the organ system being sampled, the yield was generally higher. Specific target amplification
can be performed on fresh and even processed samples. While this appears highly promising,
data for its use in miliary TB are to be generated.
Other Tests
If present, choroidal tubercles are pathognomonic of miliary TB. A dilated ophthalmoscopic
examination may offer a valuable clue to the diagnosis of miliary TB. Positron emission
tomographic (PET) can help distinguish infection from malignant lesions but it should be
noted that 1 to 3 mm lesions may be too small to generate a positive signal. Pulmonary
function tests often show abnormalities, but no characteristic pattern have been identified that
would increase the diagnostic yield of other studies.
Differential Diagnosis
The differential diagnosis of febrile illnesses with miliary chest X-Ray infiltrates is broad and
includes infectious and noninfectious entities. Infectious diseases include other nontubercu-
lous mycobacterial infections. Fungal infection mostly due to endemic fungi (histoplasmosis,
coccidioidomycosis, blastomycosis, paracoccidioidomycosis) can mimic miliary TB. Appro-
priate exposure and travel history may provide important clues. Bacterial infections described
in the literature include legionella infection, nocardiosis, pyogenic bacteria (Staphylococcus
aureus,H. influenzae), psittacosis, tularemia, bartonellosis, brucellosis, and melioidosis. Viral
infections (varicella, cytomegalovirus, influenza, measles) and parasitic infections (toxoplas-
mosis, strongyloidiasis, schistosomiasis) can produce similar patterns.
Neoplastic diseases, including lymphoma, lymphangitic spread of various cancers, or
mesothelioma, are in the differential diagnosis as are other diseases including sarcoidosis,
amyloidosis, hypersensitivity pneumonitis, alveolar hemorrhage, storage disorders, pneumo-
conioses, and foreign-body-induced vasculitis related to injection drug use.
TREATMENT
While many patients control TB even without therapy, miliary TB is uniformly fatal if not
treated. Even when treated, the mortality related to miliary TB remains about 10% to 20% in
children and 20% to 30% in adults. Delay in the diagnosis or initiation of treatment contributes
to the high mortality. Currently, there are no randomized trials evaluating the efficacy of
different regimens for the treatment of miliary TB.
Antituberculous Chemotherapy
The American Thoracic Society, CDC, and the Infectious Diseases Society of America have
issued joint guidelines for the treatment of TB, which address treatment of miliary TB (58).
Based on a number of clinical trials, the guidelines recommend four basic regimens for treating
patients with TB caused by drug-susceptible organisms. These regimens are applicable to most
patients with TB, although modifications are made for specific populations. Each regimen has
an initial phase of two months followed by a choice of several options for the continuation
phase of either four or seven months. The choice of treatment in the initial phase is empiric as
susceptibility data are usually not available or only available at the end of the initial phase of
treatment. Susceptibility data should be available at the beginning of the continuation phase
and should be used to direct therapy if drug-resistance is identified.
The initial drug regimen is based on knowledge of the likely drug susceptibility, and four
drugs are used in the initial phase of treatment when the total duration of treatment is six
months. The treatment regimen for most adults with previously untreated TB consists of a two-
month initial phase of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol
(EMB). In the continuation phase treatment is given for either four or seven months and
consists, in most cases, of INH and RIF alone. Most patients will be treated with the four-
month continuation therapy for a total duration of treatment of six months.
The recommendations for disseminated TB are essentially the same as for pulmonary TB.
Since extrapulmonary TB is less common than pulmonary TB, these recommendations are based
upon retrospective review of a relatively small number of patients with extrapulmonary TB.
Miliary Tuberculosis in Critical Care 427