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The effects of Eculizumab on the pathology of malignant atrophic papulosis.
[malignant atrophic papulosis]
Degos
disease
is
a
frequently
fatal
and
incurable
occlusive
vasculopathy
most
commonly
affecting
the
skin
,
gastrointestinal
tract
and
brain
.
Vascular
C
5
b
-
9
deposition
and
a
type
I
interferon
(
IFN
)
rich
microenvironment
are
held
to
be
pathogenetically
important
in
the
evolution
of
the
vascular
changes
.
We
recently
discovered
the
use
of
eculizumab
as
a
salvage
drug
in
the
treatment
of
near
fatal
Malignant
atrophic
papulosis
(
MAP
)
.
The
effects
of
eculizumab
on
the
pathology
of
MAP
are
explored
.
Archival
skin
and
gastrointestinal
biopsy
material
was
procured
over
a
2
.
5
-
year
period
before
and
after
eculizumab
therapy
in
our
index
case
.
Routine
light
microscopy
and
immunohistochemical
assessment
for
C
3
d
,
C
4
d
,
C
5
b
-
9
,
MxA
and
caspase
3
were
examined
.
Direct
immunofluorescent
studies
were
also
conducted
on
select
biopsy
material
.
The
patient
had
received
eculizumab
as
a
emergent
life
saving
measure
and
following
rapid
improvement
he
continued
with
biweekly
infusions
for
4
years
.
Although
improved
he
continues
to
have
signs
and
symptoms
of
persistent
abdominal
disease
.
Pre-
Eculizumab
biopsies
showed
an
active
thrombotic
microangiopathy
associated
with
a
high
type
I
interferon
signature
and
extensive
vascular
deposits
of
C
5
b
-
9
in
skin
and
gastrointestinal
biopsies
.
Endothelial
cell
apoptosis
as
revealed
by
Caspase
3
expression
was
noted
.
Inflammation
comprising
lymphocytes
and
macrophages
along
with
mesenchymal
mucin
was
observed
as
well
.
Post-eculizumab
biopsies
did
not
show
active
luminal
thrombosis
but
only
chronic
sequelae
of
prior
episodes
of
vascular
injury
.
There
was
no
discernible
caspase
3
expression
.
After
12
months
of
therapy
,
C
5
b
-
9
was
no
longer
detectable
in
tissue
.
The
high
type
I
IFN
signature
and
inflammation
along
with
mucin
deposition
was
not
altered
by
the
drug
.
In
addition
,
there
was
little
effect
of
the
drug
on
the
occlusive
fibrointimal
arteriopathy
which
appears
to
be
one
characterized
by
extensive
myofibroblastic
expansion
of
the
intima
potentially
as
revealed
by
staining
for
smooth
muscle
actin
without
immunoreactivity
for
desmin
and
myogenin
.
Complement
activation
and
enhanced
endothelial
cell
apoptosis
play
an
important
role
in
the
thrombotic
complications
of
MAP
.
However
,
the
larger
vessel
proliferative
intimal
changes
appear
to
be
independent
of
complement
activation
and
may
be
on
the
basis
of
other
upstream
mechanisms
.
Monitoring
C
5
b
-
9
deposition
in
tissue
is
likely
not
of
great
value
in
assessing
treatment
response
to
eculizumab
given
the
persistence
of
C
5
b
-
9
in
tissue
for
several
months
despite
clinically
effective
C
5
blocking
therapy
.
A
more
integrated
approach
addressing
upstream
and
downstream
pathways
in
addition
to
those
attributable
to
complement
activation
are
critical
for
the
successful
treatment
of
MAP
.
Eculizumab
may
be
used
as
salvage
therapy
in
critically
ill
patients
with
thrombotic
microangiopathy
.
