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]

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.

According to its clinical manifestations, pulmonary tuberculosis may be classified as primary or secondary (or post-primary) tuberculosis:

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.

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:

• Pleural effusion - results from invasion of the pleural space by M. tuberculosis. This occurs more frequently when the focus of infection is subpleural.
• Cavitation - results from rapid enlargement of the Ghon focus, with ensuing necrosis of its nucleus.
• Lymphadenopathy - the spread of M. tuberculosis from the lungs to lymph leads to the enlargement of lymph nodes, especially of the paratracheal and perihilar regions.
• Airway obstruction - with symptoms of shortness of breath and wheezing. Commonly occurs in cases of severe enlargement of the lymph nodes, that compress the airways and possibly lead to distal collapse, partial obstruction with wheezing, or hyperinflation.
• Pneumonia - may occur when there is rupture and leakage of lymph node content into the airways.
• Bronchiectasis - progressive pneumonia may damage a specific segment of the lung, or an entire lobe, leading to bronchiectasis.

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.

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

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.

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

• Fever
• Night sweats
• Weakness
• Malaise
• Anorexia
• Weight loss
• Cough (90% cases) - nonproductive at the outset, more frequent during the morning, that gradually progresses to productive cough, with purulent sputum, with occasional streaks of blood
• Hemoptysis (20-30% cases) may occur in the following cases:

• Rupture of a blood vessel on a cavity wall (severe hemoptysis)
• Rupture of a pulmonary artery aneurysm adjacent or within a tuberculous cavity (Rasmussen's aneurysm)
• Formation of an aspergilloma in a lung cavity

• Pleuritic chest pain
• Dyspnea (in severe disease)
• ARDS

Complications

Tuberculosis may be localized to the lungs, or involve other organs and regions of the body. Depending on the pulmonary, or extrapulmonary nature of the lesion, potential complications that may arise include:

Parenchymal Lesions

Complication	Description
Tuberculoma	Single or multiple lesions of > 0.5 cm May occur in primary or secundary TB Main finding on Chest X-ray in 5% cases of secondary TB Results from the surrounding of M. tuberculosis with inflammatory or connective tissue. The center of the tuberculoma is often necrotic Satellite lesions (80%) Nodular or diffused calcifications in 20-30% cases
Cicatrization	Common in secondary TB Marked fibrosis in ≤40% of secondary TB cases, which may present as: Upper love atelectasis Compensatory hyperinflation of the lower lobe Hilar retraction Mediastinal shift Unspecific X-Ray findings: Parenchymal bands Fibrotic cavities Fibrotic nodules Traction bronchiectasis
Thin-walled cavity	Present in active and inactive disease May regress after treatment Air-filled sect may persist May be misidentified as an emphysematous bulla or pneumatocelle.
Aspergilloma	Mass of hyphae, cell debris and mucus, commonly located in a cavity or bronchus 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	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 Concomitant infection with bacteria or bacteria may occur Complicates assessment of TB activity in the lung with the X-ray.
Bronchogenic carcinoma	May be misinterpreted as TB progression Scar formation in TB may lead to carcinoma May cause reactivation of TB

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 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

Vascular Lesions

Complication	Description

Mediastinal Lesions

Complication	Description

Pleural Lesions

Complication	Description

Chest Wall Lesions

Complication	Description

Prognosis

If untreated, active tuberculosis 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 adequate treatment, these patients have a good prognosis.