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.

Cluster analysis reveals the clinical spectrum of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a clonal-inflammatory neoplasm driven by mutations in MAPK pathway proto-oncogenes, such as BRAF. Clinical manifestations are protean, affecting virtually every system. This cohort study analyzed 661 patients with ECD to classify them based on clinical features and mutational profiles using unsupervised clustering.

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.

Characterization and treatment outcomes of malignant histiocytoses in a retrospective series of 141 cases in France.

Malignant histiocytoses (MH) are rare and poorly understood cancers, with no established therapeutic guidelines. We conducted a national retrospective study of MH diagnosed in France between 2000 and 2023. All cases underwent centralized histological review, and several malignant tumors with a stroma highly enriched in histiocytes were excluded.

Real-life use of the PEXIVAS reduced-dose glucocorticoid regimen in granulomatosis with polyangiitis and microscopic polyangiitis.

Background: The PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC.

Hypereosinophilia and Hypereosinophilic Syndromes: First Findings From a Nationwide Multicenter Cohort.

Background: Hypereosinophilic syndromes (HES) are a heterogenous group of eosinophilic disorders. To date, only retrospective studies of limited sample-size and/or follow-up duration are available.

Methods: The COHESion study is a national prospective multicenter multidisciplinary cohort recruiting both adults or children with the spectrum of eosinophilic disorders (including reactive HE/HES [HE/HES-R], idiopathic HES [HES-I], lymphocytic HES [HES-L], neoplastic HE/HES [HE/HES-N], HE of unknown significance [HE-US], as well as IgG4-related disease [IgG4RD] or ANCA-negative eosinophilic granulomatosis with polyangiitis [EGPA] overlaps).

Long-term follow-up of the STOPAGO study.

In an open prospective, multicenter study enrolling 48 selected patients with chronic immune thrombocytopenia who achieved complete response for 1 year on thrombopoietin receptor agonists, half of the patients maintained a sustained response off treatment 4 years after treatment discontinuation.

Efficacy and safety of mammalian target of rapamycin inhibitors in systemic mastocytosis: A nationwide French pilot study.

Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM.

Involvement of the JAK-STAT pathway in the molecular landscape of tyrosine kinase fusion-negative hypereosinophilic syndromes: A nationwide CEREO study.

We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion-negative hypereosinophilia (HE)/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50/64 (78%) patients (compared to 8/44 (18%) patients with idiopathic HE/HES/HE used as controls; p < .001).

Histological characterization of liver involvement in systemic mastocytosis.

Background And Aims: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools.

Disease patterns and specific trajectories of anti-MDA5-related disease: a multicentre retrospective study of 70 adult patients.

Introduction: This study aimed to provide an updated analysis of the different prognostic trajectories of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies.

Methods: Among a cohort of 70 patients, baseline characteristics and phenotypes, treatments and outcomes were analyzed. A Cox proportional hazards model was used to identify factors associated with poor outcomes, i.

Dysregulation of neutrophil oxidant production and interleukin-1-related cytokines in granulomatosis with polyangiitis.

Objectives: Neutrophils play a key role in ANCA-associated vasculitis, both as targets of autoimmunity and as facilitators of vascular damage. In granulomatosis with polyangiitis (GPA), the data regarding the production of reactive oxygen species (ROS) in neutrophils are unclear. Further, recent data suggests that ROS production could have an anti-inflammatory effect through the regulation of inflammasomes and IL-1-related cytokines.

Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA.

Pathophysiologic implications of elevated prevalence of hereditary alpha-tryptasemia in all mastocytosis subtypes.

Background: Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal.