In this study, we aimed to evaluate the factors affecting the development of damage and mortality in patients with AAV treated at our tertiary referral center. This retrospective study included data on patients with AAV who fulfilled the Chapel Hill Consensus Conference (CHCC) criteria. Patients were divided into c-ANCA/PR3( +) and p-ANCA/MPO ( +) groups based on ANCA immunofluorescence and/or ELISA results, and relapse, damage, and mortality data were compared across the groups. Data from 254 patients (n = 136, 53.5% female) were included in the analysis. Clinical diagnosis was GPA in 186 (73.2%) and MPA in 68 (26.8%) patients. During the follow-up, 217 of 242 (89.7%) patients developed damage, and the median VDI score of the cohort was 2 (IQR: 2). VDI scores were higher in the first period (1997-2011) than in the second period (2011-2021) in the entire cohort (p = 0.012) and in patients with GPA compared with MPA (p = 0.034). Five-year and overall survival rates were 88.1% and 80.3% in the entire cohort; 87.8% and 81% in c-ANCA/PR3 ( +); 86.2% and 76% in p-ANCA/MPO ( +) (Log-Rank: p = 0.35); 91% and 84.5% in GPA; 81% and 67.2% in MPA patients (Log-Rank: p < 0.001). Development of malignancy, severe infection, and active/persistent disease after the induction phase were associated with higher mortality in patients with AAV. In our AAV cohort, permanent organ damage was detected in the majority of the patients. Although the median VDI score decreased over time, mortality did not change.

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.

A delayed diagnosis of polyarteritis nodosa may lead to critical limb-threatening ischemia (CLTI). A 74-year-old woman presented with left-foot pain and was treated with oral vasodilators and antiplatelet agents. However, the distal ischemia progressed to CLTI, including gangrene of the fingers and toes, and bilateral foot dropping appeared because of peroneal nerve paralysis. Angiography of the extremities revealed obstruction and stenosis of medium-sized arteries. Based on the progressive distal gangrene, mononeuropathy multiplex, and pathological findings of necrotic vasculitis, polyarteritis nodosa was diagnosed, and the patient's condition improved. A biopsy and neurological examination are essential for the appropriate diagnosis of PAN and immediate treatment.

Objectives: This study investigated whether serum soluble CD200 (sCD200) and soluble receptor for CD200 (sCD200R) concentrations and serum sCD200/sCD200R ratios at diagnosis could predict cross-sectional activity in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: We included 70 patients with AAV in this pilot study, retrospectively reviewed their medical records, and collected clinical data at the time of AAV diagnosis. We also measured sCD200 and sCD200R in stored blood samples collected at diagnosis. In medical records, AAV activity at diagnosis had been assessed according to the Birmingham Vasculitis Activity Score (BVAS). The prediction potential of serum sCD200 and sCD200R concentrations and serum sCD200/sCD200R ratios for BVAS was evaluated using Pearson correlation analysis. Results: Among the 70 patients, the median age was 63.5 years, with 29 males and 41 females. Among the three CD200-related variables at diagnosis, serum sCD200/sCD200R ratios at diagnosis were significantly correlated with cross-sectional BVAS; however, serum sCD200 and sCD200R concentrations were not correlated with it. These results may indicate that serum sCD200/sCD200R ratios may better help predict cross-sectional AAV activity by increasing the range of opposing changes in the two variables. On the other hand, both serum sCD200 concentrations and serum sCD200/sCD200R ratios showed significant correlations with cross-sectional myeloperoxidase-ANCA titre, five-factor score, and serum creatinine levels at diagnosis. Conclusions: In this study, we demonstrated that serum sCD200/sCD200R ratios at diagnosis can be a useful and convenient biomarker to predict cross-sectional AAV activity calculated according to BVAS.

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.

Background/Objectives: Previous studies have revealed the predictive potential of remnant cholesterol (RC) for acute coronary syndrome (ACS) occurrence in the general population. However, whether this association applies to patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), in which a lipid paradox exists, remains unclear. We investigated whether RC levels at diagnosis could predict ACS occurrence during follow-up in patients with AAV. Methods: This study included 139 patients with AAV. ACS was defined as ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina occurring after AAV diagnosis. RC levels were calculated as (total cholesterol)-(low-density lipoprotein cholesterol)-(high-density lipoprotein cholesterol). Patients were categorised into three groups by RC tertiles: highest (≥26.2 mg/dL), middle (19.1-26.1 mg/dL), and lowest (≤19.0 mg/dL) tertile groups. Results: The median age of the 139 patients (male, 31.7%) was 58.0 years. During follow-up, six, two, and one patients were diagnosed with ACS in the highest, middle, and lowest tertile groups, respectively. Patients in the highest tertile group exhibited a significantly lower ACS-free survival rate than those in the lowest tertile (p = 0.030). In the multivariable Cox hazards model, male sex (hazard ratio [HR] 9.054, 95% confidence interval [CI] 1.786-45.910), Birmingham vasculitis activity score (HR 1.147, 95% CI 1.033-1.274), and the highest tertile of RC levels (HR 10.818, 95% CI 1.867-62.689) were significantly and independently associated with ACS occurrence during follow-up in patients with AAV. Conclusions: Our findings indicate that RC levels at diagnosis may predict ACS occurrence during follow-up in patients with AAV, regardless of the traditional cardiovascular risk factors.

Objective: This study investigated whether circulating growth differentiation factor 15 (GDF15) at diagnosis could estimate the Birmingham Vasculitis Activity Score (BVAS) and potentially predict all-cause mortality and end-stage kidney disease (ESKD) during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: This study included 79 patients selected from a cohort of Korean patients with AAV. Circulating GDF15 was measured from patients' sera collected at diagnosis and stored at -80 °C. Clinical data at diagnosis and during follow-up were reviewed. Results: The median age was 64.0 years (40.5% men, and 59.5% women). Median circulating GDF15 was measured as 995.0 pg/mL. Of the 79 patients, 6 (7.6%) died and 20 (25.3%) progressed to ESKD during the disease course. Circulating GDF15 levels were significantly correlated with BVAS (r = 0.340) at diagnosis. Patients with circulating GDF15 ≥ 3350.5 pg/mL exhibited a significantly higher risk of the highest tertile of BVAS than those without (relative risk [RR], 11.229). Similarly, patients with circulating GDF15 ≥ 2239.5 pg/mL and ≥2208.5 pg/mL showed higher risks of all-cause mortality (RR, 7.733) and progression to ESKD (RR 7.125) than those without. Patients with circulating GDF15 ≥ 2239.5 pg/mL and ≥2208.5 pg/mL also showed significantly lower patient and ESKD-free survival rates than those without. Conclusions: Circulating GDF15 at diagnosis is useful in estimating BVAS and potentially predicts all-cause mortality and ESKD progression in patients with AAV.

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are heterogeneous disorders. The aim of this study was to identify and characterize subgroups of patients based on sex, ANCA, age at diagnosis, and organ involvement.

In total, 1,167 patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were retrospectively recruited to the study. Data including cumulative involvement of 10 different organ systems, end-stage kidney disease (ESKD), sex, proteinase (PR) 3-ANCA, myeloperoxidase (MPO)-ANCA, age at diagnosis, disease duration, and relapse were obtained from medical records. Clinical variables were analyzed for associations with sex, age at diagnosis, and relapse using logistic regression analysis. Thirteen clinical variables were included in hierarchical cluster analyses using the Ward method.

In patients with GPA, PR3-ANCA, renal and pulmonary involvement, and ESKD were significantly associated with male sex, whereas MPO-ANCA was associated with female sex. Patients with GPA who were younger than 32 years of age at diagnosis were significantly more often females and had more ear-nose-throat involvement than patients older than 32 years. In patients with MPA, female patients were significantly younger at diagnosis than male patients. Relapse was significantly associated with young age at diagnosis and pulmonary involvement in GPA and with musculoskeletal involvement in MPA. Hierarchical cluster analyses identified five and seven patient clusters among individuals with GPA and MPA, respectively. PR3-/MPO-ANCA defined the largest clusters, whereas heart, gastrointestinal, and central nervous system involvement were hallmarks for three clusters for both patients with GPA and MPA.

Sex, age at diagnosis, and specific organ involvements define clinically relevant subgroups among patients with ANCA-associated vasculitides.

In this study, we investigated whether serum glutathione peroxidase-1 (GPX-3) concentration at diagnosis could be used to assess vasculitis activity and damage at diagnosis in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

We included 71 immunosuppressive drug-naïve patients newly diagnosed with AAV. Medical records were retrospectively reviewed and serum GPX-3 concentration was measured using serum samples collected and stored at diagnosis. The degree of vascular activity and extent of damage were assessed using the Birmingham vasculitis activity score (BVAS) and vasculitis damage index (VDI), respectively. Poor outcomes including all-cause mortality, end-stage kidney disease, and cerebrovascular and cardiovascular diseases were also investigated.

The median age of the study subjects was 63.0 years, 26 and 45 patients were males and females, respectively. The median GPX-3 concentration was measured as 82.8 ng/mL. Serum GPX-3 concentration at diagnosis was inversely correlated with BVAS (r = -0.280), VDI (r = -0.263), and C-reactive protein (r = -0.261) at diagnosis, whereas, it was positively correlated with haemoglobin (r = 0.255), and serum albumin (r = 0.240) at diagnosis, respectively. However, serum GPX-3 concentration at diagnosis was not significantly associated with poor outcomes during follow-up in patients with AAV.

In this study, we demonstrated for the first time that serum GPX-3 concentration at diagnosis correlates with vasculitis activity and damage at diagnosis in patients with AAV, suggesting a possible role of serum GPX-3 as a complementary biomarker for assessing AAV activity in real clinical practice.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis associated with varying clinical presentations and overlapping multiorgan involvement. Asthma is a predominant feature of EGPA, typically in its prodromal phase, often severe, and precedes vasculitic complications. However, there is paucity of studies describing the prevalence and characteristics of EGPA in the asthma population.

To describe the clinical and serological characteristics and longitudinal therapeutic outcomes of patients with EGPA in the severe asthma (SA) cohort.

A retrospective study of patients with EGPA attending the multidisciplinary SA clinic in a tertiary hospital from 2011 to 2023 was conducted. Baseline demographics, organ manifestations, biological markers, lung function, and therapeutic outcomes were assessed.

Twenty-three of 596 patients in the SA registry were identified to have EGPA. Median time interval between asthma and EGPA diagnosis was 10 years (range, 2.5-32 years). Almost all patients (95.7%) had peak blood eosinophil count of more than 1.0 × 109/L (range, 0.47-14.08 × 109/L). Upper airway involvement was the most detected manifestation in addition to asthma, followed by neuropathy and renal involvement. Patients who were treated with biologic therapy were significantly younger and had more upper airway, renal, and pulmonary involvement and lower Five Factor Score.

The prevalence of EGPA in the SA population was 3.9% in our cohort. Its diagnosis requires high clinical suspicion in patients with SA and blood eosinophilia, prompting stringent evaluation for extrapulmonary manifestations and multidisciplinary involvement.

Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify the high-risk population.

We included EGPA patients hospitalized in our centre from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac MRI and endomyocardial biopsy results, the patients were divided into three groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared.

A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-Control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, P < 0.01), ANCA positivity decreased (41.33/31.82/14.86%, P < 0.01) and lung involvement was reduced (73.33/72.73/43.24%, P = 0.02). In EGPA-EM, cardiac troponin was further elevated (0.27 vs 6.00 ng/ml, P < 0.01), ejection fractions decreased (57.79 vs 33.20%, P < 0.01) while more ST-T abnormality was observed (41.89 vs 20.45%, P = 0.02). The prognosis of EGPA-EM was significantly worse, with a 14.86% death rate and 2-year event-free survival rate below 50%. Furthermore, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [area under the receiver operating characteristic curve 0.85 (95% CI 0.78-0.92), sensitivity 0.78, specificity 0.86].

We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given in a timely manner and anti-IL-5 antibodies should be be tested in trials.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an immune-mediated, inflammatory, multisystemic disease that is considered a form of ANCA-associated vasculitis and whose association with asthma and blood and tissue eosinophilia differentiate it from other types of vasculitis. Nevertheless, diagnosis of EGPA may be difficult or delayed not only because of the rarity of the disease, but also because other diseases can present with similar manifestations.

We review a series of key areas in EGPA, namely, laboratory and clinical indicators of disease, diagnosis, role of biomarkers, induction and maintenance therapy, and use of traditional and novel drugs. This narrative review was based on a thorough search of PubMed.

Clinicians should be aware of the limitations of available tools for diagnosing EGPA, and more efforts should be made to identify clinical and laboratory red flags, with the purpose of achieving an early diagnosis before irreversible damage occurs. New effective therapies are available, although future research should target an approach that spares glucocorticoids, reduces the risk of flares and organ damage, and maintains long-term remission with minimum adverse effects.

Diagnosing vasculitis is challenging because it lacks pathognomonic signs and symptoms. Gastrointestinal vasculitis further complicates the picture, given its high mortality risk and the potential absence of systemic manifestations; thus, a systematic approach that includes ruling out vasculitis mimickers is useful. We report the case of a 29-year-old male evaluated for suspected intestinal vasculitis due to recurrent rectal bleeding, weight loss, fatigue, elevated inflammatory markers, high immunoglobulin E (IgE) levels, and positive anti-neutrophil cytoplasmic antibodies (ANCA), coupled with computed tomography (CT) showing diffuse parietal thickening of the anus, rectum, and sigmoid colon. These findings raised suspicion for eosinophilic granulomatosis with polyangiitis, prompting high-dose corticosteroid therapy before definitive diagnosis. However, contrast-enhanced magnetic resonance imaging (MRI) later revealed phleboliths and venous lakes, indicating gastrointestinal diffuse cavernous hemangioma (GDCH). Sirolimus was introduced to facilitate steroid tapering and to reduce bleeding, ultimately leading to significant lesion regression and symptom resolution. This case underscores the importance of excluding vasculitis mimickers - particularly vascular malformations - when evaluating potential gastrointestinal vasculitis.

The aim was to investigate the ability of serum sulfatide levels at diagnosis to reflect the cross-sectional activity and further longitudinally predict the occurrence of end-stage kidney disease (ESKD) during the follow-up period in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), regardless of kidney involvement at diagnosis. This study included 67 patients first diagnosed with AAV with available clinical data, including Birmingham Vasculitis Activity Score (BVAS), erythrocyte sedimentation rate, C-reactive protein, and blood samples at diagnosis. Serum sulfatide levels were assessed using stored serum samples at the time of diagnosis. The median age of the 67 patients (40.3% men and 59.7% women) was 61.0 years. During follow-up, 10 (14.9%) patients progressed to ESKD, and 4 (6.0%) died. Serum sulfatide levels significantly correlated with Five-Factor Score (r = -0.242), erythrocyte sedimentation rate (r = -0.315), and renal manifestation of the BVAS items (r = -0.296), but not BVAS at diagnosis. The cutoff of serum sulfatide levels at diagnosis for ESKD progression was 332.5 pg/mL. However, no significant cutoff of serum sulfatide levels for all-cause mortality was obtained. Patients with serum sulfatide levels ≤ 332.5 pg/mL at diagnosis exhibited both significantly higher frequency of ESKD progression (22.7% vs 0%, P = .012) and lower ESKD-free survival rate than those without (P = .011). This study highlighted the clinical usefulness of measuring serum sulfatide levels at the time of diagnosis as a biomarker to predict ESKD progression in patients with AAV regardless of kidney involvement at diagnosis.

Objective: In this study, we develop a new formula for predicting all-cause mortality in an ethnicity/region-specific cohort of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: We included 290 Korean patients with AAV in this study and retrospectively reviewed their medical records regarding clinical data at diagnosis and during follow-up. We introduce a new index, called the NFPM value after the initials of New Formula for Predicting Mortality, which we derived using the independent predictors of all-cause mortality obtained in the multivariable Cox proportional hazard analysis. The cut-offs of the parameters for mortality were determined using the highest or lowest tertile of each parameter according to its positive or negative association with all-cause mortality, respectively. Results: The median age was 60.0 years and 35.9% were male patients. Of the 290 patients, 39 died during follow-up (13.4%). In the multivariable Cox analysis, male sex, the five-factor score (FFS), and serum albumin were independent predictors of all-cause mortality. A new formula was developed as follows: NFPM = male sex (yes = 1 or no = 0) + FFS ≥ 2.0 (yes = 1 or no = 0) + serum albumin ≤ 3.2 mg/dL (yes = 1 or no = 0). We demonstrated that patients with a NFPM value ≥ 2 seemed to have an increased risk for all-cause mortality compared to those with a NFPM value < 2. Conclusions: This study demonstrated that it could be clinically useful and significant to develop a new formula to predict all-cause mortality using independent predictors in each different ethnicity/region-specific cohort of AAV.

This study aimed to identify new clinical phenotypes of microscopic polyangiitis (MPA) using a principal components analysis (PCA)-based cluster analysis.

A total of 189 patients with MPA between May 2005 and December 2021 were enrolled from a multicenter cohort in Japan (REVEAL cohort). Categorical PCA and cluster analysis were performed based on clinical, laboratory, and radiological findings. Clinical characteristics and outcomes, including all-cause mortality, respiratory-related mortality, end-stage renal disease (ESRD), and relapse were compared between each cluster.

Eleven clinical variables were transformed into four components using categorical PCA and synthetic variables were created. Additionally, a cluster analysis was performed using these variables to classify patients with MPA into subgroups. Four distinct clinical subgroups were identified: Cluster 1 included the renal involvements and diffuse alveolar hemorrhage (DAH)-dominant group (N=33). Cluster 2 comprised the elderly onset systemic inflammation group (N=75). Cluster 3 included patients in the younger-onset limited-organ disease group (N=45). Cluster 4 was comprised of an ILD-predominant group without kidney involvement (N=36). 61 patients died during follow-up, with 32 dying of respiratory-related causes. Additionally, 19 patients developed ESRD and 70 relapsed. Cluster 1 showed the worst ESRD-free survival and relapse rates, whereas Cluster 2 showed the worst overall survival and respiratory-related death-free survival rates among the four groups.

Our study identified four unique subgroups with different MPA outcomes. Individualized treatments for each subgroup may be required to improve the prognosis of MPA.

Severe gastrointestinal lesions are associated with a poor prognosis in eosinophilic granulomatosis with polyangiitis (EGPA). The goal of this study was to develop an effective predictive model for gastrointestinal lesions and to examine clinical patterns, associated factors, treatment, and outcomes of gastrointestinal lesions in EGPA.

We retrospectively enrolled 165 EGPA patients. The independent associated factors were analyzed using multivariate logistic regression. A nomogram was conducted to quantify the predictive factors. The correlation between different organ lesions was calculated to explore the clinical patterns.

A total of 52 patients had gastrointestinal lesions, and 22 developed severe disorders. Common manifestations included abdominal pain (78%), diarrhea (40.4%), and nausea and/or vomiting (32.7%). Severe gastrointestinal lesions included hemorrhage (26.9%), ulcers (17.3%), obstruction (9.6%), and pancreatitis (5.8%). Eosinophilic tissue infiltration, weight loss, and myalgia were independently associated with gastrointestinal involvement. Patients with severe gastrointestinal lesions had a shorter duration from initial symptoms to EGPA diagnosis, less frequent asthma, and ear-nose-throat involvement, and were more likely to receive methylprednisolone pulse. Weight loss, central nervous system involvement, myalgia, and eosinophilic tissue infiltration were retained in the nomogram. An eosinophil ratio of over 19.2% identified gastrointestinal lesions. Significantly more patients with gastrointestinal involvement had a Five Factor Score ≥ 2. Five well-defined clinical models were identified, including the brain-gut pattern.

Severe gastrointestinal lesions are common in EGPA and early detection is critical. Eosinophils are an important factor associated with gastrointestinal involvement of EGPA. We developed a model to predict the risk of gastrointestinal lesions. The brain-gut pattern might deserve further investigation in EGPA.

Several studies have examined the utility of quadriceps femoris muscle biopsies for diagnosing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to investigate the effects of glucocorticoid therapy on the muscle biopsy findings of patients with AAV. Data from patients with AAV who underwent a biopsy of the bilateral vastus lateralis of the quadriceps femoris at Tokyo Metropolitan Tama Medical Center between January 2015 and December 2023 were retrospectively analyzed. In total, 126 patients with suspected small vessel vasculitis (SVV) or medium vessel vasculitis (MVV) underwent a muscle biopsy at the study center. Of these, the present study included 71 patients with a final diagnosis of AAV who received a muscle biopsy of the bilateral vastus lateralis at disease onset and began glucocorticoid therapy at the study center. Of the 71 patients, 41 (57.7%) had a positive muscle biopsy finding as defined by the presence of inflammatory infiltrates with fibrinoid necrosis in the vessels. Fifty-six and 15 patients underwent a biopsy before and after starting glucocorticoid therapy, respectively. Of the former, 33 (58.9%) had a positive finding compared to eight (53.3%) of the latter (Pearson's chi-square test: p = 0.697). Among the patients with a positive biopsy result, 22 (53.7%) and 19 (46.3%) had a unilaterally and bilaterally positive finding, respectively. Glucocorticoid therapy did not significantly affect the findings of quadriceps femoris muscle biopsies. Unilateral biopsies may have a lower diagnostic sensitivity for AAV than bilateral biopsies.

Eosinophilic granulomatosis with polyangiitis (EGPA), as a heterogeneous component of antineutrophil cytoplasmic antibody-associated vasculitis, may be induced by a series of environmental and genetic factors, involved with a variety of immune cells and immune components, and presented with various clinical manifestations, with multiple organs and systems (respiratory, skin, heart, kidney, nerve, etc.) involved. The choice of glucocorticoid (GC) dosage and immunosuppressant in traditional treatment strategies varies greatly from individual to individual and is not universally applicable in all the EGPA phenotype spectrum, especially in relapsing or refractory diseases. With the understanding of the heterogeneity of EGPA, a variety of therapeutic approaches are emerging and improving the traditional treatment model. In this review, we summarized the heterogeneity of EGPA etiology and pathogenesis. Clinical and pathological manifestations of the same organ involved also show significant differences and there are even gender differences. Biological treatments that mainly target type 2 inflammatory pathways are widely used in clinical practice for remission induction and maintenance of EGPA. Targeted biological therapy has shown excellent performance in reducing GC dosage and controlling symptoms and recurrence. However, a large number of high-quality randomized controlled studies are still under research for relapsing or refractory EGPA with special organ involvement. We believe that EGPA has a highly heterogeneous phenotype spectrum, and the treatment patterns targeting key molecules in the pathogenesis are of great value for individual treatment of EGPA.

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is characterised by small vessel necrotising inflammatory vasculitis. Prior to immunosupressant therapy availability it usually led to a fatal outcome. Current treatment has changed ANCA-associated vasculitis into a condition with a significant response rate, although with a not negligible relapse occurrence and cumulative organ lesions, mostly due to drug-related toxicities. The use of glucocorticoids, cyclophosphamide and other immunosupressants (such as azathioprine, mychophenolate and methotrexate) was optimised in a series of clinical trials that established the treatment of reference. In recent years, a better knowledge of B lymphocyte function and the role of complement inhibition has transformed the course of this disease while minimising treatment-related adverse effects. This multidisciplinary document of recommendations is based on the consensus of three scientific societies (Internal Medicine, Nephrology and Rheumatology) and on the best available evidence on diagnosis, treatment and follow-up of patients with ANCA-associated vasculitis, including some special situations. The aim of this document is to provide updated information and well-grounded clinical recommendations to practising physicians as to how to improve the diagnosis and treatment outcome of our patients.

To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort).

Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes, were collected retrospectively. The patients were stratified into MPZ continuation (n = 53) and discontinuation (n = 7) groups, and drug retention was statistically compared using the log-rank test.

The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after 5 years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027).

MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.

Polyarteritis nodosa is a relatively uncommon type of systemic necrotizing vasculitis that primarily affects medium-sized arteries. While gastrointestinal involvement is known in polyarteritis nodosa, heavy gastrointestinal bleeding due to gastric ulceration is relatively uncommon. We present the case of an 81-year-old male of Chinese ethnicity who experienced severe gastrointestinal bleeding as a result of polyarteritis nodosa and an innovative treatment approach for a better patient outcomes.

Upon admission to the medical intensive care unit, the patient underwent a comprehensive diagnostic assessment, including examinations for cardiovascular and dermatological abnormalities, laboratory tests, autoantibody and tumor marker assessments, and imaging studies (such as endoscopies, whole-body computed tomography, and positron emission tomography-computed tomography scans), and a skin biopsy. The patient had tachycardia, hypotension, and extensive skin abnormalities on the lower extremities along with anemia, low platelets, and abnormal renal function. Upper gastrointestinal endoscopy revealed gastric and duodenal ulcers. Additional examinations, including electronic colonoscopy, capsule endoscopy, and whole-body computed tomography, were negative. A positron emission tomography-computed tomography scan showed increased uptake in the arterial walls and skin, which supported the diagnosis of polyarteritis nodosa, later confirmed by a biopsy of the skin on the lower extremities. Methylprednisolone, octreotide, and omeprazole were administered, leading to improvement in gastrointestinal symptoms, ulcer healing, and skin recovery. The patient continued with prednisone for 1 month.

This case serves to inform gastroenterologists about the need to consider polyarteritis nodosa in severe upper gastrointestinal bleeding and underscores the importance of prompt, medication-based treatment for successful patient outcome.

Granulomatosis with polyangiitis is an ANCA-associated vasculitis that involves small to medium-sized vessels. The extent of renal involvement varies, which is also associated with disease prognosis, with aggressive renal involvement having worse outcomes. Rapidly progressive glomerulonephritis with severe inflammatory features and extensive crescent formation can be challenging to treat. Usually, induction regimes utilize a combination of pulse dose methylprednisolone followed by rituximab or cyclophosphamide. Resistant diseases pose additional treatment challenges, and individualized treatment regimens have been described without accumulated outcome data. Cyclophosphamide, rituximab, azathioprine, methotrexate, and mycophenolate with or without plasmapheresis have been variably used, but there is a lack of consensus on a standardized regime in literature. Our case adds to the existing literature on the treatment-refractory granulomatosis with polyangiitis, which was treated with high-dose corticosteroid in combination with rituximab, low-dose cyclophosphamide, plasmapheresis, and brief use of hemodialysis. It also reiterates that the use of a variety of low-dose cyclophosphamide with rituximab could be beneficial for treatment-refractory cases or patients with severe renal involvement, in addition to better tolerance with low dose cyclophosphamide in comparison with full-dose cyclophosphamide.

This study investigated poor prognostic factors for the relapse of interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA) after remission induction therapy.

We enrolled patients diagnosed with MPA complicated by ILD according to the Chapel Hill Consensus definition from 2001 to 2023 in multiple institutions in the REVEAL cohort. All patients who were treated with immunosuppressive therapy were followed up, and those who relapsed with ILD were extracted in this study. We explored the risk factors for predicting ILD relapse in patients with MPA-ILD by comparing the demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission.

Of 243 patients with MPA, 134 (55.1%) with MPA-ILD were enrolled. Among them, 28 (20.9%) relapsed during a mean follow-up of 4.2 years. The initial serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) levels and the prevalence of usual interstitial pneumonia (UIP) pattern were significantly higher in the relapsed group. The biomarkers were also risk factors for relapse in multivariate Cox regression analysis. The best cut-off values of KL-6, SP-D for predicting ILD relapse were 430 U/mL and 89.5 ng/mL, respectively. We created prediction models based on the best cut-off values for KL-6, SP-D, and the presence of the UIP pattern (KSU model). The 10-year relapse rate was significantly different among patients with MPA-ILD stratified by the number of risk factors based on the KSU model. A higher relapse rate was associated with higher all-cause mortality.

The initial serum high KL-6 and SP-D levels and the prevalence of the UIP pattern were associated with ILD relapse in patients with MPA-ILD. Our multicentre cohort study indicated that the KSU model, which consists of KL-6 ≥ 430 U/mL, SP-D ≥ 89.5 ng/mL, and the presence of the UIP pattern, is a useful predictor of ILD relapse in patients with MPA after immunosuppressive therapy.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a chronic inflammatory disease belonging to the spectrum of small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs), also characterized by eosinophilic infiltration of target organs. Peripheral neuropathy (PN) affects about 2/3 of the patients as a presenting symptom and typically represents a vasculitic involvement. A few studies have addressed the role of intravenous immunoglobulin (IVIg) for the treatment of PN in EGPA. This monocentric retrospective study aims at assessing the effectiveness and safety of IVIg in patients with PN as the main acute manifestation at EGPA onset. The treatment with IVIg appears to be effective in inducing sustained remission, reducing the risk of relapses and improving the long-term disability due to its effects on PN.

This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).

Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model.

The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094).

This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

This study aimed to compare the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria with the European Medicines Agency (EMA) algorithm for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

All consecutive, newly diagnosed patients with AAV according to the 2012 Chapel Hill Consensus Conference who visited Keio University Hospital between March 2012 and May 2022 were retrospectively reviewed. Patients were reclassified according to the EMA algorithm and the 2022 ACR/EULAR criteria, and their clinical characteristics were statistically analyzed.

A total of 114 patients with AAV were included in the analyses. Using the EMA algorithm as a reference, reclassification of the patients revealed sensitivity and specificity of the 2022 ACR/EULAR criteria of 100% and 96% for eosinophilic granulomatosis with polyangiitis, 40% and 97% for granulomatosis with polyangiitis (GPA), and 90% and 49% for microscopic polyangiitis (MPA), respectively. Approximately half of patients classified as EMA-GPA or EMA-unclassifiable were reclassified as 2022-MPA; these patients were older, were more disposed to be positive for myeloperoxidase (MPO)-ANCA, and had interstitial lung disease (ILD) more frequently than patients with 2022-GPA or non-2022-MPA. Further, some patients positive for MPO-ANCA with biopsy-proven granulomatous inflammation were also reclassified from EMA-GPA to 2022-MPA. Over the mean observation period of 4.0 years, 16 patients died. Overall survival for each classification group differed significantly from the 2022 ACR/EULAR criteria (P = 0.02), but not with the EMA algorithm (P = 0.21).

Among the patients classified as EMA-GPA or EMA-unclassifiable, older patients with MPO-ANCA and ILD tended to be reclassified as 2022-MPA. The 2022 ACR/EULAR criteria were more useful in prognostic prediction than the EMA algorithm.

Alpha-1-Antitrypsin (A1AT) is a protease inhibitor encoded by the SERPINA1 gene. A1AT serves as the primary natural inhibitor of Proteinase 3 (PR3), an enzyme found in neutrophils. PR3 is an antigenic target of Anti-Neutrophil Cytoplasmic Antibodies (ANCA). While numerous studies have established a connection between Single Nucleotide Polymorphisms (SNPs) in the SERPINA1 gene and ANCA-Associated Vasculitis (AAV), limited research has delved into the impact of these polymorphisms on the prognosis of these patients.

The present study's objective is to investigate mortality disparities among Brazilian AAV patients carrying SERPINA1 SNPs (rs7151526, rs28929454) compared to non-carriers. Additionally, the authors analyzed demographic, clinical, and serologic data in these two groups.

In this single-center prospective cohort study, the authors enrolled AAV patients who were monitored for a duration of up to three years. The identification of SNPs was conducted through RT-PCR. Survival analysis, including Kaplan-Meier survival curves, and Cox proportional regression analysis was subsequently performed to evaluate outcomes.

The authors assessed 115 patients (65.2% with granulomatosis with polyangiitis, 17.4% with eosinophilic granulomatosis with polyangiitis, and 17.4% with microscopic polyangiitis). All patients were aged ≥ 18 years, with 37.4% being female, and 54.7% identified as White. The association between SERPINA1 SNPs proved to be the most significant factor linked to mortality in the cohort (HR = 6.2, 95% CI 1.4‒27.1, p = 0.015). SERPINA1 SNP carriers exhibited a lower mean survival [rs7151526: 57.4 (42.7‒72.2) years, p < 0.007; rs28929454: 54.9 (40.9‒68.9) years, p < 0.0001] than non-carriers (68.0 [67.2‒69.0] years).

SERPINA1 SNPs are associated with increased mortality in Brazilian AAV patients.

Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes.

This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups.

Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose.

Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections.

Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings.

This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM).

After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012).

Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients.

To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL) and autonomic dysfunction in patients with vasculitis.

Patients with vasculitis (with or without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey.

Three hundred and twelve patients (71% female) responded. Median age was 61-70 years. Median duration of vasculitis was 4 years (<2 months to >15 years). Vasculitic types included granulomatosis with polyangiitis (34%), unspecified ANCA-associated vasculitis (13%), microscopic polyangiitis (11%), eosinophilic granulomatosis with polyangiitis (11%), giant cell arteritis (10%), non-systemic vasculitic neuropathy (2%) and other (19%). Many patients reported foot/hand symptoms suggestive of neuropathy, including numbness (64%), pain (54%) or weakness (40%). Two hundred and forty-two patients (78%) met our definition of probable vasculitic neuropathy: diagnosis of neuropathy by vasculitis team OR numbness OR weakness in feet/hands. Only 52% had been formally diagnosed with neuropathy. Compared with 70 patients without neuropathy, neuropathy patients had greater disability measured by the inflammatory Rasch-built Overall Disability Scale (centile mean 63.1 [s.d. 17.3] vs 75.2 [16.7]; P < 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 [interquartile range 1-4] vs 0.5 [0-2]; P < 0.0001) and modified Rankin scale (median 2 [interquartile range 1-3] vs 2 [1-2)]; P = 0.0002); greater pain on an 11-point rating scale (mean 4.6 [s.d. 2.6] vs 3.5 [2.8]; P = 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 [s.d. 0.29] vs 0.69 [0.28]; P < 0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy).

Neuropathy is common and associated with significant disability, pain and impaired HR-QOL in patients with systemic vasculitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of ANCA-associated vasculitis (AAV) within the group of small vessel vasculitides. It is defined by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia. Almost all patients have allergic symptoms with bronchial asthma and rhinosinusitis symptoms. Further clinical manifestations vary depending on the localisation, severity, and type of disease manifestation. Eosinophilic infiltration and inflammation may result in rhinosinusitis, pneumonitis, gastrointestinal involvement, and cardiomyopathy. The latter, in particular, is associated with a poorer prognosis. As a necrotising pauci-immune small-vessel vasculitis, EGPA, similar to the other AAVs, can cause pulmonary infiltrates with alveolar haemorrhage, glomerulonephritis, cutaneous vasculitis with purpura as well as central and peripheral neurologic injuries. The presence of perinuclear ANCA (pANCA) with specificity against myeloperoxidase (MPO) is observed in approximately one-third of patients but is not specific to EGPA. MPO-ANCA-positive patients are more likely to have peripheral neurologic involvement and glomerulonephritis, whereas ANCA-negative patients are more likely to have cardiac and pulmonary involvement. What is frequently challenging in the clinical routine is to differentiate EGPA from the hypereosinophilic syndrome (HES). The therapeutic approach to EGPA depends on whether the severity of the disease is potentially organ or life-threatening. For severe forms of EGPA, acute therapy mainly includes glucocorticoids in combination with cyclophosphamide. Rituximab has come to be mentioned as an alternative treatment option in the guidelines. Various immunosuppressive therapies are available for remission maintenance. In EGPA without severe organ involvement, IL-5 blockade with mepolizumab is an approved treatment.

This study investigated whether serum syndecan1 at diagnosis reflects activity at diagnosis and predicts poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

The study included 79 patients with AAV from the cohort of Korean patients diagnosed with AAV. AAV-specific indices, including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), 36-item short-form survey (SF-36) physical and mental component summary (PCS and MCS), and vasculitis damage index (VDI), were assessed. Laboratory data including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also collected. The highest tertile and upper half of the BVAS were tentatively defined as having high AAV activity. Serum syndecan1 levels were measured in sera stored at diagnosis.

Serum syndecan1 at diagnosis was significantly correlated with AAV activity and functional status, as assessed by BVAS, FFS, SF-36 PCS, MCS, and acute-phase reactants, including ESR and CRP. Patients with serum syndecan1 ≥ 76.1 ng/mL at diagnosis, and those with serum syndecan1 ≥ 60.0 ng/mL at diagnosis showed significantly higher risks for the highest tertile and the upper half of BVAS at diagnosis than those without, respectively. Patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis had a significantly higher risk for all-cause mortality during follow-up than those without, and further, exhibited a significantly lower cumulative patients' survival rate than those without.

Serum syndecan1 at diagnosis may not only reflect AAV activity at diagnosis but may also be associated with all-cause mortality during follow-up.

Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) are rare conditions characterized by inflammatory cell infiltration in small blood vessels, leading to tissue necrosis. While most patients with AAV present antibodies against either myeloperoxidase (MPO) or proteinase 3 (PR3), rare cases of dual positivity for both antibodies (DP-ANCA) have been reported, and their impact on the clinical picture remains unclear. The goal of this study was to investigate the clinical implications, phenotypic profiles and outcomes of patients with DP-ANCA.

A retrospective screening for DP-ANCA cases was conducted at Brest University Hospital's immunology laboratory (France), analysing ANCA results from March 2013 to March 2022. Clinical, biological, imaging, and histological data were collected for each DP-ANCA case. Additionally, a comprehensive literature review on DP-ANCA was performed, combining an artificial intelligence (AI)-based search using BIBOT software with a manual PUBMED database search.

The report of our cases over the last 9 years and those from the literature yielded 103 described cases of patients with DP-ANCA. We identified four distinct phenotypic profiles: (i) idiopathic AAV (∼30%); (ii) drug-induced AAV (∼25%); (iii) autoimmune disease associated with a low risk of developing vasculitis (∼20%); and (iv) immune-disrupting comorbidities (infections, cancers, etc) not associated with AAV (∼25%).

This analysis of over a hundred DP-ANCA cases suggests substantial diversity in clinical and immunopathological presentations. Approximatively 50% of DP-ANCA patients develop AAV, either as drug-induced or idiopathic forms, while the remaining 50%, characterized by pre-existing dysimmune conditions, demonstrates a remarkably low vasculitis risk. These findings underscore the complex nature of DP-ANCA, its variable impact on patient health, and the necessity for personalized diagnostic and management approaches in these cases.

Several scores have been developed to predict mortality at anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) diagnosis. Their prognostic value in Caucasian patients with kidney involvement (AAV-GN) remains uncertain as none has been developed in this specific population. We aimed to propose a novel and more accurate score specific for them.

This multicentric study included patients diagnosed with AAV-GN since January 2000 in four nephrology centers (recorded in the Maine-Anjou AAV-GN Registry). Existing scores and baseline characteristics were assessed at diagnosis before any therapeutic intervention. A multivariable analysis was performed to build a new predictive score for death. Its prognosis performance (area under receiving operating curve and C-index) and accuracy (Brier score) was compared with existing scores. One hundred and eighty-five patients with AAV-GN from the RENVAS registry were used as a validation cohort.

A total of 228 patients with AAV-GN from the Maine-Anjou registry were included to build the new score. It included the four components most associated with death: age, history of hypertension or cardiac disease, creatinine and hemoglobin levels at diagnosis. Overall, 194 patients had all the data available to determine the performance of the new score and existing scores. The new score performed better than the previous ones in the development and in the validation cohort. Among the scores tested, only Five-Factor Score and Japanese Vasculitis Activity Score had good performance in predicting death in AAV-GN.

This original score, named DANGER (Death in ANCA Glomerulonephritis-Estimating the Risk), may be useful to predict the risk of death in AAV-GN patients. Validation in different populations is needed to clarify its role in assisting clinical decisions.