobile, red, firm mass  matted, harder, overlying skin inflamed• Dx = excisional biopsy (FNA is adequate in HIV pts)
  40. 40. Pleural Tuberculosis• Usually small to moderate unilateral effusion +/- pulmonary lesions, pleural thickening• CT scan may reveal lymphadenopathy, infiltrates, cavitation• Pleural fluid: exudative, lymphocytic predominance (neutrophils may predominate early on), ↓/↔glucose, ↑protein
  41. 41. Pleural Tuberculosis• AFB positive 5% (higher in tuberculous empyema), positive cultures 25-30%• Lymphocyte activity markers such as adenosine deaminase (ADA) and interferon- gamma (INF-γ) can be useful• Pleural effusions with an ADA <40 U/L rarely caused by TB• Caseating granulomas seen on pleural biopsy are classic and diagnostic
  42. 42. Skeletal Tuberculosis• most common = spinal TB• Tuberculous arthritis involving monoarticular weight-bearing joints• Extraspinal tuberculous osteomyelitis
  43. 43. Spinal TB (Pott’s disease)• Hx. back pain or stiffness• PE. fever, point tenderness, ↓ROM• Lesion at intervertebral disk  adjacent vertebrae (film = anterior wedging of two vertebral bodies + disk destruction)• Film: early changes = loss of the “white stripe” of the vertebral end plate (difficult to detect)• Suspected disease  CT / MRI
  44. 44. Spinal TB (Pott’s disease)• Paraspinal “cold” abscesses +/- sinus tract• Main complication = spinal cord compression• Bone Bx or aspiration Bx of abscess may confirm
  45. 45. Cold abscess Spinal TB http://images.rheumatology.org
  46. 46. CNS Tuberculosis1. Meningitis2. Intracranial tuberculoma3. Spinal tuberculous arachnoiditis
  47. 47. Tuberculous Meningitis• Nuchal rigidity may be absent• Diplopia from basilar exudate (70%)• +/- Hyponatremia (SIADH is common)• CSF: WBC 0-1,500 (lymphocyte predominance; PMN may predominate early); ↑protein, ↓glucose, positive AFB 37% (90% in pooled samples from multiple LP)
  48. 48. Tuberculous Meningitis• Classic triad of neuroradiologic findings 1. basal meningeal enhancement 2. hydrocephalus 3. cerebral or brainstem infarction
  49. 49. Intracranial Tuberculoma• solitary or multiple; usually frontal or parietal
  50. 50. Genitourinary Tuberculosis• Typically, renal function is preserved until there is (typically unilateral) granulomatous erosion into the calyceal system, or tuberculous interstitial nephritis develops• UA: sterile pyuria +/- microscopic hematuria• IVP: a moth-eaten calyx or papillary necrosis• CT may show calculi; scarring; hydronephroses; ureteral strictures; and calcifications in the kidney, seminal vesicles, prostate, and vas deferens• Three morning urine samples cultured fo MTB establish the diagnosis in 90% of cases.• Co-infection with bacteria is not unusual
  51. 51. Tuberculous Peritonitis• abdominal pain, fever, hepatomegaly, ascites• Peritoneal fluid analysis: not diagnostic, WBC 150 - 4000/mm3 (lymphocytic predominance), and SAAG < 1.1 g/dL• Dx. = peritoneal Bx & fluid for histopathology and culture
  52. 52. Extrapulmonary TB: Treatment• Same regimens as pulmonary TB• Experts recommend – TB meningitis: treat 9–12 mo – TB bone&joint: treat 9 mo• Corticosteroid is recommended for TB meningitis and pericarditis (unless suspected drug resistance)• In TB meningitis, ethambutol should be replaced by streptomycin
  53. 53. Prevention1. early detection and treatment of active cases2. education and screening of HCW3. engineering controlsEngineering Controls to Reduce TB TransmissionHigh airflow (> 6 room air changes per hour) with external exhaustHigh-efficiency particulate filters on ventilation systemUV germicidal irradiationNegative-pressure isolation roomsPersonal respiratory protection: high-efficiency particulate filtermasks or respirators
  54. 54. Thank You
  55. 55. References