With the resurgence of tuberculosis, a miliary pattern of pulmonary involvement is seen on chest radiographs with increasing frequency. As miliary tuberculosis represents a potentially lethal entity that generally responds to therapy, the radiologist must recognize this pattern and suggest its possible presence. This article addresses its pathogenesis, classic roentgenographic appearance, and changing epidemiology among adults, children, and immunocompromised patients.
is with the Department of Radiology, Stanford University School
of Medicine, Stanford, CA and
is with the Department of Radiology at the VA San Diego
Healthcare System and the University of California, San Diego,
Tuberculosis (Tb) has been the scourge of civilization since
before recorded history, afflicting humans and domestic animals
alike in all parts of the world. The multitude of names including
"the white plague," "consumption," and "phtisis" that has been
applied to Tb attests to its protean manifestations.
While the earliest classical descriptions of Tb can be found in
the writings of Hippocrates, it was the experiments of P.F.H.
Klencke in 1843 and of Jean Antoine Villemin in 1865 that
elucidated the contagious nature of the disease. The identification
of the tubercle bacillus by Koch in 1882 allowed for the
understanding of the pathogenesis of Tb.
Subsequent developments in public health measures, diagnosis, and
chemotherapeutic regimens led to a decline in the incidence and
prevalence of the disease in the United States from 1930 to 1984
that led many to envision a complete eradication of the disease,
much like smallpox. By 1985, however, approximately 4 years after
the outbreak of the AIDS epidemic, the secular decline of Tb
reverted for the first time in half a century.
With the resurgence of Tb since the advent of the AIDS epidemic,
a miliary pattern of pulmonary involvement is seen on chest
radiographs with increasing frequency in both immunocompromised as
well as immunocompetent patients. As miliary tuberculosis
represents a potentially lethal entity that generally demonstrates
favorable response to therapy, the radiologist must recognize this
pattern and suggest its possible presence in the appropriate
clinical setting. This article will address the pathogenesis of
miliary Tb, its classical roentgenographic appearance, and its
changing epidemiology among adults, children, and immunocompromised
Miliary tuberculosis develops as a sequela of the obligatory
hematogenous dissemination in primary infection or as a
complication of reactivation when tubercle bacilli are discharged
from a focal infection into the lymphatics or blood. Viable bacilli
disseminate to the capillary beds of multiple organs where they may
lodge and proliferate. This is most frequently a complication of
primary disease and generally occurs within 6 months of initial
While pulmonary involvement is most conspicuous, other organs
including the liver, spleen, and bone marrow may be affected.
Likewise, the origin of
dissemination may be pulmonary or extrapulmonary. Within the lungs,
the earliest changes detectable histologically include foci of
polymorphonuclear exudation within two to five alveoli.
This stage is undetectable radiographically. With time, however,
these foci develop into small nodules which may necrose. These
nodules are generally discrete and randomly distributed throughout
the lung parenchyma and along the pleura. They are generally first
detectable when they reach 1 mm in size but may enlarge with time.
It is the 2 to 3 mm stage that is most commonly seen
radiographically and for which the process is named: miliary from
the Latin miliarus--of the size of a millet seed. They are
generally uniform in size and of the same histologic age indicating
a single, common episode of dissemination.
Without treatment, these nodules may enlarge further, eventually
coalescing and giving rise to confluent opacities on the chest
radiograph as a result of diffuse alveolar damage--an appearance
often accompanied by adult respiratory distress syndrome (ARDS)
While miliary Tb has been classically associated with
progression of primary disease in childhood, the advent of
effective chemotherapy has resulted in a shift of disease
prevalence to the elderly. As a result of decreased exposure of the
population to Tb during childhood, an increased proportion of the
adult population is now at risk for primary Tb, which accounts for
approximately 24% of adult cases.
Radiographically detectable miliary pulmonary Tb affects somewhere
between 1% to 7% of all patients with Tb.
The elderly, children younger than 5 years, and immunocompromised
hosts remain at greatest risk.
Before the AIDS epidemic, nearly 90% of patients with miliary Tb
were younger than 1 year or older than 60 years. In patients with
AIDS-induced immunocompromise, however, this rule no longer holds
true. Both progressive primary infection, as well as reactivation
of prior disease, may result in miliary disease. Patients with AIDS
have a diminished T-cell response to infection and are more likely
to continue on to progressive primary Tb and/or disseminated Tb
infection in its miliary form when compared with non-HIV-infected
patients. In one study, 60% of patients with AIDS and Tb presented
with diffuse or miliary interstitial patterns on chest films.
Other predisposing factors for miliary disease include
immunocompromise owing to hematopoietic disease, corticosteroid
therapy, other immunosupressive medication, and renal failure.
The clinical presentation of patients with miliary Tb is often
insidious in nature with non-specific constitutional symptoms and
signs including fever, weakness, anorexia, fatigue, weight loss,
cough, tachycardia, tachypnea, and inanition. Less commonly,
hepatosplenomegaly, enlarged lymph nodes, and adventitious
pulmonary sounds may be detected. Choroidal tubercles, bilateral
poorly marginated white-gray patches on the order of ¾ 1 mm seen on
ophthalmoscopic examination, are infrequently detected but
represent perhaps one of the more specific signs suggesting
hematogenous dissemination of Tb.
Although insidious in onset, the development of miliary Tb is a
life-threatening event which may ultimately lead to death if not
treated in a timely fashion. Respiratory failure and/or
disseminated intravascular coagulation are usually the immediate
causes of patient death.
The classic description of millary Tb on chest radiographs is of
uniform 2 to 3 mm discrete nodules evenly distributed throughout
the lung parenchyma (figures 1 and 2). Sometimes, a slight basal
predominance may be detected, most likely reflecting a combination
of factors including a summation effect of the x-ray beam
traversing more lung tissue at the bases than apices as well as
gravity-induced increased blood flow at the bases resulting in
deposition of more Tb foci (figure 3). In 15% of cases, an
assymetric pattern may be seen.
However, the presence of 2- to 3-mm nodules represents a point
along a continuum of features. Initially after lymphohematogenous
dissemination, the chest radiograph may be normal for approximately
2 to 6 weeks before the nodules attain a detectable size.
This is an important concept and dictates that a normal chest
radiograph in the setting of suspected disease must be closely
followed up with an HRCT (figure 4). Empiric treatment and
isolation should not be delayed if active tuberculosis is
clinically suspected. Berger and Samortin
reported that the initial chest radiograph was normal in 12 of 14
cases of miliary Tb. Up to 10% of patients who succumb to miliary
Tb have no abnormal findings on chest radiographs. When they first
become detectable, nodules may measure only 1 mm and may best be
seen through the intercostal spaces and superimposed on the cardiac
silhouette in the lateral projection. With time, they may reach
sizes of >= 5 mm or form areas of confluent opacity (figure
The differential diagnosis of a disseminated miliary pattern on
chest radiograph is extensive. According to Felson,
more than 80 conditions can incite such a pattern. The more common
of these include other infections such as the disseminated mycoses,
viral pneumonias, inhalational diseases such as silicosis and
extrinsic allergic alveolitis, metastatic disease (particularly
thyroid carcinoma), and bronchioloalveolar carcinoma.
The presence of lymph-node enlargement is commonly associated
with miliary pulmonary Tb in children (95% incidence) but less so
in adults (12%)
(figure 3). Similarly, other evidence of primary Tb, including
focal parenchymal consolidation that may represent the source of
dissemination, has been shown to be a more frequent finding in
children (42%) than in adults (12%) (figure 6).
Reed and coworkers
have also shown that, in adults, evidence consistent with prior
tuberculous infection (such as areas of cavitation, a calcified
parenchymal granuloma, and/or calcified hilar and mediastinal lymph
nodes [Ghon-Ranke complex]) are relatively frequent findings (31%).
However, such findings are rarely seen in young children. Other
findings, such as pleural effusion, were uncommonly associated with
miliary Tb in both adults (19%) and children (11%). Concomitant
pneumothorax or pneumomediastinum are rarer still. Miliary
calcifications are virtually never seen, instead indicating
infection with Histoplasma capsulatum.
HIV-infected patients present yet a different scenario. As in
children, lymph-node enlargement is more common (43%) than in
non-HIV infected individuals (13%).
If a patient was infected with Tb before acquiring the HIV virus or
while their CD4 count was >200, findings resembling typical
post-primary infection may be seen. In HIV-infected patients, a
major differential consideration for a reticulonodular pattern on
chest radiograph is Pneumocystis carinii infection which may mimic
early miliary Tb. Similarly, cytomegalovirus pneumonitis,
Mycobacterium avium complex, and lymphocytic interstitial
pneumonitis can also produce a miliary pattern.
With proper treatment of miliary Tb, radiographic clearing over
4 to 6 weeks is the norm. While the time to normalization of the
chest radiograph is highly variable and depends on many factors,
including the age of the patient and the severity of disease at
time of initiation of treatment, complete clearing is generally
seen by 16 weeks and often after just 4 to 6 weeks.
Younger patients usually recover more rapidly than older patients.
Just as Tb has been assigned many names throughout time, its
radiologic manifestations are legion. Miliary Tb is one subset of
all forms of tuberculous infection which is often readily
identifiable on plain chest radiograph. In consideration of its
potential for morbidity and mortality and its equally favorable
response to proper timely therapy, it is essential that the
radiologist is familiar with the appearance of miliary Tb and
suggests the possibility in the proper clinical setting.
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