Tuberculous

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

changes in the patterns

of pleural
tuberculosis.
We therefore reviewed
the clinical,
laboratory,
and radiographic
characteristics
effusions.

of 26 adult

We found

disease

of older

percent

(5/26)

tivation)

patients

with

that pleural

adults

(median

age,

of the cases were

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

fluid and 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

Downloaded From: http://journal.publications.chestnet.org/ on 04/10/2014

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

sputum was less helpful.

had positive
cutaneous
protein
pleural

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

Downloaded From: http://journal.publications.chestnet.org/ on 04/10/2014

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)

The one patient

with
bilateral
had bilateral
pleural
effusions.

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

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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

shift in age in the

can lead to problems

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

was also treated

with isoniazid.
The method
diagnosis

uals

adult,

of pulmonary

is thought

for tuberPPD test for

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

fluid may reveal

a progression
polymorphonuclear
leukocytes,
by the number
of patients
with

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

and emhad such

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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2 Light

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pleural

Kovnat

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SK,

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RJ, Rivera

pulmonary

M.

Unusual

tuberculosis.

Am

radiographic

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134:1015-18
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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

Downloaded From: http://journal.publications.chestnet.org/ on 04/10/2014

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.

be the sole radiographic

tuberculosis;
however,

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