Epidemiology and pathology of miliary and extrapulmonary tuberculosis
- John Bernardo, MD
John Bernardo, MD
- Professor of Medicine and Research Professor of Biochemistry
- Boston University School of Medicine
Miliary tuberculosis (TB) refers to clinical disease resulting from the hematogenous dissemination of Mycobacterium tuberculosis. The term "miliary" was coined in 1700 by John Jacobus Manget, who likened the appearance of the involved lung with its surface covered with firm small white nodules to numerous millet seeds (picture 1).
Miliary TB can arise as a result of progressive primary infection or via reactivation of a latent focus with subsequent spread. The term miliary TB was originally a pathologic and then a radiographic description; it is now used more broadly (and incorrectly) by some to denote all forms of progressive, widely disseminated TB, whether or not disease presents with the classic radiographic or pathologic nodular appearance characteristic of hematogenous spread.
Tuberculosis may be classified according to site of disease as pulmonary or extrapulmonary; miliary disease has been classified as both an extrapulmonary and a pulmonary form of TB.
The epidemiology and pathology of miliary TB will be reviewed here. The clinical manifestations, diagnosis, treatment, and prevention of miliary TB are discussed separately. (See "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)
The epidemiology of miliary tuberculosis (TB) has been altered by use of chemotherapy for treatment of malignancy, use of biologic agents, the HIV epidemic, and immigration patterns. For reporting purposes, cases with both pulmonary and extrapulmonary disease are classified as pulmonary TB by the United States Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) [1,2].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2014. CDC, Atlanta, GA 2014. http://www.cdc.gov/tb/statistics/reports/2014/pdfs/tb-surveillance-2014-report.pdf (Accessed on February 17, 2016).
- World Health Organization. Global tuberculosis report 2015. http://www.who.int/tb/publications/global_report/en/ (Accessed on April 28, 2016).
- Sharma SK, Mohan A, Sharma A, Mitra DK. Miliary tuberculosis: new insights into an old disease. Lancet Infect Dis 2005; 5:415.
- CHAPMAN CB, WHORTON CM. Acute generalized miliary tuberculosis in adults. N Engl J Med 1946; 235:239.
- Alvarez S, McCabe WR. Extrapulmonary tuberculosis revisited: a review of experience at Boston City and other hospitals. Medicine (Baltimore) 1984; 63:25.
- Rieder HL, Kelly GD, Bloch AB, et al. Tuberculosis diagnosed at death in the United States. Chest 1991; 100:678.
- Shafer RW, Kim DS, Weiss JP, Quale JM. Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection. Medicine (Baltimore) 1991; 70:384.
- Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 5-1999. A 37-year-old man with fever and diffuse lymphadenopathy. N Engl J Med 1999; 340:545.
- Lado Lado FL, Barrio Gómez E, Carballo Arceo E, Cabarcos Ortíz de Barrón A. Clinical presentation of tuberculosis and the degree of immunodeficiency in patients with HIV infection. Scand J Infect Dis 1999; 31:387.
- O'Reilly P, McDonnell T. The spectrum of mycobacterial disease in a Dublin teaching hospital. Ir Med J 1999; 92:299.
- Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345:1098.
- Dixon WG, Hyrich KL, Watson KD, et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis 2010; 69:522.
- Kruijshaar ME, Abubakar I. Increase in extrapulmonary tuberculosis in England and Wales 1999-2006. Thorax 2009; 64:1090.
- Brudney K, Dobkin J. Resurgent tuberculosis in New York City. Human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs. Am Rev Respir Dis 1991; 144:745.
- Snider DE Jr, Rieder HL, Combs D, et al. Tuberculosis in children. Pediatr Infect Dis J 1988; 7:271.
- Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974; 99:131.
- Hussey G, Chisholm T, Kibel M. Miliary tuberculosis in children: a review of 94 cases. Pediatr Infect Dis J 1991; 10:832.
- Smith S, Jacobs RF, Wilson CB. Immunobiology of childhood tuberculosis: a window on the ontogeny of cellular immunity. J Pediatr 1997; 131:16.
- Cruz AT, Starke JR. Clinical manifestations of tuberculosis in children. Paediatr Respir Rev 2007; 8:107.
- Braun MM, Coté TR, Rabkin CS. Trends in death with tuberculosis during the AIDS era. JAMA 1993; 269:2865.
- Aguado JM, Herrero JA, Gavaldá J, et al. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA. Transplantation 1997; 63:1278.
- Muñoz P, Palomo J, Muñoz R, et al. Tuberculosis in heart transplant recipients. Clin Infect Dis 1995; 21:398.
- Sakhuja V, Jha V, Varma PP, et al. The high incidence of tuberculosis among renal transplant recipients in India. Transplantation 1996; 61:211.
- Nishizaki T, Yanaga K, Soejima Y, et al. Tuberculosis following liver transplantation: report of a case and review of the literature. Transpl Int 1996; 9:589.
- Nagasawa M, Maeda H, Okawa H, Yata J. Pulmonary miliary tuberculosis and T-cell abnormalities in a severe combined immunodeficient patient reconstituted with haploidentical bone marrow transplantation. Int J Hematol 1994; 59:303.
- Munt PW. Miliary tuberculosis in the chemotherapy era: with a clinical review in 69 American adults. Medicine (Baltimore) 1972; 51:139.
- Maartens G, Willcox PA, Benatar SR. Miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Am J Med 1990; 89:291.
- Centers for Disease Control. Extrapulmonary tuberculosis in the United States 1969-1973. DHEW publication no CDC 78-8260. Atlanta: Department of Health, Education and Welfare, 1978.
- Morano Amado LE, Amador Barciela L, Rodriguez Fernandez A, et al. Extracorporeal shock wave lithotripsy complicated with miliary tuberculosis. J Urol 1993; 149:1532.
- Federmann M, Kley HK. Miliary tuberculosis after extracorporeal shock-wave lithotripsy. N Engl J Med 1990; 323:1212.
- Yekanath H, Gross PA, Vitenson JH. Miliary tuberculosis following ureteral catheterization. Urology 1980; 16:197.
- Anyanwu CH, Nassau E, Yacoub M. Miliary tuberculosis following homograft valve replacement. Thorax 1976; 31:101.
- Qunibi WY, al-Sibai MB, Taher S, et al. Mycobacterial infection after renal transplantation--report of 14 cases and review of the literature. Q J Med 1990; 77:1039.
- Miller RA, Lanza LA, Kline JN, Geist LJ. Mycobacterium tuberculosis in lung transplant recipients. Am J Respir Crit Care Med 1995; 152:374.
- PERRY TL. Natural history and pathogenesis of miliary and meningeal tuberculosis in children; analysis of 163 cases. Pediatrics 1950; 5:988.
- Daley CL, Small PM, Schecter GF, et al. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms. N Engl J Med 1992; 326:231.
- Stead WW. Pathogenesis of tuberculosis: clinical and epidemiologic perspective. Rev Infect Dis 1989; 11 Suppl 2:S366.
- Slavin RE, Walsh TJ, Pollack AD. Late generalized tuberculosis: a clinical pathologic analysis and comparison of 100 cases in the preantibiotic and antibiotic eras. Medicine (Baltimore) 1980; 59:352.
- Proudfoot AT, Akhtar AJ, Douglas AC, Horne NW. Miliary tuberculosis in adults. Br Med J 1969; 2:273.
- O'BRIEN JR. Non-reactive tuberculosis. J Clin Pathol 1954; 7:216.
- de Noronha AL, Báfica A, Nogueira L, et al. Lung granulomas from Mycobacterium tuberculosis/HIV-1 co-infected patients display decreased in situ TNF production. Pathol Res Pract 2008; 204:155.
- Mazurek J, Ignatowicz L, Kallenius G, et al. Divergent effects of mycobacterial cell wall glycolipids on maturation and function of human monocyte-derived dendritic cells. PLoS One 2012; 7:e42515.
- Altare F, Jouanguy E, Lamhamedi S, et al. Mendelian susceptibility to mycobacterial infection in man. Curr Opin Immunol 1998; 10:413.
- Jouanguy E, Döffinger R, Dupuis S, et al. IL-12 and IFN-gamma in host defense against mycobacteria and salmonella in mice and men. Curr Opin Immunol 1999; 11:346.
- Risk factors
- - Age
- - Medical conditions
- - Other factors
- Mechanisms of disease
- - Progressive primary disease
- - Reactivation of a latent focus
- - Iatrogenic infection
- Clinicopathologic patterns of disease
- - Acute miliary tuberculosis
- - Late generalized tuberculosis
- - Anergic tuberculosis
- Host and pathogen factors