Description

• Clinical disease from widespread hematogenous dissemination of Mycobacterium tuberculosis. Originally named for “millet seed” appearance of nodules often found in lungs. Three types:
  • Acute: usually with primary infection; rapidly progressive; more severe
  • Late generalized: occurs after years of latent infection; chronic, indolent course
  • Anergic: microabscesses in place of granulomas; old disease reactivation; older patients
• Multiorgan failure and acute respiratory distress syndrome (ARDS) are also known to occur.
• System(s) affected: most commonly pulmonary/lymphatic/central nervous system (tuberculosis [TB] meningitis)/hepatic/splenic/bone marrow
• Synonym(s): disseminated TB; tuberculosis cutis disseminata

Epidemiology

Incidence

• Worldwide: 10.4 million new cases of TB in 2015 (142/100,000 population) (WHO), making TB the second leading cause of infectious disease death (1)
• 1–3% of all TB cases are miliary.
• 9,300 new cases in the United States in 2016 (2)
• Predominant sex: male (as in all types of TB)

Prevalence
Global TB prevalence (2013): 11 million, corresponding to 159/100,000 population (1)

Etiology and Pathophysiology

Mycobacterium infection in setting of impaired cell-mediated immunity

• Primary infection in immunocompromised host, recrudescent infection in once healthy host with new comorbidity, or immature immune system (majority in children <5 years of age)
• Lymphatic, then hematogenous spread from a local (typically pulmonary) focus, with failure to halt infection by granulomatous encapsulation
• Predilection for vascular organs (i.e., spleen, liver, brain, bone marrow); in most cases, multiple organs are affected. Severe disease can result in septic shock and ARDS.
• Increased macrophage response increases serum calcitriol. This improves phagocytosis but also leads to clinical hypercalcemia.
• Iatrogenic disease is also reported after solid-organ transplants, urethral catheterization, and cardiac valve transplants.

Risk Factors

Within TB-infected population, risk factors for miliary disease include HIV/AIDS, extremes of age, iatrogenic immunosuppression (i.e., organ transplant recipients, chronic corticosteroid use, TNF inhibitors for autoimmune disease), diabetes mellitus (DM), pregnancy, chronic renal failure, protein malnutrition, alcohol abuse, and immigration from high-prevalence regions.

General Prevention

• Bacillus Calmette-Guérin (BCG) vaccine
  • 78% effective at preventing severe meningeal and miliary TB in children
  • No increased BCG efficacy with a second dose
• Treatment of latent TB infection, usually with isoniazid (INH) (see “Tuberculosis, Latent (LTBI)”)

Commonly Associated Conditions

HIV/AIDS, malignancy, pregnancy, malnutrition