An
HIV-infected
child
with
prolonged
fever
and
eye
pain
Prepared
by...
Aurmporn
Oberdorfer,
M.D.,
PhD.
Virat
Sirisanthana,
M.D.
|
Department
of
Pediatrics,
Faculty
of
Medicine,
Chiang
Mai
University
|
Patient:
A
9-year-old
HIV-infected
girl |
Address:
Payoa
province
(Northern
Thailand) |
CC:
Pain
at
both
eyes
for
4
weeks.
Fever
for
3
weeks. |
Present
Illness:
>
|
4
weeks
PTA,
after
coming
back
from
swimming
in
a
river,
she
started
having
pain
at
her
both
eyes
(more
on
the
left
side).
The
pain
later
accompanied
with
tearing,
yellowish
discharge
and
photophobia.
The
eye
drop
medicine
from
the
local
hospital
could
not
relief
her
eye
pain.
|
>
|
3
weeks
PTA,
she
developed
moderate
grade
fever
and
mild
dry
cough.
Her
eye
pain
persisted.
She
lost
her
appetite
and
was
admitted
to
a
hospital
where
she
received
ceftriaxone
70MKD,
and
ampicillin
for
1
week
without
improvement.
|
>
|
1
week
PTA,
all
symptoms
persisted
and
she
started
having
abdominal
pain.
|
|
Past
medical
history:
>
|
Normal
term
labour,
birth
weight
3,500
gm.
|
>
|
At
the
age
of
3
years
she
was
diagnosed
as
having
HIV
infection.
|
>
|
Her
mother
has
a
history
of
pulmonary
tuberculosis
and
has
been
on
treatment
for
7-8
months.
|
>
|
She
has
not
gained
weight
for
1
year. |
|
Physical
examination:
|
GA:
febrile,
thin
and
fatigue.
BW=18
kg
(W/A
<
3
percentile)
Vital
signs:
T:
40
celcius,
RR:
36/min,
PR:
122/min,
BP:
110/72
mmHg
HEENT:
|
EYES;
pale
and
injected
conjuctivae,
with
epiphora,
left
corneal
ulcer(figure
1)
and
photophobia.
|
|
Oral
cavity;
whitish
patches
(thrush)
|
|
Ears;
intact
both
tympanic
membranes
|
Lymph
nodes:
Right
supraclavicular
lymphnode
enlagement:
2
cm
in
diameter,
firm,
not
tender
(figure
2)
Heart:
Tachycardia,
S3
gallop,
RV
heaving,
no
murmur
Lungs:
Medium
creppitation
both
lungs
Abdomen:
Distension,
generalized
mild
tender,
liver
4
cm
below
RCM,
span
13
cm.
Extremities:
no
clubbing
of
fingers
Skin:
hypo-
and
hyperpigmentation
scars
at
extremities.
Neurological
examination:
no
meningial
sign,
no
neurological
deficit |
|
|
 |
Figure
1
Corneal
ulcer
(courtesy
of
Winai
Chaidaroon
M.D.)
|
Figure
2
Left
supraclavicular
lymphadenopathy
|
|
|
Problem
list:
1. |
HIV-infected
child
with
prolonged
fever
|
2. |
Corneal
ulcers |
Laboratory
investigations:
|
CBC:
Hb
6.1
g/dl,
Hct
18%,
WBC
3,600/mm3
(N=74%,
L=22%,
M=16%) |
|
CD4
T-cell
count:
4%
(20
cells/mm3) |
|
Tuberculin
skin
test
:
Negative |
|
Gastric
washing
for
AFB
(x
3
days):
Negative |
|
CXR:
Cardiomegaly,
generalized
reticulo-nodular
infiltration
both
lungs
suggesting
miliary
tuberculosis.
(figure
3) |
|
LP:
WBC
13
celles/mm3
(lymphocyte
100%),
protein
81mg%,
sugar
35/129
mg%,
gram
stain
and
AFB:
no
organism
seen |
Echocardiogram:
|
|
Generalized
cardiac
dilatation,
particularly
left
size
was
larger
than
right
side.
Mild
depressed
LV
systolic
function.
Small
amount
of
pericardial
effusion.
Most
likely,
the
lesions
are
caused
by
tuberculous
myopathy. |
Opthalmology
consultation: |
|
|
Left
eye
|
Right
eye
|
Visual
Acuity |
Decreased
(6/9)
|
Decreased
(6/9) |
Conjunctiva |
Diffuse
injected |
Diffuse
injected |
Pupil |
3
mm
|
3
mm |
Cornea |
Dendritic
lesion
(figure
4) |
Faint
dendritic
lesions |
 |
 |
Figure
3
CXR
:Cardiomegaly,
generalized
reticulo-nodular
infiltration
both
lungs
suggesting
miliary
tuberculosis.
|
Figure
4
Dendritic
lesion
(courtesy
of
Winai
Chaidaroon
M.D.)
|
|
Diagnosis:
HIV-infected
child
(Category
C3)
with
miliary
tuberculosis,
and
herpes
simplex
keratitis
|
|
Treatment: |
1.
|
Miliary
tuberculosis
and
meningitis
:
INH
(15MKD),
RF
(15MKD),
PZA
(25
MKD),
S(25
MKD) |
2.
|
Herpes
simplex
keratitis:
Acyclovir
ointment
5
times/day |
3.
|
Cardiac
dysfunction:
Douzabox
(1
tb
tid),
Enalapril
(0.125MKD),
Digoxin
(6.25
microgramKD) |
4.
|
Anemia:
Ferrous
Fumarate
Co
(1.5
tb
OD) |
5.
|
Suspeced
bacteremia
on
admission:
Cefotaxime
100
MKD
IV
x
7
days |
|
|
Course
of
illness:
|
|
|
After
she
received
the
anti-tuberculous
drugs
and
cefotaxime
for
4
days,
the
fever
subsided
as
in
figure
5.
Her
abdominal
pain
decreased.
She
gained
appetite.
Her
eye
pain
and
photophobia
slowly
recovered.
Her
cardiac
condition
gradually
improved.
The
repeated
chest
radiography
1
month
after
antituberculous
drugs
and
supportive
treatment
was
shown
in
figure
6.
The
heart
size
was
within
normal
limit.
The
previous
mediastinal
(hilar)
lymphadenopathy
partially
subsided.
Although
each
nodule
of
the
"miliary"
pattern
was
smaller
in
size,
the
pulmonary
infiltration
persisted.
|
|
|
|
Figure
5
|
|
|
Figure
6
The
heart
size
was
within
normal
limit.
The
previous
mediastinal
(hilar)
lymphadenopathy
partially
subsided.
The
"miliary"
pattern
persisted,
although
each
nodule
was
smaller
in
size,
.
|
|
DISCUSSION: |
>
|
She
is
an
AIDS
case
(category
C3).
She
had
2
opportunistic
infections,
HSV
keratitis
and
tuberculosis
disease.
|
>
|
The
prolonged
fever,
pulmonary
"miliary"
pattern,
mediastinal
(hilar)
lymphadenopathy,
cardiomegaly,
pericardial
effusion,
a
visible
left
supraclevicular
node,
hepatomegaly,
anemia
and
slightly
abnormal
c.s.f.
examination
represent
the
clinical
manifestations
of
disseminated
tuberculosis.
Transmission
of
M.
tuberculosis
was
airborne,
with
inhalation
of
droplet
nuclei
produced
by
her
mother
who
had
contagious,
cavitary,
pulmonary
tuberculosis.
The
initial
pulmonary
focus
could
be
in
the
midlung
zone
which
was
the
common
site.
Small
numbers
of
bacilli
might
be
ingested
by
alveolar
macrophages.
Infected
macrophages
were
carried
by
lymphatics
to
regional
(hilar,
mediastinal,
and
supraclavicular)
lymph
nodes,
and
it
spread
hematogenously
throughout
the
body
as
evidence
by
small
nodules
"military"
in
the
lungs,
pericardial
effusion,
hepatomegaly
and
abnormal
c.s.f.
findings.
|
>
|
Although
the
fever
subsided
in
the
first
week
of
anti
tuberculous
drugs
(plus
cefotaxime),
the
pulmonary
manifestations
(increased
RR
36-44/min,
creppitation)
gradually
improved
in
2-3
weeks.
Cardiomegaly
subsided
and
mediastinal
(hilar)
lymphadenopathy
partially
subsided
on
the
repeated
CXR
1
month
after
anti
tuberculous
drugs.
It
is
not
surprising
that
the
"miliary"
pattern
persisted
on
this
repeated
CXR. |
QUESTIONS
&
ANSWERS: |
1.
What
is
the
hallmark
of
herpes
simplex
keratitis?(Ref
7-9)
|
|
|
Clinical
symptoms:
|
|
>
Pain
>
Photophobia
>
Blurred
vision
"
>
Tearing
"
>
Redness
|
|
|
|
Eye
examination:
|
|
>
corneal
vesicles
>
dendritic
ulcers
>
geographic
ulcers
|
|
2.
How
to
diagnose
the
disseminated
tuberculosis?
(Ref
12)
|
|
>
|
Clinical
signs:
general
deterioration,
high
fever,
and
dyspnea.
Clinical
signs
that
involve
other
organs
such
as
plural
effusion,
digestive
problems,
hepatosplenomegaly
and
meningeal
signs. |
>
|
Chest
radiography:
a
"Miliary"
pattern
on
the
chest
radiography-extensive,
tiny
(1-2mm)
nodules
resembling
millet
seeds,
all
the
same
size
and
spread
symmetrically
over
both
lungs. |
>
|
Smear
microscopy
of
sputum
from
cases
with
disseminated
(miliary)
tuberculosis
is
usually
negative. |
|
3.
What
are
the
clinical
characteristics
suggesting
of
disseminated
tuberculosis
or
tuberculous
meningitis?
(Ref
12) |
|
>
|
Clinical
signs:
nonspecific,
progressive
deterioration
of
the
states,
mood,
meningeal
signs |
>
|
The
tuberculin
test
is
usually
negative |
>
|
Fundoscopic
examination
shows
the
characteristic
tuberculous
lesions
(choroidal
tubercles)-round,
slightly
raised
yellow
or
whitish
lesions
of
1-3mm
in
diameter. |
>
|
Abnormal
cerebrospinal
fluid
from
lumbar
puncture |
|
4.
What
are
the
criteria
of
corticosteroid
therapy
in
tuberculosis?
(Ref
13) |
|
In
patients
with: |
|
>
tuberculous
meningitis
with
increased
intracranial
pressure |
|
>
acute
pericardial
effusion
with
tamponade |
|
>
pleural
effusion
with
a
shift
of
the
mediastinum,
and
acute
respiratory
failure |
|
>
miliary
tuberculosis
with
alveolocapillary
block
and
cyanosis |
|
>
enlarged
mediastinal
lymphnodes
that
causing
respiratory
difficulties
or
severe
collapse
consolidation
lesion |
|
(The
dosage
of
corticosteroids
should
be
in
the
anti-inflammatory
range-prednisolone,
1
to
2
mg/kg/day
for
4-6
weeks
with
gradual
withdrawal) |
5.
When
to
start
HAART
in
patients
with
tuberculosis?
(Ref
14) |
|
In
patient
with
HIV-related
tuberculosis,
the
priority
is
to
treat
tuberculosis,
especially
smear-positive
cases.
However,
with
careful
management,
patients
with
HIV-related
tuberculosis
can
have
anti-retroviral
therapy
at
the
same
times
as
tuberculosis
treatment. |
|
Possible
options
for
anti-retroviral
therapy
in
the
tuberculosis
patients
include: |
>
|
defer
anti-retroviral
therapy
until
tuberculosis
treatment
is
completed |
>
|
defer
anti-retroviral
therapy
until
the
end
of
the
initial
phase
of
tuberculosis
treatment
and
use
ethambutal
and
isoniazid
in
the
continuation
phase |
>
|
treat
tuberculosis
with
a
rifampicin-containing
regimen
and
use
of
efavirenz
+
2NRTIs;
then
change
to
a
maximally
suppressive
HAART
regimen
on
completion
of
tuberculosis
treatment. |
|
6.
Anti-retroviral
therapy
and
anti-tuberculosis
therapy:
any
drug
interaction?
(Ref
14) |
|
Rifamipicin
stimulates
the
activity
of
the
cytochrome
P450
liver
enzyme
system
that
metabolizes
PIs
and
NNRTIs.
This
can
lead
to
a
reduction
in
the
blood
levels
of
PIs
and
NNRTIs.
PIs
and
NNRTIs
can
also
enhance
or
inhibit
this
same
enzyme
system,
and
lead
to
altered
blood
levels
of
rifampicin. |
|
Isoniazid
can
produce
peripheral
neuropathy.
The
NRTIs
(didanosine,
zalcitabine,
and
stavudine)
may
produce
peripheral
neuropathy
and
there
is
a
potential
further
toxicity
if
isoniazid
is
added.
Isoniazid
also
has
an
interaction
with
abacavir |
Follow
up
of
the
case
:
"Abdominal
discomfort"
5
weeks
later
|
References
and
suggested
further
reading: |
1.
|
American
Thoracic
Society,
US
Centers
for
Disease
Control
and
Prevention:
Diagnostic
Standards
and
Classification
of
Tuberculosis
in
Adults
and
Children.
This
official
statement
of
the
American
Thoracic
Society
and
the
Centers
for
Disease
Control
and
Prevention
was
adopted
by
the
ATS
Board
of
Directors,
July
1999.
This
stat.
Am
J
Respir
Crit
Care
Med
2000
Apr;
161(4
Pt
1):
1376-95.
|
2.
|
Joint
Tuberculosis
Committee
of
the
British
Thoracic
Society:
Chemotherapy
and
management
of
tuberculosis
in
the
United
Kingdom:
recommendations
1998.
Thorax
1998
Jul;
53(7):
536-48.
|
3.
|
Kim
JH,
Langston
AA,
Gallis
HA:
Miliary
tuberculosis:
epidemiology,
clinical
manifestations,
diagnosis,
and
outcome.
Rev
Infect
Dis
1990
Jul-Aug;
12(4):
583-90.
|
4.
|
Klaus-Dieter,
L.,
Cynthia
L.,
Miliary
tuberculosis
In:
http://www.emedicine.com/med/topic1476.htm,
Last
update
February,
7
2003.
Access:
June,
30
2004 |
5.
|
Gaynor
BD,
Margolis
TP,
Cunningham
ET:
Advances
in
diagnosis
and
management
of
herpetic
uveitis.
Int
Ophthalmol
Clin
2000
Spring;
40(2):
85-109. |
6.
|
Herpetic
Eye
Disease
Study
Group:
Oral
acyclovir
for
herpes
simplex
virus
eye
disease:
effect
on
prevention
of
epithelial
keratitis
and
stromal
keratitis.
Arch
Ophthalmol
2000
Aug;
118(8):
1030-6. |
7.
|
Herpetic
Eye
Disease
Study
Group:
Acyclovir
for
the
prevention
of
recurrent
herpes
simplex
virus
eye
disease.
N
Engl
J
Med
1998
Jul
30;
339(5):
300-6. |
8.
|
Holland
EJ,
Schwartz
GS:
Classification
of
herpes
simplex
virus
keratitis.
Cornea
1999
Mar;
18(2):
144-54. |
9.
|
Jim
CW,
David
CR.
Keratitis,
Herpes
Simplex
.
In
:
http://www.emedicine.com/oph/topic100.htm,
Update:
October
30,
2002,
Access:
30
June,
2004
|
10.
|
Julka
RK;
Deb
M;
Patwari
AK
Tuberculous
meningitis
and
miliary
tuberculosis
in
children
:
a
clinico-bacteriological
profile.
Indian
Journal
of
Tuberculosis.
1998
Jan;
45(1):
19-22
|
11.
|
F.
van
den
Bos,
M.
Terken,
L.
Ypma
J.
L.
L.
Kimpen,
E.
D.
Nel,
H.
S.
Schaaf,
J.
F.
Schoemana
and
P.
R.
Donald
Tuberculous
meningitis
and
miliary
tuberculosis
in
young
children
Tropical
Medicine
&
International
Health
2004;
9
(Issue
2):
309
|
12.
|
Ait-Khaled
Nadia,
Enarson
Donald
A.
Tuberculosis
a
Manual
for
Medical
Students.World
Health
Organization
Geneva.
2003.
|
13.
|
Starke
Jeffrey
R.,
Smith
Kimberly
C.
Tuberculosis.
In:
Feigin
Ralph
D.,
Cherry
James
D.,
Demmler
Gail
J.,
Kaplan
Sheldon
L.,
editors.
Textbook
of
Pediatric
Infectious
Diseases.
5th
ed.
Philadelphia
:
Saunders;
2004.
p.1337-79. |
14.
|
World
Health
Organization.
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of
Tuberculosis:guidelines
for
national
programmes.
3rd
ed.
World
Health
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Geneva
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|
|
|
|