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Corticosteroids
in the Treatment
Tuberculous
Pleurisy*
A Double-blind,
Study
Placebo-controlled,
Cheng-Huei
Lee, M.D., F.C.C.P;
Wen-Jye
Ray-Shee
Lan, M.D., F.C.C.P;
Ying-Huang
and
Ying-Chieh
Chiang,
M.D.,
Randomized
Wang, M.D.,
Tsai, M.D.,
double-blind,
randomized
study of the role
of corticosteroids
in the treatment
of tuberculous
pleurisy
was performed
in 40 patients.
All patients
received
adequate
antituberculosis
chemotherapy
(isoniazid,
300
mg/
day; rifampin,
450
mg/day;
ethambutol,
20 mg/kg/day)
for
more than nine months.
They were randomly
assigned
to
take prednisolone
0.75 mg/kg/day
orally or placebo
for the
initial treatment,
which was tapered
gradually
for the next
two to three
months.
Twenty-one
were treated
with steroids
and 19 were given a placebo.
The two groups were identical
with regard
to age, sex, duration
from onset of symptoms
to diagnosis,
and initial
amount
of pleural
effusion.
The
mean duration
from symptoms
(fever, chest pain, dyspnea)
uberculous
pleurisy
bined
regimen
therapy
since
the
of the
published
has
been
treated
with
are
such combination
therapy
improvement
and absorption
ever, its routine
application
in general
‘
Most
that
most
1960s
when
the treatment
of tuberculosis
had not been fully
developed.
With
the
modern
multi-drug
regimen,
extrapulmonary
as well as pulmonary
tuberculosis
can
determine
the
of tuberculous
benefits
to
to
role of corticosteroids
pleurisy.
Whether
modern
patients
is unknown.
tions,
we conducted
trolled,
randomized
in: 1) relief
of
pleural
effusion,
No
our
On
this
study
therapy
in
to
these
the basis
of these
observadouble-blind,
placebo-conto see the effects
of steroids
clinical
symptoms,
and 3) prevention
without
2) absorption
of
of pleural
adhe-
sions.
Hospital,
Manuscript
Department
Taipei,
ofChest
Taiwan,
Republic
Medicine,
Chang
Gung
Memorial
of China.
received
April 25; accepted
Reprint
requests:
Dr Lee, 199 Tim Hwa
BOG
10591
Road,
Taipei,
1256
Downloaded From: http://journal.publications.chestnet.org/ on 09/09/2014
elsewhere
had
and
were
had
who
admitted
the
onset
denied
for
of pleural
a past
further
history
evaluation.
Taiwan
inflammation.
Patients
with
other
pulmonary
dis-
or conditions
which contraindicated
the use of corticosteroids,
like diabetes,
peptic ulcer and hypertension
were also excluded.
Alipatients
received
pleural
biopsy
and diagnostic
thoracocentesis
(less than 50 ml) on the first day ofhospitalization.
Those who were
eligible
for
the
study
prednisolone
placebo
with
were
plus
randomly
assigned
antituberculosis
antituberculosis
drugs
to
drugs
(placebo
treatment
(steroid
group).
with
group)
The
or
antituber-
culosis regimen
included
isoniazid,
300 mg/day;
rifampin
450 mg/
day; and ethambutol,
20 mg/kg/day
for the initial three months,
and
isoniazid
and rifampin
for the subsequent
six to nine
months.
Prednisolone
was
initially.
The
showed
improvement
administered
dosage
was
in an
tapered
and
oral
gradually
was
dose
once
diminished
of 0.75
mg/kg/day
chest
radiograph
two-thirds
if any
the
by
of
the following
conditions
existed: 1) the effusion was right-sided
and
the fluid level was only one intercostal
space higher than that of the
left hemidiaphragm;
2) the
effusion
was
left-sided
and
the
fluid
level
was at the same height
disappearance
of pleural
as the right hemidiaphragm;
3) complete
effusion.
Dosage of prednisolone
was then
diminished
week
day
chest
the
May 16.
North
METHODS
who
eases
the
the
AND
45 years
tuberculosis
granulomatous
Standard
*From
age
treatment
of pulmonary
either
well-controlled
knowledge,
in the treatment
corticosteroids
add
antimicrobial
effusion
under
Other etiologies
of pleural
effusion
such as congestive
heart
failure,
pneumonia,
malignancy
and others were excluded
through diagnostic testing, The diagnosis
of tuberculous
pleurisy
was confirmed
on
the basis of pleural
biopsy,
reported
as tuberculosis
or chronic
rapid
clinical
fluid. ‘ Howwith tubercu-
bus pleurisy
remains
controversial.
In addition,
reported
clinical
trials
were
performed
in the
be eradicated
more
study
has been
undertaken,
MATERIALS
All patients
agreement
causes
more
of pleural
to patients
to relief was 2.4 days in the steroid-treated
group, and 9.2
days in the placebo
group (p<O.O5).
Complete
reabsorption
of pleural
effusion
occurred
an average
of 54.5 days in the
steroid-treated
group and 123.2 days in the placebo
group
(p<O.Ol).
The development
of residual
pleural
thickening
was not influenced
by the administration
of corticosteroids.
No serious
side effects were noted during the treatment
in
either
group.
We conclude
that the administration
of
corticosteroids,
in conjunction
with antituberculosis
chemotherapy,
will resolve
the clinical
symptoms
more
quickly
and
hasten
the absorption
of pleural
effusion
in patients
with
tuberculous
pleurisy.
(Chest 1988; 94:1256-59)
a corn-
of corticosteroids-antirnicrobial
middle
half of this century.
articles
F.C.C.P;
F.C.C.P;
F.C.C.P
A prospective,
T
of
by 5 mg
chest
per
of admission
hospitalization
pleural
during
opacity
discontinued.
and
for all patients.
roentgenogram
monthly
until
posterioanterior
on
period.
the
persisted
days
4 and
After
lateral
patient
7 and
then
discharge,
out-patient
without
Corticosteroids
films
Each
follow-up
any
change
were
was
every
chest
visits.
for
in Tuberculous
taken
on
evaluated
week
films
by
during
were
Patients
more
Pleurisy
taken
whose
than
(Lee
three
et a!)
Table
1-Clinical
Characteristks
and 19 Patients
Steroids
of 21 Patients
Receiving
Receiving
Placebo
months
were
erized
amount
Treatme
Characteristic
nt Group
small
(less
one
third
effusion
than
and
one
two
of one
thirds
(n = 21)
(n = 19)
the
subjective
symptoms
were
period.
Statistical
comparisons
subjects)
12
12
9
7
18-44
18-45
28.4
28.9
Student’s
t-test,
Whitney
U test
Side
chi-square
(years)
Range
Mean
time
from
onset
20.6
15.4
Small
9
5
Moderate
9
9
Large
3
5
symptoms
Initial
amount
to diagnosis
(days)
of pleural
differences
between
effu-
the
two
groups
are
statistically
than
were
and
throughout
made
exact
with
test
the
unpaired
and
Mann-
patients
were
entered
into
this
study
from
October,
1983 to June,
1987.
During
the period,
one
patient
developed
renal
cell carcinoma
and four did
not return
for follow-up
visits.
Thus,
40 patients
were
eligible
for final analysis,
21 in the steroid
group
and
sions
The
(more
of corticosteroids
recorded
Fisher’s
(between
large
RESULTS
Forty-five
of
effects
carefully
test,
and
The
considered
moderate
hemithorax),
hemithorax).
abnormity.
was
hemithorax),
of one
or comput-
of the
presentation
two
of one
sonography
nature
at initial
third
thirds
chest
the
Placebo
Female
Mean
with
Steroid
Male
Age
evaluated
to determine
of pleural
study
Sex (No.
further
tomography
nonsignifi-
19 in the placebo
The characteristics
group.
(sex,
time
age,
cant.
mean
of the
40 randomized
from
onset
of
subjects
symptoms
to
tthY
DAY
350
14
P0.0l
13
300
12
p
11
<
oo5
250
10
9.2
9
8
7
()
‘SO
S
123.2
100
4
3
2.4
_____
2
SO
-
54.5
II,
0
.5
0
SThR()ID
GR.
(N:21)
1. The average
sions:
2.4
days
(steroid
respectively.
FIGURE
duration
group)
of disappearance
and
9.2
days
PLACEBO
STEID
CR
FIGURE
2. The duration
for an average
of 54.5
group)
respectively.
of disappearance
days (steroid
group)
CHEST
Downloaded From: http://journal.publications.chestnet.org/ on 09/09/2014
PLNE0
(P1=21)
(N=19)
of pleural
effu(placebo
group),
c.
GR
(14=19)
of clinical
symptoms
was
and 123.2 days (placebo
I 94 I 6 I DECEMBER,
1988
1257
diagnosis
and
shown
in Table
between
the
Clinical
initial
amount
1 . There
were
two
of pleural
no significant
multidrug
and
signs,
pain
and dyspnea
subsided
(range,
1 to 7) in the steroid
was
placebo
significant
statistically
old-fashioned
antituberculosis
regimen
results
of this study
demonstrate
that
groups.
symptoms
1 to 75) in the
effusion)
are
differences
an
group
including
fever,
benefits
in
average
of 2.4 days
and 9. 2 days (range,
pleural
The
effusion.
rapidity
group
(Fig 1). The
(p<O. 05).
Roentgenologic
evidence
of clearing
field,
with visualization
of the diaphragm
of
ent
of the
(15.8
21 patients
percent)
ofthe
treated
with
19 patients
(4.8
steroids
and
treated
with
rapidity
differ-
five
Study
Aspin
and
Smith
2-Studies
on
in three
Administration
demonstrated
investigators
tion
Mathur
50
49
Menons*
complained
than two
finding
effusion
of sustained
months.
in this
absorption
corticosteroids
chemotherapy,
adhesion
in
study
is
between
were
the
by concomitant
Tuberculous
66
Mathur
et al7
300
SM
1 g/d
Corticosteroids
mg/d
ACTH
20 mgIkg/d
300
SM
1 gtiw
300
SM
1 g/d
INH
200
SM
1 g/d
Damany
and
Grewal
and
Shahs*
Dixits*
25
102
Prednisone
0.5
mg/d
Prednisone
30 mg/d
mg/d
Intrapleural
mg/d
Intrapleural
et alt
40
INH:
isoniazid;
SM: streptomycin;
*Controlled
study;
tdouble-blind,
1258
Downloaded From: http://journal.publications.chestnet.org/ on 09/09/2014
acid;
RM:
125-250
hydrocortisone
mg
25 mg/d
15 mg/d
or
po
Intrapleural
hydrocortisone
125 mg or
PAS
13 g/d
triamquinolone
20 mg/d
INH
300
SM
1 g/d
INH
300
SM
1 g/d
INH
300
SM
1 g/d
EMB
PAS: p-amino-salicylic
randomized
study.
po
1 g/d
INH
study
po
SM
RM
Present
po
mgfkg/d
hydrocortisone
mg/d
Intrapleural
mg/d
Triamcinolone
mg/d
Intrapleural
hydrocortisone
rifampin;
300 mg)d
450
125-250
24 mg/d
hydrocortisone
prednisolone
Lee
or
20 mg/d
mg/kg/d
INH
INH
40 units/d
prednisone
INH300mg/d
102
added
to the
clearance
of
administration
prednisolone
Tanietal6
the
the
Pleurisy
regimen
INH
INH
26
et al
patient
even
pain for more
1
by statistical
analysis.
Data from other
usually
indicated
benefits
in the preven-
ofpleural
Anti-TB
6
et al
dyspnea
Figure
receiving
ously (Table 3).
While
the incidence
of pleural
adhesions
seems
lower in the group
receiving
steroids
than placebo
(4.8
vs
15.8
percent),
a significant
difference
was not
PAS 0.5
Paley
and
of
the pleural
fluid was much
more rapid.
Disappearance
ofpleural
effusion
was achieved
in a mean of54.5
days
and 123.2 days in the two groups,
respectively.
This is
in agreement
with
the observations
reported
previ-
ofCortkosteroids
30
et al2
One
chest
two groups.
When
updated
antimicrobial
placebo.
No. ofcases
O’Hara*
pain
in the steroid
group.
(14/21)
of the patients
The
most
striking
difference
in pleural
percent)
previous
studies
regarding
the role of
in the treatment
of tuberculous
pleuconducted
in the 1950s and 1960s with an
Table
days.
pleuritic
from
were
chest
exert
absorption
corticosteroids
were
free from complaints
within
two
days after treatment.
The same fact was also noted
by
Paley et al,3 Mathur
and colleagues,
and Tani et al.6
Conversely,
half (9/19) of the patients
in the placebo
group
suffered
from
acute
symptoms
for more
than
DISCUSSION
risy
ofreliefoffever,
still
and
the lung
and costo-
There
was no demonstrable
statistical
difference
between
the two groups
(p = 0.27).
Only
one patient
developed
transient
moon
face,
lower
limb edema
and epigastralgia
after administration ofprednisolone.
These
side effects
subsided
after
tapering
of the steroid
dosage.
Reports
corticosteroids
reflief
was well demonstrated
shows
that two thirds
group
(Fig 2). The
was significantly
between
the two groups
(p<0.01).
Pleural
adhesions
were
noted
in one
corticosteroids
symptomatic
2). The
modern
difference
phrenic
angle,
occurred
at an average
of 54.5
days
(range,
6 to 365) in the steroid-treated
group.
This was
in contrast
to an average
of 123. 2 days (range,
7 to
395) in the placebo-treated
of pleural
effusion
absorption
chemotherapy,
chest
(Table
with
po
mg
po
100 mg
or
20 mg/d
Prednisolone
0.75
mg/d
mgfkg/d
po
20 mg/kg/d
EMB:
ethambutol.
Corticosteroids
in Tubercutous
Pleurisy
(Lee
at a!)
Table
3-Outcome
ofCorticosteroid
Therapy
in Tuberculous
Pleurisy
Advantages
Study
Aspin
and
Clinical
Fluid
Pleural
improvement
absorption
adhesion
Transient
moon
+
+
+
Paleyeta1
+
+
+
+
+
+
No
+
+
+
Transient
et al
et a16
Mathur
et al
Damany
and
Grewal
and
Shah8
Dixit’
et al
Lee
side
effect
moon
a few
cases)
effect
+
+
+
No
side
+
+
+
No
side
effect
+
+
?
No
side
effect
+
+
+
+
Rebound
phenomenon(1)
moon
?: not
ofcorticosteroidst
be due to the
small
In the study
corticosteroids
ening in the
improvement
one
patient
developed
genologic
initiated.
oped
them
mentioned;
edema,
(Table 3). The disparity
number
ofpatients
of Tani
decreased
et
the
al,6 the
amount
in our
group
pleural
thickening,
improvement
Another
three
may possibly
in this study.
administration
of pleural
receiving
ceased
12 days after
in the placebo
thickening
any further
the
of
thick-
steroids,
to show
who
roent-
treatment
groups
was
devel-
within
six months.
None
of
improvement
on chest roent-
Transient
side
served
in only
edema,
mated
and
after
rebound
symptoms
developed,
corticosteroids
effects
one
epigastralgia.
tapering
phenomena
were
noted
it
is
not
are
added
altered
by
or not.
of corticosteroids
patient
the
causing
These
dose
“moon
were
face,
symptoms
were
of prednisolone.
of pleural
effusions
in this series.
and
ob“
leg
elimNo
ofpleural
adhesions
was
not influenced
of
however.
mine
the
in the
long-term
study
effect
management
face(1)
this
small
to deter-
ofsuch
combination
of tuberculous
pleurisy.
therapy
Prof
Robert
REFERENCES
J,
1 Aspin
Br
O’Hara
J Tuberc
2 Smith
H. Steroid-treated
1958;
MHD,
effusions
Pediatrics
3 Paley
Matsaniotis
with
1959;
79:307-14
Mathur
KS,
5
Menon
reference
Mais
EL,
Prasad
adrenal
JS.
effusion.
Steroid
SA,
pleural
R, Mathur
pleural
NK.
effusions.
of tuberculous
to
Gittens
oftuberculous
in tuberculous
pleural
pleural
corticosteroids.
22: 1074-87
MihalyJI
in the treatment
4
N. Treatment
particular
1958;
SS,
tuberculous
52:81-3
Lupini
Am Rev Tuberc
Intrapleural
Tubercle
therapy
B. Prednisone
effusions.
hydrocortisone
1960;
in tuberculous
41:358-62
effusion.
Tubercle
1964; 45:17-20
6 Tani
P Poppius
H,
tuberculous
pleurisy
Scand
44:303-09
1964;
7 Mathur
KS,
pleural
in the
light
JS,
Sapru
Mathur
effusion
with
local
KT
J
chemotherapy.
KS,
regilflens
tuberculous
in
Indian
Dixit
with
and
pleural
Cortisone
ofa
Med
RP
A
without
effusion.
therapy
follow-up
for exudative
study.
RP Treatment
instillation
Treatment
triamcinolone
9 Grewal
J.
Makipaja
Acta
Tuberc
of tuberculous
of hydrocortisone.
of pleural
addition
to
Assoc
1968;
Dis
effusion
usual
with
and
antituberculosis
51:391-93
comparative
study
corticosteroids
J Indian
Med
of
therapeutic
in the treatment
of
Assoc
1969; 52:514-
16
10 American
berculosis
1986;
Thoracic
Society.
infection
in adults
Treatment
and
children.
of tuberculosis
Am
Rev
and
Respir
tuDis
134:355-63
CHEST
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in
is necessary
ACKNOWLEDGMENT:
The authors
wish
to thank
F Heimberger
for his careful
review
ofthis
manuscript.
without
by
corticosteroids
Further
Chest
1965; 47:83-7
8 Damany
SJ, Shah
clinical
In conclusion,
the
results
of the present
study
suggest
that adrenal
corticosteroids
still play some role
in the treatment
of tuberculous
pleurisy.
Given
together
with
modern
antituberculosis
chemotherapy,
they exert
benefit
in the more
rapid
relief of clinical
symptoms
and
absorption
of pleural
effusion.
The
occurrence
administration
series,
genograms
after
a two-year
follow-up.
In contrast,
those patients
who did not develop
pleural
thickening
showed
a persistent,
gradual
decrease
in pleural
effusion
until resorption
was complete,
though
it may
be prolonged.
This implies
that once pleural
adhesion
or thickening
has
treatment,
whether
moon
N: no benefit.
initial two to six months,
though
no further
was noted
a year after
treatment.
The
pleural
showed
face(3)
Epigastralgia,
transient
+ : beneficial;
face
Transient
N
+
face(l)
?
(
Tani
(cases)
phenomenon(1)
phenomenon(1)
+
+
Menon5
effects
Rebound
Rebound
?
Smithetal
Mathur
O’Hara’
Side
I 94
I 6 I DECEMBER,
1988
1259