Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Granulomatose Eosinofílica com Poliangiite, para atualização médica.
A newsletter apresenta os resultados do estudo REPLENISH, que valida o secuquinumabe como uma nova opção biológica para a polimialgia reumática, dobrando as taxas de remissão sustentada. São discutidos também novos insights do EULAR 2026, incluindo a distinção entre entesófitos inflamatórios e mecânicos, o valor prognóstico do fator reumatoide na GEPA e o potencial das fibras dietéticas em melhorar a resposta clínica ao metotrexato na artrite reumatoide.
In this exploratory study, higher 2022 AECC scores at diagnosis were associated with greater disease activity and damage accrual. These findings should be interpreted as exploratory observations. A prospective evaluation of the clinical implications of classification scores beyond their intended purpose is needed.
The diagnostic delay in AAV varies by disease subtype and clinical presentation. EGPA shows the numerically longest time to diagnosis, while renal involvement seems to facilitate earlier diagnosis. Enhanced awareness among non is essential to reduce diagnostic delay and prevent organ damage, although outcome measures were not assessed in our study. Key Points • Diagnostic delay in ANCA-associated vasculitis varies between disease subtypes, organ involvement, and consulted specialties. • EGPA shows the numerically longest diagnostic delay, whereas renal involvement seems to facilitate earlier diagnosis. • Earlier recognition of AAV across specialties may reduce diagnostic delay and prevent organ damage.
Arthritis &Rheumatology, Volume 78, Issue 3, Page 695-704, March 2026.
Autoimmune rheumatic diseases (ARDs) are a diverse group of chronic disorders characterized by immune dysregulation and multi-organ inflammation. B cell receptor (BCR) signaling emerges as a shared, yet heterogeneously regulated, pathogenic axis across these diseases. This dysregulation drives B cell activation, autoantibody production, and ultimately tissue damage. Recent research highlights its involvement in both common and disease-specific mechanisms, which helps explain the wide variation in clinical features and therapeutic responses across ARDs. This review summarizes current evidence establishing BCR signaling as a central regulatory and therapeutic target in rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, IgG4-related disease, and ANCA-associated vasculitis. It integrates mechanistic insights with recent clinical trial data on BCR signaling-targeted therapies, discussing factors that may contribute to variability in therapeutic responses and treatment limitations. Finally, we outline current challenges and future directions for precision medicine in ARDs, with a focus on biomarker-guided strategies and innovative combination therapies to improve patient outcomes.
A newsletter destaca que a normalização da IgG total no primeiro ano de tratamento é um preditor de recaída superior à IgG4 na Doença Relacionada à IgG4. Discute também que pacientes com vasculite anti-MPO apresentam maior risco cardiovascular e menor tempo para eventos adversos do que os anti-PR3. Por fim, aborda como a fragilidade impacta a tolerância aos corticoides na polimialgia reumática e o papel dos iSGLT2 na redução da necessidade de alopurinol.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare and heterogeneous immune-mediated disorder in which eosinophilic inflammation, vasculitis, and airway disease coexist in highly variable combinations. In clinical practice, diagnosis remains challenging because no single biomarker reliably captures disease complexity, and therapeutic decisions must still be based on careful integration of clinical, laboratory, imaging, and histopathological findings. In recent years, EGPA management has evolved from a largely glucocorticoid-based approach toward a more phenotype-oriented strategy that distinguishes eosinophilic and vasculitic manifestations and incorporates targeted biologic therapies. This Perspective discusses current challenges and emerging opportunities in EGPA diagnosis and treatment, with emphasis on early recognition, multidisciplinary assessment, glucocorticoid-sparing strategies, and individualized long-term follow-up. Specific recommendations are provided on diagnostic orientation, phenotype-driven therapeutic selection, and the practical use of conventional immunosuppressants and anti-IL-5/IL-5R biologics according to disease severity and organ involvement. In addition, we propose a new treatment algorithm intended to support real-world decision-making and to facilitate a more consistent and structured approach to care. By combining expert recommendations with a forward-looking perspective on evolving therapeutic strategies, this article aims to contribute to safer, more effective, and more personalized management of patients with EGPA.
ANCA-associated vasculitis (AAV) is a rare multisystem autoimmune disease in which diagnostic delay remains common and contributes to organ damage. This study aimed to develop a multispecialty, consensus-based set of clinical, laboratory, and imaging red flags to facilitate early recognition across medical disciplines. A structured consensus process inspired by modified Delphi methodology and the RAND/UCLA Appropriateness Method was conducted. A multispecialty panel including rheumatologists, nephrologists, and specialists in internal medicine, otolaryngology, pulmonology, ophthalmology, and neurology evaluated a comprehensive list of AAV manifestations. All items were scored on a 0-10 relevance scale through inter-specialty voting. Following five intra-specialty Scientific Discussion Sessions to interpret scores and refine items, a second-round evaluation was performed, and a final meeting validated the definitive checklist. Organ-specific manifestations without a better explanation involving the upper airways, kidneys, nervous system, lungs, and eyes were consistently rated as the most relevant red flags for early AAV recognition. High relevance was attributed to refractory ENT (Ear, Nose and Throat) disease, active urinary sediment, otherwise unexplained central or peripheral neurological deficits in young individuals, inflammatory ocular involvement, and pulmonary hemorrhagic features. Systemic symptoms showed lower relevance scores and were considered supportive rather than specific indicators. In parallel, a unified panel of first-level laboratory and instrumental investigations was defined to facilitate early multisystem assessment when AAV is suspected. This multispecialty consensus-based checklist provides a pragmatic tool to support early suspicion of AAV in routine clinical practice and may help reduce diagnostic delay.
Interleukin-5 (IL-5) is central to eosinophil differentiation, survival, and activation. Subsequent studies confirmed IL-5 receptor expression and mapped downstream signaling, showing that IL-5 promotes not only survival but also trafficking and effector functions, including adhesion, degranulation, reactive oxygen species generation, mediator release (cytokines and cysteinyl leukotrienes), and extracellular trap formation. However, the roles of eosinophils vary across diseases and tissue compartments. Multi-omics analyses of blood and tissue eosinophils across transcriptomic, proteomic, and lipid-metabolic layers reveal disease- and site-specific molecular states. These data support two opposing classes of modulators that shape IL-5-driven programs: pro-inflammatory signals (IL-4/IL-13, IL-33, NOD2-mediated innate signaling, and IFN-γ) that drive inflammatory eosinophil changes and can cooperate in some settings, and counter-regulatory signals (IFN-α and all-trans retinoic acid [ATRA]) that restrain these changes. Such modulation may influence tissue retention, effector functions, and broader eosinophil activities, including antiviral and homeostatic roles. Clinical studies of anti-IL-5 and/or anti-IL-5Rα biologics in severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndromes, and other eosinophilic diseases have improved outcomes, underscoring that disease activity often depends on IL-5-driven eosinophil activation despite disease-specific IL-5-independent signals. In this review, we summarize IL-5 biology from mechanisms to therapy and discuss how integrated multi-omics signatures and clinical biomarkers may guide patient stratification, therapy selection, and treatment sequencing toward precision medicine for eosinophilic respiratory and systemic diseases. .
Purpose of review The aim of this review is to describe the substantial advances that have been made in the past 2 years on new treatment options in eosinophilic granulomatosis with polyangiitis (EGPA). Recent findings The therapeutic scenario in EGPA has been recently broadened by the publication of the results from the multicenter, double-blind randomized MANDARA trial, which proved the noninferiority of benralizumab to another anti-interleukin-5 (IL-5) drug, mepolizumab, for the induction of remission in patients with EGPA. A few real-world studies have confirmed these results. Furthermore, the first randomized controlled trial exploring the efficacy of rituximab (anti-CD20) in induction of remission of EGPA was recently published. Targeting other molecular pathways did not always show adequate control of systemic manifestations of EGPA, with only limited evidence of effectiveness from small case series. Interestingly, cases of EGPA onset in severe asthma patients treated with monoclonal antibodies were described. Summary Biological drug therapy targeting IL-5 consolidated its role in the management of EGPA, becoming the cornerstone of the treatment of this rare disease. Future guidelines should consider these recent findings to improve the management of EPGA. Notably, while selective IL-5 targeting is highly effective for remission maintenance, its role in inducing remission in EGPA remains to be fully established. Rituximab was non-superior to standard therapy in induction of remission in patients with EGPA, demonstrating a similar rate of response. The role of other targeted therapies, albeit promising in some cases, remains a matter of debate.
Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a small vessel vasculitis characterized by eosinophilia, asthma, and ear, nose, throat (ENT) involvement. Although glucocorticoids (GCs) are effective in controlling symptoms, relapses and GC dependence are common. The aim of this study was to develop predictive models for vasculitis relapse and GC‐dependent asthma and/or ENT symptoms. Methods This multicenter European retrospective cohort study included EGPA patients fulfilling the 2022 ACR/EULAR criteria. Using the PMSAMPSIZE algorithm, we developed two multivariable prediction models: one for vasculitis relapse and another for GC‐dependent asthma and/or ENT symptoms at 2 years. Internal validation was performed using bootstrapping. Results A total of 809 patients were followed for a median of 72 months (interquartile range, IQR 37‐115). Vasculitis relapse occurred in 228 patients with a 12‐year cumulative incidence of 41.2% (95% CI 36.3‐46.8). GC‐dependent asthma and/or ENT symptoms were observed in 66.4% at 2 years. Predictors of vasculitis relapse included age (nonlinear), GC‐dependent asthma before EGPA diagnosis (hazard ratio, HR 1.57), arthralgia (HR 1.27), myocarditis (HR 1.74), peripheral neuropathy (HR 1.39), MPO‐ANCA (HR 1.56), and baseline eosinophil count (nonlinear). Predictors of GC‐dependent asthma and/or ENT symptoms included older age (odds ratio, OR 0.98 per year), GC‐dependent asthma at diagnosis (OR 1.50), chronic sinusitis (OR 1.78), and baseline eosinophil count (OR 0.70 per 10 9 /L). Conclusion Using a large EGPA cohort, we developed predictive models for vasculitis relapse and GC‐dependent asthma and/or ENT symptoms. These tools may help guide treatment decisions. Prospective external validation in the current therapeutic era is warranted.
To assess the performance of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA) in a multicenter cohort in Eastern China and compare it against the 1990 ACR and 2017 mepolizumab in relapsing or refractory EGPA (MIRRA) criteria. EGPA patients diagnosed between January 2018 and March 2025 were included in the study, and the diagnosis by "an expert panel" was used as the gold standard. The sensitivity, specificity, positive/negative predictive value (PPV, NPV), accuracy and receiver operating characteristic (ROC) curves of three sets of classification criteria (1990 ACR, 2017 MIRRA and 2022 ACR/EULAR) were evaluated. A total of 96 EGPA patients and 163 controls including 91 cases of other types of vasculitis and 72 cases of eosinophilic disorders were enrolled. 2022 ACR/EULAR classification criteria had the highest sensitivity of 87.5% and accuracy of 94.2% compared with 1990 ACR and 2017 MIRRA criteria. However, the specificity (98.2%) was slightly lower than that of the 1990 ACR and 2017 MIRRA criteria in the entire control. Thirty-five patients (36.5%) fulfilled all three criteria. The most sensitive item was eosinophilia (eosinophil ratio > 10% or count ≥ 1 × 109/L), with a sensitivity of 90.6%, followed by eosinophil ratio > 10% (89.6%) and eosinophil count ≥ 1 × 109/L (82.3%). The most specific item was vascular wall eosinophils (98.6%). The 2022 ACR/EULAR classification criteria demonstrated significant improvement in sensitivity and accuracy while maintaining a relatively high level of specificity. It is noticing that these criteria should not be used for the diagnosis of EGPA. Key Points • 2022 ACR/EULAR EGPA classification criteria were validated in a cohort of China. • 2022 ACR/EULAR criteria had higher sensitivity and accuracy compared to 1990 ACR criteria and 2017
Interlukin‐5 (IL‐5) plays a crucial role in the pathogenesis of eosinophilic granulomatosis with polyangiitis (EGPA) by promoting eosinophil differentiation, activation, and survival. We present here a typical case of EGPA in which treatment with IL‐5 pathway inhibitors is prescribed, showing to be beneficial for the patient. We discuss available evidence proving the association between IL‐5 and clinical activity in EGPA and review the clinical efficacy and safety of currently approved IL‐5 pathway inhibitors (i.e. mepolizumab and benralizumab) that improve disease control, reduce relapse rates, and have significant glucocorticoid‐sparing effects in EGPA by reducing eosinophilic inflammation.
Immunoglobulin G4-related disease (IgG4-RD) is a rare, multisystemic fibro-inflammatory condition affecting various organs, including kidneys, lungs, nasal cavity, pancreas, salivary glands, and orbit. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) is a multi-systemic inflammatory vascular disease encompassing eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA). It often overlaps with the organs or tissues affected by IgG4-RD. Clinically, some individuals with IgG4-RD are ANCA-positive, while some with AAV exhibit elevated IgG4 levels or IgG4-positive plasma cell infiltration, making these conditions difficult to distinguish. Reports have documented cases of overlap syndromes involving IgG4-RD and AAV, highlighting shared pathogenic mechanisms that may include macrophages, B cells, CD4+T cells, and inflammatory cytokines. However, the pathophysiological mechanism underlying these overlap syndromes remains unclear. This review examines potential pathophysiological links between IgG4-RD and AAVs (GPA/MPA) overlap syndromes.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody-associated vasculitis causing multi-organ damage and long-term disability. Various treatments including IL-5-targeting agents and other biologics have recently emerged, prompting regular updates of clinical practice guidelines. This scoping review and systematic review (SR) aimed to evaluate the efficacy and safety of rituximab and benralizumab in EGPA. A scoping review was conducted to identify relevant clinical questions, followed by an SR of trials published between December 2018 and July 2023. Studies comparing rituximab or benralizumab with standard treatments were included. Risk of bias (RoB) was assessed using RoB 2 and quality of evidence was rated using GRADE. One randomised controlled trial (RCT; n = 105) comparing rituximab with conventional therapy, showed a 180-day remission rate of 63.5% vs. 60.4% (risk ratio 1.05, 95% CI 0.78-1.42), with very low certainty due to serious RoB and imprecision. Another RCT compared benralizumab with mepolizumab, showing similar rates of remission (58.6% vs. 55.7%), relapse (30%), and glucocorticoid tapering, with low certainty owing to imprecision. Rituximab showed no clear benefit over conventional therapy, whereas benralizumab demonstrated comparable efficacy and safety to mepolizumab. However, evidence remains limited, and further EGPA-specific trials are needed.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis in which cardiac involvement is a primary cause of mortality. Complete heart block presenting as Adams-Stokes syndrome is a rare but critical complication. Notably, to our knowledge, EGPA initially manifesting as Adams-Stokes syndrome has not been previously documented, based on a comprehensive review of the literature. We report a 27-year-old female presenting with recurrent syncope and seizures. Laboratory tests revealed significant eosinophilia (49.5%), and cardiac workup confirmed third-degree atrioventricular block. A diagnosis of EGPA was established based on the 2022 ACR/EULAR criteria (score=13). Emergency treatment involved temporary pacing and methylprednisolone pulse therapy, followed by mepolizumab induction. Sinus rhythm recovered within 24 hours. During a two-month follow-up, the patient maintained remission with normalized eosinophil counts and improved cardiac function. This case highlights the importance of including EGPA in the differential diagnosis of unexplained high-grade heart block and supports the efficacy of early immunosuppressive therapy in reversing life-threatening cardiac complications.
To assess the 2022 American College of Rheumatology (ACR)/EULAR classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in children with chronic small-to-medium vessel vasculitis. A cohort of 574 patients, identified by physician's diagnosis (MD-diagnosis) in A Registry of Childhood Vasculitis, was classified by computation of registry data as having granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or eosinophilic GPA after applying (1) ACR/EULAR AAV criteria and (2) pediatric-adapted European Medicines Agency (Ped-EMA) classification algorithm (incorporating Ankara GPA criteria). Venn diagrams compared the resulting GPA and MPA cohorts with MD-diagnosis. Sensitivity and specificity of criteria for GPA were evaluated against MD-diagnosis. Fisher exact test evaluated differences in the frequencies of individual clinical features in GPA versus MPA. Comparing ACR/EULAR criteria against the Ped-EMA algorithm for classifying AAV, more patients were classified as GPA or MPA (n = 396 vs 360, respectively), fewer had GPA (n = 261 vs 288, respectively), more had MPA (n = 135 vs 72, respectively), and fewer GPA cases coclassified as MPA (12% vs 28%, respectively); there were more differences between GPA and MPA in Pediatric Vasculitis Activity Score-defined clinical features (n = 14 vs 10, respectively). When classifying GPA by ACR/EULAR or Ankara criteria, sensitivity (74.5% vs 72.1%, respectively) was comparable, and specificity for ACR/EULAR criteria (93.9% vs 79.9%, respectively) was improved. The 2022 ACR/EULAR classification criteria for AAV perform at least as well as previous pediatric criteria and provide categorical MPA criteria where none existed previously; the criteria for GPA and MPA now specifically differentiate each other, with more differences between them in the frequencies of clinical features. Our findings support the preferential use of ACR/EULAR over Ankara criteria for GPA in pediatrics.
Real-world practice patterns of eosinophilic granulomatosis with polyangiitis (EGPA) remain poorly defined. This study aimed to describe current diagnostic and therapeutic approaches across experienced European centres, identifying areas of convergence and variability to inform future standardization of care. We distributed a 44-item online survey covering diagnostic evaluation, treatment strategies, patient-reported outcome measures (PROMs) and the role of patient advocacy groups. The survey was reviewed by an expert panel and disseminated within the European EGPA Study Group. Responses were collected anonymously between April and August 2025 for statistical analysis. Fifty-four experts from six countries participated, most with long-standing experience and substantial EGPA caseloads. Multidisciplinary care and screening for cardiac and renal involvement were widely adopted; histological confirmation was reported in fewer than 25% of cases. Treatment strategies varied considerably: over half of respondents initiated anti-IL-5 therapy at diagnosis, and the combination of glucocorticoids, rituximab and mepolizumab was the preferred induction regimen in severe disease. CS tapering protocols differed, with most clinicians targeting withdrawal within 12 months. PROMs and disease-specific questionnaires were used inconsistently, despite broad recognition of their value. Advocacy groups were viewed as crucial, particularly for patient education and referral. This first multinational survey reveals substantial heterogeneity in real-world diagnostic and therapeutic practice, reflecting gaps in validated criteria, standardized activity measures and treatment algorithms. These findings highlight the need for coordinated prospective research and harmonized evidence-based guidance to optimize outcomes for patients with EGPA.
This study describes data from bronchoscopies performed at the diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) in Chinese patients. We conducted a retrospective study between May 2005 to May 2023 in patients with EGPA who underwent bronchoscopy at the initial diagnosis of the disease. Clinical manifestations and bronchoscopic findings were analysed. 109 patients with EGPA were included, 59 males (54.1%). The most common clinical manifestations were asthma in 104 patients (95.4%), rhinosinusitis in 101 patients (92.7%), and peripheral neuropathy in 70 patients (64.2%). Eosinophilia (>1.0×109/L) was present in 87 patients (79.8%). ANCA positivity was found in 18 patients (16.5%). The most common chest imaging findings were ground-glass opacities in 61 patients (56.0%), bronchial wall thickening and bronchiectasis in 53 patients (48.5%), and consolidation in 52 patients (47.7%). All 109 patients underwent bronchoscopy at diagnosis of the disease. The most common bronchoscopic findings were mucosal oedema and inflammatory changes in 95 patients (87.2%), with specific changes being less common, including tracheobronchial stenosis in 12 patients (11.0%), mucosal nodules and masses in 10 patients (9.2%), and bleeding in 1 patient (0.9%). Transbronchial biopsy (TBB) was performed in 93 patients, with 76 (81.7%) showing pathological support for EGPA, including eosinophilic infiltration in 72 patients (77.4%), vasculitis in 23 patients (24.7%), and granulomas in 7 patients (7.5%). 2 patients underwent transbronchial needle aspiration biopsies of mediastinal lymph nodes, and pathology revealed eosinophilic infiltration and granulomas in both cases. Bronchoalveolar lavage (BAL) was performed in 89 patients, with 67 (75.3%) showing eosinophilia (>1%), and the median percentage of eosinophils was 9 (1, 33%). Bronchoscopy plays a crucial role in patients with EGPA by detecting endobronchial lesions, providing definitive pathological evidence, and identifying eosinophilic infiltration or
Serious infections in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) represent a contributor to morbidity and mortality. Patients are susceptible to both typical and opportunistic infections due to immunocompromise resulting from immunosuppressive treatments and disease activity. Over the past decade, studies predominantly in retrospective cohorts have outlined the incidence and nature of serious infections, including organ involvement and pathogens, as well as various risk factors for serious infections. This review summarises the recent literature on serious infections and discusses risk factors for these infections; we have categorised them into baseline characteristics, laboratory values, end-organ damage, and immunosuppressive treatments. It discusses emerging data on the role of reduced glucocorticoid regimens and trimethoprim-sulfamethoxazole prophylaxis in preventing serious infections. Finally, implications on clinical practice and important avenues for future research are discussed.
To characterize adult hospitalizations for eosinophilic granulomatosis with polyangiitis (EGPA) in the United States and identify clinical and sociodemographic factors independently associated with in‑hospital mortality. We conducted a retrospective analysis of the National Inpatient Sample Database (2016-2022) to identify adult EGPA hospitalizations. Demographics, comorbidities, complications, insurance type, income quartile, length of stay, and total charges were compared between survivors and nonsurvivors. Variables with p ≤ 0.2 in univariable analysis were entered into multivariable logistic regression to determine independent predictors of in‑hospital death. Among 12,900 EGPA hospitalizations, 355 patients died (2.75%). Nonsurvivors were older, had longer hospitalizations, and incurred higher total hospital charges. In multivariable analysis, cardiac disease (OR: 1.94; 95% CI: 1.157-3.237), central nervous system (CNS) involvement (OR: 2.91; 95% CI: 1.004-8.453), gastrointestinal (GI) disease (OR: 3.05; 95% CI: 1.159-8.042), infection (OR: 3.87; 95% CI: 2.123-7.046), interstitial lung disease (OR: 2.62; 95% CI: 1.227-5.598), and renal disease (OR: 5.20; 95% CI: 2.784-9.708) were independently associated with in‑hospital mortality. Demographic and socioeconomic variables, including sex, race/ethnicity, insurance type, and income quartile, were not independent predictors of in-hospital death. In this nationally representative cohort, in‑hospital mortality for EGPA was 2.75%. Renal, infectious, cardiac, CNS, GI, and pulmonary complications were strongly associated with death. These findings underscore the need for early recognition and aggressive management of organ‑threatening disease and infection in hospitalized EGPA patients.