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Miliary Tuberculosis in Critical Care
Helmut Albrecht
Division of Infectious Diseases, University of South Carolina, Columbia, South Carolina, U.S.A.INTRODUCTION
In the developing world tuberculosis (TB) continues to be a major cause of morbidity and
mortality. In industrialized countries TB has essentially become a public health issue. While
diagnostic and therapeutic issues remain, disease in most cases is not threatening enough to
warrant admission to the critical care unit. Miliary TB, however, is often rapidly fatal,
providing a diagnostic and therapeutic challenge to even the most skilled intensivists.
The term miliary was first introduced by John Jacobus Manget in 1700, when he likened the
multiple small white nodules scattered over the surface of the lungs of affected patients to millet
seeds (Fig. 1). While miliary TB was initially an anatomic and later a radiologic term, it now
denotes all forms of progressive, widely disseminated TB. Synonyms include hematogenous TB,
generalized TB, disseminated TB, septic TB, and Landouzy sepsis. As a disease entity, miliary TB
is not due to infection with particularly virulent pathogens but is generally precipitated by host
issues. Affected patients are typically predisposed by a weakened immune system, most notably
defects in cellular immunity, resulting in the unchecked lymphohematogenous dissemination of
Mycobacterium tuberculosis. The development and widespread use of more potent immunosup-
pressive agents, as well as the emergence of HIV/AIDS in recent years, have resulted in an
increased proportion of TB cases presenting with disseminated disease.
EPIDEMIOLOGY
Estimates for incidence and prevalence rates are often based on convenience samples, as
population-based data are not available. Autopsy- and hospital-based case series, however,
generally suffer from selection and allocation bias.
A large Boston City Hospital series collected in the pre-antibiotic era found that 20% of
all patients with TB had evidence of disseminated infection at autopsy (1). In the 1970s, another
study from Boston City Hospital found that only 0.4% of patients with TB had a miliary disease
pattern (2). Since the advent of the HIV epidemic, most case series have reported that miliary
TB accounted for approximately 1% to 2% of all cases of TB and 8% of all cases of
extrapulmonary TB (3). Rates as high as 38%, however, have been reported in case series from
hospitals with high HIV case rates (4). In the 2006 surveillance report from the Centers for
Disease Control and Prevention (CDC), 1.8% of all cases of TB were classified as miliary (5). In
general, the incidence of miliary TB in a given institution is going to depend on the rate of TB
in the population served and the proportion of patients with increased risk for dissemination.
PATHOPHYSIOLOGY
Predisposing Conditions
Age and predisposing medical conditions (Table 1) are the most significant risk factors for the
development of miliary TB. Miliary TB, however, should never be excluded from the
differential diagnosis merely because a patient has no underlying medical illness. In all large
case series, a significant percentage of patients have no demonstrable high-risk condition for
dissemination. Race, ethnicity, and gender can affect TB demographics, but appear to have
little effect on the proportion of patients presenting with miliary TB.
Age
In the pre-antibiotic era, miliary TB was predominantly a disease of infants, children, and
adolescents (1,3). Due to the delayed development of the cellular immune system, children
under the age of three years are at highest risk for progressive disease (6). While TB nowadays