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.
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.
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.
Immune-mediated cochleovestibular dysfunction has gained recognition as an important yet frequently overlooked entity in recent decades. These disorders-ranging from isolated inner-ear syndromes to cochleovestibular manifestations of systemic autoimmune diseases-exhibit humoral or cellular immune attacks on inner-ear structures, commonly accompanied by microvascular injury and inflammatory cascades. Despite increasing awareness, the precise pathophysiological mechanisms remain incompletely understood for most conditions, and diagnostic and therapeutic approaches vary considerably. This narrative review summarizes current evidence on immune-mediated cochleovestibular disorders, dividing them into two main categories (1): primary Isolated disorders (delayed endolymphatic hydrops, bilateral vestibulopathy, and Ménière's disease with established or suspected autoimmune features) (2) cochleovestibular manifestations of rheumatologic diseases (systemic lupus erythematosus, multiple sclerosis, autoimmune thyroid disease, Behçet's disease, Vogt-Koyanagi-Harada disease, psoriasis, Cogan's syndrome, Susac syndrome, Sarcoidosis, Rheumatoid arthritis, Necrotizing vasculitides with polyangiitis and Giant cell arteritis). We examine their clinical features, proposed immune and microvascular mechanisms, diagnostic evaluation, and current management strategies, with particular emphasis on immunomodulatory and immunosuppressive therapies. Systemic corticosteroids at high doses are the primary treatment for most of these disorders, though the ideal duration, tapering protocols, and indications for steroid-sparing medications differ significantly across various syndromes. Evidence supporting many adjunctive therapies is limited or conflicting, underscoring the need for higher-quality clinical trials. Early recognition and prompt immunomodulatory treatment can often reverse or stabilize symptoms in immune-mediated cochleovestibular dysfunction. This review offers a clinically oriented synthesis of current evidence, elucidating the complex immunological underpinnings and the corresponding therapeutic landscape of these disorders. By integrating otologic and rheumatologic perspectives, we aim to heighten awareness, promote earlier diagnosis, and inform more effective treatment of patients presenting with vertigo, hearing loss, or imbalance suggestive of immune-mediated inner-ear pathology.
Antineutrophil cytoplasmic autoantibody-associated vasculitides can be classified by clinical phenotype or antineutrophil cytoplasmic autoantibody specificity, with overlapping yet distinct characteristics. Transcriptomic analyses of kidney biopsies from 2 French antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) cohorts revealed a pronounced type I interferon signature in microscopic polyangiitis (microscopic polyangiitis/myeloperoxidase-AAV) compared with granulomatosis with polyangiitis (granulomatosis with polyangiitis/proteinase 3-AAV). Among biopsies with high interferon scores, 66% were myeloperoxidase-AAV and 28% proteinase 3-AAV. The interferon score was associated with decreased kidney survival. These findings highlight AAV patient heterogeneity and support targeted treatment approaches.
The aim of this study was to investigate the relationship between antineutrophil cytoplasmic antibodies (ANCA) specificity and the risk of major adverse cardiovascular events (MACE) in patients with ANCA-associated vasculitis (AAV). We conducted a retrospective study using the ANCA-associated vasculitis Toulouse cohort. The incidence of MACE, defined as myocardial infarction (MI) and/or stroke and/or all-cause death, was compared among patients according to their ANCA specificity. We also applied Cox regression models adjusted for traditional cardiovascular risk factors, age and sex to assess the risk of MI, stroke and MACE. A total of 402 patients were included, of whom 166 (41%) had antiproteinase 3 (anti-PR3) ANCA and 236 (59%) had antimyeloperoxidase (anti-MPO) ANCA. We identified 78 MACE during the follow-up period, including 15 MIs, 12 strokes and 62 deaths. The incidence rate of MACE in the ANCA+anti-PR3+ group was 21.4 per 1000 patient-years compared with 33.1 per 1000 patient-years in the ANCA+anti-MPO+ group (p=0.036). The time elapsed between the diagnosis of AAV and MACE occurrence was significantly shorter in the ANCA+anti-MPO+ group. The Cox regression model found that patients with anti-MPO ANCA tend to present more MACE, but the association was not statistically significant (HR 1.62; 95% CI 0.98 to 2.66; p=0.06). An association was found between the presence of anti-PR3 ANCA and a lower risk of strokes (HR 0.61; 95% CI 0.37 to 0.99; p=0.049) and none with the risk of MI. Patients with anti-MPO ANCA appear to be at a higher risk of a composite MACE-all-cause mortality outcome than patients with anti-PR3 ANCA.
Abstract Objectives Rituximab (RTX) is a standard maintenance therapy for ANCA-associated vasculitis. Its efficacy in Japan remains unclear, where microscopic polyangiitis (MPA) predominates and clinical characteristics differ from Western-dominated RCT populations. Methods Japanese patients with MPA or granulomatosis with polyangiitis (GPA) enrolled in a nationwide registry were included. Exposure was RTX use during maintenance therapy. The primary endpoint was major relapse-free survival at 104 weeks. The secondary endpoint was any relapse-free survival (major or minor) at 104 weeks. Baseline differences were adjusted using inverse probability of treatment weighting (IPTW) based on key demographic and disease-related covariates. Results A total of 389 patients were analyzed, with 85 in the RTX group. The RTX group included a higher proportion of GPA cases (37/85 vs. 74/304), resulting in baseline imbalance. After IPTW, no major relapses were observed in the RTX group, whereas the major relapse-free survival at 104 weeks was 94.8% in the non-RTX group. The RTX group showed significantly higher any relapse-free survival at 104 weeks (95.4% vs. 83.3%; HR for any relapse, 0.27; 95% CI, 0.09–0.74; p = 0.02). Conclusions Our findings suggest that RTX may be an effective option for remission maintenance in Japanese patients with MPA or GPA.
Objective Ear, nose and throat (ENT) manifestations are common in ANCA‐associated vasculitis (AAV). There is unmet need for drugs to target these manifestations. Granuloma formation is characteristic of proteinase 3 (PR3)‐AAV. In a zebrafish model, niclosamide inhibits PR3‐induced granuloma formation. We hypothesised that intranasal niclosamide would reduce AAV‐associated ENT symptoms. Methods PROTECT‐V was a randomised, double‐blind, placebo‐controlled platform trial evaluating pre‐exposure prophylaxis agents against COVID‐19 infection. This sub‐analysis includes patients from a single centre, with AAV, enrolled into the intranasal niclosamide arm. Clinical data were retrospectively collected for nine months before, during, and nine months after treatment. Researchers were blinded to treatment allocation. Results Of thirty‐two (14 niclosamide; 18 placebo) patients, 11 (34%) were female; median age was 69 years (IQR 59‐75). Median prior AAV disease duration was 5.4 years (IQR 1.9‐13.1); 19 (59%) had active disease in the year prior to treatment. Median treatment exposure was 200 days (IQR 109‐251). During treatment, ENT symptoms were identified in 1/14 (7%) of the niclosamide group compared with 7/18 (39%) of the placebo group (p = 0.04). No significant difference between groups was found in the nine months before or after treatment. Among PR3‐ANCA‐positive patients, 0/10 in the niclosamide group compared to 5/9 (56%) in the placebo group had ENT symptoms during treatment. Conclusion These data are a signal of potential clinical effect on ENT manifestations in AAV. They support a role for the IL6/STAT3 pathway in AAV; intranasal niclosamide or other drug candidates in this pathway warrant further evaluation.
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
Abstract Objectives To examine contemporary trends in mortality due to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in Europe. Methods We utilised publicly available data from Eurostat on deaths recorded with GPA or MPA as the underlying cause of death for the period 2011–2021. Crude and standardised mortality rates (SMRs) were calculated for each country and linear regression used to determine changes in mortality rates over time. Crude mortality rate was also stratified by age and sex. To investigate the association between geography and mortality rate, the SMR for each country was displayed on a choropleth map and plotted against the country’s latitude. Results Our analysis of 29 European countries showed a stable mortality rate due to GPA and MPA between 2011–2021, but rising age at death median age-band 70–74 at the start and 75–79 at the end of the study period. There were differences between countries with the highest mortality rate in Denmark (SMR 31.03 per 10 million) and the lowest in Romania (SMR 0.77 per 10 million). Mortality rates were higher in adults aged over 80 years and there were more deaths in men compared with women. A latitudinal gradient in SMR was seen in GPA but not MPA, with the highest mortality rates in Scandinavia. Conclusion Despite major advances in disease management, our results show that deaths due to GPA and MPA were stable over the last decade, indicating an ongoing need to improve the treatment of these diseases.
Background Interstitial Lung Disease (ILD) can occur in association with ANCA‐associated Vasculitis (AAV‐ILD) or as an isolated entity with positive ANCA (ANCA‐ILD). However, data on the epidemiology and outcomes of these conditions remain limited. Methods A European multicentre retrospective study encompassed patients with AAV‐ILD or ANCA‐ILD. Baseline and subsequent chest CT studies were centrally reviewed. Primary outcomes included forced vital capacity (FVC) decline, respiratory failure, and mortality. Results 162 patients (MPO‐ANCA 85%); 123 (76%) had AAV‐ILD and 39 (24%) ANCA‐ILD. At baseline, Usual Interstitial Pneumonia (UIP) was the most frequent radiologic pattern (57%), while half had a radiological fibrosis grade >10%. Kidney involvement was present in 73%, most commonly Berden focal class. UIP and Non‐specific interstitial pneumonia (NSIP) patterns showed greater annual FVC decline than other patterns (UIP: −1.99%, NSIP: −3.76%, [p=0.35] others: +0.36%). An adjusted mixed‐effects model indicated that rituximab was associated with mean FVC % improvement at 12 months (+6.02%; p=0.07). Radiologic progression occurred in ~50%, mainly in younger patients with higher fibrosis severity grade. Respiratory failure (19%) was associated with fibrosis severity (grade 4: HR 4.7; p=0.029) and baseline FVC% (HR 0.95; p=0.002). Over a median 4.2‐year follow‐up, 48% died. Age (HR 1.08; p=0.04) and baseline FVC% (HR 0.97; p=0.05) were independent predictors of mortality. Conclusion At baseline, higher fibrosis severity, UIP, and lower FVC% were associated with worse outcomes. Immunosuppressives, such as rituximab, may help preserve lung function. The need for early identification and individualized treatment in ILD associated with AAV or ANCA is underscored.
Antineutrophil cytoplasmic antibodies (ANCA) are a key biomarker for ANCA-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Although indirect immunofluorescence (IIF) has traditionally been the reference technique, its diagnostic value in contemporary real-world practice remains uncertain. The aim of this study was to evaluate the diagnostic performance of IIF ANCA testing in routine clinical practice. We conducted a retrospective study of all patients with an ANCA request at a tertiary hospital over a four-year period. All IIF-positive sera were subsequently tested for anti-PR3 and anti-MPO antibodies by chemiluminescent immunoassay (CLIA). Clinical data, test indication and final diagnoses were retrieved from electronic medical records. We included 5,157 patients and IIF was positive in 653 (12.7%): perinuclear ANCA (P-ANCA) in 17.9%, cytoplasmic ANCA (C-ANCA) in 13.3% and atypical ANCA (A-ANCA) in 68.8%. CLIA was negative in 97.3% of A-ANCA. AAV was diagnosed in 47 patients, and 42 (89.4%) had positive IIF. For GPA and MPA, IIF showed a sensitivity of 93% and specificity of 88%, with a very high negative predictive value (NPV) (99.9%) but low positive predictive value (PPV) (6.1%). Specificity improved to 96.8% when restricted to typical patterns (C-ANCA or P-ANCA) and to 99.6% when combined with positive CLIA results >20 IU/ml. Almost all AAV cases were diagnosed in patients with high pre-test probability (such as renal disease, lung infiltrates, or peripheral neuropathies) and interstitial lung disease was the most frequent non-AAV diagnosis in IIF-positive patients. ANCA IIF retains good diagnostic efficiency and a very high NPV for GPA and MPA, but has low PPV, particularly when tested for nonspecific symptoms.
Abstract Objectives Subglottic stenosis (SGS) is a challenging manifestation of granulomatosis with polyangiitis (GPA), often relapsing and poorly responsive to immunosuppressive treatment. Current guidelines lack specific recommendations for SGS management and evidence is limited. This study aimed to identify features of SGS associated with a more aggressive course and to assess the efficacy of available treatments in preventing relapses. Methods We conducted a multicenter, retrospective cohort study including GPA patients with SGS. Patients were stratified into higher relapsers (≥2 flares) and lower relapsers (≤1 flare). Clinical and treatment features were compared across groups. Univariate and multivariate analyses were conducted to identify independent predictors of relapse and multiple flares. Kaplan–Meier curves assessed time-to-relapse across regimens. Results Eighty-nine patients were included (30% male). Forty-eight patients (54%) were higher relapsers, with a median time-to-relapse of 36 months. Systemic immunosuppressive therapy was associated with fewer relapses (82% vs 18%, p = 0.04) compared to local treatments alone. Glucocorticoids in induction regimens reduced relapse risk (86% vs 12%, p = 0.03). Cyclophosphamide (CYC) was associated with the longest relapse-free survival and reduced 5-year relapse risk (OR 0.3, p = 0.049). By contrast, glucocorticoid monotherapy in either induction or maintenance phase was associated with higher relapse rate (p = 0.006). No specific maintenance regimen was significantly protective, though rituximab and DMARDs showed a trend toward improved outcomes. Conclusions Systemic immunosuppressive therapy, particularly CYC-based induction, was associated with fewer SGS relapses and prolonged relapse-free survival, while glucocorticoid monotherapy was less effective. Prospective studies are needed to optimize induction and maintenance strategies in GPA-related SGS.
Ocular manifestations frequently occur in ANCA-associated vasculitides (AAV). Orbital inflammatory disease (OID) is a subset with limited management guidelines. This systematic review evaluated interventions for AAV-OID. We searched Embase, MEDLINE, Web of Science, ClinicalTrials.gov, and Cochrane Central without language or date restrictions for clinical trials, case-control studies, observational studies, and case series (≥5 patients) of adults treated for AAV-OID. Included studies reported therapy type and clinical response after ≥1 month. The primary outcome was clinical response, defined as any improvement in signs or symptoms, up to and including remission. Secondary outcomes included remission, relapse, sustained remission (>6 months), and serious adverse events. Two reviewers independently screened records and appraised studies using the Newcastle-Ottawa Scale (NOS). A qualitative synthesis and meta-analysis of proportions were performed using a random effects model. Of 1001 studies screened, 18 met inclusion criteria (277 patients; 14 retrospective cohorts, 4 case series). Most (17/18) had NOS scores ≥5. Thirteen studies included rituximab (RTX), 10 cyclophosphamide, 7 RTX + another immunosuppressant (IS), 11 conventional IS, and 7 surgical therapies. Most studies involved refractory/relapsing cases. In 4 RTX monotherapy series, 95% (95 %CI 89-100%, p < 0.001) had a clinical response and 84% (95%CI 72-95%, p < 0.001) achieved remission at 6 months. Our results suggest high remission rates of OID with RTX but highlight the need for high-quality prospective studies examining treatments for AAV-OID.
Objective The objective of the study was to determine risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) after reinduction of remission with rituximab and discontinuation of maintenance therapy. Methods This is a post hoc analysis of the RITAZAREM clinical trial. Patients aged 15 years or older with AAV and a positive test for anti–proteinase‐3 or anti‐myeloperoxidase‐ANCA who achieved remission after reinduction with rituximab and glucocorticoids were randomized at month 4 to receive continued rituximab or azathioprine for a maintenance period up to 24 months, followed by observation until relapse or up to 48 months. Generalized estimating equations logistic regression identified baseline and time‐varying risk factors for relapse by the next visit for the two study phases: maintenance (months 4–24) and off‐treatment (months 24–48). Results Among 170 patients (median [interquartile range] age 59 [48–68] years, disease duration 5 [2–10] years), 99 relapses occurred (46 during maintenance). During maintenance, musculoskeletal involvement (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.1–7.2; P = 0.03) and higher patient global assessment (OR: 1.1, 95% CI: 1.0–1.2; P = 0.04) were associated with relapse. During the off‐treatment phase, presence of CD19 + B cells (OR: 2.5, 95% CI: 1.2–5.1; P = 0.01) and reappearance of ANCA (OR: 3.2, 95% CI: 1.3–7.7; P = 0.01) were each associated with higher relapse risk. Multivariable analysis identified markers of inflammation (changes in platelets, white blood cells, and IgA) associated with relapse. Conclusion Risk factors for relapse in AAV vary by treatment phase. Monitoring markers of inflammation and immune reconstitution may identify patients at risk for relapse, particularly after treatment withdrawal.
A newsletter aborda as atualizações do ACR 2025 sobre a investigação de vasculites cutâneas, enfatizando a diferenciação entre quadros limitados à pele e manifestações sistêmicas. Destaca também que a doença pulmonar intersticial é uma complicação frequente e grave na esclerose sistêmica limitada, especialmente em pacientes com anticorpo anti-topoisomerase I positivo.
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.
To evaluate the utility of magnetic resonance imaging (MRI)-guided muscle biopsy (MB) in diagnosing small- to medium-vessel vasculitis. We retrospectively included patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) or polyarteritis nodosa (PAN) between April 2020 and March 2025 who underwent MRI and MB. The primary outcome was the diagnostic sensitivity of MRI-guided MB for AAV and PAN. The secondary outcome was the diagnostic sensitivity for PAN alone. MB was considered positive when it demonstrated either necrotizing vasculitis or non-necrotizing vasculitis. Eighteen patients who underwent MRI and MB were included: 11 patients had AAV and 7 had PAN. The median interval between MRI and MB was 3.5 days. The mean Birmingham Vasculitis Activity Score was 13.6. Muscle pain was observed in 11 patients; however, none of the patients exhibited elevated creatine kinase levels. The sensitivity of MB for diagnosing AAV and PAN was 83.3% (15/18; 95% confidence intervals [CI] 58.6-96.4%), whereas that for PAN alone was 85.7% (6/7; 95% CI 42.1-96.3%). No biopsy-related complications were observed. There were no apparent differences in clinical characteristics between the MB-positive and MB-negative groups. MRI-guided MB may represent a diagnostic option for small- to medium-vessel vasculitis, even in patients without muscle pain or when other suitable biopsy sites are unavailable. Although this was a small exploratory retrospective single-center study, these findings should be validated in larger multicenter prospective studies.
To investigate the concordance between organ involvement at diagnosis and relapse in granulomatosis with polyangiitis and factors associated with new disease features at relapse. Data from a national database of newly diagnosed patients was analysed. Clinical features were recorded at diagnosis and relapse, grouped by organ system. ORs and HRs were used to assess associations between baseline features and first relapse. Factors independently associated with new organ involvement at relapse were identified using multivariable logistic regression. Among 795 patients (median follow-up 3.5 years), 394 (50%) relapsed; organ involvement at relapse was available for 376 patients. Relapses most often affected ear, nose and throat (ENT), lungs and kidneys. Organ involvement at diagnosis was associated with a higher likelihood of relapse in the same organ: eyes (OR 6.69), lungs (OR 3.35), kidneys (OR 3.58), nervous system (OR 2.90), and mucocutaneous (OR 4.53). Major manifestations associated with a higher likelihood of recurrence were scleritis, pachymeningitis, subglottic stenosis and worsening renal function. For 56% of patients, the first relapse affected only the initially involved organs. Of the 165 patients with new organ manifestations, these were rarely isolated (n=34) and usually occurred alongside involvement of at least one previously affected organ (n=131). In multivariable analysis, systemic, ENT and lung manifestations at diagnosis were associated with a lower risk of new organ disease at relapse. Although new features can still emerge, organ involvement at diagnosis is associated with a higher likelihood of relapse in the same organ.
Inflammatory ratios derived from routine complete blood counts, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), have been proposed as activity markers in ANCA-associated vasculitis (AAV), but their interpretation is limited by heterogeneous sampling and treatment-related confounding. We conducted a single-center cross-sectional study including adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Patients were sampled during active disease (new-onset prior to induction or relapse prior to escalation) or during stringent glucocorticoid-free remission (BVASv3 = 0). Healthy controls (HCs) were included for secondary comparisons. Ratios were compared across groups and correlated with BVASv3 and c-reactive protein (CRP). Between-group differences (active vs. remission; remission vs. healthy controls) were additionally quantified using age- and sex-adjusted log-linear models (log-transformed outcomes), reported as ratios of geometric means. Discriminative performance for active disease versus remission was assessed using unadjusted ROC analyses and age- and sex-adjusted logistic regression models. Sensitivity analyses stratified remission by maintenance immunosuppression at sampling. The study included 99 AAV patients (28 active, 71 remission) and 258 HCs. NLR, PLR, and MLR were significantly higher in active disease than in remission (all p ≤ 0.004), and remained significantly higher after age/sex adjustment in log-linear models (geometric mean ratios [Active/Remission]: NLR 1.97, PLR 1.64, MLR 1.40). NLR and PLR correlated moderately with BVASv3 (ρ = 0.506 and 0.478, respectively; both p < 0.001) and CRP. Discriminative performance was strongest for NLR and PLR: in age- and sex-adjusted models, AUC increased from 0.664 (age/sex only) to 0.832 after adding NLR and 0.827 after adding PLR (whereas the AUC after adding MLR was 0.724). During glucocorticoid-free remission, ratios remained higher than in HCs (geometric mean ratios: NLR 1.55 [1.39-1.74], PLR 1.18 [1.08-1.29], MLR 1.40 [1.27-1.55]; all p < 0.001). Treatment
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.
Avacopan (AVAC), an oral selective C5a receptor inhibitor, has been approved for treatment in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Outside randomized controlled studies, real-world data are scarce. The aim of this study was to provide further insight into the clinical experience of AVAC. We analysed data from 16 patients with severe AAV included in an AVAC compassionate use programme. Disease activity was estimated with the Birmingham Vasculitis Activity Score (BVAS). Fatigue was assessed using the Multidimensional Assessment of Fatigue (MAF). Thirteen patients (81%) were diagnosed with granulomatosis with polyangiitis (GPA) and three (19%) with microscopic polyangiitis. The mean age at AVAC initiation was 51 (range 16-74) years. The median [interquartile range (IQR)] BVAS score was 10 (3.25-13.25) at baseline and 0 (0-0) at 6 months (p < 0.0001). All but one reached clinical remission. Prednisolone was tapered from a median (IQR) dose of 25 (20-60) to 2.5 (0-5) mg/day at 6 months (p = 0.0001). Eight patients discontinued prednisolone [median time 2.5 month1 week to 10 months)]. The median (IQR) estimated glomerular filtration rate in patients with renal AAV (n = 10) increased from 50 (13-75) to 58 (15.5-88) mL/min/1.73 m2 at 6 months (p = 0.055). One patient progressed to end-stage kidney disease, while another was able to discontinue haemodialysis. Serious adverse events were seen in five of the 16 patients (31.3%). The MAF score decreased, with a mean difference of 6.65 (p = 0.05) at 6 months. The use of AVAC in a case series with mainly GPA patients led to rapid clinical improvement, reduction of corticosteroid doses, and improvement in fatigue. The findings demonstrate beneficial effects of AVAC as add-on therapy in severe AAV.
To investigate the clinical characteristics of muscle-dominant ANCA-associated vasculitis (muscle-dominant AAV) in a consecutive single-center cohort. We retrospectively analyzed consecutive patients newly diagnosed with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) at a single center. Cases with muscle-dominant AAV were defined as those with muscle involvement due to AAV in the absence of other organ manifestations, including glomerulonephritis, cutaneous vasculitis, vasculitic neuropathy, or alveolar hemorrhage. We compared the muscle-dominant AAV group with all remaining AAV patients, who served as the comparison group. Among 72 consecutive patients newly diagnosed with MPA or GPA, 8 (11%) were classified as having muscle-dominant AAV. All patients with muscle-dominant AAV (100%) were MPO-ANCA-positive. In all patients with muscle-dominant AAV, serum creatine kinase levels remained within the normal range despite MRI-confirmed muscle inflammation. Compared with the comparison group, the muscle-dominant AAV group had significantly higher rheumatoid factor (RF) levels. ROC analysis identified an exploratory RF cutoff value of 47.55 U/mL (AUC = 0.79). The prevalence of interstitial lung disease (ILD) tended to be more frequent in the muscle-dominant AAV group than in the comparison group (75 vs. 37.5%, p = 0.060). Muscle-dominant AAV was characterized by MPO-ANCA positivity, elevated RF levels, normal CK levels, and MRI-confirmed muscle involvement. ILD was often observed but did not reach statistical significance. These findings suggest a possible clinical pattern within AAV, which we tentatively refer to as the hypothesized IMARM pattern (ILD, MPO-ANCA, RF, myopathy).
Despite previous reports on the risk factors for relapse in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), none have evaluated the relationship between serum syndecan-1 levels and AAV relapse. Therefore, this study aimed to investigate the association between serum syndecan-1 levels at AAV diagnosis and subsequent relapses in patients with AAV, hypothesizing that higher levels would be associated with increased risk of relapse. This single-center, medical record-based cohort study included 60 consecutive patients with microscopic polyangiitis or granulomatosis with polyangiitis treated at Aichi Medical University Hospital in Japan in 2018-2022. The relationship between serum syndecan-1 levels at diagnosis and subsequent first relapse was assessed using multivariable Cox proportional hazards models after adjusting for age, sex, estimated glomerular filtration rate, antineutrophil cytoplasmic antibody (ANCA) titers, Birmingham Vasculitis Activity Score, and AAV classification. The cumulative probability of relapse was calculated using the Kaplan-Meier method and log-rank test. Statistical significance was set at p<0.05. During a median follow-up period of 48 (range, 24 to 64) months, 20 (33.3%) patients experienced at least one relapse. Patients with high-serum syndecan-1 levels (adjusted hazard ratio=19.0, 95% CI: 1.17-307.8) were associated with an increased risk of relapse compared with those with low serum syndecan-1 levels. Among patients with ANCA-associated vasculitis, high-serum syndecan-1 levels at diagnosis were associated with an increased risk of relapse.
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.