Search

Objective: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL‐PAN). Methods: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease‐related damage, and survival were analyzed. Results: Three hundred fifty‐eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty‐five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow‐up, relapse occurred in 48.5% of patients. One, 5‐ and 10‐year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 μmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. Conclusion: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 μmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN. [ABSTRACT FROM AUTHOR]

Objective: Somatic variants in UBA1 cause VEXAS, a recently described, systemic autoinflammatory disease. Research on VEXAS has largely focused on highly symptomatic patients. We sought to determine the prevalence of canonical, VEXAS‐associated somatic variants and their disease penetrance in a diverse, unselected population. Methods: We analyzed clinical‐grade whole genome sequencing data from 245,368 participants in the All of Us Research Program. We compared persons carrying a canonical VEXAS‐associated somatic variant to age, sex, and ancestry matched controls across the domains of diagnoses, medications, and laboratory values. Results: 74 participants were identified who carry one VEXAS‐defining somatic variant, UBA1 c.121A>C, p.Met41Leu. The variant allele fraction ranged from 4.5% to 33%. No other canonical VEXAS‐associated variants were identified. Of the 74 carriers, 62 (84%) were women, 20 (27%) were African American, and 14 (19%) were American Admixed/Latino. There was no statistically significant association between case/control status and any VEXAS‐associated diagnosis code, medication prescription, or laboratory value. Conclusion: We report the largest cohort to date of persons with the VEXAS‐associated p.Met41Leu somatic variant. This cohort differed substantially from reported cohorts of patients with clinical VEXAS, having a higher proportion of persons who were young, female, and of diverse ancestry. Variant allele fractions were lower than reported in clinical VEXAS cohorts, and bioinformatic analysis detected no clinical manifestations of VEXAS. Thus, the UBA1 p.Met41Leu somatic variant displayed incomplete penetrance for VEXAS. Further study is needed to determine the natural history of VEXAS‐associated somatic variants in the predisease phase. [ABSTRACT FROM AUTHOR]

Objective: Accurate clinical assessment of disease activity in Takayasu arteritis (TAK) can be challenging. 18F‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) can directly measure vascular inflammation. This study details the development of a new type of disease activity index called the Takayasu's Arteritis Integrated Disease Activity Index (TAIDAI). Methods: Clinical symptoms for TAIDAI were identified from a literature review. Each symptom was paired with FDG‐PET findings in corresponding arterial territories. Constitutional symptoms were paired with acute phase reactant levels. One point was given for each clinical symptom paired with supporting FDG‐PET or laboratory abnormalities and summed into the TAIDAI score. A TAIDAI of ≥1 defined active disease. To assess performance of TAIDAI, face validity, content validity, and sensitivity to change were evaluated within a prospective observational cohort study of patients with TAK. Results: Seventeen clinical symptoms were paired with imaging or laboratory abnormalities. In a cohort of 96 patients contributing 204 study visits, TAIDAI showed excellent sensitivity (96.3%) and good specificity (79.2%) compared to physician's clinical assessment. TAIDAI significantly correlated with physician global assessment, PET Vascular Activity Score, patient global assessment, and acute phase reactant levels. In patients treated with either tumor necrosis factor inhibitors or tocilizumab, a TAIDAI of 0 was achieved in 21 (91%) of 23 patients who met a predefined definition of clinical response. Conclusion: TAIDAI is new type of disease activity index in TAK in which clinical symptoms are integrated with specific laboratory and imaging findings. TAIDAI should be validated in future randomized controlled trials in TAK. [ABSTRACT FROM AUTHOR]

Objective: To examine and compare disease activity over time in giant cell arteritis (GCA) and Takayasu arteritis (TAK) using multimodal assessment combining clinical, laboratory, and imaging‐based testing. Methods: Patients with GCA or TAK were enrolled into a single‐center prospective, observational cohort at any point in the disease course. Patients underwent standardized assessment, including 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) at enrollment and follow‐up visits. Each FDG‐PET finding was subjectively interpreted as active or inactive vasculitis. Global arterial FDG uptake was quantified by the PET Vascular Activity Score (PETVAS). Patients were stratified by disease duration at enrollment (0–2 years; 2–5 years; >5 years). Fisher exact and Mann‐Whitney U tests, Spearman's correlation, and linear regression were used for statistical analyses. Results: A total of 126 patients with large vessel vasculitis (GCA = 50; TAK = 76) were evaluated across 319 visits. Clinical disease activity was present in 33% of patients in the second to fifth year of disease and in 24% of patients evaluated >5 years after diagnosis. Active vasculitis by PET was observed in 66% of patients in years 2 to 5 after diagnosis and in 50% of patients enrolled >5 years into disease. PETVASs were consistently higher in GCA than TAK in the early and later phases of disease and significantly decreased over time in GCA but not TAK. Correlations between clinical, laboratory, and imaging findings were complex and varied with disease duration. Conclusion: Disease activity in GCA and TAK is common throughout the disease course. Patterns of vascular PET activity at diagnosis and later in disease differ between GCA and TAK. [ABSTRACT FROM AUTHOR]

Objective: To assess whether vascular activity seen on 18F‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) scan is associated with angiographic change in large vessel vasculitis (LVV). Methods: Patients with LVV were recruited into a prospective cohort. All patients underwent magnetic resonance angiography or computed tomography angiography and FDG‐PET imaging. Follow‐up imaging using the same imaging modalities was obtained ≥6 months later per a standardized imaging protocol. Arterial damage, defined as stenosis, occlusion, or aneurysm, and corresponding FDG uptake were evaluated in 17 arterial territories. On follow‐up, development of new lesions was recorded, and existing lesions were characterized as improved, worsened, or unchanged. Results: A total of 1,091 arterial territories from 70 patients with LVV (38 patients with Takayasu arteritis, 32 patients with giant cell arteritis) were evaluated. Over a median 1.6 years of follow‐up, new lesions developed only in 8 arterial territories in 5 patients with Takayasu arteritis. Arterial lesions improved in 16 territories and worsened in 6 territories. Most arterial territories that did not have vascular activity on FDG‐PET scan at baseline had no angiographic change over the follow‐up period (787 [99%] of 793). Few territories with baseline FDG‐PET activity had angiographic change over time (24 [8%] of 298), but of the territories that developed angiographic change, 80% had FDG‐PET activity at baseline. Within the same patient, an arterial territory with baseline FDG‐PET activity had significantly increased risk for angiographic change compared to a paired arterial territory without FDG‐PET activity (odds ratio 19.49 [95% confidence interval 2.44–156.02]; P < 0.01). Concomitant edema and wall thickening further increased risk for angiographic change. Conclusion: Development of angiographic change was infrequent in this cohort of patients with LVV. A lack of baseline FDG‐PET activity was strongly associated with stable angiographic disease. In cases of angiographic progression, change was preceded by the presence of FDG‐PET activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article offers information about the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome and disease taxonomy in rheumatology. It mentions that VEXAS syndrome, discovered through the use of a genotype-first approach, whereby a large genetic database was analyzed for commonalities among patients, with minimal consideration of clinical phenotype.

Objective: Relapsing polychondritis (RP) is a systemic inflammatory disorder of cartilage that lacks validated disease activity measures. Our objective was to test physician global assessment (PhGA), a measure of disease activity commonly used in rheumatic diseases, in a cohort of patients with RP, which has not been done before.Methods: Adult patients in an observational cohort of RP underwent standardized, comprehensive evaluation at approximately 6-month intervals. PhGA was scored by 3 physicians from the evaluating institution on a scale of 0-10 for each visit. A random subset of 20 visits was scored by 3 independent physicians not affiliated with the evaluating institution. Treatment change between consecutive visits was categorized as increased, decreased, or unchanged.Results: In total, 78 patients were evaluated over 164 visits. The intraclass correlation coefficient (ICC2,1 ) for the 3 raters from the evaluating institution was excellent (0.79 [95% confidence interval (95% CI) 0.73, 0.84]) but was poor in the subset of cases scored by the additional raters (ICC2,1 0.27 [95% CI -0.01, 0.53]). Median PhGA was 3 (range 0-7). PhGA weakly correlated with C-reactive protein level (rs = 0.30, P < 0.01). In response to increased treatment, median PhGA decreased from 3 (interquartile range [IQR] 2, 4) to 2 (IQR 2, 3) (P < 0.01) but rarely went to 0.Conclusion: Within a single center, PhGA can be used to quantify disease activity and monitor disease response in RP. Persistent disease activity despite treatment, rather than a relapsing-remitting pattern, is observed for most patients with RP. Reliability of PhGA may not generalize across different institutions. A validated disease-specific activity index is needed in RP. [ABSTRACT FROM AUTHOR]

Objective: In addition to aiding in diagnosis, histopathologic findings from temporal artery biopsy (TAB) specimens in giant cell arteritis (GCA) may be valuable for their associations with clinical features of the disease. This study was undertaken to compare histopathologic findings on TAB with biopsy interpretation and demographic, clinical, and imaging features at time of diagnosis. Methods: Patients with a clinical diagnosis of GCA who had a TAB were selected from an international, multicenter observational cohort of vasculitis. Associations between demographic, clinical, radiographic, and histopathologic features were identified using bivariate testing and multivariate regression modeling. Results: Of 705 patients with GCA who underwent TAB, 69% had histopathologic evidence of definite vasculitis. Specific histopathologic findings included the presence of giant cells (51%), fragmentation of the internal elastic lamina (41%), intimal thickening (33%), and predominantly mononuclear leukocyte infiltration (32%). Histopathologic interpretation of definite vasculitis was independently associated with giant cells (odds ratio [OR] 151.8 [95% confidence interval (95% CI) 60.2–551.6]), predominantly mononuclear leukocyte infiltration (OR 11.8 [95% CI 5.9–24.9]), and fragmentation of the internal elastic lamina (OR 3.7 [95% CI 1.9–7.4]). A halo sign on temporal artery ultrasound and luminal damage of large arteries on angiography were significantly associated with presence of giant cells (OR 2.6 [95% CI 1.1–6.5] and OR 2.4 [95% CI 1.1–5.2], respectively). Specific histopathologic findings were associated with older age, but no associations were identified with vision loss or other clinical features. Conclusion: Histopathologic findings in GCA are strongly associated with the clinical diagnosis of GCA but have a limited role in identifying patterns of disease. [ABSTRACT FROM AUTHOR]

Objective: To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome) from a single‐center cohort of Italian patients with vasculitis, using a clinically oriented phenotype‐first approach. Methods: We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment‐resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin‐activating enzyme E1 (UBA‐1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue. Results: Seven patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA‐1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients. Conclusion: To our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA‐associated vasculitis reported herein warrants further investigation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Little is known about temporal changes in nasal bacteria in granulomatosis with polyangiitis (GPA). This study was undertaken to examine longitudinal changes in the nasal microbiome in association with relapse in GPA patients. Methods: Bacterial 16S ribosomal RNA gene sequencing was performed on nasal swabs from 19 patients with GPA who were followed up longitudinally for a total of 78 visits, including 9 patients who experienced a relapse and 10 patients who remained in remission. Relative abundance of bacteria and ratios between bacteria were examined. Generalized estimating equation models were used to evaluate the association between bacterial composition and 1) disease activity and 2) levels of antineutrophil cytoplasmic antibody (ANCA) with specificity for proteinase 3 (PR3), adjusted for medication. Results: Corynebacterium and Staphylococcus were the most abundant bacterial genera across all nasal samples. Patients with quiescent disease maintained a stable ratio of Corynebacterium to Staphylococcus across visits. In contrast, in patients who experienced a relapse, a significantly lower ratio was observed at the visit prior to relapse, followed by a higher ratio at the time of relapse (adjusted P < 0.01). Species‐level analysis identified an association between a higher abundance of nasal Corynebacterium tuberculostearicum and 1) relapse (adjusted P = 0.04) and 2) higher PR3‐ANCA levels (adjusted P = 0.02). Conclusion: In GPA, significant changes occur in the nasal microbiome over time and are associated with disease activity. The occurrence of these changes months prior to the onset of relapse supports a pathogenic role of nasal bacteria in GPA. Our results uphold existing hypotheses implicating Staphylococcus as an instigator of disease and have generated a novel finding involving Corynebacterium as a potential mediator of disease in GPA. [ABSTRACT FROM AUTHOR]

Objective: To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).Methods: Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel.Results: We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations.Conclusion: This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases. [ABSTRACT FROM AUTHOR]

Objective: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN).Methods: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel.Results: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted.Conclusion: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN. [ABSTRACT FROM AUTHOR]

Objective: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis.Methods: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel.Results: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions.Conclusion: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the concerns and health‐related behaviors in patients with vasculitis during the early phase of the coronavirus disease 2019 (COVID‐19) pandemic in North America. Methods: Patients with vasculitis in North America were invited to complete an online survey through the Vasculitis Patient‐Powered Research Network in collaboration with the Vasculitis Foundation and the Relapsing Polychondritis Foundation. Questions focused on concerns and behaviors related to doctors' visits, tests, medication, and telehealth use. Factors affecting their concern and health‐related behaviors were determined. Results: Data from 662 patients were included: 90% of patients were White, 78% were women, 83% expressed moderate or high levels of concern about COVID‐19, and 87% reported that their vasculitis moderately or extremely affected their level of concern. Older age, female sex, lung disease, and immunosuppression were associated with greater concern. Doctors' visits, laboratory tests, and other tests were avoided by 66%, 46%, and 40% of patients, respectively. Younger age, urban location, higher income, higher concern levels, and prednisone use (>10 mg/day) were associated with greater likelihood of avoiding visits or tests. Ten percent of patients on immunosuppressive therapy stopped their medication. Twenty‐nine percent patients on rituximab avoided an infusion. Forty‐four percent of patients had telehealth visits; more visits were reported for younger patients, for patients on glucocorticoids, and in Canada versus the United States. Conclusion: During the COVID‐19 pandemic, patients with vasculitis have high levels of concern and exhibit potentially harmful health‐related behaviors. Health care use varies across different demographic groups and geographic regions. Specific strategies are warranted to facilitate engagement of these patients with the health care system during the pandemic. [ABSTRACT FROM AUTHOR]

Objective: To assess the relationship between measures of disease assessment in patients with large vessel vasculitis.Methods: Patients with giant cell arteritis (GCA) or Takayasu arteritis (TAK) were recruited into a prospective, observational cohort. Assessments within the following outcomes were independently recorded: 1) patient-reported outcomes (Multidimensional Fatigue Inventory, patient global assessment of disease activity [PtGA], Short Form 36 health survey [SF-36], Brief Illness Perception Questionnaire), 2) physician global assessment of disease activity (PhGA), 3) laboratory outcomes (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR]), and 4) imaging outcomes (PETVAS, a qualitative score of vascular 18 F-fluorodeoxyglucose-positron emission tomography activity).Results: Analyses were performed on 112 patients (GCA = 56, TAK = 56), over 296 visits, with a median follow-up of 6 months. Correlation network analysis revealed assessment measures clustered independently by type of outcome. PhGA was centrally linked to all other outcome types, but correlations were modest (ρ = 0.12-0.32; P < 0.05). PETVAS, CRP level, and PtGA were independently associated with clinically active disease. All 4 patient-reported outcomes strongly correlated with each other (ρ = 0.35-0.60; P < 0.0001). Patient-reported outcomes were not correlated with PETVAS, and only PtGA correlated with CRP level (ρ = 0.16; P < 0.01). Patients whose clinical assessment changed from active disease to remission (n = 29) had a corresponding significant decrease in ESR, CRP level, and PETVAS at the remission visit. Patients whose clinical assessment changed from remission to active disease (n = 11) had a corresponding significant increase in CRP level and PtGA at the active visit.Conclusion: Measures of disease assessment in large vessel vasculitis consist of independent, yet complementary, outcomes, supporting the need to develop composite outcome measures or a standard set of measures covering multiple types of outcomes. [ABSTRACT FROM AUTHOR]

Objective: Relapsing polychondritis (RP) is a systemic disease. Failure to recognize RP can lead to diagnostic delay and further complications, including death. This study was undertaken to identify clinical patterns in a prospective cohort of patients with RP. Methods: Patient subgroups were identified using latent class analysis based on 8 clinical variables: saddle‐nose deformity, subglottic stenosis, tracheomalacia, bronchomalacia, ear chondritis, tenosynovitis/synovitis, inflammatory eye disease, and audiovestibular disease. Model selection was based on Akaike's information criterion. Results: Seventy‐three patients were included in this study. Patients were classified into 1 of 3 subgroups: type 1 RP (14%), type 2 RP (29%), and type 3 RP (58%). Type 1 RP was characterized by ear chondritis (100%), tracheomalacia (100%), saddle‐nose deformity (90%), and subglottic stenosis (80%). These patients had the shortest median time to diagnosis (1 year), highest disease activity, and greatest frequency of admission to the intensive care unit and tracheostomy. Type 2 RP was characterized by tracheomalacia (100%) and bronchomalacia (52%), but no saddle‐nose deformity or subglottic stenosis. These patients had the longest median time to diagnosis (10 years) and highest percentage of work disability. Type 3 RP was characterized by tenosynovitis/synovitis (60%) and ear chondritis (55%). There were no significant differences in sex, race, or treatment strategies between the 3 subgroups. Conclusion: Our findings indicate that there are 3 subgroups of patients with RP, with differences in time to diagnosis, clinical and radiologic characteristics, and disease‐related complications. Recognizing a broader spectrum of clinical patterns in RP, beyond cartilaginous involvement of the ear and upper airway, may facilitate more timely diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Diagnostic assessment in giant cell arteritis (GCA) is rapidly changing as vascular imaging becomes more available. This study was undertaken to determine if clinical GCA subsets have distinct profiles or reflect differential diagnostic assessments. Methods: Patients were recruited from an international cohort and divided into 4 subsets based on a temporal artery (TA) abnormality (positive TA biopsy [TAB] or halo sign on TA ultrasound [TA‐US]) and/or evidence of large vessel (LV) involvement on imaging: 1) both TA abnormality and LV involvement (TA+/LV+ GCA); 2) TA abnormality without LV involvement (TA+/LV− GCA); 3) LV involvement without TA abnormality (TA−/LV+ GCA); and 4) clinically diagnosed GCA without LV involvement or TA abnormality (TA−/LV− GCA). Results: Nine hundred forty‐one patients with GCA were recruited from 72 international study sites. Most patients received multiple forms of diagnostic assessment, including TAB (n = 705 [75%]), TA‐US (n = 328 [35%]), and LV imaging (n = 534 [57%]). Assessment using TAB, TA‐US, and LV imaging confirmed the diagnosis of GCA in 66%, 79%, and 40% of cases, respectively. GCA subsets had distinct profiles independent of diagnostic assessment strategies. TA+/LV− were the most common subset (51%), with a high burden of cranial ischemia. Those in the TA−/LV− subset (26%) had a high prevalence of cranial ischemia and musculoskeletal symptoms. Patients in the TA−/LV+ subset (12%) had prevalent upper extremity vascular abnormalities and a low prevalence of vision loss, and those in the TA+/LV+ subset (11%) were older and had a high prevalence of cranial ischemia, constitutional symptoms, and elevated acute‐phase reactant levels. Conclusion: Vascular imaging is increasingly incorporated into the diagnostic assessment of GCA and identifies clinical subsets of patients based on involvement of temporal and extracranial arteries. [ABSTRACT FROM AUTHOR]

Objective: Pseudostenosis is a magnetic resonance angiography (MRA) artifact that mimics arterial stenosis. The study objective was to compare imaging and clinical aspects of stenosis and pseudostenosis in a cohort of large‐vessel vasculitis (LVV), including giant‐cell arteritis (GCA) and Takayasu's arteritis (TAK). Methods: Patients with LVV and comparator conditions (healthy or vasculopathies) underwent MRA of the aortic arch vessels. The subclavian and axillary arteries were systematically assessed for presence of stenosis and pseudostenosis by two independent readers. Serial and delayed imaging and clinical assessments were used to confirm suspected pseudostenoses. Multivariable regression analyses were used to identify associations between angiographic pathology and clinical findings. Results: One hundred eighty‐four MRA scans were analyzed from patients with GCA (n = 36), TAK (n = 47), and comparators (n = 25). Pseudostenoses were frequently observed (48 of 184 scans, 26%) in the distal subclavian artery only on the side of injection and were shorter in length compared with true stenoses (25 mm vs 78 mm, P < 0.01). There was no difference in prevalence of pseudostenosis by diagnosis (GCA = 33%, TAK = 23%, comparator = 20%, P = 0.44), disease activity status (P = 0.31), or treatment status (P = 1.00). Percent and length of true stenosis were independently associated with pulse and blood pressure abnormalities in the upper extremity. Adjusting for length and stenosis degree, absence of collateral arteries was associated with arm claudication (odds ratio = 2.37, P = 0.03). Conclusion: Although a pseudostenosis could be falsely interpreted as an arterial stenosis, radiographic and associated clinical features can help distinguish true disease from arterial susceptibility artifacts. In addition, the peripheral vascular examination can help to confirm a suspected true stenosis, as specific aspects of angiographic pathology are associated with vascular examination abnormalities in LVV. [ABSTRACT FROM AUTHOR]

Objective: To assess patient-reported symptoms and burden of disease in relapsing polychondritis (RP).Methods: Patients with RP completed a disease-specific online survey to identify symptoms attributed to illness. Patients were divided into subgroups based upon presence or absence of ear/nose, airway, or joint involvement. Pathway to diagnosis, treatment, and disease-related complications were assessed within each subgroup.Results: Data from 304 respondents were included in this analysis. Prior to diagnosis, most patients with RP went to the emergency room (54%), saw > 3 physicians (54%), and had symptoms for >5 years (64%). A concomitant diagnosis of fibromyalgia and absence of ear/nose or joint involvement was associated with diagnostic delay >1 year. Common diagnoses prior to RP diagnosis included asthma in patients with airway involvement (35% versus 22%; P = 0.03) and ear infection in patients with ear/nose involvement (51% versus 6%; P < 0.01). Patients with joint involvement were more likely to receive a glucocorticoid-sparing agent (85% versus 13%; P < 0.01). Most patients reported a major complication, including disability (25%), tracheomalacia (16%), or hearing loss (34%). Patients with airway involvement reported more tracheomalacia (20% versus 4%; P < 0.01). Disability (24% versus 7%; P < 0.01) and hearing loss (39% versus 11%; P < 0.01) were prevalent in the joint involvement subgroup.Conclusion: Patient-reported data in RP highlight a significant burden of disease. Patterns of organ involvement may lead to diagnostic delay and influence treatment decisions, ultimately impacting the development of disease-related complications. Timely diagnosis, standardization of treatment approaches, and prevention of disease-related complications are major unmet needs in RP. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical value of 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects. Methods: Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG‐PET imaging, and patients with LVV underwent serial imaging at 6‐month intervals. We calculated sensitivity and specificity of FDG‐PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse. Results: A total of 170 FDG‐PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG‐PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG‐PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow‐up period of 15 months. Conclusion: FDG‐PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG‐PET scan activity during clinical remission was associated with future clinical relapse. [ABSTRACT FROM AUTHOR]

Objective: Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce autoreactivity in individuals at risk of autoimmune diseases. The objective of this study was to assess whether medications implicated in cases of drug‐induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug‐induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation. Methods: Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy. The ability of these drugs to interfere with NET degradation by serum nuclei was assessed. Pathways of drug‐induced NET formation were studied with pharmacologic inhibitors of reactive oxygen species (ROS), peptidylarginine deiminases (PADs), and muscarinic receptors, and by assessment of intracellular calcium levels by flow cytometry. To determine if NET protein cargo varies by drug stimulus and/or neutrophil source, proteomic analysis of NET lysates induced by specific medications was compared using neutrophils from healthy donors and from patients with autoimmune diseases. Results: Hydralazine and procainamide significantly induced NET formation while minocycline and clozapine did not. None of the medications significantly impaired NET degradation. NETosis induced by these drugs required NADPH oxidase and PAD4 activation. Procainamide triggered NETs via muscarinic receptor engagement on neutrophils, while hydralazine modulated calcium release from intracellular stores. Differences in protein cargo, particularly histone content, were observed in NETs induced by hydralazine and procainamide. Conclusion: Medications commonly implicated in drug‐induced autoimmunity trigger NET formation displaying distinct protein cargo, via common and specific pathways. NETosis may play a role in the pathogenesis of drug‐induced autoimmunity. [ABSTRACT FROM AUTHOR]

The article explores the role of neutrophils as important shapers of the immunologic landscape in systemic auto-immune and chronic inflammatory diseases. It cites the role of reactive oxygen species (ROS) in the progression of inflammatory disorders in immunity-based pathways as it can function as antimicrobial effectors and as signaling molecules that regulate processes like transcriptional activity, authophagy and neutrophil extracellullar traps (NETs) production.

Objective To discover biomarkers involved in the pathophysiology of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and to determine whether low-density granulocytes (LDGs) contribute to gene expression signatures in AAV. Methods The source of clinical data and linked biologic specimens was a randomized controlled treatment trial in AAV. RNA sequencing of whole blood from patients with AAV was performed during active disease at the baseline visit and during remission 6 months later. Gene expression was compared between patients who met versus those who did not meet the primary trial outcome of clinical remission at 6 months (responders versus nonresponders). Measurement of neutrophil-related gene expression was confirmed in peripheral blood mononuclear cells (PBMCs) to validate the findings in whole blood. A negative-selection strategy isolated LDGs from PBMC fractions. Results Differential expression between responders (n = 77) and nonresponders (n = 35) was detected in 2,346 transcripts at the baseline visit ( P < 0.05). Unsupervised hierarchical clustering demonstrated a cluster of granulocyte-related genes, including myeloperoxidase (MPO) and proteinase 3 (PR3). A granulocyte multigene composite score was significantly higher in nonresponders than in responders ( P < 0.01) and during active disease than during remission ( P < 0.01). This signature strongly overlapped an LDG signature identified previously in lupus (false discovery rate by gene set enrichment analysis <0.01). Transcription of PR3 measured in PBMCs was associated with active disease and treatment response ( P < 0.01). LDGs isolated from patients with AAV spontaneously formed neutrophil extracellular traps containing PR3 and MPO. Conclusion In AAV, increased expression of a granulocyte gene signature is associated with disease activity and decreased response to treatment. The source of this signature is likely LDGs, a potentially pathogenic cell type in AAV. [ABSTRACT FROM AUTHOR]

Objective To determine the reliability and validity of an objective structured clinical examination (OSCE) for musculoskeletal ultrasound (MSUS). Methods A 9-station OSCE was administered to 35 rheumatology fellows trained in MSUS and to 3 expert faculty (controls). Participants were unaware of joint health (5 diseased/4 healthy). Faculty assessors (n = 9) graded image quality with predefined checklists and a 0-5 global rating, blinded to who performed the study. Interrater reliability, correlation between a written multiple choice question examination (MCQ) and OSCE performance, and comparison of fellow OSCE results with those of the faculty were measured to determine OSCE reliability, concurrent validity, and construct validity. Results Assessors' interrater reliability was good (intraclass correlation coefficient [ICC] 0.7). Score reliability was good in the normal wrist and ankle stations (ICC 0.7) and moderate in the abnormal wrist and ankle stations (ICC 0.4). MCQ grades significantly correlated with OSCE grades (r = 0.52, P < 0.01). The fellows in the bottom quartile of the MCQ scored 3.07 on the OSCE, significantly worse than the top quartile fellows (3.32) and the faculty (3.29; P < 0.01). Scores also significantly discriminated bottom quartile fellows from faculty in the normal wrist and ankle stations (3.38 versus 3.78; P < 0.01), but not in the abnormal stations (3.37 versus 3.49; P = 0.08). Conclusion MSUS OSCE is a reliable and valid method for evaluation of MSUS skill. Normal joint assessment stations are more reliable than abnormal joint assessment stations and better discriminate poorly performing fellows from faculty. Therefore, MSUS OSCE with normal joints can be used for the assessment of MSUS skill competency. [ABSTRACT FROM AUTHOR]

Objective To compare illness perceptions among patients with different forms of vasculitis, identify risk factors for negative illness perceptions, and determine the association between illness perceptions and fatigue. Methods Participants were recruited from an online vasculitis registry to complete the revised Illness Perception Questionnaire (IPQ-R). The mean scores on each IPQ-R dimension were compared across different types of vasculitis. Cluster analysis and stepwise regression identified predictors of negative illness perception. Fatigue was measured using the general subscale of the Multidimensional Fatigue Inventory (MFI-20). Patient-reported measures of disease activity and IPQ-R dimensions were assessed in relation to MFI-20 scores using linear regression in sequential, additive models with model-fit comparisons. Results In total, 692 participants with 9 types of vasculitis completed the IPQ-R. For 6 of the 8 IPQ-R dimensions, there were no significant differences in mean scores between the different vasculitides. Scores in the identity and cyclical dimensions were significantly higher in Behçet's disease compared with other types of vasculitis (13.5 versus 10.7 for identity and 4.0 versus 3.2 for cyclical [ P < 0.05]). Younger age (odds ratio [OR] 1.04, 95% confidence interval [95% CI] 1.02-1.06), depression (OR 4.94, 95% CI 2.90-8.41), active disease status (OR 2.05, 95% CI 1.27-3.29), and poor overall health (OR 3.92, 95% CI 0.88-17.56) were associated with negative illness perceptions. The sequential models demonstrated that the IPQ-R dimensions explained an equivalent proportion of variability in fatigue scores compared with measures of disease activity. Conclusion Illness perceptions are similar across different types of vasculitis, and younger age is a risk factor for negative illness perceptions. Illness perceptions explain differences in fatigue scores beyond what can be explained by measures of disease activity. [ABSTRACT FROM AUTHOR]

Objective A novel rodent model and a recent randomized trial of hyperuricemic adolescents with hypertension suggest a pathogenetic role of uric acid in hypertension, but it remains unknown whether these findings would be applicable to adult populations where the larger disease burden exists. We conducted a systematic review and meta-analysis to determine if hyperuricemia was associated with incident hypertension, particularly in various demographic subgroups. Methods We searched major electronic databases using medical subject headings and keywords without language restrictions (through April 2010). We included prospective cohort studies with data on incident hypertension related to serum uric acid levels. Data abstraction was conducted in duplicate. We analyzed age, sex, and race subgroups. Results A total of 18 prospective cohort studies representing data from 55,607 participants were included. Hyperuricemia was associated with an increased risk for incident hypertension (adjusted risk ratio [RR] 1.41, 95% confidence interval [95% CI] 1.23-1.58). For a 1 mg/dl increase in uric acid level, the pooled RR for incident hypertension after adjusting for potential confounding was 1.13 (95% CI 1.06-1.20). These effects were significantly larger in younger study populations ( P = 0.02) and tended to be larger in women ( P = 0.059). Two studies suggested that the effect may also be larger among African American individuals. Furthermore, later publication year and US-based studies were significantly associated with a lower effect estimate ( P values <0.02). Conclusion Hyperuricemia is associated with an increased risk for incident hypertension, independent of traditional hypertension risk factors. This risk appears more pronounced in younger individuals and women. [ABSTRACT FROM AUTHOR]

The article present a case study of a 32‐year‐old woman with Takayasu arteritis (TAK) 4 years earlier based on vascular headaches, arm claudication, and severe aortic arch disease. It mentions Magnetic resonance angiography demonstrated stenosis of the left common carotid and left subclavian arteries, unchanged since diagnosis; and also mentions physical examination revealed a decreased left carotid pulse with associated bruit, reduced blood pressure of the left arm, and left radial artery.

The article describes the case of a 71-year old male who was detected with transmural monoclear cell infiltration with disruption of the internal elastic membrane and giant cells with consistent with giant cell arteritis.