Schweizerische medizinische Wochenschrift,
Год журнала:
2024,
Номер
155(3), С. 3879 - 3879
Опубликована: Март 14, 2024
STUDY
AIMS:
VEXAS
syndrome
is
a
recently
discovered
monogenic
auto-inflammatory
disease
caused
by
somatic
mutation
in
the
UBA1
gene
that
manifests
with
rheumatologic
and
haematologic
features.
In
this
report,
we
present
first
Swiss
cohort,
detailing
its
manifestations
treatment
outcomes
among
patients.
METHODS:
Data
were
retrospectively
collected
from
nine
hospitals
across
Switzerland,
representing
broad
geographic
distribution.
Treating
physicians
completed
standardised
case
report
form
for
each
patient.
The
principal
investigator
co-investigators
analysed
all
forms.
RESULTS:
We
identified
23
patients
between
July
2022
2023,
of
which
17
are
described.
All
male.
They
presented
skin
(88%),
general
symptoms
(82%),
venous
thromboembolism
(59%),
ocular
manifestation
lung
infiltrates
(59%)
articular
(47%).
Central
nervous
system
kidney
very
rare,
heart
digestive
absent.
Macrocytic
anaemia
was
throughout
progression
but
only
two-thirds
(12/17,
71%)
at
time
diagnosis.
Clinical
response
reached
cases
treated
ruxolitinib
(4/4,
100%),
upadacitinib
(1/1,
azacytidine
(5/5,
100%)
haematopoietic
stem
cell
transplantation
(2/2,
100%).
deaths
attributed
to
infections
CONCLUSION:
This
study
corroborates
clinical
spectrum
described
other
cohorts.
It
suggests
not
limited
macrocytic
anaemia.
study,
has
been
used
effectively
myelodysplastic
syndrome.
addition,
Janus
kinase
(JAK)
inhibitors,
particularly
ruxolitinib,
have
successfully
even
those
without
two
successful
treatments
transplantation.
Annals of Hematology,
Год журнала:
2024,
Номер
103(3), С. 993 - 997
Опубликована: Янв. 12, 2024
Abstract
The
VEXAS
syndrome,
a
genetically
defined
autoimmune
disease,
associated
with
various
hematological
neoplasms
has
been
attracting
growing
attention
since
its
initial
description
in
2020.
While
therapeutic
strategies
have
explored
case
studies,
the
optimal
treatment
strategy
is
still
under
investigation
and
allogeneic
cell
transplantation
considered
only
curative
treatment.
Here,
we
describe
2
patients
who
achieved
complete
molecular
remission
of
underlying
UBA1
mutant
clone
outside
context
HCT.
Both
received
hypomethylating
agent
azacitidine,
deep
triggered
de-escalation
even
cessation
sustained
one
them.
Prospective
studies
are
necessary
to
clarify
which
will
benefit
most
from
therapy
understand
variability
response
different
strategies.
American Journal of Hematology,
Год журнала:
2023,
Номер
99(2), С. 254 - 262
Опубликована: Дек. 18, 2023
Abstract
VEXAS
is
a
prototypic
hemato‐inflammatory
disease
combining
rheumatologic
and
hematologic
disorders
in
molecularly
defined
nosological
entity.
In
this
nationwide
study,
we
aimed
at
screenshotting
the
current
diagnostic
capabilities
clinical‐genomic
features
of
VEXAS,
tracked
UBA1
longitudinal
clonal
dynamics
upon
different
therapeutics,
including
allogeneic
hematopoietic
cell
transplant.
We
leveraged
collaboration
between
Italian
Society
Experimental
Hematology
Rheumatology
disseminated
national
survey
to
collect
clinical
molecular
patient
information.
Overall,
13/29
centers
performed
genomic
testing
locally,
Sanger
sequencing
(46%),
next‐generation
(23%),
droplet
digital
polymerase
chain
reaction
(8%),
or
combination
(23%).
A
total
41
male
patients
were
identified,
majority
(51%)
with
threonine
substitutions
Met41
hotspot,
followed
by
valine
leucine
(27%
8%).
Median
age
diagnosis
was
67
years.
All
displayed
anemia
(median
hemoglobin
9.1
g/dL),
macrocytosis.
Bone
marrow
vacuoles
observed
most
cases
(89%).
The
common
association
polychondritis
(49%).
concomitant
myelodysplastic
neoplasm/syndrome
(MDS)
diagnosed
71%
(
n
=
28),
chiefly
exhibiting
lower
Revised
International
Prognostic
Scoring
System
risk
profiles.
Karyotype
normal
all
patients,
except
three
MDS
showing
‐Y,
t(12;16)(q13;q24),
+8.
frequently
mutated
gene
DNMT3A
10),
TET2
3).
At
last
follow‐up,
five
died
two
progressed
acute
leukemia.
Longitudinal
demonstrated
mutational
clearance
following
collected
interdisciplinary
cohort,
characterized
heterogeneous
manifestations
treatments
used.
cases.
Patients
exhibited
various
dynamics.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Янв. 25, 2024
VEXAS
syndrome
is
an
acquired
autoinflammatory
disease
characterized
in
most
cases
by
cytopenias
and
macrocytic
anemia.
Dyshematopoiesis
a
frequent
finding
chronic
inflammatory
conditions
therefore,
are
not
easily
classified
patients.
Here
we
report
series
of
7
patients
affected
associated
cytopenias,
treated
at
our
center.
The
use
NGS,
together
with
morphological
assays,
integrated
the
WHO
2022
criteria,
allowed
to
identify
three
subsets
cytopenias:
ICUS
(idiopathic
cytopenia
uncertain
significance),
CCUS
(clonal
significance)
high
risk
clonal
evolution,
MDS.
This
approach
could
help
better
understand
nature
guide
specific
targeted
treatments
order
achieve
long
lasting
responses.
Experimental Dermatology,
Год журнала:
2024,
Номер
33(3)
Опубликована: Март 1, 2024
Abstract
VEXAS
(vacuoles,
E1
enzyme,
X‐linked,
autoinflammatory
and
somatic
mutation)
syndrome
is
a
novel
autoinflammatory,
late‐onset,
disorder
first
identified
in
2020.
It
caused
by
mutations
the
UBA1
gene.
The
most
prominent
clinical
features
reported
patients
are
cutaneous
haematological,
having
characteristic
skin
as
initial
presenting
findings
of
disease.
severe
treatment‐resistant
condition
with
high
morbidity
mortality
rates.
Here,
we
examine
all
case
reports
series
through
March
2023
focusing
on
those
manifestations.
We
discuss
these
manifestations
their
treatment
strategies.
In
many
cases,
it
might
be
suspected
diagnosed
dermatologists,
highlighting
vital
role
initiating
timely
multidisciplinary
care.
British Journal of Haematology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 8, 2025
Summary
There
is
still
no
standard
of
care
and
unmet
medical
needs
in
refractory/advanced
VEXAS
(vacuoles
myeloid
progenitors,
E1
ubiquitin
activating
enzyme,
X‐linked,
autoinflammatory
manifestations
somatic)
syndrome
with
or
without
associated
haematological
neoplasm.
We
report
the
clinical
outcome
four
multirefractory/advanced
patients
treated
acute
leukaemia‐like
therapeutic
approaches.
All
responded
to
inflammatory/haematological
VEXAS‐related
features,
which
were
measurable
residual
disease
response
(partial
complete).
Prospective
studies
evaluating
new
effective
strategies
order
reduce
clonal
burden
are
warranted.
Brain Sciences,
Год журнала:
2025,
Номер
15(6), С. 573 - 573
Опубликована: Май 26, 2025
VEXAS
syndrome
and
Alzheimer’s
disease
(AD),
though
distinct
in
clinical
manifestations,
share
overlapping
pathophysiological
mechanisms,
including
systemic
inflammation,
protein
misfolding,
vascular
dysfunction.
syndrome,
a
rare
autoinflammatory
disorder
characterized
by
somatic
UBA1
mutations,
hematologic
abnormalities,
presents
primarily
older
males.
Meanwhile,
AD,
the
leading
cause
of
dementia,
involves
progressive
neurodegeneration
driven
amyloid-beta
plaques,
tau
tangles,
chronic
neuroinflammation.
This
article
explores
potential
connections
between
two
conditions,
focusing
on
neurovascular
changes
cellular
stress.
Systemic
inflammation
observed
may
potentiate
neuroinflammatory
processes
as
circulating
proinflammatory
cytokines
have
capacity
to
cross
blood–brain
barrier
(BBB),
thereby
inducing
glial
activation
promoting
Additionally,
coexisting
dysfunctions
characteristic
both
conditions
synergistically
contribute
accelerated
cognitive
decline.
Both
involve
disruption
ubiquitin–proteasome
system,
with
mutations
being
specific
VEXAS.
Given
established
role
maintaining
neuronal
homeostasis,
investigating
molecular
mechanisms
provide
valuable
insights
into
their
pathophysiology.
The
review
underscores
need
for
further
research
elucidate
these
links
improve
therapeutic
strategies,
especially
individuals
affected
disorders.
