Tuberculosis natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Tuberculosis can have pulmonary and extra-pulmonary manifestations as well as severe parenchymal, vascular, pleural and chest wall complications. Pulmonary complications include pleural effusions, cavitations, lymphadenopathy, airway obstruction, pneumonia and bronchiectasis. The hematogenous dissemination of infection can lead to miliary tuberculosis. The post-primary infection can be due to either a recent infection or reactivation of an old infection. Without treatment, 1/3 of patients with active tuberculosis die within 1 year of diagnosis, and more than 50% die during the first 5 years. With early diagnosis and optimal medical therapy, M. tuberculosis infections have a good prognosis.

Natural History

Without treatment, 1/3 of patients with active tuberculosis die within 1 year of the diagnosis, and more than 50% during the first 5 years. Patients who have a positive sputum smear test for M. tuberculosis have a 5-year mortality rate of 65%. Those who survive past 5 years have a 60% probability of spontaneous remission. [1]

Primary Pulmonary Tuberculosis

Primary tuberculosis develops soon after infection with M. tuberculosis and differs from clinical illness. In endemic regions, this form of TB is frequently seen at younger ages. Primary TB may be asymptomatic, or include mild symptoms, such as cough, fever and chest pain, related to pleurisy. Some patients may develop concomitant symptoms, such as erythema nodosum in the lower limbs and phlyctenulosis. The initial lesion (Ghon focus) often resolves spontaneously, becoming a calcified nodule that may be identified on the chest X-Ray. Pleuritic chest pain often results from the pleural reaction to the underlying Ghon focus.[1]

Primary tuberculosis progresses more rapidly in patients with impaired immune system and in children, who commonly have immature cellular immunity. Progression of the disease leads to the enlargement of the Ghon focus. The disease may have the following manifestations:[1]

Primary infection leads to dissemination of M. tuberculosis through the blood. Hematogenous dissemination is often contained by an healthy immune system, however, in cases of compromised immune response, miliary tuberculosis may occur. Dissemination of the mycobacteria may lead to the formation of granulomatous lesions in other organs, which may develop different forms of the disease.[1]

Chest X-Ray of patient with Miliary TuberculosisImage from Wikimedia Commons[2]

Secondary Pulmonary Tuberculosis

Also known as "adult-type" or "post primary tuberculosis". May result from recent infection with M. tuberculosis, or from the reactivation of an endogenous focus that contained the latent form of the disease. Without treatment, about 1/3 of patients dies within months of disease onset. Of the remaining 2/3, some may experience remission, while others develop a chronic condition with debilitating symptoms. The surviving patients may show fibrotic and calcified lesions, as well as cavitations in some areas of the lungs, which may be later appreciated on a chest X-Ray.[1]

Disease onset is insidious and unspecific, presenting with symptoms that may include:

Complications

Tuberculosis may be localized to the lungs, or involve other organs and regions of the body. Pulmonary TB may lead to permanent damage of the lungs and affected structures. Depending on the pulmonary, or extrapulmonary nature of the lesions, potential complications that may arise include:[3][4]

Parenchymal Lesions

Complication Description
Tuberculoma
Cicatrization
  • Common in secondary TB
  • Marked fibrosis in ≤40% of secondary TB cases, which may present as:
  • Unspecific X-Ray findings may include:[3]
  • Parenchymal bands
  • Fibrotic cavities
  • Fibrotic nodules
  • Traction bronchiectasis
Thin-walled cavity
  • Present in active and inactive forms of the disease
  • May regress with treatment
  • Air-filled cysts may persist[8]
  • May be misidentified as an emphysematous bulla or pneumatocelle.
Aspergilloma
  • Mass of hyphae, cell debris and mucus, commonly located in a cavity or bronchus[9][10][11]
  • Previous history of chronic cavitary TB in 25-55% of cases presenting with aspergilloma
  • Frequently concomitant with hemoptysis in 50-90% of the cases
  • X-ray shows a mobile mass ringed by an air shadow
  • CT shows a mobile mass, generally interspaced with air shadows
  • May be calcified
Lung destruction[3]
Bronchogenic carcinoma[3]
  • May be misinterpreted as TB progression
  • Scar formation in TB may lead to carcinoma
  • May cause reactivation of TB[12][13]

Airway Lesions

Complication Description
Bronchiectasis
  • Result from the bronchial wall involvement, with fibrosis, and secondary bronchial dilation, often called traction bronchiectasis
  • Identified on CT in 30-60% of cases of secondary TB, and in 71-86% of cases of inactive TB[14][15]
  • Highly suggestive of TB when located at the apical-posterior segment of the lung
Tracheobronchial stenosis
  • Predominance on the left main bronchus
  • Caused by:
  • Granulomatous tracheobronchial wall changes
  • Enlargement of peribronchial lymph nodes pressing on the tracheobronchial wall
  • Endobronchial involvement in 2-4% of the cases
  • Tracheobronchial narrowing from the formation of intraluminal granulation tissue
  • CT scan findings may include:
Broncholithiasis

Vascular Lesions

Complication Description
Pulmonary or bronchial arteritis and thrombosis
Bronchial artery dilatation
Rasmussen's aneurysm
  • Results from the replacement of normal media and adventitia by granulation tissue that weakens the arterial wall
  • Commonly presents with hemoptysis
  • Life-threatening when massive hemoptysis occurs

Mediastinal Lesions

Complication Description
Esophagobronchial fistula
Esophagomediastinal fistula
  • Common envolvement of the subcarinal region
Constrictive pericarditis
  • Complicates 1% of TB cases[25]
  • Frequently caused by extension of tuberculous lymphadenitis
  • May occur in miliary TB[6]
  • Common findings on CT may include:
Lymph node calcification
Fibrosing mediastinitis
  • Rare[30]
  • May present with mild symptoms, such as:
  • CT findings may include:
  • May cause bronchial obstruction, and consequently:[30][31]
Extranodal extension
  • Commonly affects the following structures:

Pleural Lesions

Complication Description
Bronchopleural fistula
  • May occur:
  • Spontaneously
  • After trauma
  • After surgery
  • Diagnostic findings include:
  • Increased sputum production
  • Changes in the air-fluid level
  • Air trapping in the pleural space
  • Spread of pneumonic infiltration to the contralateral lung
Fibrothorax and chronic empyema
  • Pleural infection may occur following:[33][34]
  • Rupture of a subpleural focus of infection
  • Lymph node infection caused by hematogenous dissemination
  • Pleural thickening
  • Calcification
Pneumothorax
  • Occurs in about 5% of patients with secondary TB
  • Rare in miliary TB
  • Present in severe stages of tuberculous lung disease
  • Commonly follows empyema and bronchopleural fistula
  • Consider active TB if after reexpansion, apical changes are noted

Chest Wall Lesions

Complication Description
Tuberculous spondylitis (Pott's disease)
  • Hematogenous spread of pulmonary TB
  • Commonly affected areas include:
  • X-ray findings in the early stage of the disease may include:
  • Vertebral end plate irregularities
  • Reduction of the intervertebral disk space
  • Adjacent bone sclerosis
  • Paravertebral abscess
  • Peripheral rim enhancement
  • Area of low-attenuation at the center of the abscess, after enhancement
Rib tuberculosis
  • Characterized by:
Malignancy
Swelling of the soft-tissue
  • Enhancement of a mass around the region of the empyema
  • Attenuation of soft tissues surrounding the empyema

Prognosis

  • If untreated, active TB is often fatal. According to studies performed in several countries, 1/3 of the untreated patients died within 1 year after the diagnosis, while > 50% died within the first 5 years. However, with early diagnosis and adequate treatment, these patients have a good prognosis.[1]
  • Symptoms of uncomplicated TB usually improve after 2-3 weeks of treatment initiation.[4]
  • Improvements in the chest X-ray require several weeks to months to be noted.[4]

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