Advances in Rheumatology,
Journal Year:
2024,
Volume and Issue:
64(1)
Published: Oct. 9, 2024
Systemic
vasculitis
is
a
group
of
rare
diseases
that
share
an
essential
characteristic:
inflammation
blood
vessel
walls.
This
injury
occurs
during
the
disease
course,
but
specific
features
vary
for
each
entity.
In
this
paper,
we
will
address
relevant
aspects
newest
monogenic
mutation
vasculitis,
such
as
deficiency
adenosine
deaminase
2
(ADA2)
and
VEXAS
syndrome
(UBA1),
other
Cogan
Susac
may
some
similarities
with
them.
Annals of the Rheumatic Diseases,
Journal Year:
2023,
Volume and Issue:
83(3), P. 372 - 381
Published: Dec. 9, 2023
Vacuoles,
E1
enzyme,
X-linked,
autoinflammatory,
somatic
(VEXAS)
syndrome
is
an
acquired
autoinflammatory
monogenic
disease
with
a
poor
prognosis
whose
determinants
are
not
well
understood.
We
aimed
to
describe
serious
infectious
complications
and
their
potential
risk
factors.
Retrospective
multicentre
study
including
patients
VEXAS
from
the
French
Registry.
Episodes
of
infections
were
described,
factors
analysed
using
multivariable
Cox
proportional
hazards
models.
Seventy-four
133
included.
The
most
common
sites
infection
lung
(59%),
skin
(10%)
urinary
tract
(9%).
Microbiological
confirmation
was
obtained
in
76%:
52%
bacterial,
30%
viral,
15%
fungal
3%
mycobacterial.
Among
pulmonary
infections,
main
pathogens
SARS-CoV-2
(28%),
Legionella
pneumophila
(21%)
Pneumocystis
jirovecii
(19%).
Sixteen
per
cent
severe
occurred
without
any
immunosuppressive
treatment
daily
glucocorticoid
dose
≤10
mg.
In
multivariate
analysis,
age
>75
years
(HR
(95%
CI)
1.81
(1.02
3.24)),
p.Met41Val
mutation
(2.29
(1.10
5.10))
arthralgia
(2.14
(1.18
3.52))
associated
infections.
JAK
inhibitors
(3.84
(1.89
7.81))
compared
biologics
azacitidine.
After
median
follow-up
4.4
(2.5-7.7)
years,
27
(36%)
died,
15
(56%)
due
high
incidence
especially
older
carrying
treated
inhibitors.
frequency
atypical
treatment,
may
indicate
intrinsic
immunodeficiency.
American Journal of Hematology,
Journal Year:
2023,
Volume and Issue:
99(2), P. 254 - 262
Published: Dec. 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.
RMD Open,
Journal Year:
2023,
Volume and Issue:
9(3), P. e003332 - e003332
Published: Aug. 1, 2023
The
VEXAS
syndrome
(vacuoles,
E1
enzyme,
X-linked,
autoinflammatory,
somatic)
is
an
adult-onset
systemic
autoinflammatory
condition
that
caused
by
acquired
deficiency
of
the
UBA1
gene
in
hematopoietic
progenitor
cells.
clinical
spectrum
currently
comprises
a
broad
range
phenotypes
such
as
vasculitis,
relapsing
polychondritis
and
Sweet’s
syndrome.
In
past,
patients
have
left
clinicians
puzzled
true
nature
this
disease
has
not
been
captured
until
late
2020.
This
viewpoint
describes
relevant
features
reviews
different
approaches
to
establish
diagnosis.
Finally,
future
directions
within
field
inflammatory
diseases
somatic
mutations
are
being
discussed.
Journal of Allergy and Clinical Immunology,
Journal Year:
2024,
Volume and Issue:
153(3), P. 615 - 628.e4
Published: Jan. 6, 2024
Autoimmunity
in
inborn
errors
of
immunity
(IEI)
has
a
multifactorial
pathogenesis
and
develops
upon
genetic
predisposition
conjunction
with
gene
regulation,
environmental
modifiers,
infectious
triggers.
Based
on
incremental
data
availability
due
to
up-front
application
omics-technologies,
more
granular
dynamic
view
mechanisms
manifestations
is
warranted.
Here
we
present
comprehensive
novel
concept
autoimmunity
IEI
that
considers
multiple
layers
interdependent
elements
connects
101
causative
genes
or
deletions
according
the
quality
allelic
variants
47
molecular
pathways
22
immune
effector
mechanisms.
Furthermore,
list
50
resulting
together
corresponding
human
phenotype
ontology
(HPO)
terms
review
types
frequencies
most
relevant
clinical
presentations.
Together,
this
concept,
i),
extends
historical
anatomical
central
versus
peripheral
tolerance
towards
tolerance,
ii),
delineates
underlying
protean
manifestations,
thereby,
iii),
points
suitable
precision
therapy
for
IEI.
The
multilayer
autoimmune
will
facilitate
research
design
provide
guidance
use
medicine
irrespective
depth
available
each
health
care
scenario.
Journal of Thoracic Disease,
Journal Year:
2025,
Volume and Issue:
17(1), P. 461 - 475
Published: Jan. 1, 2025
This
review
is
describing
the
diagnostic
and
therapeutic
approach
to
tracheobronchial
involvement
in
relapsing
polychondritis
(RP),
with
a
focus
on
differential
diagnoses
of
inflammatory
origin.
RP
systemic
auto-immune
disease
that
mainly
affects
cartilage
structures,
progressing
through
flare-ups
between
phases
remission
ultimately
leading
deformation
involved
cartilages.
Besides
damage
auricular
or
nasal
cartilage,
cardiac
are
most
severe,
can
seriously
alter
prognosis.
Tracheobronchial
lesions
assessed
multimodal
approach.
Mapping
tracheal
achieved
using
dynamic
thoracic
imaging
flexible
bronchoscopy.
Measurement
pulmonary
function
(with
new
emphasis
pulse
oscillometry)
useful
diagnose
obstructive
ventilatory
impairment,
be
used
follow
patients,
after
therapeutics
implementation.
Diagnosis
difficult
absence
specific
tools,
especially
because
there
large
number
diagnoses,
particular
diseases.
Nuclear
help
detection
metabolic
activity
cartilages,
sharpen
final
diagnosis.
The
prognosis
has
improved,
thanks
upgraded
interventional
bronchoscopy
techniques,
development
immunosuppressant
including
targeted
therapies,
such
as
tumor
necrosis
factor-α
(TNF-α)
inhibitors,
offering
patients
several
treatment
options,
addition
supportive
care.
