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

Natural History

Without treatment, 1/3 of patients with active tuberculosis dies 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 these 5 years, have 60% of probability of undergoing spontaneous remission. [1]

According to its clinical manifestations, pulmonary tuberculosis may be classified as primary or secondary (or post-primary) tuberculosis:[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 be manifested with:[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 courses with hemoptysis (50-90%)
  • 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]
  • Common in end-stage of TB
  • Involvement of the airways and parenchyma
  • May follow primary TB or secondary TB
  • Spreads across the lung with cavitation and fibrosis[6]
  • Concomitant infection with bacteria or bacteria may occur
  • Complicates assessment of TB activity in the lung with the X-ray.
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 of 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 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 (2-4% cases)
  • Tracheobronchial narrowing from intraluminal granulation tissue
  • On CT scan appears as:
  • Uniform wall thickening
  • Mediastinal lymph node enlargement
  • Concentrical luminal narrowing
Broncholithiasis
  • Calcified material within the tracheobronchial lumen, with origin on a calcified lymph node[16]
  • Rare complication
  • Recurrent pneumonia and hemoptysis are frequent in broncholithiasis[16][17][18]
  • On X-ray, common finding include:
  • Change in position of the calcified material
  • Airway obstruction
  • Atelectasis
  • Air trapping on expiration
  • Mucoid impaction

Vascular Lesions

Complication Description
Pulmonary or bronchial arteritis and thrombosis
  • Perform acid-fast staining whenever in presence of necrotizing granulomatous pulmonary vasculitis to rule out TB[19]
Bronchial artery dilatation
  • Common in parenchymal tuberculosis or TB complicated by bronchiectasis[20][21]
  • CT is the imaging test of choice, allowing identification of dilated bronchial arteries, therefore avoiding biopsy of an hypertrophied bronchial artery instead of a lymph node.[20]
Rasmussen's aneurysm
  • Results from the replacement of normal media and adventitia by granulation tissue that weakens arterial wall

Mediastinal Lesions

Complication Description
Esophagobronchial fistula
Esophagomediastinal fistula
  • Rare
  • Complication of tuberculous lymphadenitis
  • May lead to:[23][24]
  • Strictures
  • Mediastinal or tracheobronchial fistulas
  • Traction diverticula
  • 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 include:
Lymph node calcification
  • 83-96% of pediatric cases occur with lymphadenopathy[26][27][28]
  • Commonly affected adults:[29]
  • Pubertal women
  • Elderly
  • Immunosuppressed patients
Fibrosing mediastinitis
  • May present with mild symptoms, such as:
  • Low-grade fever
  • Cough
  • Related to compression of neighboring structures (airways, esophagus and superior vena cava)[31]
  • Granulomas may lead to fibrosing mediastinitis[30]
  • X-ray findings may include:
  • CT findings may include:
  • Hilar or mediastinal mass
  • Calcification
  • Tracheobronchial narrowing
  • Obstruction of the superior vena cava
  • Pulmonary infiltrates
  • 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
  • Chronic empyema may follow tuberculous pleurisy
  • CT findings in chronic tuberculous empyema may include:
  • Pleural thickening
  • Calcification
  • Disease inactivity is marked by absence of effusion with persistence of pleural thickening[35][36][37]
  • Infected pleura may alter lipid and cholesterol transfer across the membrane causing lipid accumulation in the pleural fluid[38][39]
Pneumothorax
  • Occurs in about 5% of patients with secondary TB
  • Rare in miliary TB
  • In TB, it is present in severe 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:
  • Abscesses
  • Bone destruction
  • Masses of the soft tissues, possibly calcified, which may, or may not show lung or pleural involvement at the CT scan[42][43]
Malignancy
  • Rarely associated with tuberculous empyema (mean of 25 years of chronic empyema until the diagnosis of malignancy)[45][46][47]
  • Malignancy frequency according to the histopathologic diagnosis:[47]
  • Malignant lymphoma
  • Squamous cell carcinoma
  • Mesothelioma
  • Malignant fibrous histiocytoma
  • Liposarcoma
  • Rhabdomyosarcoma
  • Angiosarcoma
  • Hemangioendothelioma
  • Prolonged inflammatory process in malignant lymphoma
  • Action of oncogenic substances in the pleura or prolonged stimulation of mesothelial cells in other types of malignancy
  • X-ray findings include:[47]
Swelling of the soft-tissue
  • CT scan findings may include:
  • Enhancement of a mass around the region of the empyema
  • Attenuation of soft tissues surrounding the empyema
  • Perform biopsy to differentiate between infection and malignancy

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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