Diagnosis

Tuberculosis

Etiology

Cause

• Mycobacterium tuberculosis is the predominant human pathogen

• Other: M bovis, M africanum, and M canetii

Pathophysiology [hsn]

1. Spread most commonly by airborne droplet (rarely ingestion of contaminated milk)

2. Slow-growing intracellular pathogens --> subacute and progressive disease

3. Visible growth on solid media: 3 to 8 weeks (diagnostic challenge)

4. Genetic variability --> differences in virulence:

   • May remain dormant within infected cells --> may or may not cause disease

   • 90% develop latent infection

   • Weaken immune system (HIV/AIDS or elderly) --> TB bacteria can become active

5. The bacilli may escape immunologic controls and disseminate lymphohematogenously within the lung and to virtually any other organ and cause granuloma --> caseation tissue necrosis

6. Clinical manifestation:

   • Most often found in the lungs: cough, fever, weight loss, night sweats, and malaise

   • Most common extrapulmonary dissemination: pleura, lymph nodes, kidneys, long bones, vertebrae, and meninges

7. Clinical variations:

   1. Primary TB: Pulmonary infiltrate or atelectasis, lymphadenopathy, rarely miliary pattern (progressive primary disease)

   2. Post-primary TB (reactivation and reinfection): Patchy consolidation, cavitation

   3. HIV-TB coinfection: Mediastinal lymphadenopathy and extrapulmonary disease

   4. Chronic TB: Cavitation, fibrosis, bronchiectasis, bronchopleural fistula

Risk factors

• Tobacco use

• Excessive alcohol use

• Immunocompromised state:

  • Immune senescence of older age

  • Genetic diseases causing immunodeficiency

  • Human immunodeficiency virus (HIV)

  • Transplantation

  • Prolonged corticosteroid use

  • Cytoreductive chemotherapy

  • Tumor necrosis factor (TNF) antagonists

  • Malnutrition

  • Diabetes

Complications [hsn]

• Septic shock

• Airway obstruction

• Pneumonia, bronchiectasis, empyema, hemoptysis

• Broncho-pleural fistula

• Meningitis

• Osteomyelitis

• Peritonitis

• Renal abscess

• Infertility

• Drug toxicity: Hepatitis, peripheral neuropathy, ocular toxicity, rash, cranial nerve VIII dysfunction, renal failure, GI side effects, myaliga, arthralgia, anxiety, confusion, psychosis

Epidemiology

Incidence per 100.000 [hsn][pca][sia][hh3][wci]

Approach

• Blood test

• Blood gas

• Sputum culture: Acid-fast bacilli

• Blood culture: 2 to 8 weeks for visible growth of acid-fast bacilli

• Urine culture

• Fluorescence microscopy: Acid-fast bacilli

• Sputum cytology

• Laryngeal swab

• Tuberculin skin test (Mantoux skin test): diagnostic and predictive limitations [hsn]

• Interferon-Gamma Release Assay (IGRA): diagnostic and predictive limitations

• PCR: improved diagnostic accuracy but inaccessible in many high-prevalence regions

• Chest X-ray

• Bronchoscopy

• Bronchoalveolar lavage

• Biopsy

• HIV serology

• Lumbar puncture

• CT

• MR

• Echocardiography

Treatment

1. Anti-TB regimens vary depending on: [hsn]

   • The stage and anatomic location

   • The immune status and age of the host

   • The presence of comorbidities

   • Drug toxicities (hepatitis, neuropathy, ocular, rash, kidney, myalgia, anxiety)

   • Resistance patterns of the bacterium

2. Profylaxis: Bacille Calmette-Guerin (BCG) Vaccine

3. Latent infection: weekly isoniazid plus rifampin for 3 months

4. Active Tuberculosis Infection - 4 drugs: isoniazid, rifampin, ethambutol, and pyrazinamide

   • Initial intensive bactericidal phase: 8 weeks of daily isoniazid, rifapentine, pyrazinamide, and moxifloxacin

   • Continuation phase sterilizes slowly replicating and dormant tubercle bacilli: 9-16 weeks of daily rifapentine, isoniazid, and moxifloxacin

5. Drug-Resistant Tuberculosis: Extended period (18 to 21 months) with delamanid, bedaquiline, pretomanid, linezolid, amoxicillin-clavulanate, meropenem-clavulanate, imipenem-cilastatin, cotrimoxazole, and macrolides

Differential diagnoses

Actinomycosis, Acute respiratory distress syndrome, Adrenal insufficiency, Albuminuria, Alcoholism, Anorexia nervosa, Ascites, Aspergillosis, Blastomycosis, Bone marrow failure, Bronchiectasis, Bronchitis, Cardiac tamponade, Cat scratch disease, Cerebral venous sinus thrombosis, Chronic granulomatous disease, Colorectal cancer, COPD, Crohn disease, Cytomegalovirus, Diabetes mellitus, Disseminated intravascular coagulation, Encephalitis, Endocarditis, Eosinophilic granuloma, Eosinophilic pneumonia, Epididymal tuberculosis, Erythema induratum, Erythema nodosum, Fever of unknown origin, Fungal infection, Hidradenitis suppurativa, Histoplasmosis, HIV, Hyponatremia, Influenza, Lactic acidosis, Leishmaniasis, Leprosy, Leukemia, Lung abscess, Lung cancer, Lymphoma, Measles, Meningitis, Mycobacterial infection, Nocardiosis, Pancreatic abscess, Pericarditis, Pneumoconiosis, Pneumocystis jiroveci pneumonia, Pneumonia, Polyarteritis nodosa, Pott disease, Pulmonary alveolar microlithiasis, Renal cell carcinoma, Rheumatoid arthritis, Sarcoidosis, Silicosis, Spontaneous bacterial peritonitis, Squamous cell carcinoma, Stroke, Syphilis, Syringoma, Systemic lupus erythematosus, Tularemia, Ulcerative colitis, Wegener's granulomatosis