Professional Documents
Culture Documents
Tuberculous Pleural Effusions
Tuberculous Pleural Effusions
DavidM.
Epstein,
Steven
Pleural
M.D.,
M. Albel&i,
a number
While
changing
F.C.C.P.;
M.D.;
and
and
mal tuberculosis,
M.D.
have
documented
the
spectrum
little
M.D.;
T Miller,
radiographic
relatively
R. Kline,
Lewis
Wallace
reports
of recent
clinical
Effusions*
attention
of parenchy-
has been
paid
to
of 26 adult
We found
disease
of older
percent
(5/26)
tivation)
patients
with
that pleural
adults
(median
age,
disease.
This
shift
tuberculous
tuberculosis
56 years)
in
age
led
pleural
a
and that
19
(reac-
to problems
in
diagnosis,
since many of these older patients had underlying
or coexisting
disease
that could have caused
a pleural
effusion.
Both specimens
leural
tuberculosis
cause
of exudative
of pleural
remains
an
pleural
important
for identifying
cases
effusions
are thought
to be small
have high
protein
levels
(above
clinical
chymal
attention
tuberculosis
has been
pleural
tuberculosis.
with
the
with
evidence
large
and
or moderate
5 g/dl) and
in size,
glucose
of paren-
in this country,337
relatively
little
paid to changes
in the patterns
of
We have
number
recently
of older
of preexisting
been
patients,
who
developed
tuberculous
effusions.
The purpose
report
is to systematically
review
our recent
ence
with
patients
with
tuberculous
effusions,
special
emphasis
on the following
the age distribution
of pleural
many
effusions
could
be
(reactivation)
were
exudates,
fluid
that
questions:
tuberculosis?
attributed
pleural
identified
over
Hospital
Veterans
From
the
Department
of this
experiwith
(1) What is
(2) How
to
tuberculosis?
of
Radiology
and
the
Division
of
diovascular
and Pulmonary
Medicine,
University
of Pennsylvania
School
of Medicine
and Hospital
of the University
of Pennsylvania,
Philadelphia.
Manuscript
received
May 16; revision
accepted
July 25.
Reprint
requests:
Dr Epstein,
Hospital,
University
ofPennsylvan,a,
3400
Spruce
Street,
Philadelphia
less
had glucose
than
30
levels
mg/dl.
in
Pleural
diagnostic
consideration
in
exudative
pleural
effusions.
of all cultures
positive
lomas,
and
19104
106
Car-
seven
of pleural
a review
least
one
of
(2) positive
fluid;
(3) caseating
granuloma
with
culosis,
purified
protein
pleural
effusion
although
who
divided
then
to the
met
following
fbllows:
mal
tuberculosis;
mal
disease.
The
(1) a history
diagnosis
are
not
All
were
disease,
fluid,
clinical
of
these
criteria:
The
criteria
one
and
(3) hilar
criteria
included
reviewed
PPD
method
with
status,
showing
PPD
pleural
more
effusion,
Three
primary
subsequent
chest
specilic
biochemical
of diagnosis,
(2)
according
were
test;
as
(2) chest
of parenchy-
or without
than
and
tuberculosis.
as having
pleural
disease
(reactivation)
test
had
tuberculosis
PPD
with
an
tuber-
no evidence
adenopathy
with
disease
primary
We
pleural
pleural
positive
for postprimary
in the
available
year
(PPD)
probably
for
exudative
biopsy.
or a positive
for
postprimary
or
pleural
of sputum
an
alone
for
(1)
from
either
evidence
of a newly
within
bacilli
in a pleural
criteria
met
fluid
(4) culture
patients
and
study
pleural
of tuberculin
previous
of pulmonary
of the
granupleural
tuberculosis:
from
with
derivative
primary
classified
pleural
in this
pleural
biopsy;
as sufficient
the
for
granulomas
into
of
that
years,
indicating
for acid-fast
pleural
of a positive
development
the
biopsy
last seven
patients
for
granulomas
(1) documentation
roentgenogram
of the
in pleural
most
were
records
tuberculosis
noncaseating
tuberculosis.
Patients
from
in the
tuberculosis
or noncaseating
accept
from
the Philadelphia
identified
by (1) a
records
smear
Mycobacteriuns
effusion
of pleural
1985)
specimens
criteria
for M ycobacterium
specimen;
exudative
each
following
biopsy
for
and
medical
charts,
culture
not
fluid
to
and
were
of pathology
positive
positive
diagnosis
(1978
at discharge.
of the
of the
years
tuberculosis
review
as a diagnosis
From
a definite
of Pennsylvania
Hospital.
Patients
search
(3)
tuberculosis
at
with
past
for M ycobacterium
(2) a computerized
METHODS
AND
patients
the
of the University
Administration
review
were
test
have
26
tuberculosis
definitively
*
and four
were
tuberculosis
is an important
adult or elderly
patients with
did
primary
vs
(3) How was
the diagnosis
of pleural
tuberculosis
successfully
made?
(4) Were
the traditional
concepts
about
pleural
fluid findings
valid in our patients?
postprimary
the effusions
pleural
impressed
commonly
tuberculosis,
of
of tuberculin.
Lymphocytosis
of the
not a uniform
finding;
only 62 percent
of
the
We
The
spectrum
Examination
our patients
had greater
than 50 percent
lymphocytes
on
their initial examinations
of pleural
fluid, and four patients
had greater
than 90 percent
polymorphonuclear
cells. All of
Traditionally,
tuberculosis.3
radiographic
the diagnosis.
All patients
who were not anergic
reactions
to first-strength
purified
MATERIALS
concentrations
greater
than 60 mg/mI,
and be almost
uniformly
lymphocytic
in nature.4
While
a number
of recent
reports
have emphasized
a
changing
derivative
fluid was
treatable
effusions.2
of primary
in establishing
biopsy
pleural
tuberculosis
has been
considered
a manifestation of primary
tuberculosis
seen largely
in children
and has, in fact, been used by some authors
as a criterion
useful
has become
due to postprimary
were
parenchydisease
one
prior
year
were
prior
to
treatment
patients
or
could
or postprimary
not
disease
be
and
analysis.
roentgenograms
and
attention
to
symptoms,
and
cellular
analysis
additional
radiographic
Tuberculous
Pleural
medical
records
underlying
of the
pleural
findings,
and
course.
Effusions
(Epstein
eta!)
Table
1-Clinical
Data
Total
23
18
5
58
Cough
11
14
LDH,
IU
Fever
11
16
WBCs
per
12
Polymorphonuclear
6
5
3
3
leukocytes,
Lymphocytes,
11
of patients
Median
age,
yr
Dyspnea
pain
Chest
Weight
loss
Positive
PPD
Negative
test
PPD
test
Anergic
PPD
4
disease
8
18
with
who
were
a median
age
had a pleural
As
culosis.
symptoms
in
18 patients
II
were
patients
matic.
had
lung,
fever
each.
Fifteen
patients
of the
in
Table
1,
and
cough,
Only
one
patients
and
three
the
most
which
had
had
less
frequent
patients
had carcinoma
and one patient
had
and biopsy.
Invariably,
the results
from biopsy
available
prior
to growth
of the culture,
which
six weeks.
The presence
of granulomas
alone
in
fluid
became
Table
2-Method
available.
was
from
The
of Diagnosis
Primary
Data
No.
Tuberculosis
of patients
Pleural
Positive
Positive
of Pleural
missed
Positive
had
fluid.
2,300
(2,300-8,050)
40
(2-97)
31
(5-32)
65
(3-97)
69
(68-84)
numbers
ered
to have
pleural
findings
primary
Total
23
fluid
progressive
year.
One
of
with
therapy,
these
with
Table
4-Chest
Roentgenogram
Data
of patients
of
Tuberculosis
Total
18
23
11
15
Left
Bilateral
..
Small
Medium
11
Large
Left
...
Bilateral
Same
...
...
disease
.
1
side
Opposite
as effusion
side
from
1
effusion
1
1
Adenopathy
CHEST
initial
effusion
Right
Only
Postprimary
4.
disease
was consid-
Tuberculosis
in Table
Primary
of
Tuberculosis
smear
level
patients
had
a recrudescence
in Pleural
Parenchymal
glucose
effusion
at three
months.
She then
had subsequent
resolution
of her pleural
effusion.
One patient
who was
not treated
showed
no change
in the pleural
effusion
at
of these
patients
tuberculosis.
13
or
four
Three
hilar
adenopathy
with
a
follow-up
was available
showed
improvement
to
or without
treatment,
had
50 percent
parenchymal
This patient
never
are presented
one patient
had ipsilateral
pleural
effusion.
Radiographic
in 12 patients.
Ten patients
complete
resolution,
with
within
one
improvement
had
leukocytes;
90 percent.
Right
culture
patients
of 16 patients
smear
are
analysis
of the pleural
fluid
and is summarized
in Table
10
parentheses
positive
of these
culture
culture
within
a subsequent
Four
and cellular
in 16 patients
radiographic
Pleural
Postprimary
Tuberculosis
18
(272-2.978)
(200-198,000)
a severely
depressed
than 30 mg/dl.
No.
Tuberculosis
culture
of sputum
who
in
fluid
Positive
Positive
was
biopsy
Granulomas
Pleural
sufficient
evidence
for
the biopsy
or pleural
diagnosis
1,491
polymorphonuclear
had greater
than
The
identified
medical
problems
inheart
failure,
rheumatoid
arthritis,
renal transplantation,
asthma,
drug
the specimen
from biopsy
treatment
until
cultures
(42-106)
(22-5,600)
abuse,
and gastric
surgery
for ulcer disease.
The diagnosis
was made
equally
by findings
in the
pleural
fluid and pleural
biopsy
(eight
each) (Table 2).
Two patients
had positive
results
from both the pleural
fluid
were
takes
(4.1-8.4)
104
values;
(44 percent)
greater
patients
were observed
was asymptodisease;
five
coexisting
median
the pleural
3. Seven
women)
25 to 82 years)
primary
tuber-
patient
alcoholism,
three
colon,
or bladder,
lymphoma.
Other
cluded
congestive
diabetes
mellitus,
are
Biochemical
was available
of 54 years (range,
effusion
due
to
shown
percent
5.8
(0-150)
a pleural
biopsy.
The
other
patient
had a negative
pleural
biopsy.
The PPD
reaction
was positive
in all
patients
who were not anergic.
(15 men
3,800
percent
patients
from
Tuberculosis
There
cu mm
data
five
RESULTS
Primary
527
(2.2-6.8)
ranges.
Other
62
Tuberculosis
15
disease
4.5
mg/dl
*Table
Postprimary
Tuberculosis
g/dl
Glucose,
Alcoholism
Malignant
Protein,
test unavaIlable
Coexisting
Fluids
Primary
Tuberculosis
Tuberculosis
54
No.
of Pleural
3-Analysis
Postprimary
Primary
Data
Table
Data
I 91/1/
...
. .
...
.
JANUARY.
1987
1
1
1
107
one year,
and one
showed
an increase
Postprimary
There
mented
patient
who also
in pleural
effusion.
was
not
treated
five
Tuberculosis
were
pleural
years
pleural
five patients
(19 percent)
with
effusion
due
to postprimary
docutuber-
ing numbers
without
prior
prevalence
prior treatment
with artificial
pneumothorax
culosis,
and the other three had a positive
under
pleural
one
year
effusion.
One
prior
to
of these
the
development
patients
of
of diagnosis
is summarized
in Table
The
was
in one
who
positive
culture
of pleural
Biochemical
able in
counts
all cell
nance.
than
missed
analysis
fluid
of the
patient
and
negative
pleural
2.
had
was
avail-
four patients
and is presented
in Table 3. Cell
were available
in three
of the fbur patients,
and
counts
revealed
a strong
lymphocytic
predomiNone of the effusions
had a glucose
level of less
30 mg/dl.
The
radiographic
Interestingly,
disease
had
findings
are
one patient
with
his pleural
effusion
listed
unilateral
on the
in
Table
4.
parenchymal
opposite
side.
Three
of the five patients
showed
improvement
to
complete
resolution
of the pleural
effusion
within
one
year. One patient
had no change
at four months
and
was lost to follow-up.
The last patient
showed
residual
loculated
pleural
effusion
at two
This patient
was the only one
antituberculosis
years
who
after diagnosis.
did not receive
chemotherapy.
DIScUSsIoN
When
a tuberculous
absence
of radiologically
effusion
apparent
occurs
in the
tuberculosis,
it is
to be the sequel
to a primary
six months
previously;
however,
effusion
may occur at any stage of
active infection
and may be seen with both primary
and
postprimary
disease.
Tuberculous
pleural
effusion
is
thought
to result
from rupture
of a subpleural
caseous
focus in the lung into the pleural
space.24
The fluid is
generally
a serous
exudate
but may be serosanguineous and usually
contains
few tubercle
bacilli.
It accumulates
most
tuberculoproteins.
sion
may
probably
be the
as a hypersensitivity
Rarely,
tuberculous
result
or contamination
by
Although
tuberculous
disease,
active
65 percent
pulmonary
or
of hematogenous
adjacent
pleurisy
or
poor
culosis
in the
living
conditions,
infected
initially
of the untreated
extrapulmonary
reaction
to
pleural
effudissemination
lymph
nodes.
is a self-limited
patients
disease
develop
within
108
in an
working
in
elderly
crowded
individ-
environments
or
Primary
be related
to these
increased
debilitating
adults
susceptible
conditions.
may
with
in young
to healthy
tubersame
poor
susceptibility
disease
and
caused
immunosuppres-
Several
authors
have noted
an increased
inciof primary
tuberculosis
in older
patients
and
attributed
some
of the unusual
radiographic
to actually
represent
aspects
of primary
adult
population.6
disease
Indeed,
this concept;
the
primary
tuberculous
median
age
pleurisy
percent)
The
culosis
of 18 patients
have
cause
cancer,
common
underlying
a pleural
more
usual
of our patients
was 54, with
than
60 years
six
or coexisting
can
tuberolder
disease
which
heart
failure,
Congestive
and
pulmonary
in the elderly
that
with
(33
of age.
incidence
of pleural
in diagnosis.
Many
effusion.
pneumonia,
diseases
the
seen
in the unsuspected
our observations
support
greater
patients
may
particularly
are entering
adulthood
exposure.9#{176} The increased
socioeconomic
embolism
are
cause pleural
effusions.
Interestingly,
five of our patients
older
than
55 years with primary
tuberculosis
had such coexisting
diseases
that actually
obscured
the correct
diagnosis.
These
patients
included
two with hepatic
disease
and
ascites,
two with congestive
heart failure
(one of whom
also had rheumatoid
arthritis),
and one with histiocytic
lymphoma.
pleural
usually
considered
infection
three
to
tuberculous
pleural
living
sion.9
dence
have
and
tuberculosis
related
manifestations
biopsy.
fluid
of individuals
tuberculous
to be
by chronic
with isoniazid.
The method
diagnosis
uals
adult,
of pulmonary
is thought
in an
considisolated
patient,
is often thought
to be due to a disease
other than tuberculosis;
however,
as the overall
of tuberculosis
has been
declining,
increas-
coexisting
disease,
including
gastric
surgery
for peptic
ulcer
disease,
chronic
lymphocytic
leukemia,
and
chronic
alcoholism.
Two of the five patients
had had
than
primary
tuberculosis
has been
of childhood.
Therefore,
an
effusion
elderly
process
incidence
culosis
(four men and one woman).
The median
age was
58 years
(range,
51 to 63 years).
All five patients
were
symptomatic
(Table
1). Three
of the five patients
had
greater
of its occurrence.28
Traditionally,
ered
a disease
None
had
their
diagnosis
were
lost to follow-up
without
antituberculosis
chemotherapy.
was subsequently
established
recognized
and
receiving
appropriate
The correct
diagnosis
from
pleural
fluid six weeks
later.
In our series an almost
equal
a positive
number
culture
of patients
of
had
the diagnosis
of pleural
tuberculosis
established
from
smear
and culture
of the pleural
fluid as from pleural
biopsy
including
microscopy
and culture.
Three
patients had a positive
pleural
biopsy
and pleural
fluid. In
most series
the diagnostic
yield from culture
of pleural
fluid is less than 30 percent,
although
Sible?
reported
positive
cultures
in 70 percent
positive
cultures
of pleural
biopsy
was
performed
fluid
of his
in 16 patients,
positive
diagnosis
established
or culture
(88 percent).
These
cases.24
with either
results
are
Pleural
Pleural
14 of whom
to other
series
in the literature.2
Although
accept
the isolated
finding
of noncaseating
Tuberculous
We had
in 40 percent.
Effusions
had
granulomas
comparable
we did not
granulomas
(Epstein eta!)
as diagnostic
this a positive
absent
of pleural
tuberculosis,
we did consider
result
when
there
was other
corroborat-
or scarce
document
ing evidence
of tuberculosis
including
a positive
culture,
positive
sputum,
or positive
pleural
fluid.
In
the six patients
where
the diagnosis
of tuberculosis
was
diagnosis
presenting
missed,
their
all had
emphasizes
results
of
of sputum
Cultures
the
positive
cultures
the
importance
cultures,
even
were
patients
with
The
analysis
fluid.
in only
20 percent
parenchymal
fluid
from
(12/19)
percent
pleural
patients
with
our
patients
had
on their
particularly
was
primary
of effusions
only
62
more
tuberculosis,
where
seven
percent)
of 16 had a polymorphonuclear
predominance.
Although
it is well known
specimens
of pleural
from
predominantly
we were
impressed
granulocytic
Unfortunately,
than
50
initial
examination
of
impressive
in those
(43
leukocytic
that serial
predominance
we have
on the initial
no information
examination.
on serial
As
might
be
expected,
either
criteria,
by
but
all
pleural
effusions
age,
of the
correct
coexisting
One
diagnoses
of these
other
pyema
terium
greater
patients,
pleural
patients
rheumatoid
four patients
with
had
arthritis,
may have
their
pleural
rheumatoid
a bronchopleural
fistula
that was culture
negative
tuberculosis.
The pleural
panel,
and
We
pleural
with
presumed
emexcept
for Mycobacfluid glucose
level was
than 50 mg/dl
in 13 (65 percent)
of 20 of our
which
is considered
typical
of tuberculous
effusions.
Mesothelial
cells
are said
to be
primary
hilar
finding
ade-
in adults
it
should
can
Furthermore,
effusion
suggest
be
occur
Many
in
of
any
to
rule
A,
Ruffle
that
adult
out
a PPD
pleural
an
fluid
of pleural
with anergy
test
and
with
the
pleural
indicator
culture,
biopsy
undiagnosed
possibility
be
pleural
of pleural
tuber-
culosis.
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1Hirsch
effusion:
P, Nebut
laboratory
2 Light
RW.
Pleural
tests
Tuberculous
diseases.
3 Khan
M,
M,
cases.
pleural
Kovnat
D,
Lea
Bachus
and
culosis
in the
adult.
JAMA
HW,
Mejia
E.
1977;
RW,
ed.
1983:119-25
J, Snider
M, Brody
spectrum
Pleural
34:106-12
Light
Febiger,
B, Whitcomb
roeotgenographic
1979;
In:
and
J.
Chretien
Thorax
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Philadelphia:
Clinical
J,
Bignon
in 300
of pulmonary
C.
tuber-
62:31-8
Tuberculous
pleurisy.
Chest
1973;
63:
88-92
5 Miller
W/T,
MacGregor
radiographic
ogy
Tuberculosis:
Am
PL,
Sostman
HD,
JD,
et al. Adult-onset
1983;
frequency
Roentgenol
Curtis
1978;
AM,
Ravin
pulmonary
of unusual
130:867-75
CE,
JIT,
Chen
tuberculosis.
Radiol-
148:357-62
FP,
findings
RR.
findings.
Park
in adult
SK,
Awe
RJ, Rivera
pulmonary
M.
Unusual
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Am
radiographic
J Roentgenol
1980;
134:1015-18
8 Sibley
JC.
9 Woodring
liams
Stead
Tuberc
IC.
tuberculosis,
WW,
primary
in
Med
CR,
the
1968;
of tuberculous
Fried
AM,
the radiographic
Roentgenol
Schlueter
tuberculosis
pathogenesis
pleurisy
with
62:314-23
H,
Update:
Am
Kerby
of
reinfection
1950;
MacVandiviere
Melvin
spectrum
Intern
Rev
JH,
TD,
monary
10
of 200 cases
A study
Am
1986;
Jordahl
DP,
in
adults:
of chronic
Dillon
ML,
features
Wilof pul-
146:497-506
CW.
The
confusion
tuberculosis.
clinical
with
Ann
68:731-45
CHEST
have
effusion
tuberculosis.
a reliable
fluid
in
effusion.
the
without
is not
performed
tuberculosis.
arthritis
will
effusions
diagnosis.
tuberculosis.
7 Hadlock
neoplasms,
Two of our
patients
pleural
that tuberculous
with
reactivation
lymphocytosis
patients
of Berger
such a low glucose
malignant
pyema.
of these
patients
Despite
these
patients
are debilitated
or immunosuppressed.
Coexisting
underlying
disease
which
can commonly
produce
pleural
effi.isions
may hamper
establishment
Godwin
In their
experience,
seen in patients
with
not
important
or elderly
effusion.
6 Choyke
Mejia.4
was only
is an
in adult
pleural
nopathy
may
with
primary
greater
than 5 g of protein.
Furthermore,
four patients
had a pleural
fluid glucose
level of less than 30 mg/dl.
This very low glucose
level was not seen in any of the
and
level
most
4 Berger
had
We could
tuberculosis
and
were
protein
or lactic
dehydrogenase
only 10 (50 percent)
of 20
pleural
to be considered
with an exudative
tuberculosis,
changes.
exudative
(LDH)
effusion.2
observation.
summary,
remembered
association
of interesting
findings.
While
have found
that the great majorhad highly
lymphocytic
effusions
of
lymphocytes
fluid. This
of
tuberculosis.
our
patients
(Berger
and Mejia4 report
only 88 percent
had
more
than
50 percent
lymphocytes),
percent
This
careful
follow-up
of
a negative
biopsy.
useful
coexisting
of pleural
revealed
a number
previous
investigators
ity of their
patients
of pleural
of
with
In
in tuberculous
this
I 91 / 1 / JANUARY,
1987
109