Pulmonary Tuberculosis

Pulmonary tuberculosis, typically affecting socioeconomically disadvantaged populations, is an infection of the lungs by Mycobacterium tuberculosis, characterised by granuloma formation with central caseous necrosis and upper zone predominant consolidative changes with potential cavitation.

Description

Pulmonary tuberculosis (TB) is a major health burden worldwide, caused by the bacterium Mycobacterium tuberculosis. It primarily affects the lungs, though dissemination to other organs is not uncommon (extrapulmonary TB). The disease is characterised by the formation of granulomas – a type of localised inflammatory response – which often lead to architectural distortion of lung parenchyma, manifesting as fibrotic changes or cavitation on imaging.

Pathogenesis

Mycobacterium tuberculosis, an acid-fast bacillus, is transmitted via airborne droplets. Following inhalation, the bacterium is then phagocytosed by alveolar macrophages but resists destruction, survives, and replicates within the macrophages, initiating an immune response. This response leads to the formation of granulomas, which contain the infection but also lead to tissue damage. These granulomas often undergo central caseous necrosis, a distinctive feature of tuberculosis. Over time, progressive destructive disease marked by fibrosis or cavitation may occur.

Subtypes

Pulmonary tuberculosis can be categorised into:

• Primary TB: This occurs following initial infection with Mycobacterium tuberculosis, often in children. Radiologically, it is represented by a Ghon focus (usually subpleural, often in the mid to lower zones) and hilar or paratracheal lymphadenopathy.
• Secondary/Post-primary (Reactivation) TB: This occurs when dormant bacteria within a previously infected individual reactivate, typically in the setting of immunosuppression. The apical and posterior segments of the upper lobes and superior segment of the lower lobes are preferentially involved.
• Miliary TB: This represents haematogenous dissemination of the bacterium, appearing as a ‘miliary’ pattern on imaging, characterised by innumerable tiny nodules throughout the lungs.

Epidemiology, Risk Factors & Associations

• TB is a global health issue, with the highest incidence seen in Africa, followed by Southeast Asia and the Western Pacific. These regions account for 85% of cases.
• Approximately a quarter of the world’s population (around 1.7 billion people) has latent TB, with about 10 million people developing active TB each year.
• Despite available treatment, TB remains a leading cause of death from a single infectious agent. It was estimated to cause 1.4 million deaths worldwide in 2019.

Risk factors include:

• Close contact with an individual with active TB or high-risk settings (healthcare facility)
• Low socioeconomic conditions such as poverty, overcrowding (prisons, homeless shelters and refugee camps) and malnutrition.
• Immunocompromised states: HIV/AIDS is a significant risk factor, increasing susceptibility by 20-37 times.
• Other medical conditions including diabetes mellitus and chronic kidney disease increase susceptibility.
• Smoking and chronic alcohol abuse also contribute to increased risk.

Clinical Features

Symptoms of TB depend on the organ system involved. Pulmonary TB, the most common form, typically presents with:

• Persistent cough
• Haemoptysis – massive haemoptysis may indicate erosion of a bronchial artery or rupture of a Rasmussen aneurysm.
• Night sweats
• Weight loss
• Fever

Extrapulmonary TB can affect nearly any organ system and will have symptoms related to the organ involved.

Complications

The complications of tuberculosis (TB) are varied and can be severe, impacting multiple organ systems:

Pulmonary Complications

• Progressive pulmonary TB: Without treatment, pulmonary TB can progress to extensive lung damage, resulting in cavitations, fibrosis, and calcifications.
• Miliary TB: Disseminated disease leading to tiny lesions resembling millet seeds in multiple organs.
• Respiratory failure: Extensive lung involvement may lead to respiratory failure due to destruction of lung parenchyma.
• Haemoptysis: Rupture of a Rasmussen aneurysm can cause haemoptysis, which may be life-threatening. Rasmussen aneurysms are pulmonary artery aneurysms adjacent to or within a tuberculous cavity.

Extrapulmonary Complications

TB can affect almost any organ system, leading to a diverse range of complications.

• Tuberculous meningitis: The most severe form of TB with a high mortality rate, even with treatment. It can cause a range of neurological deficits.
• Skeletal TB: Also known as Pott’s disease, it can lead to vertebral destruction, spinal deformities, and paralysis in severe cases.
• Genitourinary TB: Can lead to renal failure, infertility, and pelvic inflammatory disease.
• Abdominal TB: Can result in bowel obstruction (typically affects terminal ileum), peritonitis, and liver abscesses.
• Disseminated TB (Miliary TB): This is a severe form of TB where the bacteria spread throughout the body. It can be fatal without treatment.
• Multidrug-resistant TB (MDR-TB) and Extensively drug-resistant TB (XDR-TB): These are forms of TB that do not respond to the standard anti-TB drugs. According to the WHO, in 2019, about 3.3% of new TB cases and 18% of previously treated cases were MDR/RR-TB.
• Association with HIV/AIDS: TB is one of the leading causes of death among people living with HIV, accounting for around one in three AIDS-related deaths.

Pathological Features

Histopathology

• Macroscopic: Lung tissue shows areas of consolidation, cavitation, and fibrosis.
• Microscopic: Granulomas with central caseous necrosis, Langhans giant cells, and surrounding epithelioid cells and lymphocytes.

Serology

• Tuberculin skin test (Mantoux test) or interferon-gamma release assays (IGRAs) may suggest TB infection.

Biochemistry

• Inflammatory markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may be elevated.

Radiological Features

General Features

• Primary infection may show Ranke’s complex, comprising a small parenchymal lesion (Ghon’s focus) and enlarged hilar or mediastinal lymph nodes
• Secondary infection has a strong predilection for apical and posterior segments of the upper lobe, superior segment of the lower lobe, due to high oxygen tension and impaired lymphatic drainage
• Typical imaging features include upper lobe consolidative changes, cavitation, fibrotic changes, and nodal involvement.
• In healed or quiescent disease, calcifications may be seen within granulomas or nodal groups.
• The ‘tree-in-bud’ sign due to endobronchial spread is a characteristic feature.
• Pleural involvement may present as pleural thickening or effusion, typically exudative.

XR

• Traditional chest radiographs demonstrate upper lobe consolidation, cavitation, and in the case of miliary TB, innumerable tiny nodules.

CT

Primary TB

• Ghon focus: Small parenchymal lesion, typically subpleural, often in the mid to lower zones.
• Lymphadenopathy: Enlarged hilar or mediastinal lymph nodes.
• Pleural effusion: May be present.

Secondary TB

• Upper lobe predilection: Lesions more commonly found in the apical and posterior segments of the upper lobes or superior segments of lower lobes.
• Cavitation: Thick-walled cavities, often with irregular or ragged inner walls.
• Tree-in-bud nodules: Representing endobronchial spread.
• Volume loss and fibrosis: May lead to bronchiectasis and architectural distortion.
• Tuberculomas or granulomas: Well-circumscribed nodules, can calcify over time.

Grading and Staging

The American Thoracic Society (ATS) provides guidelines for the diagnosis and grading of TB severity. It incorporates the extent of disease on chest radiography, degree of sputum smear positivity, and systemic symptoms.

Diagnosis

The diagnosis of pulmonary tuberculosis requires integration of clinical suspicion, radiological findings, positive bacteriology (smear, culture or PCR from sputum or tissue) and occasionally histological confirmation.

Differential Diagnosis

• Bacterial pneumonia – Typically showing acute onset symptoms with lobar consolidation.
• Lung cancer – often seen as a solitary pulmonary nodule or mass in older patients with smoking history.
• Fungal infections (e.g., histoplasmosis, aspergillosis, coccidioidomycosis) – can mimic tuberculosis radiographically but tend to occur in distinct geographical regions.
• Sarcoidosis – Features non-caseating granulomas, bilateral hilar lymphadenopathy and lung parenchymal involvement without cavitation. Often seen in a younger age group.

Management

Early suspicion of tuberculosis should prompt referral to a respiratory or infectious disease specialist for further investigation. Management involves a prolonged course of anti-tuberculous therapy, tailored according to drug susceptibility testing. Monitoring for therapy response and potential side effects is also crucial.