1. health and fitness
2. disease

Treatment
of Autoimmune
Children
with
By W.
M
ANY
CYTOSTATIC
responses.
velopment
efficacy
of
of purine
anemia/LlT
to adults,’4’1#{176}’17
and
the
children
Several
with
proved
its
The
in
by
Imuran
hemolytic
II.
II.,
l)orn
His
diagnosed
febrile
appeared,
months
anemia
early
illness
at
vomiting
was
admitted
anemia
were
available
ment
porarily,
age
by
were
of
as
a result
direct
patient
autoimage
group
on
3 small
nonrelated
After
clinical
At
with
all
( =gamma11
the
to
age
was
4
made.
Cross
erythrocytes
antibody.
Treat-
condition
our
of
lied
test
19S
or
un-
of acquired
Swiss
the
child’s
transferred
the
test
of the
an
symptoms
diagnosis
antigbobulin
reacted
was
healthy,
first
the
Laboratory
improved
with
this
anemia.
Central
type
the
of
the
positive
ACTH
first
unremarkable.
where
nongamma
this
is the
autoantihodies.
child
progressive
and
of
this
communication
3 months,
which
suppression
application
treating
with
sixth
hospital,
the
de-
autoimmune
children
in
were
of
the
1)
the
rapidly
a strongly
prednisone
and
the
autoantibodies
and
with
is
the
small
associated
development
and
shown
“incomplete’
1961,
by
knowledge
a brief
1 (Fic.
to a local
with
antibodies
to he
10,
and
with
he
hemolytic
The
Octoher
birth
and
justify
trials
with
difficulties
to
The
particularly
of our
infants
immunologic
led
6-mercaptopurine.
in clinical
best
inherent
in
impair
property
of
deal
to the
use
to
this
diseases,
CASE
parents.
found
with
publications
anemia.
acquired
been
a derivative
,
been
but
achieved
MAsSIIo
autoimmune
describing
success
L.
drugs
)
has
and
treatment
hemolytic
new
Anemia
(Imuran)
AND
have
for
antagonists
rejection
communication
FII-rZIG
( Imuran
hemolytic
mune
H.
search
azathioprine
homograft
Azathioprine
AGENTS
The
of
Hemolytic
only
hospital
at
tern-
the
age
of 7 months.
On
skeletal
boy
skin
Laboratory
leucocytes
palpable.
The
16 nucleated
per
liver
cu.mm.
red
very
clean
pale
and
and
no
cells
was
was
with
per
felt
apathetic,
petechiae
tone
of muscles
The
lymph
nodes
Hb
Findings:
16,800
was
was
The
normal.
were
not
were
The
deformities.
abdomen
was
the
admission,
development.
was normal.
were
not
#{189}
fingerbreadth
3.5
Gm.
per
essentially
100
white
hut
were
of normal
seen.
The
head,
enlarged
below
physical
There
were
thorax
and
the
the
costal
cent,
reticubocytes
93
differential
count.
cells.
The
per
sternal
From
time Departnzent
of Pediatrics
(Director:
Prof. A. Prader),
University
Switzerland,
and the Department
of Pediatrics
(Director:
Prof. G. de Toni),
Ge,iova,
Italy.
This work wa.c supported
by a grant from the Swiss
National
Foundation.
First submitted
Oct. 25, 1965; accepted
for publication
May 1, 1966.
\V. 11. 1-ImTzmc, M.D.:
Professor
of Pediatrics,
University
of Zurich,
Zuricim,
L. \IASSmMO,
M.D.:
Professor
of Pediatrics,
University
of Genova,
Genova,
Italy.
spleen
margin.
normal
blood
no
and
cent,
There
marrow
of Zurich,
University
of
Switzerland.
840
BLOOD,
VOL.
28,
No.
6
(DECEMBER),
1966
1MURAN
IN
-
HH.geb
TREATMENT
10 5 61
5551
OF
AUTOIMMUNE
1962
HEMOLYTIC
1963
.
/1962
,
841
ANEMIA
1964
.
. .**,
.
,
.
.
,
x
‘
IV
V
V
VII
ViU IX
*
XI
1965
#{149}
y V
XII
Theropie:
Prednison
mo
Azothioprine
,
#{149}__
I
-
Bluttronsfus.
Blut:
-
-
Reti
Hb%
100
400
.
Coombs-Td,rekt
+
-
Fig.
showed
the
intense
marrow
erythroid
cells.
acterized
as an
1. Progress
hyperplasia
Total
per cent,
bilirubin
Direct
and indirect
1.-Case
protein
with
was
3.2 mg. per
antiglobulin
“incomplete”
5.5
cent,
test
chart.
an
Gm.
otherwise
per
osmotic
showed
non-gamma
normal
cent,
serum
resistance
+ + + . The
globulin
distribution
iron
221
slightly
antibody
antibody
of
gamma
diminished.
was char-
with
great
thermic
amplitude.
A
of
diagnosis
bodies
severe
of nongamma
with
Treatment
tuted.
The
On
the
was
in quite
During
good
the
therapy
came
to
per
cent.
were
in most
made.*
as
a
doses
of prednisone
transfusion
above
of
8 Gm.
The
child
months
Each
soon
instances,
direct
change
anemia
with
warm
as
seemed
(40
packed
per
cent
recovered
several
time,
the
to
antiglobulin
test was
in the characteristics
mg./day)
was
erythrocytes
and
the
rapidly
was
reticulocyte
and
within
decrease
the
dose
be
attempts
to
new
signs
however,
was
reduced
active
to below
precipitated
positive
of the
of
by
throughout
antibodies
intercurrent
therapy.
test his
patient’s
to thank
course
to institute
seemed
while
antigens
hospital
admission,
and
Dr.
at home.
A. Fischer,
azathioprine
advisable
it
standard
immunoelectrophoresis
#{176}We
wish
the
to
a second
still
from
on steroid
September
quantitative
Hitzkirch,
The
this time.
However,
a gradual
from nongamma
to gamma-type
to
capacity
be-
These,
infections.
impaired.
It was therefore
of the young
age of the
decided
patient,
prednisone
10 mg./day.
therapy,
tissue
1963,
weeks
hemolysis
soft
During
instigiven.
count
two
was noted.
As a side effect
of the longstanding
prednisone
rounding
of the face developed
and growth
of bone
and
forming
anti-
condition.
following
apparent
hemolytic
made.
high
day
rose
to 10-25
acquired
was
relatively
second
hemoglobin
dropped
acute
type
his
most
Because
antibody-
therapy.
13 to
determination
for
a marked
was grossly
valuable
Novemeber
of immunogbobuhelp
in controlling
11,
842
1111-zIG
lins
( gammaG,
was
immunized
weekly
antibody
per
gammaA,
intervals.
titers
ml.;
range
On
17,
was
discontinued.
cent
0.2-2.0
very
per
the
cent.
develop
attack
child
the
disease.
exacerbation
became,
and
Once
prednisone
took
rapidly,
July
the
1965,
child
had
This
was
development.
growth02
(Fig.
Summary:
process
year
)
was
by
age
of
of
be
was
was
made.
not
and
the
and
the
height,
typical
per
13
cent
to
nor
who
9,
did
had
and
a
1964.
No
antiglobulin
test
mental
weight,
and
example
of
de-
skeletal
“catch-up”
child
though
the
he
admission,
thank
determinations.
Dr.
justified.
very
S.
a
severe
The
hemo-
prednisone
azathio-
hyperhemolysis
prednisone
and
was
stopped,
therapy
that
with
being
given.
Imuran
rapid
After
one
(FIG.3)
of a healthy
jaundice
of
of the
per
cent.
and
high
fever,
the
“Schweiz.
and
newborn
was
hospital,
hands
On
from
fever
and
from
noted,
done.
where
but
At the
a diagnosis
hepatosplenomegaly
February
prostration
and
&
1963,
26,
hospital,
he
and pallor.
Serumn-
a normal
was
transfusion
to a local
edema
11 Gm.
family
the
no exchange
ill with
Barandun
of
The
both
after being
discharged
study
because
of high
was
doses
Imuran
was
child
is normal.
admitted
was
developed
Treatment
prednisone
and
with
with
fully
is a boy
was
boy
autoantibodies.
subsequently
intense
bronchitis
shortly
for further
to
July
physical
development.
Once
measured
hemoglobin
#{176}Wewish
sister,
was
were
grossly
below
normal,
age made
rapid
progress.
By
warm
considered
and
The
antibody
his
of
it
above
2-5
since
and
for
a
even
skeletal
13, 1962,
age of 6 months,
to this hospital
On
with
dose
dose
infections,
given
3-month-old
controlled,
agent
August
otitis
be
started
1964,
remained
from
a rapid
incomplete
took place,
even
without
treatment,
4 months
acute
contact
been
values
normal
therefore
Precocious
bilirubinemia
intercurrent
weight,
which
time the bone
CASE2
born
from
close
to
with
withdrawn.
of observation
G. M.,
the
this
the
23,
values
dropped
was
1964,
time,
April
slowly
)
5,
same
on
have
normal
and
this
growth
pregnancy.
finally
stopped,
and
same
the
has occurred
negative.
considered
barely
successfully
“catch-up”
drugs
reached
growth
controlled
were
At
suffer
was
February
hemoglobin
after
No
anemia
could
( Imuran
prine
even
#{149}
impaired
was
not
apparently
hemolytic
grossly
in
2).
An
acquired
the
did
Height
at the
are
( Imuran
On
count
treatment
place.
and
he
at 4
following
1 I. U.
results
azathioprine
and
of the hemolytic
process
has remained,
completely
vebopment
increased
These
mg.IKg.Iday).
period
The
1:1024.*
with
reduced
cough,
of
of
mg.IKg.Iday).
reticubocyte
whooping
typical
titer
(3.0
slowly
Subsequently,
age.
(2.0
this
and
a
treatment
mg./day
During
per
lytic
25
to
prednisone
Gm.
in
1963,
MASSIMO
after
the end
of this
course,
the
tetanus,
3 I. U. per ml.; diphtheria
of this
of 18 mg./day
increased
he
positive
for children
a dose
was
Fourteen
days
were
determined:
December
with
3 injections
pertussis,
normal
) showed
normal
values.
of tetanus/diphtheria/pertussis-antigens
gamma1
with
AND
was
at the
admitted
marked
Impfinstitut”
anefor
the
IMUIIAN
IN
TREATMENT
OF
Hemolyfic
AUTOIMMUNE
HEMOLYTIC
H Herbert,
anemia.
843
ANEMIA
9560/63
prednisone
60-2.5
mg/di.
cm
100
50/.
90
80
70
60
chronological
Fig.
steroid
velocity
2.-Case
1.
medicatiomi;
is even
after
greater
Growth
and
age, years
development
are
grossly
suppression
of prednisone,
than
normal
( “catch-up
up to the age of 2 10/12;
it has IU) inhibitimig
effect.
A: Height
curve in terms of percentiles.
mia.
Purulent
spleen
otitis
5 cm.
Laboratory
Cu.
mm.,
seen
the
CDE/cDE,
(with
was
Only
crisis
following
was
smear.
groups:
0,
was
with
of 1:32,
remission
necessitated
In
spite
the
discontinuation
of
therapy,
of this,
Rh
pos.,
with
five
cells
(1:160),
inwere
of 1:32).
and
mg./day)
anesthesia
hemobytic
process
hemolytic
hyper-
anti-Rh
general
not
normo-
genotype
positive
(25-30
the
1,800,000/
probable
bromeline
its
given
erythroid
a specificity
of
reinstitution
continuous
intense
under
and
4 cm.,
and
was
prednisone
of
red
strongly
long-term
(liver
cent,
with
mastoidotomy
a
per
There
antibiotics,
.
microspherocytosis
antibodies
at a titer
with
Gm.
test
warm
after
given.
5.4
)
growth”
by
is resumed
Imnuran
was
hepatosplenomegaly
Marked
Blood
after
year
was
antigbobulin
was
hemolytic
marked
was noted.
cent.
blood
trypsin
immediately
)
Hb
instituted
transfusions
prednisone,
per
Direct
However,
the
32-50
incomplete
mercaptopurine.
ing
edge
marrow.
MN.
demonstrated
blood
present;
in the
hone
negative;
Therapy
still
costal
Inuestigation:
were
in
direct
the
reticubocytes
blastemia
plasia
was
below
impaired
growth
crises
than
6two
achieved.
the
prednisone,
steroid
treatment.
less
and
a
new
Dur-
5 mg./day
occurred
of
during
844
ANI)
HITZ1C.
Hemolytic anemia.
MASSIM()
9560/63
H Herbert,
prednisone
60-
2.5 mg/d.
/
D
E
0
weight
age
0
I
2
chronological
Fig.
normal
2B.-Development
mean.
vhich
the
dose
infection,
control
of
had
to he
a second
partcentesis
of the
hemolytic
process
On
July
17,
( 10
General
and
her
1964.
per
cent
was
1964,
and
rise
increased
of the
to 33,
treatment
a moderate,
hemolytic
activity
50
mg./day
although
was
the
not
maturation
each
in
crisis
Despite
obtained
was
this,
and
the
(2.5
satisfactory
until
episode
with
drop
to 10 per
cent,
the
(=3
and
May
the
of the
dosage
satisfactory,
with
At the
beginning
11 Kg.,
liver
a low
end
Hb
of
Novem-
to 6.8
Gm.
of azathioprine
Under
subsidence
this
of the
noted.
dose
of June
at 2 cm.
begun.
of treatment.
In the beginning
of January
1965 the child had a bout of bronchopneumonia
during
which
prednisone
(2 mg./Kg./day)
was given
and the azathioprine
discontinued.
After
this
period,
azathioprine
(2.5
mg./Kg./day)
was
together
test
9, 1964.
was
course
4 mg./Kg./day).
completely
by
satisfactory
daily)
as the
to
initiated
no
on
mg./Kg.
15 days
relation
antiglohulin
therefore
removed
improvement.
first
were
hemolytic
reticubocytes
then
be
azathioprine
for
conditions
of a new
bone
needed.
spleen
was
unsustained
given
hematobogic
Because
was
with
was
and
to 15 mg./day;
could
The
and
therapy
)
mg./day
age, years
weight
increased
and
remained
strongly
positive.
This resulted
in a moderate
ACTH
height,
3
from
of prednisone
the
general
the
costal
(5 mg./day),
condition
edge.
with
a satisfactory
is good-height
The
blood
picture
result.
82 cm.,
was
was
given
weight
essentially
IMURAN
IN
ThEATMENT
GM.geb
OF
V1H62
13
HEMOLYT1C
1963
,
-
845
ANEMIA
1964
NI
Therapie
Prednison
AUTOIMMUNE
U
.
.
.
.tI
IA
X
0
Xi
II
1965
Iii
Mercoptopru
I
V
V
V!I
II
X
XI
X
XII
II
III
V
IV
0!
VI
-
o
_______
-
-.
Azathioprine
mq
Imuron
Bluttronsfus
Moso,dotomie
Blut:
Poroce,s
SpIn’,k?om,
Retii..
Hb’i.
100,
400
i
Coombs -T
direkt
44-
4+
9
(+
4.)
+
Fig.
(+‘
(#{247}
+
3.-Case
*
2. Progress
( Hh
per
cent,
12.5 Gm. per cent,
red cells
white
cells
10,600 per cu.mm.
per
cent,
El,
normal
B!,
antigbobulin
which
were
proved
gradually
only
when
In this
Summary:
around
27 per
L
the
age
and
drug
the
first
despite
of
transient
signs
its
benefit.
in a definite
reduction
in
achieved
when
azathioprine
The
3
(SEE
he
pertussis,
after
treated
had
and
an
attack
in
hemolytic
many
three
infections
attacks
anemia
the
new
of acute
another
anemia
hospital
some
which
even
seemed
ferred
to our
department.
to
episodes
infections.
Splenectomy
institution
of azathioprine
1, 2, 9)
with
months
aggravate
later
the
started
hemolysis
hyperhemolysis
produced
therapy
only
resulted
results
were
parents
of this boy are first cousins.
was complicated
by toxemia;
birth
was normal,
but from
the age of 4
a hemolytic
numerous
im-
4)
(FIG.
tonsillitis,
meningoencephalitis).
bronchitis,
of
hemolysis,
hut the best
was given concurrently.
(bronchopneumonia,
of
The
.
development,
therapy,
hemolytic
REFS.
4
N 70
)
200,000/cu.mm.
Growth
and
prednisone
controlled
M. L. was born
August
29, 1960. The
The first child was stillborn.
This pregnancy
weight
was 3.3 Kg. His early
development
months
platelets
treatment
the abnormal
and prednisone
CASE
+
of autoimmune
administration
after
+
or decreased.
Prednisone
them
the
cent;
stopped
f
per cu.mm.,
reticulocytes
following
differential:
4,100,000
(titer
1:5).
the long-lasting
was
+
chart.
with
M 3 per
positive
during
4 months.
hut
some
this
boy
of
partially,
occurred,
moderate
cent,
test was
weakly
grossly
retarded
t
#{247}+
blood
could
not
anemia.
At
anemia
child
age
appeared,
transfusions.
he improved
The
gastroenteritis,
the
of
2 years,
which
was
A second
bout
by transfusions,
was
therfore
trans-
of
846
ANI)
IIITZI(;
._:__.
ML..geb29VIII60
1963
.
1 herapie:
.
.
nx
1964
V
.
xi
xi
1965
-
.
,
.
,
iii
*
*
MA5SIMO
VI
ii
‘
/1
-
Prednison
u
0k
mq
L
i1_L1
t
..
I
Azathioprine
50
.
Imuron
---
U
Bluttransfus
Blut:
Reti
i..
Hb%
iooJ
4ooJ
:H ::‘
20
p
i(s)
p
Coombs-T.
direk?
*
++
+
-
i)
Fig.
On
He
frontal
was
kelow
the
admission,
jaundice.
and
had
maxillary
Laboratory
Findings:
reticubocytes
and
masia
anisochromia;
28
in
Antiglobulin
test:
agglutinins
titer.
From
a wide,
heart.
direct
were
found,
the patient’s
very
marked
with
open
was 3.5 Gm.
per
cent.
On the smear:
cent,
red
aniso-,
).
Leucocytosis
)
4 cm.
.
There
palpalle
4 cm.
1,650,000
per cu.
polychro-
poikibocytosis,
( hasophils
erythroblastosis
cells
were
cells
mild
prominent
(4 x
fontanelle
spleen
and
anemia
macrocephaly,
and
white
±
(+)
Liver
100
preponderant
1.2 mg.
per cent;
the bone
marrow
( indirect
and
of the
+++
chart.
ill with
appearance,
marked
per
with
mm.
plasia
Hb
32 per
2, orthochromics
2, polychrornatics
was
16,200-22,000
per
lymphocytosis.
Bilirubin
was
2.0 mg.
per cent
direct
0.8 mg. per cent).
Marked
erythroid
hyper(210.7
per cent).
Blood
groups:
B, llh+,
MN.
strongly
positive,
indirect
negative.
Incomplete
and in addition
incomplete
cold aggbutinins
red cells cold antibodies
active
on erythrocytes
warm
in a low
0 Rh +
eluted.
Since
the
and
because
extended.
hemoglobin
received
the
hones
+
3. Progress
seriously
was
mongoloid
a soft systolic
murmur
the costal
edge.
mm.,
were
boy
a
4.-Case
(+)
formula
TIi erapy
lib,
return
to negative).
family
comes
from
of the mongol-like
They
the
revealed
in the
with
electrophoretic
designation
of HI)
47Gm,pA
with
could
prednisone
of reticubocytes
Five
weeks
a region
features
patient
with
and
mobility
L6.,,,
. By
be identified.1’
(40 mg./ day)
to normal
and
later,
however,
of
a high
incidence
of thalassemia
the
child,
investigations
were
in his
father
similar
to
fingerprinting
was
the
HI)
immediately
reversion
recurrence
of the
of
existence
of a new
L. This
and peptide
has
since
analysis
successful
(rise
antihemoglohin
the hyperhemolysis
in
test
1MURAN
TREATMENT
IN
made
OF
continuous
prednisone
four
more
dose
of 5-10
mg.
July
7, 1964,
On
hemolytic
In
rise
April,
reduced
was
tions
are
physical
dose
son
of
with
warm
autoantibodies.
years
and
was
prednisone.
a drop
next
15 months,
the
maintenance
altogether,
and
the
the
normal
with
added
a transient
noted
with
test
May
azathioprine
hematologic
is slightly
condi-
positive.
The
range.
parents
is
hemolytic
process
blood
maintenance
in
and
antiglobulin
acquired
hemolytic
was
After
was
and
General
consanguineous
treated
mg./Kg./day),
be reduced.
improvement
of reticulocytes.
stopped
an
example
anemia
became
then
to
at
Therefore,
apparently
age
high
for
a
new
incomplete
the
with
of corticosteroids
occurred.
a year,
of
due
evident
transfusions,
therapy
of severe
hyperhemolysis
was started
which,
within
body
( =2.5
could
steady
1 mg./Kg./day.
acute
The
first
Despite
episodes
thioprine
of
is within
This
Summary:
and
was
satisfactory
hemogbobinopathy
of
33 mg./day
prednisone
development
the
increases
prednisone
dosage
count,
a slow and
in hemoglobin
presently
During
drastic
mg./day.
azathioprine,
to the
847
ANEMIA
necessary.
necessitated
to 30-40
1965,
HEMOLYTIC
therapy
crises
with
the hope
that the
rise of the reticubocyte
continuous
AUTOIMSIUNE
of 2
doses
of
1 1/2 years,
treatment
checked
the
five
with
azaautoanti-
formation.
DiscussioN
Autoimmune
hemolytic
fants.2
Corticosteroids
and
their
beneficial
though
it is difficult
this
paper,
certain
1. The
only
2. The
facts
have
as long
effect
tamed
3. The
disease
in
was
effect
were
by
enhanced
even
though
Coombs’
Tests
remained
therapy,
until
a remission
normal
antibody
despite
corticosteroid
small
of
corticosteroids
was
giving
azathioprine
steroid
therapy
positive,
and
was
graft
via
effects
the
cial
effect
of
“cellular,”
tosis
of red
cases,
using
A major
profound
with
growth
not
steroid
despite
blood
tagged
problem
inhibition
immunity.”
and
“humoral,”
inhibitory
the
“cellular
Imuran
One
did
red
blood
not
is
and
benefit
oh-
50
and
azathio-
occurred
occur.
in
cases
and
hypothesis
that,
can
case,
and
of
immunity
explanation
the
one
effect
of Imuran
on the prevention
of transplantation
depressed
This
in
is
of the
benefi-
here
is that
reported
as a result,
be studied
phagocyin
further
cells.
in the
treatment
effects
on
relatively
small
was not clinically
the
corticosteroid
possible
therapy
immunity
cells
temporary
occurred.
rejection.4’1#{176} Presumably
on
in-
stopped.
Most
of the clinical
data
on the “immunosuppressive”
closely
related
drug,
6-mercaptopurine,
are based
kidney
and
given.
response
to bacterial
antigens
and azathioprine
therapy.
A
children
potentially
fatal condition
“immunosuppression,”
alIn the cases
recorded
in
to he considered.
as they
continued,
prine
4.
is a rare
“immunosuppressive”
lasted
the
anemia
are standard
treatment
in this
effect
is usually
attributed
to
to define
this effect
more
exactly.
normal
doses
of
detectable
of
children
growth.
Imuran
and,
It
with
corticosteroids
is of
some
our patients,
at the same
time,
in
is their
importance
interference
“immunosuppres-
that
with
848
HITZIG
sion”
was
sufficient
ol)viously
not
did
produce
and
other
side
and
side
of these
drugs
the
than
case
the
those
currently
high
older
children
and
they
of
the
treatment
followed
with
).
of the
Prolongation
in
height,
weight,
The
the
whole
prognosis
gloomy,20
apeutic
attaining
has
more
or less
tion
of tolerance
sive
chemicals.
should
as
the
vicious
certainly
of
new
and
circle
be
7.22
be
possil)le
to
therapeutic
are carried
expected;
of
treat-
to take
injection
( in
advantage
of
Case
1).
as this is
only after
4 to 8 weeks
allowed
to taper
it off.
is
be
2.5
and,
be
if
stopped,
of 3 to 4 months,
mg./Kg./day
to be
8 to 12 months
growth’2)
maturation
sought
can
or
sufficient
with
50
(Case
without
treatment
(“catch-up”
intellectual
is,
sufficiently
as
seems
than
that
increases
by
should
response
more
a given
in
I)Ossil)Ie
( see
controlled
as far
much
should
he
as
steroid-sparing
success
azathioprine
in Case
1, data
on
should
I)e collected
period.
hemolytic
since
the
equilibrium.
anemia,
watching
treatment
seriously
out.
which
introduction
and
formerly
of steroids
of affected
period
According
enhanced
of autoimmune
considered
be
or a booster
be given
azathioprine
for
the
azathioprine,
that
immunosuppressive
)
infants
should
if the
as
uninfluenced
hyperhemolysis
of
be greatly
Taking
into account
tions,
immunosuppressive
break
be
in clear-cut
starting
About
80 per cent
remission
after
a differing
can
can
result
a period
improved
tolerable
evident
should
be continued
for
of the dose to nothing.
treatment
greatly
such
he
corticoids
of autoimmune
armamentarium.
complete
of
action
a better
If the
and development
skeletal
and
and
use
“immunosuppres-
drug
cure
increased.
treatment
Because
growth
throughout
of
he doubled
of the
resulting
the
it may
with
a potent
It should
should
antigens
dose4’M-’7
can
justifiable.
beneficial
terms,
mechanism
( in
steroid
azathioprine
reduction
This
exact
before
of signs
dose
recommended
not
is
did
psychoses,
of combining
steroid
dose seems
advisable
sufficient
time
should
be
by gradual
The
of the
in
antibody
forming
capacity
the exposure
to infection
the
mg./m2/day.
2
hemolysis
IlOrmal
recurrence
appear,
ulcers,
way
should
immunization
I)OS5iI)le.
Reduction
of the
of azathioprine
treatment;
Evidence
Imuran
therefore
“immunosuppressive
spontaneous
therapy
Furthermore,
with
the child’s
own
During
therapy
this
no
steroid
of primary
)
nature
defined
on
or the
doses.
a course
best
maximal
children
with
seem
advisable:
to taper
cortisone
addition,
and
available.
process,
ment,
the
the
be
specifically
is chronic
hemolytic
In
of cortisone
gastrointestinal
to obtain
can
in treating
precautions
attempts
mellitus,
When
drugs
act
disease
several
the
effects.
which
Nevertheless,
following
process.
actions
to determine
order
in
action
hemolytic
MASSIMO
of corticosteroids.
Imuran
minimal
the
physiologic
is needed
sive”
index
the
diabetes
effects
work
with
find
control
have
osteoporosis,
Further
steroids
to
not
AND
to the
present
by
anemia
more
ther-
data,
dramatic
also
forma-
immunosuppres-
carefully
all the possibilities
is therefore
a very
valuable
before
quite
the
children
survive,
either
of time
or establishing
a
accelerated
hemolytic
was
into
of complicameans
to
in children.
measures,
It
such
IMUHAN
iN
OF
THEATMENT
AUTOIMMUNE
HEMOLYTIC
ANEMIA
849
SUMMARY
Three
cases
(liseas(’
of autoimmune
very
i5
complicated
was
dental.
=
1)rile
allowed
probably,
to
in
with
a rare
Corticosteroid
ly effective
anemia
months
in infants
of life.
bemogbobinopathy,
treatment
controlling
in
heniolytic
first
few
the
the
which
larges
in
disease.
doses
are
One
may
was
descril)ed.
case
have
partially
been
and
Immunosuppressive
This
3)
( No.
coinci-
temporari-
( azathio-
therapy
Imuran,
2-5 mg./Kg./day)
produced
a complete
cure
in Case
1 and
a marked
decrease
in steroid
doses
in the other
two
cases.
Most
a vicious
circle
of autoimmunity
was broken
by this drug.
Failure
weight
gain
cut
rare
steroids
on
“catch-up
growth”
in
tions
regarding
lrecautions
mode
of action
of these
was
Case
more
even
1,
and
drugs
than
compensated
though
dosage
Imuran
for
was
of azathioprine
is discussed
in an
by
being
are
attempt
the
clear-
given.
stated.
IndicaThe
to explain
exact
the
nature
of immunosuppression.
SUMMARIO
Es
describite
inorbo
Cs
tres
rar
complicate
coincidentia.
C
un
Le
rar
transientemente
de peso
corporee
per
permitteva
un
marcate
II pare
per
esseva
plus
de
proceder
es
commentate.
objectivo
cm
un
del
le
nette
cautemente
de explicar
de
in
peso
esseva
in be uso
modo
de
be natura
de
de
action
in
durante
le
in
Es
Le
rumpite
de
steroides
be prime
caso
in
be desiderato
dosage
es
e
duo.
esseva
notate
pharmacos
kg
caso
altere
be uso
resaliente
iste
per
in be prime
autoimmunitate
azathioprina.
de
un
partialmente
2 e 5 mg
steroides
continuate.
esseva
immunosup-
inter
complete
dosage
)
tertie
therapia
de
Iste
possibilemente
esseva
Un
curation
infantes.
( Ic
casos
doses
dosage
vitiose
in
esseva
morbo.
crescentia
Imuran
del
isto
grande
le
un circubo
per
Un
in un
non-augmento
que
Le
in
produceva
que
facto
vita.
hemolytic
sed
Imuran,
reduction
Le
que
del
del
maestrar
i.e.,
die)
pharmaco.
despecto
in
azathioprina,
probabilissime
iste
menses
anemia
a corticosteroide
efficace
(con
1NTERLINCUA
hemoglobinopathia,
therapia
pressive
IN
autoimmun
le prime
durante
per
de
casos
del
pharmaco
analysate
con
Ic
used
in
de immunosuppression.
ACKNOWLEDGMENT
We
these
are
grateful
to
the
Wellcome
Foundation
for
advice
and
for
the
Imuran
studies.
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