Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

OBJECTIVES: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. METHODS: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. RESULTS: The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CONCLUSION: CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

Vasculitic neuropathy-related disability, pain, quality of life, and autonomic symptoms: A survey of 312 patients.

OBJECTIVES: To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL), and autonomic dysfunction in patients with vasculitis. METHODS: Patients with vasculitis (with or without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey. RESULTS: 312 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%). 242 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 (SD 17.3) vs 75.2 (16.7); p< 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 (IQR 1-4) vs 0.5 (0-2); p< 0.0001), and modified Rankin scale (median 2 (IQR 1-3) vs 2 (1-2); p= 0.0002); greater pain on an 11-point rating scale (mean 4.6 (SD 2.6) vs 3.5 (2.8); p= 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 (SD 0.29) vs 0.69 (0.28); p<0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy). CONCLUSION: Neuropathy is common and associated with significant disability, pain, and impaired HR-QOL in patients with systemic vasculitis.

EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update.

BACKGROUND: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. METHODS: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. RESULTS: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. CONCLUSIONS: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

Association Between HLA-DPB1 and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Children.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare, life-threatening inflammation of blood vessels that can affect both adults and children. Compared to adult-onset disease, AAV is especially rare in children, with an annual prevalence of 0.5-6.4 cases per million children. The etiology of AAV remains largely unknown, and both environmental and genetic factors are likely involved. The present study was undertaken to explore the genetic susceptibility factors recently identified in adult patients, including HLA-DP and HLA-DQ, in pediatric patients. METHODS: We performed a genome-wide association study of pediatric AAV in patients of European ancestry (n = 63 AAV cases, n = 315 population-matched controls). RESULTS: We identified a significant genetic association between pediatric AAV and the HLA-DPB1*04:01 allele (P = 1.5 × 10-8 , odds ratio [OR] 3.5), with a stronger association observed in children with proteinase 3-ANCA positivity than in children with myeloperoxidase-ANCA positivity. Among the HLA alleles, the HLA-DPB1*04:01 allele was the most highly associated with AAV, although not significantly, in a follow-up adult AAV cohort (P = 2.6 × 10-4 , OR 0.4). T cell receptor and interferon signaling pathways were also shown to be enriched in the pediatric AAV cohort. CONCLUSION: The HLA-DPB1 locus showed an association with pediatric AAV, as similarly shown previously in adult AAV. Despite the difference in the age of onset, these findings suggest that childhood- and adult-onset vasculitis share a common genetic predisposition. The identification of genetic variants contributing to AAV is an important step to improved classification tools and treatment strategies.

2022 American College of Rheumatology/EULAR Classification Criteria for Giant Cell Arteritis.

OBJECTIVE: To develop and validate updated classification criteria for giant cell arteritis (GCA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate items, 2) prospective collection of candidate items present at the time of diagnosis, 3) expert panel review of cases, 4) data-driven reduction of candidate items, 5) derivation of a points-based risk classification score in a development data set, and 6) validation in an independent data set. RESULTS: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C-reactive protein ≥10 mg/liter (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging, and fluorodeoxyglucose-positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% confidence interval [95% CI] 0.88-0.94) with a sensitivity of 87.0% (95% CI 82.0-91.0%) and specificity of 94.8% (95% CI 91.0-97.4%). CONCLUSION: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.

2022 American College of Rheumatology/EULAR classification criteria for Takayasu arteritis.

OBJECTIVE: To develop and validate new classification criteria for Takayasu arteritis (TAK). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate criteria items, (2) collection of candidate items present at diagnosis, (3) expert panel review of cases, (4) data-driven reduction of candidate items, (5) derivation of a points-based classification score in a development data set and (6) validation in an independent data set. RESULTS: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large-vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1) and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% CI 0.94 to 0.99) with a sensitivity of 93.8% (95% CI 88.6% to 97.1%) and specificity of 99.2% (95% CI 96.7% to 100.0%). CONCLUSION: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research.

2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis.

OBJECTIVE: To develop and validate updated classification criteria for giant cell arteritis (GCA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate items, (2) prospective collection of candidate items present at the time of diagnosis, (3) expert panel review of cases, (4) data-driven reduction of candidate items, (5) derivation of a points-based risk classification score in a development data set and (6) validation in an independent data set. RESULTS: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C reactive protein ≥10 mg/L (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging and fluorodeoxyglucose-positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% CI 0.88 to 0.94) with a sensitivity of 87.0% (95% CI 82.0% to 91.0%) and specificity of 94.8% (95% CI 91.0% to 97.4%). CONCLUSION: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.

2022 American College of Rheumatology/EULAR Classification Criteria for Takayasu Arteritis.

OBJECTIVE: To develop and validate new classification criteria for Takayasu arteritis (TAK). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate criteria items, 2) collection of candidate items present at diagnosis, 3) expert panel review of cases, 4) data-driven reduction of candidate items, 5) derivation of a points-based classification score in a development data set, and 6) validation in an independent data set. RESULTS: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large-vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1), and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% confidence interval [95% CI] 0.94-0.99) with a sensitivity of 93.8% (95% CI 88.6-97.1%) and specificity of 99.2% (95% CI 96.7-100.0%). CONCLUSION: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research.

The Sound of Interconnectivity; The European Vasculitis Society 2022 Report.

The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Granulomatosis With Polyangiitis.

OBJECTIVE: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting, or sino-nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3 ANCA positivity (+5); pulmonary nodules, mass, or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci-immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (-1); and eosinophil count ≥1 × 109 /liter (-4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% confidence interval [95% CI] 87-96%) and the specificity was 94% (95% CI 89-97%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis With Polyangiitis.

OBJECTIVE: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1 × 109 /liter (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3 ANCA positivity (-3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1), and hematuria (-1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% confidence interval [95% CI] 77-91%) and the specificity was 99% (95% CI 98-100%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for EGPA demonstrate strong performance characteristics and are validated for use in research.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Microscopic Polyangiitis.

OBJECTIVE: To develop and validate classification criteria for microscopic polyangiitis (MPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti-myeloperoxidase-ANCA positivity (+6), pauci-immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino-nasal symptoms or signs (-3), cytoplasmic ANCA or anti-proteinase 3 ANCA positivity (-1), and eosinophil count ≥1 × 109 /liter (-4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% confidence interval [95% CI] 85-95%) and the specificity was 94% (95% CI 92-96%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis.

OBJECTIVE: To develop and validate classification criteria for microscopic polyangiitis (MPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti-myeloperoxidase-ANCA positivity (+6), pauci-immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino-nasal symptoms or signs (-3), cytoplasmic ANCA or anti-proteinase 3 ANCA positivity (-1) and eosinophil count ≥1×109/L (-4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% CI 85% to 95%) and the specificity was 94% (95% CI 92% to 96%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis.

OBJECTIVE: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting or sino-nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3 ANCA positivity (+5); pulmonary nodules, mass or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci-immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (-1); and eosinophil count ≥1×109 /L (-4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% CI 87% to 96%) and the specificity was 94% (95% CI 89% to 97%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis.

OBJECTIVE: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1×109/L (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3-ANCA positivity (-3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1) and haematuria (-1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% CI 77% to 91%) and the specificity was 99% (95% CI 98% to 100%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis demonstrate strong performance characteristics and are validated for use in research.

Different Disease Endotypes in Phenotypically Similar Vasculitides Affecting Small-to-Medium Sized Blood Vessels.

Objectives: Chronic primary vasculitis describes a group of complex and rare diseases that are characterized by blood vessel inflammation. Classification of vasculitis subtypes is based predominantly on the size of the involved vessels and clinical phenotype. There is a recognized need to improve classification, especially for small-to-medium sized vessel vasculitides, that, ideally, is based on the underlying biology with a view to informing treatment. Methods: We performed RNA-Seq on blood samples from children (n = 41) and from adults (n = 11) with small-to-medium sized vessel vasculitis, and used unsupervised hierarchical clustering of gene expression patterns in combination with clinical metadata to define disease subtypes. Results: Differential gene expression at the time of diagnosis separated patients into two primary endotypes that differed in the expression of ~3,800 genes in children, and ~1,600 genes in adults. These endotypes were also present during disease flares, and both adult and pediatric endotypes could be discriminated based on the expression of just 20 differentially expressed genes. Endotypes were associated with distinct biological processes, namely neutrophil degranulation and T cell receptor signaling. Conclusions: Phenotypically similar subsets of small-to-medium sized vessel vasculitis may have different mechanistic drivers involving innate vs. adaptive immune processes. Discovery of these differentiating immune features provides a mechanistic-based alternative for subclassification of vasculitis.