Synopsis
Tuberculosis (TB) refers to infection with organisms of the Mycobacterium tuberculosis complex (which includes Mycobacterium tuberculosis, Mycobacterium africanum, and Mycobacterium bovis). It remains a major global health concern and, along with HIV, is a leading cause of death due to infectious disease.
The World Health Organization (WHO) estimates that 1.4 million people died of TB in 2019, including 208 000 HIV-positive patients. TB is more common in men than women. Most cases occur among people aged 15-59 years.
In the United States, wide disparities exist in the geographic distribution of cases, with most cases occurring in New York, New Jersey, California, Texas, and Florida. More than two-thirds of the patients come from urban areas with populations > 500 000. There are also racial and ethnic disparities in the burden of the disease, with clustering seen in the urban poor, people with alcohol use disorder, people who use intravenous (IV) drugs, undomiciled people, migrant farm workers, and prison inmates. Foreign-born persons from countries with a high prevalence of TB, HIV-infected patients, and employees and residents of long-term health care facilities, mental institutions, hospitals, and clinics are groups with an elevated risk of the disease.
The causative organism in the United States is usually M tuberculosis, an aerobic, slow growing, acid-fast bacillus. Humans are the only reservoir of infection. Almost all infections are acquired via inhalation of droplet nuclei aerosolized by coughing, sneezing, or talking that contain infectious particles. These particles dry while airborne and remain suspended for long periods; when inhaled, they can reach the terminal air passages. Most cases require prolonged and multiple aerosol exposures. Sputum smear positivity, frequent in the presence of lung cavitation, and the intensity and frequency of coughing determine the infectiousness of the source. Patients with AIDS and pulmonary TB may be highly contagious in the absence of cavitary lesions on chest x-ray due to very high bacillary load.
Rarely, M bovis can cause disease in humans, accounting for < 2% of cases in the United States. Infection occurs most commonly via consumption of contaminated, unpasteurized dairy products. Those at increased risk also include dairy or cattle farmers, slaughterhouse workers, and hunters.
Mycobacterium africanum is typically seen in parts of Africa.
The tubercular bacilli from the infective droplet are taken up by the alveolar macrophages, particularly in the upper and mid-lung zones, which have the highest air flow rates. The breach of the bacteria into the subpleural interstitium causes a local inflammation and consolidation with an exudate and cellular infiltrate. This hallmark of primary pulmonary infection is called the Ghon focus. The bacilli are then rapidly taken up by the mediastinal lymph nodes (hilar and/or paratracheal), resulting in their enlargement and liquefaction, which liberates bacilli that can spread hematogenously throughout the body, seeding different organs. The Ghon focus and the mediastinal lymph node enlargement form the primary or Ranke complex. In most patients, the infection remains latent, being forever contained by the development of cell-mediated immunity that results within 3 weeks to 3 months in a positive skin (tuberculin) test. However, in 5%-10% of patients, mostly within 2-3 years, this initial infection evolves toward active TB. This progression is more common in immunosuppressed states such as AIDS and in children younger than 5.
Several factors can trigger reactivation of latent infection and lead to active disease. HIV infection, poorly controlled diabetes, renal failure, malignancies, chemotherapy, steroid use, and malnutrition are some of the risk factors for reactivation. The use of tumor necrosis factor antagonists such as infliximab has been reported to trigger reactivation of TB. Although most cases in adults reflect reactivation of previous infection (also known as post-primary TB), exogenous reinfection is possible, especially in areas where TB is common.
Symptoms are nonspecific and include anorexia, fatigue, anemia, weight loss, fevers, and night sweats. Cough is usually productive, and hemoptysis may occur. Pleural involvement may lead to chest pain and dyspnea. Physical examination findings include rales and signs of consolidation. Auscultation over cavities may reveal amphoric breath sounds (like the sound made by blowing across the mouth of a jar). Signs of pleural effusion may also be found. Pericarditis and pericardial effusion can occur.
The clinical manifestations of TB in HIV-infected patients correlate with the degree of immunosuppression. In general, patients with early HIV present with similar features to those without HIV. Patients with advanced HIV and TB may present with unusual manifestations such as the involvement of middle and lower lobes, negative purified protein derivative (PPD) testing, less cavitary disease, and more frequent extrapulmonary disease, especially lymphadenitis and pleurisy. In these patients, TB can also present with acute respiratory failure and acute respiratory distress syndrome. In older adults, newly acquired pulmonary TB may present with nonresolving pneumonitis of the middle and lower lobes.
Evidence of disseminated disease may be seen with a miliary pattern of lung infiltration, abnormal liver enzymes, especially alkaline phosphatase, pancytopenia, and adrenal insufficiency. Central nervous system involvement with TB meningitis may occur.
Look For
Chest X-Ray Findings:
Primary pulmonary TB:
Homogeneous, dense, segmental, or lobar air space consolidation is seen. In 25% of cases, consolidation is multifocal and in 10%, it is bilateral. Cavitation or miliary disease or both occur in 2%-5% of patients. Enlarged lymph nodes in adults are seen in 10%-30% of patients and are usually unilateral and hilar or paratracheal. Bilateral lymph node enlargement or enlarged lymph nodes without parenchymal consolidation is uncommon in adults. In children, lymph node enlargement will be seen 90%-95% of the time. Pleural effusions can be seen in 5%-10% of children and 30%-40% of adults.
Post-primary TB:
50%-70% of patients demonstrate foci of consolidations with ill-defined margins. These tend to coalesce and are associated with small satellite foci in the adjacent lung. These typically occur in the apical or posterior segments of an upper lobe, usually limited to one segment or parts of several segments of a lobe. After endobronchial spread, there can be involvement of several lobes. 5%-10% of patients will have hilar and mediastinal lymphadenopathy. Cavitation is present in 20%-45% of patients. Cavities are typically located in the apical or posterior segments of the upper lobes or superior segments of lower lobes. They may be single or multiple and have thin or thick walls.
Tuberculomas may be the only or main abnormality in 5% of patients. These are 1- to 4-cm single nodules with smooth and well-defined margins. Satellite lesions, which are small well-defined nodules near the main lesion, can also be seen. Tuberculomas remain stable for a long time and may calcify. In 20%-25% of patients, small 2- to 10-mm nodules, focal to one or two regions of the lungs, typically the apical or posterior segments of the upper lobes or superior segment of lower lobes, may be the main or only finding by chest x-ray. Miliary TB presents as innumerable 1- to 2-mm nodules.
HIV-infected patients with pulmonary TB:
Typically, these patients have a greater incidence of enlarged hilar and mediastinal lymph nodes, lower lobe disease, extensive parenchymal disease, and lower incidence of cavitation. If patients have an essentially normal immune response, (> 200 CD4 cells/µL), appearance is similar to that described above for post-primary TB. Significantly immunosuppressed patients typically have miliary disease or findings similar to those described above for primary TB. Patients with low CD4 counts may have a normal chest x-ray. Chest x-ray findings often demonstrate worsening of disease after antiretroviral treatment with immune reconstitution.
CT Findings:
Primary pulmonary TB:
One-half of enlarged lymph nodes will have low attenuation (< 30 Hounsfield Units [HU]). Contrast-enhanced studies demonstrate low attenuation of the central region of affected lymph nodes and rim enhancement. One-fifth of cases demonstrate inhomogeneous enhancement, and one-fifth homogeneous enhancement or no enhancement.
Post-primary TB:
Focal areas of consolidation as described above. Mediastinal lymphadenopathy is more commonly seen on CT. The lymph nodes appear similar as seen in primary TB. CT identifies cavitation more frequently. Tuberculomas typically have little or no enhancement after IV contrast. Nodular opacities (described above) on high-resolution CT (HRCT) are centrilobular and associated with branching linear opacities as seen with “tree-in-bud” appearance. On HRCT, miliary nodules are sharply defined and measure 1-4 mm. Most have a random distribution. Other abnormalities include nodular thickening of interlobular septa and fissures, nodular irregularity of vessels, and foci of ground-glass opacity. Bronchiectasis is often seen, particularly in those with healed disease. Bilateral in 60% of patients.
HIV-infected patients with pulmonary TB:
The most common finding on CT is hilar and mediastinal lymph node enlargement. These are typically of low attenuation and rim enhancing. In patients with a normal chest x-ray, CT typically demonstrates miliary nodules, centrilobular nodules, tuberculomas, and enlarged lymph nodes.
The full text and image collection is available to VisualDx subscribers.
Prepare for Everything
Get the only system designed for point-of-care visual diagnosis of common and rare medical disorders as well as emerging and re-emerging infectious diseases.
Your first 30 days are free. Cancel any time.