IgG4-related disease (IgG4-RD) is a systemic, chronic immune-mediated inflammatory disorder that, similar to sarcoidosis, can affect various organs and tissues. IgG4-related periaortitis (PAo)/retroperitoneal fibrosis (RPF) is among the five major manifestations of IgG4-RD. Despite introduction of the ACR and EULAR classification criteria for IgG4-RD in 2019, diagnosing IgG4-related PAo/RPF and periarteritis (PA) remains challenging because obtaining biopsies from these lesions is difficult. Additionally, while glucocorticoids are highly effective in treating IgG4-RD, managing aortic or arterial lesions poses unique challenges.

This brief review discusses the utility of Japanese organ-specific diagnostic criteria for IgG4-related PAo/RPF and PA, along with recent advances in treatment strategies including management of organ-specific issues related to these lesions.

First, we analyzed 99 patients with IgG4-related PAo/RPF and PA based on expert diagnoses to propose organ-specific diagnostic criteria. Next, we retrospectively analyzed an additional 110 patients with IgG4-related PAo/RPF and PA, as well as 73 mimickers with clinical features requiring differentiation from true IgG4-RD to validate the proposed criteria.

Histopathological specimens were obtained from only 33 patients (20 periaortic, 5 coronary arteries, 4 iliac arteries, 1 mesenteric artery, and 5 retroperitoneal lesions not involving arteries). Among these, 71.4 % showed storiform fibrosis, and 71.4 % displayed obliterative phlebitis. The mean number of IgG4-positive plasma cells exceeded 10 per high-power field in all specimens, and the IgG4/IgG-positive cell ratio exceeded 40 % in 32 specimens (91.4 %). Radiographic findings were essential for diagnosing IgG4-related PAo/RPF and PA, supported by elevated serum IgG4 levels and the presence of characteristic involvement of other organs affected by IgG4-RD. Validation analysis confirmed that incorporating "imaging findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-Pao/PA/RPF lesions" improved sensitivity from 68.4 % to 77.2 %, with only a minimal reduction in specificity (from 97.4 % to 94.7 %).

Diagnosing IgG4-related PAo/RPF and PA remains challenging even when using the latest diagnostic or classification criteria, compared to diagnosing IgG4-RD involving other major organs, such as lacrimal and salivary glands, pancreas, and kidneys. In addition, when treating patients with IgG4-related PAo/RPF and PA, organ-specific factors must be considered when developing treatment strategies.

Data on the presentation and management of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in private practice are limited.

We sought to characterize the profiles and disease burden of patients with EGPA in a real-world private practice setting.

This was a retrospective, noninterventional, longitudinal study (GSK ID: 217426) of US Allergy Partners network data. For patients with a diagnosis of EGPA, confirmed by 2 or more EGPA clinical features, index was defined as their first visit with an Allergy Partners physician (January 2007-June 2021); postindex lasted until loss of follow-up or study end (December 2021). Patient characteristics at index, physician characteristics at any time, symptoms, treatment characteristics, and clinical outcomes postindex were assessed.

Of 52 patients (median follow-up, 3.7 years), 75% were diagnosed with EGPA outside the Allergy Partners network. Each patient received care from a median (Q1-Q3) of 4.0 (3.0-5.0) physician specialties. Most had asthma (92%), rhinitis (75%), and sinusitis (62%) and experienced a mean ± SD of 18.1 ± 4.3 distinct self-reported symptoms. Most (85%) used oral corticosteroids, with 73% (32 of 44) on daily doses of more than 12 mg; 60% used mepolizumab. Overall, 75% of patients (39 of 52) achieved a response (improved/controlled symptoms); 46% (24 of 52) achieved controlled status after worsened, unchanged, or active symptoms, and of these 38% (9 of 24) relapsed.

The complex private practice presentation of EGPA, with heterogeneous patient response to standard treatments, highlights a significant disease burden and continued need for optimized treatment strategies within a multidisciplinary team approach.

Diseases that develop necrotizing vasculitis of cutaneous muscular arteries include cutaneous arteritis (CA) and polyarteritis nodosa (PAN). It is difficult to distinguish them based on skin biopsy findings alone. This study demonstrated that artificial intelligence (AI) can discriminate them based on skin biopsy findings and revealed where AI focuses on the image. Ninety-three hematoxylin-and-eosin images of CA and 19 PAN images were used. Among them, 85 CA and 17 PAN images were used to train AI; thereafter, AI was challenged to classify the remaining images. The same test images were evaluated by 26 pathologists with different years of experience. AI accuracy was 75.2 %, whereas that of pathologists was 42.8 %. Gradient-weighted class activation mapping (Grad-CAM) indicated that AI focused on connective tissues around the affected vessels rather than the affected vessels. Twenty-two of the 26 pathologists were randomly divided into two groups of 11 each, one of which referred to Grad-CAM images and was challenged in the second-round test of images different from the first round. The accuracy significantly improved after referring to Grad-CAM images, whereas it was equivalent to the first round without referring to Grad-CAM images. In the survey after the second-round test, pathologists who referred to Grad-CAM images suggested that inflammation and fibrosis in the surrounding connective tissues in PAN might be abundant compared to CA. AI may be useful for histological differentiation between CA and PAN and can help pathologists improve the ability of discriminating CA and PAN based on histological findings of skin biopsy specimens.

This article provides gastroenterologists with an overview of small bowel involvement in systemic vasculitis. Though various vasculitides can impact the small bowel, we highlight those with a more frequent and clinically significant GI involvement.

Recent advances, including increased accessibility to cross-sectional imaging, capsule endoscopy and device-assisted enteroscopy, have improved detection of gastrointestinal manifestations in systemic vasculitis. Studies have also explored the genetic and inflammatory pathways involved in these diseases, although high-quality evidence on diagnosis and treatment remains limited, leading to reliance on expert consensus.

Small bowel involvement is common in Behçet's disease and small vessel vasculitis, presenting with symptoms ranging from mild to severe, including massive bleeding, ischemia, and perforation, often indicating a poorer prognosis. Diagnosis is challenging, but in patients with a known or suspected history of vasculitis, it should prompt contrast-enhanced abdominal imaging and endoscopic evaluation. Treatment decisions should be made collaboratively by a multidisciplinary team, with immunosuppressive therapy remaining the cornerstone.

Spinal hypertrophic pachymeningitis (HP) is an extremely rare disorder characterized by the thickening of the spinal dura mater, which harbors distinct repertoires of immune cells due to the unique partitioning of the arachnoid blood-CSF barrier. The objectives were to identify the pathogenesis and therapeutic strategies for spinal HP.

This retrospective cohort study analyzed the clinical and pathologic profiles of patients with idiopathic/immune-mediated HP including spinal HP.

Among 61 patients with idiopathic/immune-mediated HP, all 6 Japanese patients with spinal HP, with a median observation period of 88.8 months, were myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)-seropositive. The MPO-ANCA+ spinal HP cohort had the following characteristics: (1) a predominance of older women; (2) all patients were classified as having microscopic polyangiitis based on the 2022 American College of Rheumatology/European League Against Rheumatism criteria; (3) 83% of patients developed subacute/chronic myelopathy due to extramedullary spinal cord compression; (4) 50% of patients had lesion extension to the epidural compartment and vertebral column; (5) 50% of patients presented with chronic sinusitis, otitis media, or mastoiditis; (6) 33% of patients had involvement of the lower airways or kidneys; (7) a higher disease activity of the nervous system was noted based on the Birmingham Vasculitis Activity Score (BVAS), in contrast to MPO-ANCA+ cranial HP; (8) granulomatous inflammation with myofibroblasts, immune cells including granulocytes, and B-cell follicle-like structures were observed in the thickened dura mater; (9) immunotherapies (with or without surgical decompression) were effective in reducing the modified Rankin Scale score and reduced BVAS during the first active insults; (10) combined immunotherapies with glucocorticoids and cyclophosphamide/rituximab helped in reducing relapses in the long term; and (11) surgical decompression, including laminectomy and duraplasty, was necessary for compressive myelopathy. These data suggest that MPO-ANCA+ spinal HP shares common features with MPO-ANCA+ cranial HP (1, 2, 6, 8, 9, and 10), but also has unique clinical features (3, 4, 5, 7, and 11).

Our findings highlight the significant pathogenic role of ANCA in spinal HP. MPO-ANCA+ spinal HP, as an organ-threatening disease, should be positioned as having unique characteristics, whether limited to the CNS or as part of a generalized form in ANCA-associated vasculitis.

Adult-onset IgA vasculitis (IgAV) often presents with severe renal and gastrointestinal (GI) complications, yet therapeutic guidelines for life-threatening manifestations remain unclear.

We conducted a systematic text-mining analysis of all PubMed-indexed case reports of IgAV treated with therapeutic plasma exchange (TPE).

We describe an 80-year-old woman with refractory GI bleeding and rapidly progressive glomerulonephritis. Despite high-dose corticosteroids and cyclophosphamide, GI bleeding persisted and necessitated multiple transcatheter embolization. A total of seven sessions of TPE using fresh frozen plasma successfully controlled disease activity, resulting in improvement of GI bleeding. Literature review suggests that TPE may provide additive benefits in IgAV patients, particularly in those unresponsive to standard immunosuppressants.

This case supports the utility of TPE as a valuable adjunctive therapy in severe IgAV with organ-threatening manifestations and highlights the need for further studies to define optimal indications.

To determine the incidence rate (IR) and predictors of myocardial infarction (MI) in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) as well as to estimate the IR ratio (IRR) of MI in AAV versus the background population.

325 patients diagnosed with AAV 1997-2016 in Skåne, Sweden were included. Data were collected from the time of AAV diagnosis, and each patient was grouped with 10 age-matched and sex-matched reference subjects from the background population. MI after AAV diagnosis was identified using Swedish Web-System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies and the Skåne Healthcare Register, and IR of first MI calculated. The IRR was computed by dividing the IR for 282 AAV patients by the corresponding rate in the 2763 reference subjects. Predictors of MI were analysed using Cox regression.

37 patients (11%) with AAV suffered an initial MI, yielding an IR of 1.6/100 person-years of follow-up (95% CI 1.2 to 2.2). The highest rate was recorded in the 3 months following AAV diagnosis, at 11.8/100 person-years (95% CI 6.2 to 22.7). The IRR of MI in AAV/reference was 1.9 (95% CI 1.3 to 2.8), highest in patients with myeloperoxidase-ANCA+disease (IRR 2.5, 95% CI 1.5 to 4.3) and those with high disease activity at diagnosis (2.1, 95% CI 1.3 to 3.3). Age at AAV diagnosis independently predicted MI.

The MI IR is greater in individuals diagnosed with AAV compared with background population, especially those with more severe disease, and highest in the 3 months following diagnosis. Age at diagnosis is the single independent predictor of MI in AAV in this study.

To describe oral health complications and related quality of life in patients with vasculitis. Survey to assess clinical variables, pertinent to oral and dental health in patients with vasculitis and using the Oral Health Impact Profile 14 (OHIP14) questionnaire. 226 patients answered the survey. Globally, 179 (79.2%) patients reported good oral and dental health before the vasculitis diagnosis, while 92 (40.7%) patients reported a worsening since the diagnosis of vasculitis. Patients with a worsened oral health had a longer disease duration (10.0 (1.0) vs. 7.4 (0.7) years; p < 0.05), and had more relapses in the previous 2 years (34.8% vs. 16.4%; p < 0.005). The median OHIP14 score was 4 (IQR: 0-10); 97 (48.7%) patients scored > 4 points. Patients with Takayasu arteritis and Behçet disease showed worse OHIP14 scores, had a longer disease course but were younger than those with better scores or other vasculitis diagnoses. A high proportion of patients with vasculitis, especially those with Takayasu arteritis or Behçet disease, reported oral or dental complications, with subsequent impaired oral health-related quality of life.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic necrotizing vasculitis that predominantly affects small vessels. Glucocorticoids are the standard therapeutic agents for AAV; however, their long-term use can cause damage. Avacopan is a small-molecule complement component 5a receptor antagonist that reduces vasculitis and can potentially be used as an alternative to glucocorticoids. However, its therapeutic efficacy remains unknown, and drug-induced liver injury (DILI) is a concern associated with its use.

A 74-year-old woman with a history of granulomatosis with polyangiitis was admitted to our hospital with a 1-week history of fatigue and anorexia.

She had started avacopan 3 months before hospitalization. Blood tests showed severe liver injury, and since other diseases were ruled out, she was diagnosed with DILI secondary to avacopan.

Avacopan was discontinued, and glucocorticoid doses were increased and ursodeoxycholic acid was administered; however, the liver injury did not resolve. Therefore, mycophenolate mofetil (MMF) was started.

The liver injury was resolved after starting MMF.

MMF is effective in treating DILI caused by avacopan.

Increasing evidence indicates a substantial correlation between the immune cells and the risk of allergic purpura. We utilized Mendelian randomization (MR) to investigate causal effect of immune cell on allergic purpura.

Genetic instrumental variables for immune cells were sourced from an extensive genome-wide association study (GWAS) comprising 3757 participants. Summary statistics of allergic purpura, involving 470 cases and 216,099 controls, were obtained from FinnGen. The primary analysis employed the inverse-variance weighted (IVW) method. Rigorous sensitivity analyses including MR-Egger, weighted median and MR-PRESSO were conducted to ensure the reliability of the causal estimate.

We identified two immunophenotypes associated with an increased risk of allergic purpura: HLA-DR on CD14 + CD16- monocyte (OR: 1.2379; 95% CI: 1.0612-1.4440; P = 0.0066) and CD11b on basophil (OR: 1.2973; 95% CI: 1.0905-1.5433; P = 0.0033). The sensitivity analyses consistently yielded similar results for these immunophenotypes.

Our analyses confirmed a potential causal effect of HLA-DR on CD14 + CD16- monocyte, as well as CD11b on basophils, in relation to the risk of allergic purpura. Further studies are necessary to clarify the mechanisms by which these immunophenotypes influence the development of allergic purpura.

The present cohort study aimed to evaluate the value of CCL23 in diagnosis, disease activity, and prognosis in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

CCL23 levels in serum samples from 317 patients with AAV and 83 healthy controls (HCs) were measured using a customized immune response kit.

Patients with AAV had significantly elevated CL23 levels compared with HCs. CCL23 level was closely related to disease activity and was better than birmingham vasculitis activity score (BVAS) in distinguishing disease relapse from remission (area under curve: CCL23 = 0.942, BVAS = 0.84). Elevated CCL23 level was associated with poor prognosis within a 1 year follow-up period in patients with AAV (p = 0.0001). The ability of CCL23 to predict the poor prognosis of disease is better than that of five-factor score. Furthermore, elevated CCL23 levels were a risk factor for renal involvement (odds ratio = 1.722, p = 0.033), and were significantly related to serum creatinine (r = 0.381, p = 0.009) and eGFR (r = - 0.382, p = 0.01) at the time of diagnosis. High CCL23 level at diagnosis was associated with increased adverse outcomes during 1 year follow-up in patients with AAV with renal involvement (p = 0.0242).

Elevated serum CCL23 level was closely related with disease activity and renal involvement in patients with AAV, can be a potential biomarker for diagnosis, and can predict prognosis in patients with AAV, especially adverse renal prognosis.

Immunoglobulin A (IgA) vasculitis is a common systemic vasculitis in children, involving the skin, joint, gastrointestinal tract and kidneys. Scrotal involvement is a less common manifestation in the course of IgA vasculitis, which alters disease management. The purpose of this study was to present the characteristics of patients with IgA vasculitis with scrotal involvement and to compare patients with and without scrotal involvement. We also aimed to investigate the relationship between scrotal involvement and disease activity and inflammatory markers. This medical record review study was conducted in 234 male patients under the age of 18 years who were diagnosed with IgA vasculitis and followed for at least 6 months in the Pediatric Rheumatology Clinic. Demographic characteristics, clinical findings, laboratory findings, and pediatric vasculitis activity score (PVAS) of IgA vasculitis patients were recorded. CRP to albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were calculated using the patients' complete blood count parameters and C reactive protein (CRP) levels. Two hundred thirty four male patients with IgA vasculitis were included in the study. Scrotum involvement was detected in 34 (14.5%) of patients. The mean age at diagnosis of 34 patients with scrotal involvement was 7.37 (4.41-8.43) years. Of the 34 patients, 15 had scrotal pain, swelling and rash, 12 had scrotal pain and swelling, and 2 had only scrotal swelling. Two (5.9%) patients had penile involvement with scrotal involvement. Patients were divided into two groups as those with scrotal involvement (n = 34, 10.2%) and those without (n = 200, 89.8%). Local edema, widespread skin involvement, hematuria, penile involvement, PVAS and CAR were significantly higher in IgA patients with scrotal involvement than in those without (p < 0.001, p < 0.001, p = 0.019, p = 0.001, p < 0.001, and p = 0.004, respectively).

Widespread purpura, local edema, penile involvement and hematuria are more common in patients with scrotal involvement than those without. PVAS and some systemic inflammatory markers such as CAR may be helpful in predicting scrotal involvement.

• IgA vasculitis is the most common type of vasculitis in childhood and scrotal involvement is very rare during the course of the disease. • PVAS is a scoring system used to measure the severity of childhood vasculitis.

• PVAS might be promising surrogate tool for predicting scrotal involvement in patients with IgA vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by inflammation and destruction of small blood vessels. AAV could be fatal if left untreated. Prompt diagnosis and treatment are crucial to protect AAV-related organs and tissue. Plasmapheresis, a therapeutic intervention aimed at removing harmful substances from the blood, devotes benefits to AAV treatment. However, the specific immune mechanism underlying its effectiveness remains unclear. In our research, we used single-cell RNA sequencing (scRNA-seq) to study the variation of peripheral blood mononuclear cells (PBMCs) before and after plasmapheresis in AAV patients. From this work, we explored a novel method for monocyte classification. In addition, flow cytometry was used to detect the relationship between the monocyte clusters and AAV activity under the new monocyte clustering method. Our scRNA-seq results revealed significant changes in monocyte clusters following treatment, which could be classified into three clusters (CD14+ monocytes, FCGR1A+ monocytes, and FCGR3A+ monocytes). In addition, our flow cytometry results showed that FCGR3A+ (CD16+) monocytes were positively correlated with AAV activity, whereas FCGR1A+ (CD16-CD64+) monocytes were negatively correlated with AAV activity. This may be related to the different biological effects of CD16 and CD64 on monocytes after interacting with the Fc region of ANCAs. In conclusion, our research sheds light on the immune landscape of AAV before and after plasmapheresis, identifying specific monocyte clusters linked to disease activity. These findings offer insights for novel monitoring methods and therapeutic targets in AAV.

This study determined whether alkaline phosphatase (ALP) can be used to distinguish giant cell arteritis (GCA) complications in patients with polymyalgia rheumatica (PMR).

This retrospective study included patients diagnosed with PMR between January 2014 and October 2023 at our hospital. The predictive accuracy of biomarkers for diagnosing GCA was evaluated. Logistic regression was performed to identify factors predicting GCA complications.

In total, 128 participants were included in this study and divided into two groups: isolated PMR (n = 111) and PMR with GCA (n = 17). The median ALP level of PMR with GCA group was significantly higher than that of the isolated PMR group (242.0 [interquartile range, 221.0-595.0] vs. 187.0 [interquartile range 97.5-254.5] U/L, P < .001). Setting a cut-off value of 214 U/L for ALP yielded a sensitivity and specificity of 0.88 and 0.55, respectively, for diagnosing GCA. Multivariate analysis revealed that ALP was a significant independent variable in the complications of GCA (odds ratio, 25.2; P = .032).

ALP can help distinguish GCA complications in patients with PMR.

To assess the prevalence and outcomes among regimens of glucocorticoid tapering for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in real-world practice.

We retrospectively examined the Japan Collaborative Registry of Antineutrophil Cytoplasmic Antibodies-associated Vasculitis (J-CANVAS) registry, and evaluated the prevalence of glucocorticoid tapering regimens in the PEXIVAS trial. In patients with newly diagnosed MPA and GPA, we compared outcomes among standard and reduced pace regimens. Relapse-free survival rates were compared after propensity score matching.

Of 364 eligible patients, 113 (31.0%) received standard tapering and 251 slower tapering. After matching, 87 pairs no significant difference was observed in relapse-free survival (P = .506). Regarding the reduced regimen, there were so few patients (14/364, 3.8%) that statistical analysis was not performed.

The glucocorticoid tapering for MPA and GPA in Japanese real-world practice was found to be generally slower than the standard regimen revealing a huge evidence-practice gap. Additionally, slower tapering did not improve relapse-free survival and might cause unnecessary glucocorticoid exposure.

Sex differences in the risk factors, diagnosis, treatment, and outcomes of patients with cardiovascular disease have been well described; however, the bulk of the literature has focused on heart disease in women. Data on sex differences in peripheral vascular disease are ill defined, and there is a need to report and understand those sex-related differences to mitigate adverse outcomes related to those disparities. Although peripheral vascular disease is a highly diverse group of disorders affecting the arteries, veins, and lymphatics, this scientific statement focuses on disorders affecting the peripheral arteries to include the aorta and its branch vessels. The purpose of this scientific statement is to report the current status of sex-based differences and disparities in peripheral vascular disease and to provide research priorities to achieve health equity for women with peripheral vascular disease.

We applied the 2022 American College of Rheumatology (ACR)/European Alliance of Association for Rheumatology (EULAR) criteria to Korean patients previously diagnosed with giant cell arteritis (GCA) according to the 1990 ACR criteria and validated its clinical efficiency.

Nine patients with GCA were included. The proportion of patients meeting each item of the 1990 ACR criteria and the 2022 ACR/EULAR criteria were assessed.

The median age was 65.0 years, and 77.8% of the patients were women. Seven (77.8%) patients had polymyalgia rheumatica. All nine patients were reclassified as having GCA according to the 2022 ACR/EULAR criteria. Among the 10 items of the 2022 ACR/EULAR criteria, the item contributing the most to the reclassification was elevated acute-phase reactant levels (100%), followed by new temporal headache (77.8%) and fluorodeoxyglucose positron emission tomography activity throughout the aorta (77.5%).

In this study, for the first time, we demonstrated a concordance rate of 100% between the two criteria in Korean patients previously diagnosed with GCA. Moreover, we also clarified the major contributors to the reclassification according to the 2022 ACR/EULAR criteria.

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis primarily affecting the respiratory tract and kidneys, with external genital and urethral lesions (EGUL) being exceedingly rare. We present a case of a middle-aged man with relapsing proteinase 3-antineutrophil antibody-positive GPA who developed isolated granulomatous, ulcerative balanitis, and urethritis. His condition abruptly worsened after a prolonged indolent course, requiring treatment with glucocorticoids and rituximab, leading to successful remission. To better characterize EGUL in GPA, a systematic literature search was performed in PubMed, Scopus, and the NPO Japanese Society of Medical Abstracts databases using keywords related to GPA and EGUL. Cases meeting the American College of Rheumatology or Japanese Ministry of Health, Labor, and Welfare criteria for GPA and the 2012 Chapel Hill Consensus Conference definitions were included for analysis. Our review identified that EGUL often presents as an initial symptom and can be classified by the presence or absence of preceding urethritis. Cases with preceding urethritis had a higher risk of severe complications with extensive penile or urethral involvement. In contrast, penile lesions without preceding urethritis typically presented as characteristic mucosal lesions localized around the glans. In females, GPA-associated urethritis frequently led to periurethral mass formation, vaginal involvement, and significant sequelae. Given the potential for delayed diagnosis and serious complications, clinicians should be vigilant for EGUL in patients with suspected or diagnosed GPA. Future prospective studies with larger cohorts are needed to elucidate the prevalence, clinical spectrum, and optimal management of these rare but significant manifestations of GPA.

This study aims to evaluate the impact of early steroid discontinuation on total dosage and outcomes in pediatric immunoglobulin A (IgA) vasculitis patients with uncontrolled abdominal pain. This retrospective cohort study included children younger than 16 years with newly diagnosed IgA vasculitis hospitalized for abdominal pain who received their first dose of steroids between April 1, 2013, and March 31, 2019, at 14 hospitals. Patients were divided into two groups: the standard (STD) group, which received steroid therapy for at least 8 consecutive days, and the early discontinuation attempt (EDA) group, which attempted discontinuation within 7 days. EDA was further divided into two subgroups: the early discontinuation (ED) group, which completed steroid treatment within a week, and the readministration (RA) group, which required readministration. Total steroid dosage, duration of therapy, hospital stay, and complications were compared. A total of 272 patients were analyzed: STD (n = 190) and EDA (n = 82). There were no significant differences in baseline characteristics. EDA had a shorter hospital stay (8.5 vs. 15.0 days, p < 0.01), fewer total steroid days (6 vs. 17.5 days, p < 0.01), and lower total steroid dosage (5.4 mg/kg vs. 15.4 mg/kg, p < 0.01) compared to STD, with no significant differences in complications. Among EDA patients, 22 (27%) required steroid readministration due to symptom recurrence; however, symptoms resolved in all RA patients, with lower total steroid dosage and duration compared to STD, without prolonging hospital stay. Conclusion: Discontinuing steroids within 7 days for abdominal pain in children with IgA vasculitis reduces total steroid dosage without increasing complications, even with occasional readministration. Clinical trial registration: Approval no. 2019-0394.

Kawasaki disease (KD) is a common pediatric vasculitis, with coronary artery lesions (CALs) representing its most severe complication. Early identification of high-risk patients, including those with disease resistant to first-line treatments, is essential to guide personalized therapeutic approaches. Given the limited reliability of current scoring systems, there has been growing interest in the development of new prognostic models based on machine learning algorithms and artificial intelligence (AI). AI has the potential to revolutionize the management of KD by improving patient stratification and supporting more targeted treatment strategies. This narrative review examines recent applications of AI in stratifying patients with KD, with a particular focus on the ability of models to predict intravenous immunoglobulin resistance and the risk of CALs. We analyzed studies published between January 2019 and April 2024 that incorporated AI-based predictive models. In total, 21 papers met the inclusion criteria and were subject to technical and statistical review; 90% of these were conducted in patients from Asian hospitals. Most of the studies (18/21; 85.7%) were retrospective, and two-thirds included fewer than 1000 patients. Significant heterogeneity in study design and parameter selection was observed across the studies. Resistance to intravenous immunoglobulin emerged as a key factor in AI-based models for predicting CALs. Only five models demonstrated a sensitivity > 80%, and four studies provided access to the underlying algorithms and datasets. Challenges such as small sample sizes, class imbalance, and the need for multicenter validation currently limit the clinical applicability of machine-learning-based predictive models. The effectiveness of AI models is heavily influenced by the quantity and quality of data, labeling accuracy, and the completeness of the training datasets. Additionally, issues such as noise and missing data can negatively affect model performance and generalizability. These limitations highlight the need for rigorous validation and open access to model code to ensure transparency and reproducibility. Collaboration and data sharing will be essential for refining AI algorithms, improving patient stratification, and optimizing treatment strategies.

To compare the nature of the first relapse of giant cell arteritis to baseline disease using ultrasonography METHODS: Patients with suspected new and relapsing giant cell arteritis between January 2017 and December 2023 underwent protocolised ultrasonography to examine the superficial temporal and axillary arteries plus other areas as clinically indicated. The nature of disease was categorised as affecting superficial temporal, axillary or mixed disease. Patients where other arteries were needed for diagnosis or relapse were categorised separately. Patients with clinically and sonological evidence of polymyalgia rheumatica were distinctly categorised.

66 patients were included. At diagnosis and first relapse, 48/66 and 20/66 patients respectively had superficial temporal artery involvement. At diagnosis and first relapse, 23/66 and 40/66 respectively patients had axillary artery involvement. Patients without superficial temporal artery disease at diagnosis did not relapse in the superficial temporal artery. 7/66 patients suffered a polymyalgia rheumatica relapse. 5 of those 7 had superficial temporal arterial involvement at diagnosis.

This is the first study that reports on the nature of relapsing giant cell arteritis using sonological appearances. Relapsing disease is more common in the extracranial arteries and may be mistaken for polymyalgia rheumatica. True polymyalgia rheumatica relapses are uncommon. Relapses in patients with giant cell arteritis should be assessed using ultrasonography and should include the imaging of the axillary artery.

To evaluate differences in presentation and outcome of GCA patients with and without large vessel vasculitis (LVV) and according to the extent and severity of LVV.

Consecutive patients diagnosed with GCA between 2003 and 2020 who have had FDG PET imaging at diagnosis ≤3 days after initiation of glucocorticoids (GC) and followed for ≥12 months at the University Hospitals Leuven (Belgium) were included retrospectively. PET scans were visually scored (0-3) in seven vascular areas and a total vascular score (TVS) was calculated. LVV was defined as FDG uptake ≥2 in any large vessel.

We included 238 GCA patients, of which 169 (71%) had LVV. LVV patients were younger (69 vs 74 years, P < 0.001) and more frequently female (72% vs 49%, P = 0.001). In patients without PMR symptoms, the presence of LVV was associated with relapse (aOR 3.05 [95% CI 1.32-7.43], P = 0.011) and with a lower probability of stopping GC (aHR 0.59 [95% CI 0.37-0.94], P = 0.025). However, in those with PMR symptoms, there was no difference in relapse risk (aOR 1.20 [95% CI 0.53-2.66], P = 0.657) and in the probability of stopping GC (aHR 1.25 [95% CI 0.75-2.09], P = 0.394) between patients with and without LVV. A higher TVS was associated with an increased risk of relapse (aOR 1.09 [95% CI 1.04-1.15], P = 0.001) in patients without PMR symptoms, but not in those with PMR symptoms (aOR 1.01 [95% CI 0.96-1.07], P = 0.693).

LVV is a risk factor for relapse in GCA patients without PMR symptoms with a higher relapse risk in those with higher TVS.

Post-dialysis fever is commonly reported in patients undergoing hemodialysis (HD). However, it is often challenging to identify the underlying cause owing to the wide variety of potential factors that can lead to fever. In this case, a 66-year-old Japanese man experienced recurrent fever after HD treatment. Initially, antibiotics were prescribed to treat pneumonia, but it was later discovered that the pneumonia was an alveolar hemorrhage caused by cryoglobulinemic vasculitis. It is believed that cryoglobulin was sensitized by cold exposure owing to the dialysate temperature, which resulted in fever being experienced only after HD. Although treatment for vasculitis required prednisolone and rituximab, simple plasma exchange and a dialysate temperature of 37.5 °C dramatically suppressed the occurrence of post-dialysis fever. Cryoglobulinemia should be considered as a potential cause of fever, as it may be a common occurrence in patients undergoing HD and could be overlooked as a possible cause of localized fever following HD treatment.

IgA vasculitis (IgAV) can present as skin-limited or systemic disease, which can be severe in adults. Predictive markers for visceral involvement are suboptimal. Considering haptoglobin's role as an acute phase reactant, we evaluated whether its differential expression in IgAV patients' skin and leukocytes is also reflected systemically in a larger cohort of adult IgAV patients. Additionally, soluble form of haptoglobin scavenger receptor CD163 was measured in IgAV patient serum.

We re-analyzed RNA sequencing data from leukocytes and skin biopsies of treatment-naïve adult IgAV patients: (1) IgAV nephritis (n = 3), (2) skin-limited IgAV (n = 3), and healthy controls (n = 3). Haptoglobin serum level was measured in 178, and haptoglobin genotyping was performed in 91 treatment-naïve adult IgAV patients. Serum sCD163 was measured in 60 IgAV patients and 22 HC.

Transcriptomic data of leukocytes and skin of IgAV nephritis patients identified haptoglobin as a hub gene, based on protein-protein interaction network. Haptoglobin serum level was elevated in IgAV patients with nephritis or gastrointestinal involvement compared to other IgAV patients. Patients who relapsed during follow-up had decreased haptoglobin serum level at disease presentation compared to non-relapsing patients. Haptoglobin genotyping did not show differences between genotype groups regarding clinical presentation and laboratory parameters. Serum sCD163 was significantly higher in IgAV nephritis patients compared to HC.

We identified haptoglobin as a novel marker of visceral involvement and relapse in adult IgAV, while sCD163 is linked to renal involvement. Further studies will confirm the clinical utility of haptoglobin as biomarker in IgAV. Key Points • Haptoglobin expression is upregulated in leukocytes and skin of adult IgAV with renal involvement. • Haptoglobin serum level is elevated in IgAV patients with visceral involvement. • Patients with IgAV relapse have lower haptoglobin at disease presentation.

Antineutrophil cytoplasm antibody-associated vasculitis (AAV) with interstitial lung disease (AAV-ILD) is the main manifestation of AAV involving the lung, further increasing the risk of poor prognosis in patients with AAV. This study aimed to investigate the risk factors associated with mortality in patients with AAV-ILD.

In Web of Science, PubMed, Embase and Scopus databases, a comprehensive search was performed for English studies on AAV and ILD published from inception date until May 17, 2024. Hazard ratios (HR) and 95% confidence intervals (CI) of mortality-related risk factors in AAV-ILD were collected, and subgroup analyses were carried out based on different candidate risk factors. Cochran's Q statistic and inconsistency value were utilized to assess the heterogeneity of included studies. Sensitivity analysis was executed using one-by-one elimination method, and publication bias was evaluated with Egger's test and the trim-and-fill method.

A total of 654 patients with AAV-ILD in eight studies were included for the pooled analysis of mortality risk factors. The results showed that age (HR = 1.06, 95%CI: 1.04, 1.08), ever smoker (HR = 1.61, 95%CI: 1.13, 2.29), usual interstitial pneumonia pattern (HR = 2.07, 95%CI: 1.43, 3.00), acute exacerbation (HR = 2.73, 95%CI: 1.70, 4.40) and microscopic polyangiitis (HR = 4.03, 95%CI: 1.70, 9.55) were associated with an increased risk of AAV-ILD mortality. Conversely, percent predicted forced vital capacity (HR = 0.97, 95%CI: 0.96, 0.99) and immunosuppressant for induction (HR = 0.40, 95%CI: 0.28, 0.58) were associated with a reduced risk of AAV-ILD mortality. Male (HR = 1.27, 95%CI: 0.90, 1.80), nervous system involvement (HR = 0.99, 95%CI: 0.65, 1.52), renal involvement (HR = 1.24, 95%CI: 0.97, 1.95) and five factor score ≥ 1 (HR = 1.00, 95%CI: 0.67, 1.48) showed no significant correlation with mortality risk in patients with AAV-ILD. Heterogeneity test indicated no significant heterogeneity among the pooled studies. The results of sensitivity analysis, Egger's test and the trim-and-fill method revealed that the pooled findings were stable and reliable.

The pooled analyses demonstrated that age, ever smoker, usual interstitial pneumonia pattern, acute exacerbation and microscopic polyangiitis were risk factors for mortality in patients with AAV-ILD, while percent predicted forced vital capacity and immunosuppressant therapy for induction serve as protective factors against mortality. A systematic understanding of the risk factors for AAV-ILD may provide clues for developing effective interventions and managements to improve poor prognosis in patients. Key Points • Increase of age, ever smoker, usual interstitial pneumonia pattern, acute exacerbation and microscopic polyangiitis were risk factors for poor prognosis in patients with AAV-ILD. • High level of percent predicted forced vital capacity and immunosuppressant therapy for induction serve as protective factors against poor prognosis. • Male, nervous system involvement, renal involvement and five factor score ≥ 1 showed no significant correlation with poor prognosis in patients with AAV-ILD.

Integrating clinical and histological parameters into prognostic scores may enhance the prediction of progression to kidney failure in anti-neutrophil cytoplasm antibodies-associated vasculitis (AAV). This study aimed to evaluate the prognostic performance of histological classifications and scoring systems for kidney survival in AAV.

This retrospective cohort study included 101 AAV patients with kidney involvement diagnosed by biopsy and followed for ≥12 months. The main outcome was the time to kidney failure. The prognostic performance of each histological and prognostic score was evaluated using Harrell's C statistic and Akaike's Information Criteria.

Among the 101 patients, 37 progressed to kidney failure over a median follow-up of 75 months (IQR 39-123). The Harrell's C statistic was 0.702 (0.620-0.784), 0.606 (0.473-0.738), 0.801 (0.736-0.867), 0.782 (0.706-0.858) and 0.817 (0.749-0.885) for the EUVAS/Berden classification, Mayo Clinic Chronicity Score, Percentage of ANCA Crescentic Score (PACS), ANCA renal risk score (ARRS), and the improved ANCA kidney risk score (AKRiS), respectively. The AKRiS best discriminated the risk of kidney failure progression among subgroups. The AKRiS performance decreased with longer follow-up intervals. Adding the peak estimated glomerular filtration rate attained post-therapy improved the AKRiS performance at all follow-up intervals. Kidney relapses precipitated kidney failure in 71% of cases that progressed after the first year of follow-up.

The novel AKRiS enhances the prediction of kidney failure in AAV with kidney involvement. As the prognostic yield of AKRiS decreases over time, a second calculation of AKRiS, including post-therapy kidney function, may improve its long-term performance.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a rare disease that manifests as necrotizing vasculitis involving small vessels without immune complex deposition. Granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) are included in this disease entity. Diagnosis and differentiation of AAV is challenging because of the diverse and overlapping clinical manifestations and lack of pathognomonic findings. Therefore, AAV classification criteria have been developed to increase the likelihood of diagnosis using multidisciplinary approaches, including clinical, radiologic, laboratory, and pathologic findings. The new American College of Rheumatology and European Alliance of Associations for Rheumatology classification criteria were released in 2022 to classify AAVs using weighted criteria and threshold scores. They are expected to make the classification of GPA, EGPA, and MPA more accurate in the setting of suspected small-vessel vasculitis. The criteria present key thoracic imaging discriminators of GPA as "pulmonary nodules, masses, or cavitation" and MPA as "interstitial fibrosis," whereas, radiologic criteria of EGPA are not present. ANCA positivity and eosinophil count are included as key laboratory discriminators. It is essential for radiologists to familiarize themselves with imaging findings of each AAV and know the key imaging discriminators to aid in the differential diagnosis of AAVs. By reviewing the radiologic findings of thoracic manifestations of each AAV and applying the new criteria in a series of cases, the authors aim to provide a practical and stepwise approach to AAV for radiologists. ©RSNA, 2025 Supplemental material is available for this article.

This study aims to establish the sensitivity and negative predictive value of a multimodal pathway incorporating ultrasonography, 18-fluorodeoxyglucose labelled PET-CT and temporal artery biopsy for the diagnosis of giant cell arteritis.

In total, 1000 consecutive referrals for a new diagnosis of giant cell arteritis were analysed. All patients had a protocolized examination. Patients with a negative ultrasonography and a CRP of ≥20 mg/L received an extended ultrasound examination. If that was negative, and there was no other explanation for their presentation, a second test in the form of either a temporal artery biopsy or an 18-fluorodeoxyglucose labelled PET-CT was offered. We calculated the sensitivity and negative predictive value of the interventions for diagnosing giant cell arteritis.

279/1000 patients had positive ultrasonography for giant cell arteritis. 202 had bilateral superficial temporal arterial involvement. Ultrasonography of the axillary artery and other head/neck arteries increased the yield by 53 and 24 patients, respectively. 181 patients were referred for a second test. 24/139 temporal artery biopsies and 7/42 18-fluorodeoxyglucose labelled PET-CT scans were positive. The sensitivity and negative predictive value rise from 62.3% and 84.7%, respectively, for imaging superficial temporal arteries alone, to 95.7% and 98.0%, respectively, for extended ultrasonography plus a second test.

This is the first real-world evidence of the utility of ultrasonography for the diagnosis of giant cell arteritis as part of a multimodal diagnostic pathway.

Arterial affection in Behçet's disease is serious and can be aneurysmal or thrombotic. The literature on the characteristics of arterial aneurysms in Behçet's disease remains scarce. This is a case report of a 19-year-old young male who was operated on for a false aneurysm of the left carotid bulb Aneurysm whose etiological investigation revealed Behçet's disease immediately complicated by the arterial localization. The false aneurysm was excised and the carotid bulb was repaired with polytetrafluoroethylene prosthesis.

The incidence of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) shows disparate results due to variable classification criteria and heterogeneous population series. We aimed to estimate the incidence of AAV in a well-defined population with standardized classification criteria.

This was a population-based study of AAV patients diagnosed from January 2000 to December 2023 in Cantabria, northern Spain. Patients were classified according to ACR/EULAR 2022 into granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or unclassified vasculitis if the criteria were not met. Eosinophilic granulomatosis with polyangiitis patients were not included. The annual incidence rates were estimated by cases over 1 000 000 (106) (95% CI) including overall AVV, type of AAV, sex and year of diagnosis. A literature review was also performed.

We included 152 patients [80M/72F; mean age 70.6 (13.18) years]. They were classified as MPA (67; 44%), GPA (64; 42.2%), and unclassified vasculitis (21; 13.8%). Annual incidence was 13.4 (95% CI: 10, 16.8)/106 [male 14.5 (95% CI: 10.5, 18.5); female 12.1 (95% CI: 8.7, 15.6)]. The Annual incidence of MPA was 5.9 (95% CI: 4, 7.8)/106 and GPA 5.6 (95% CI: 3.9, 7.3)/106. The mean annual incidence increased from 6.1 (95% CI: 4.5, 7.7)/106 to 16.5 (595% CI: .6, 27.4)/106 in the last 3 years, particularly in GPA from 2.3 (95% CI: 0.3, 4.9)/106 to 8.2 (95% CI: 2, 14.5)/106. The prevalence of AAV was 184.7 (95% CI: 181, 188)/106.

During a 20-year period we found that the incidence of AAV (GPA and MPA) in northern Spain was higher than in southern Spain, but lower than northern European countries. An increase in the incidence was observed in the last years.

Pneumocystis jirovecii pneumonia (PJP) is a common opportunistic infection. With the wide application of glucocorticosteroids and immunosuppressants, the incidence and mortality rates of PJP in connective tissue disease (CTD) patients with interstitial lung disease (ILD) are increasing.

We retrospectively enrolled consecutive CTD-ILD patients with PJP in our center between January 2014 and December 2022. Cox regression models were constructed to explore prognostic factors in CTD-ILD-PJP patients.

There were 159 CTD-ILD patients [60 (51, 68) years, 61.0% female] with PJP, 78 (49.1%) of whom died. Compared with those in the CTD-non-ILD-PJP group, there were more pneumomediastinum cases (16.4% vs. 6.7%, p = 0.030) and significantly higher all-cause mortality rates (49.1% vs. 33.7%, p = 0.019) in the CTD-ILD-PJP group. Multivariate analysis indicated that IIM (HR = 2.635, 95% CI: 1.383-5.019), pneumomediastinum (HR = 2.877, 95% CI: 1.483-5.582), oral candidiasis infection (HR = 2.596, 95% CI: 1.229-5.483), aspergilli infection (HR = 2.886, 95% CI: 1.412-5.900), and lower minimal albumin (Alb) (HR = 0.872, 95% CI: 0.819-0.927) were independent risk factors associated with poor survival in CTD-ILD-PJP patients.

CTD-ILD-PJP patients were mainly middle-aged females and had higher mortality rates than CTD-PJP patients without ILD. IIM, pneumomediastinum, oral candidiasis infection, aspergilli infection, and lower minimal Alb were independent risk factors associated with poor survival in CTD-ILD-PJP patients. Key Points • CTD-ILD-PJP patients had higher mortality rates than CTD-PJP patients without ILD. • IIM, pneumomediastinum, oral candidiasis infection, aspergilli infection, and lower minimal Alb were independent survival risk factors in CTD-ILD-PJP patients. • The study explored susceptibility and prognostic risk factors of CTD-ILD-PJP patients, to reduce the incidence and mortality.

This case highlights the atypical presentation of eosinophilic granulomatosis with polyangiitis (EGPA) with neurological and cardiac complications, emphasizing the necessity of early recognition and aggressive treatment to prevent morbidity and mortality.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are autoimmune inflammatory small-vessel disorders with potentially life-threatening organ manifestations. Recent disease definitions and classification criteria allow distinction between granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and non-granulomatous microscopic polyangiitis (MPA). The discovery of ANCA-autoantibodies directed against proteolytic enzymes of neutrophil granules-has enabled earlier diagnosis of AAV and paved the way to stage-adapted treatments. ANCA testing initially relied on different immunofluorescence patterns, i.e., cytoplasmic ANCA (C-ANCA) vs. perinuclear ANCA (P-ANCA), in ethanol-fixed neutrophils. This is nowadays outperformed by well-standardized immunoassays against the ANCA target antigens proteinase 3 (PR3) and myeloperoxidase (MPO) for the diagnosis of small-vessel vasculitides. The discovery of ANCA has contributed substantially to unravelling the pathogenesis of AAV, which comprises neutrophil degranulation, NETosis with concurrently amplified ANCA antigen presentation, and intra- and transmural vascular inflammation involving the alternative complement system in susceptible individuals. There is a genetic disposition concerning certain HLA alleles and polymorphisms of the proteinase 3 gene. Furthermore, epigenetic modifications impact on disease activity and relapse. During follow-up, the ANCA titer is not a reliable mirror of disease activity; however, PR3-ANCA positivity is associated with a greater likelihood of relapse and a better treatment response to rituximab as compared to cyclophosphamide/azathioprine. Within the past 60 years, the discovery of ANCA has revolutionized the ability to diagnose, understand, classify, and treat AAV in a targeted manner.

The peripheral nervous system is a classic target organ in systemic vasculitis. In addition, the skeletal muscle can also be affected. Myalgia, muscle weakness and sensory deficits are typical signs, which can lead to severe functional limitations and impaired of quality of life. Vasculitic involvement of the skeletal muscle (vasculitic myopathy [VM]) and peripheral nerves (vasculitic neuropathy [VN]) occurs predominantly in polyarteritis nodosa and small-vessel vasculitis. VM presents with elevated markers of inflammation and is typically characterized by immobilizing myalgia with normal creatine kinase activity and diffuse or patchy areas of hyperintensity on T2-weighted MRI ("MRI myositis without myositis"). In VN, sensor motor deficits predominantly affect the lower extremity in the area supplied by several peripheral nerves (e.g., mononeuritis multiplex) with acute to subacute history. The histopathological examination of nerve and muscle biopsies is the gold standard for the diagnosis of vasculitic manifestations and has a significant impact on the therapeutic approach.

To assess the association of trimethoprim sulfamethoxazole (TMP-SMX) prophylaxis with serious infections in rituximab-treated patients with granulomatosis with polyangiitis (GPA).

This retrospective cohort study included adults with GPA (2011-2020) within the United States Merative™ Marketscan® Research Databases with ≥6 months' enrolment prior to first (index) rituximab treatment. We defined TMP-SMX prophylaxis as a ≥28-day prescription dispensed after or overlapping the index date. Serious infection was a hospital primary diagnosis for infection (excluding viral or mycobacterial codes). Secondary outcomes were outpatient infection, Pneumocystis jirovecii pneumonia (PJP) and adverse events potentially attributable to TMP-SMX. Cox proportional hazards regression assessed the association of time-varying TMP-SMX with outcomes of interest, adjusting for potential confounders. Individuals were followed until the outcome of interest, end of database enrolment or 31 Decamber 2020.

Among 919 rituximab-treated individuals (53% female), mean (s.d.) age was 52.1 (16) years and 281 (31%) were dispensed TMP-SMX within 30 days of index date. Over a median of 496 (interquartile range 138-979) days, 130 serious infections occurred among 104 individuals (incidence 6.1 [95% CI: 5.0, 7.4] per 100 person-years). Time-varying TMP-SMX was negatively associated with serious infection (adjusted hazard ratio [aHR] 0.5; 95% CI: 0.3, 0.9). The aHR for outpatient infections was 0.8 (95% CI: 0.6, 1.1). The estimate for PJP was imprecise (13 events, unadjusted HR 0.2; 95% CI: 0.03-1.8). TMP-SMX was potentially associated with adverse events (aHR 1.3; 95% CI: 0.9, 1.9).

TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of optimal prophylaxis strategies.

There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission maintenance agent in microscopic polyangiitis (MPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well for serious adverse events (SAEs) in MPA/GPA patients during RTX maintenance.

A retrospective cohort of newly diagnosed/relapsing GPA/MPA patients who received RTX maintenance (≥1 RTX cycle, ≥6 months follow-up) following complete remission (BVAS version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious infections, COronaVIrus-Disease 2019 (COVID-19)-associated hospitalizations, deaths, cardiovascular events, malignancies and hypogammaglobulinemia. The incidence rates (IRs) and relapse-free survival were estimated through Kaplan-Meier plots. Cox regression was conducted to investigate factors associated with the time-to-relapse.

A total of 101 patients were included: 48% females, 69% GPA, 53% newly diagnosed, median age 63 years. During follow-up (294.5 patient-years, median: 3 RTX cycles), 30 relapses (57% major) occurred among 24 patients (24%, IR 10.2/100 patient-years). Kidney involvement (adjusted hazard ratio/aHR: 0.20; 95% CI: 0.06-0.74, P = 0.016), prior induction with RTX plus CYC (vs RTX monotherapy: aHR = 0.02; 95% CI: 0.001-0.43, P = 0.012) and shorter time interval until complete remission (aHR = 1.07; 95% CI: 1.01-1.14, P = 0.023) were associated with decreased relapse risk. We recorded 17 serious infections (IR 5.8/100 patient-years), 11 COVID-19-associated hospitalizations (IR 3.7/100 patient-years), 4 malignancies (IR 1.4/100 patient-years), 6 cardiovascular events (IR 2/100 patient-years) and 10 deaths (IR 3.4/100 patient-years).

In this real-world study, relapses during RTX maintenance occurred in approximately 1 out of 4 patients. Kidney involvement, induction with RTX plus CYC, and earlier achievement of complete remission were associated with lower relapse risk. The serious infections rate was consistent with previous reports, whereas an increased rate of COVID-19-associated hospitalizations was observed.