American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel.

Objective: Vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality.

Methods: Given the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS.

Two-year efficacy and safety of anti-interleukin-5/receptor therapy for eosinophilic granulomatosis with polyangiitis.

Objectives: To summarise the efficacy and safety of 2 years of anti-interleukin-5/receptor (anti-IL-5/R) therapy in patients with eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: Patients were randomised 1:1 to receive benralizumab or mepolizumab every 4 weeks during the 52-week double-blind period of the MANDARA trial. Patients entered an open-label extension (OLE) in which they continued benralizumab (benralizumab/benralizumab) or switched from mepolizumab to benralizumab (mepolizumab/benralizumab).

Impaired cytotoxic function and exhausted phenotype of natural killer cells in VEXAS syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory disorder caused by acquired somatic UBA1 mutations in hematopoietic stem cells, affecting peripheral myeloid and natural killer (NK) cells. Given the high rate of severe infections observed in VEXAS patients, we hypothesized that NK cell dysfunction contributes to this increased susceptibility. We conducted a comprehensive immune characterization of peripheral NK cells in patients with VEXAS (n=40), patients with autoinflammatory diseases without UBA1 mutations (n=22), and elderly gender-matched healthy controls (HCs) (n=16).

Rituximab Versus Conventional Therapy for Remission Induction in Eosinophilic Granulomatosis With Polyangiitis : A Randomized Controlled Trial.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Rituximab has emerged as the standard of care in other types of ANCA-associated vasculitis, but controlled studies on its use in EGPA are yet lacking.

Objective: To compare rituximab with conventional strategy for the induction of remission in patients with EGPA.

Prognosis of essential mixed cryoglobulinemia and connective tissue disease-related cryoglobulinemia after rituximab-induced remission.

Objectives: Rituximab (RTX) and glucocorticoids are the first line treatment for essential (EM) and connective tissue disease (CTD)-related mixed cryoglobulinemia vasculitis (CryoVas). Data on long term outcomes of these CryoVas are lacking. We aimed to describe the prognosis of patients with EM and CTD-related CryoVas.

Advances in the treatment of ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) consists of a group of small-vessel vasculitides that often present with organ-threatening or life-threatening manifestations. Current immunosuppressive treatments have improved survival and rates of remission, but are not curative, have frequent toxicities, and do not effectively prevent relapse. Clinical trials have established the role of rituximab, an anti-CD20 B cell-depleting monoclonal antibody, in both the remission-induction and maintenance phases of the disease and demonstrated that glucocorticoid doses can be substantially reduced from historical dosing levels without affecting treatment efficacy.

Cluster analysis identifies three clinical patterns of patients with systemic autoimmune diseases and anti-Ku antibodies.

Objective: To determine distinct patterns of patients with autoimmune diseases harbouring anti-Ku antibodies and their respective prognosis.

Methods: Anti-Ku-positive patients were retrieved through four immunology departments. Clusters were derived from unsupervised multiple correspondence analysis, not including the disease's diagnosis, followed by hierarchical clustering.

Efficacy and glucocorticoid sparing of dupilumab in IgG4-related disease: a case series and literature review.

Objectives: IgG4-related disease (IgG4-RD) is a multisystem fibro-inflammatory disorder for which glucocorticoids (GC) represent the initial therapeutic intervention. Second-line treatments are not currently codified. The use of dupilumab, an inhibitor of interleukin (IL)-4 and IL-13 signalling, has recently been described as a potential alternative treatment.

Glucocorticoids versus glucocorticoids plus cyclophosphamide in eosinophilic granulomatosis with polyangiitis without poor-prognosis factors: a target trial emulation study.

Objectives: Current recommendations suggest treating eosinophilic granulomatosis with polyangiitis (EGPA) without severe manifestations with glucocorticoids (GCs) and EGPA with severe manifestations with GCs plus cyclophosphamide (CYC) regardless of poor-prognostic factors. However, GCs plus CYC and GCs alone have never been compared in EGPA without poor-prognosis factors assessed by the 1996 Five Factor Score (FFS). We aimed to compare the efficacy of GCs plus CYC vs GCs alone for the treatment of EGPA without poor-prognosis, including among patients with severe manifestations.

Efficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from the FRENVEX group.

VEXAS (Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic) syndrome is a severe monogenic disorder caused by somatic UBA1 mutations, characterized by inflammation, cytopenias and frequent association with myelodysplastic neoplasms (MDS). Steroid dependence is common, and targeted therapies have demonstrated limited efficacy. Azacitidine (AZA), a hypomethylating agent used in MDS, has shown potential in VEXAS but data remain limited.

Data-Driven Clustering Approach to Identify Different Phenotypes of Primary Central Nervous System Vasculitis.

Background: To determine whether hierarchical unsupervised cluster analysis identifies a phenotypic distinction in adult patients with primary CNS vasculitis (PCNSV).

Methods: An agglomerative hierarchical cluster analysis based on the Ward method was conducted, including 153 patients with complete baseline phenotypic characterization in the COVAC' registry.

Results: The hierarchical analysis identified two main clusters.

The emerging concept of ANCA-associated vasculitis related to inborn errors of immunity.

ANCA-associated vasculitis (AAV) is a group of rare small vessels vasculitis that preferentially affect the kidneys, lungs and upper airways. Although the detailed pathophysiology remains unclear, genetic background has been shown to play a role in sporadic forms of AAV. The discovery of these susceptibility genes (and associated biological pathways) involved in AAV have shaped the current understanding of AAV pathophysiology.

Impact of mepolizumab on the AAV-PRO questionnaire in eosinophilic granulomatosis with polyangiitis: data from a European multicentre study.

Objectives: To prospectively evaluate the impact and the rapidity of the effect of mepolizumab on the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire and patient global assessment (PtGA) in an international, multicentre cohort of patients with eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: Patients with active EGPA initiating treatment with mepolizumab were included. PtGA and the AAV-PRO score were assessed at baseline and after 7, 14, 30, 90 and 180 days.

Treatment of mixed connective tissue disease: A multicenter retrospective study.

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic disorder that belongs to connective tissue diseases (CTD). Few studies are available on MCTD treatment.

Methods: We conducted an observational study within the French MCTD cohort.

Pilot Study of Diagnostic Performances of Vascular Biomarkers Soluble fms-Like Tyrosine Kinase and Placental Growth Factor in Scleroderma Renal Crisis.

Introduction: Scleroderma renal crisis (SRC) is a major vascular complication of systemic sclerosis (SSc), associated with high morbidity and mortality. In this retrospective study, we evaluated the potential prognostic and diagnostic roles of angiogenesis molecules, placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and sFlt1/PlGF ratio as biomarkers in SRC.

Methods: Sera samples from 27 patients with a history of SRC (SSc-SRC+) were collected following event occurence.

Immune checkpoint inhibitors-induced large vessel vasculitis: clinical characteristics and management from a European multicentre study.

Objective: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but frequently cause immune-related adverse events (IrAEs). ICI-induced large vessel vasculitis (LVV) is a rare IrAE, with limited available data. We aimed to describe and compare clinical characteristics and evolution of ICI-induced LVV to primary LVV.

Relevance of anti-platelet factor 4/heparin antibodies and platelet activation in systemic inflammatory diseases and thrombosis disorders: insight from the COVID-19 pandemic.

Background: The increased interest in anti-platelet factor 4 (PF4)-heparin complex (anti-PF4/H) antibodies following the COVID-19 pandemic has established them as crucial players in immunothrombosis.

Objectives: We aimed to investigate the involvement of anti-PF4/H antibodies during COVID-19 and after vaccination, particularly in patients with systemic inflammatory disease (SID).

Methods: This retrospective study analyzed the presence of anti-PF4/H antibodies and their ability to induce platelet activation in COVID-19 patients with and without suspected heparin-induced thrombocytopenia (HIT), vaccine-induced immune thrombotic thrombocytopenia (VITT) patients, and in controls and SID patients following COVID-19 vaccination.

Inflammatory Signatures in VEXAS Syndrome, Myelodysplasia Cutis, and Sweet Syndrome.

Importance: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a monogenic disease caused by UBA1 somatic variants in hematopoietic progenitor cells, mostly involving adult men. It is associated with inflammatory-related symptoms, frequently involving the skin and hematological disorders. Recently described myelodysplasia cutis (MDS-cutis) is a cutaneous manifestation of myelodysplasia in which clonal myelodysplastic cells infiltrate the skin.

Symptomatic Occlusive Retinal Vasculitis as an Unusual Presentation of Biopsy-Proven Sarcoidosis: A Case Series.

Purpose: The presentation of ocular sarcoidosis may involve different parts of the eye and/or adnexal tissues. Uveitis is the most common manifestation, and when it involves the posterior segment, it often presents as peripheral multifocal choroiditis. The occurrence of symptomatic occlusive retinal vasculitis (ORV) associated with ocular sarcoidosis is not well described in the literature.