Extrapulmonary tuberculosis, part 1: Pleural and lymph node disease

Pleural tuberculosis and lymph node involvement are the most common extrapulmonary manifestations of tuberculosis. Most patients with pleural involvement complain of pleuritic chest pain, nonproductive cough, and dyspnea. The pleural effusion is usually unilateral and small to moderate in size. The diagnosis depends on the demonstration of acid-fast bacilli in pleural fluid or biopsy specimens, or the presence of caseous granulomas in the pleura. The gold standard for the diagnosis of lymph node tuberculosis is the identification of mycobacteria in smears on fine-needle aspiration cytopathology, histopathology, or mycobacterial culture. On ultrasonography and CT, the lymph nodes show enlargement with hypoechoic/hypodense areas that demonstrate central necrosis and peripheral rim enhancement or calcification. Treatment involves the combination of 4 antituberculosis drugs for 2 months, followed by 2-drug therapy for 4 months. (J Respir Dis. 2005;26(8):326-332) In the past decade, there has been a significant increase in the prevalence of tuberculosis and its extrapulmonary manifestations worldwide.1 Factors that have contributed to this include the rising number of immunosuppressed persons, the development of drugresistant strains of Mycobacterium tuberculosis, aging-population demographics, and an increase in the number of health care workers who are exposed to tuberculosis.2 The incidence of extrapulmonary manifestations is approximately 50% in patients who have both AIDS and tuberculosis, compared with 10% to 15% in HIV-negative patients with tuberculosis.3 Tuberculosis that involves the lymph nodes, bone (excluding the spine), peripheral joints, or skin is classified as a less severe form of disease. The severe forms include meningitis, abdominal involvement, miliary tuberculosis, pericarditis, bilateral or extensive pleural effusion, spinal involvement, and genitourinary involvement. In some patients, it can be difficult to make the diagnosis of extrapulmonary tuberculosis. Although imaging studiesor a positive tuberculin skin test may support the diagnosis, negative results do not exclude extrapulmonary tuberculosis.4 However, recognition of the common and uncommon radiologic findings can be helpful. In a series of articles, we will focus on the more common forms of extrapulmonary tuberculosis. In this article, we will review the presentation and diagnosis of pleural and lymph node (peripheral and mediastinal) involvement. In coming issues of The Journal of Respiratory Diseases, we will discuss CNS, abdominal, and skeletal manifestations of tuberculosis.PLEURAL TUBERCULOSIS Lymph node involvement and pleural tuberculosis are the 2 most common extrapulmonary manifestations of tuberculosis. Most cases are caused by M tuberculosis; a fewcases caused by other mycobacteria, including Mycobacterium bovis, have been reported.5 Tuberculous pleural effusion is usually seen in children and young adults. It characteristically occurs 3 to 7 months after initial infection with M tuberculosis. An upward shift in the age spectrum and a more frequent association with reactivation disease have been reported in many series in the past decade.6,7 Underlying pulmonary parenchymal disease is also being documented, thereby confounding the classification of pleural disease as extrapulmonary tuberculosis. In general, patients who have tuberculous pleural effusion are younger than patients who have parenchymal tuberculosis.8Pathogenesis Neutrophils appear to play a key role in the initiation of inflammatory reactions in tuberculous effusion. In addition, pleural mesothelial cells produce a neutrophil chemotactic cytokine, interleukin (IL)-8, and a mononuclear cell chemotactic cytokine, monocyte chemotactic peptide-1 (MCP-1). MCP-1 is produced by inflammatory macrophages and endothelial cells. This cytokine may be at least partly responsible forthe recruitment of macrophages.