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: Mashal Awais, M.D.[2]; João André Alves Silva, M.D. [3]

Overview

Tuberculosis complications are pulmonary and extra-pulmonary. Moreover, they include severe parenchymal, vascular, pleural and chest wall complications. The pulmonary complications of tuberculosis include pneumonia, pleural effusions, bronchiectasis, cavitations, and lymphadenopathy. The hematogenous spread of infection resuts in miliary tuberculosis. Without effective medical therapy, 1/3 of patients with active tuberculosis die within 1 year of diagnosis, and more than 50% die during the first 5 years. However, M. tuberculosis infections carry a good prognosis if diagnosed early and treated effectively.

Natural History

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

Primary Pulmonary Tuberculosis

Primary tuberculosis occurs soon after infection with M. tuberculosis and differs from clinical illness. In endemic areas, primary TB is usually observed at a young age. Primary TB may be completely asymptomatic, or iinvolves mild symptoms, such as fever, cough, and chest pain, due to pleurisy. Some patients can have other 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 usually occurs as a result of the pleural reaction to the underlying Ghon focus.[1]

The progression of primary TB is more rapidly in patients with impaired immunity and in children. Progression of primary tuberculosis results in 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. With impaired immune response, miliary tuberculosis may occur resulting in the formation of granulomatous lesions in several organs.[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 containing the latent form of the infection. Without effective medical therapy, approximately 1/3 of patients die within months of disease onset. Of the remaining 2/3, some can develop spontaneous remission, while others experience a chronic infection with severe symptoms. The survivors may have fibrotic and calcified lesions, and cavitations in some areas of the lungs, that can be detected later on a chest X-Ray.[1]

The onset of illness is insidious and nonspecific, and the symptoms include:

Complications

Tuberculosis may be localized to the lungs, or affects other organs of the body. Pulmonary TB can result in permanent damage of the lungs and affected organs. According to the pulmonary, or extrapulmonary nature of the lesions, the possible complications may 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
  • Found in both the active and inactive forms of the disease
  • May regress with treatment
  • Air-filled cysts may persist[8]
  • Maybe misidentified as an emphysematous bulla or pneumatocele.
Aspergilloma
  • Mass of hyphae, cell debris and mucus, usually present in a cavity or bronchus[9][10][11]
  • Previous history of chronic cavitary TB in 25-55% of cases presenting with aspergilloma
  • Often occurs with hemoptysis in 50-90% of the cases
  • X-ray reveals a mobile mass ringed by an air shadow
  • CT reveals a mobile mass, generally interspaced with air shadows
  • Maybe calcified
Lung destruction[3]
Bronchogenic carcinoma[3]
  • Maybe misinterpreted as TB progression
  • Scar formation in TB may lead to carcinoma
  • May cause reactivation of TB[12][13]

Airway Lesions

Complication Description
Bronchiectasis
  • It occurs due to 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]
  • Indicative 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 involvement 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 endplate 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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