Tuberculosis

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)

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

From Mason: Murray and Nadel's Textbook of Respiratory Medicine

Risk for Reactivation of TB

Clinical Features

Primary 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

Clinical Features

Reactivation 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

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

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)

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

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)

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

CXR – Primary TB

• Progressive primary TB– progressive parenchymal consolidation often

including secondary foci in the upper lobes– multiple cavitary lesions– single large abscess

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

CXR – Reactivation TB

Alveolar opacity (exudative)↓

Reticulonodular opacity (fibroproductive)↓

Fibrotic scar?Infectivity?

Only serial CXR can reliably differentiate active from inactive disease

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

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

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

Other Methods

• Nucleic Acid Amplification Tests• The Ligase Chain Reaction• Interferon-γ Release Assay (IGRA)• Serology

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.

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

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

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.

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

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

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

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

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

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

Miliary TB

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

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)

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

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

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

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 TB3. anergic individuals with known TB contact

• > 20 million Thais have LTBI >> impossible to treat all

• Tx. INH 9 mo or Rifampicin 4 mo

EXTRAPULMONARY TB

Extrapulmonary TB

1. 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)

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)

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

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

Skeletal Tuberculosis

• most common = spinal TB• Tuberculous arthritis involving monoarticular

weight-bearing joints• Extraspinal tuberculous osteomyelitis

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

Spinal TB (Pott’s disease)

• Paraspinal “cold” abscesses +/- sinus tract• Main complication = spinal cord compression• Bone Bx or aspiration Bx of abscess may

confirm

Cold abscess Spinal TB

http://images.rheumatology.org

CNS Tuberculosis

1. Meningitis2. Intracranial tuberculoma3. Spinal tuberculous arachnoiditis

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)

Tuberculous Meningitis

• Classic triad of neuroradiologic findings1. basal meningeal enhancement2. hydrocephalus3. cerebral or brainstem infarction

Intracranial Tuberculoma

• solitary or multiple; usually frontal or parietal

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

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

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

Prevention

1. early detection and treatment of active cases2. education and screening of HCW3. engineering controls

Engineering Controls to Reduce TB TransmissionHigh airflow (> 6 room air changes per hour) with external exhaust

High-efficiency particulate filters on ventilation systemUV germicidal irradiationNegative-pressure isolation roomsPersonal respiratory protection: high-efficiency particulate filter masks or respirators

Thank You

References