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1.
  • Stamatis, Pavlos, et al. (författare)
  • Myocardial infarction in a population-based cohort of patients with biopsy-confirmed giant cell arteritis in southern Sweden
  • 2024
  • Ingår i: RMD Open. - 2056-5933. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To determine the incidence rate (IR) of myocardial infarction (MI), relative risk of MI, and impact of incident MI on mortality in individuals with biopsy-confirmed giant cell arteritis (GCA). Methods MIs in individuals diagnosed with GCA 1998-2016 in Skåne, Sweden were identified by searching the SWEDEHEART register, a record of all patients receiving care for MI in a coronary care unit (CCU). The regional diagnosis database, with subsequent case review, identified GCA patients receiving care for MI outside of a CCU. A cohort of 10 reference subjects for each GCA case, matched for age, sex and area of residence, was used to calculate the incidence rate ratio (IRR) of MI in GCA to that in the general population. Results The GCA cohort comprised 1134 individuals. During 7958 person-years of follow-up, 102 were diagnosed with incident MI, yielding an IR of 12.8 per 1000 person-years (95% CI 10.3 to 15.3). The IR was highest in the 30 days following GCA diagnosis and declined thereafter. The IRR of MI in GCA to that of the background population was 1.29 (95% CI 1.05 to 1.59). Mortality was higher in GCA patients who experienced incident MI than in those without MI (HR 2.8; 95% CI 2.2 to 3.6). Conclusions The highest incidence of MI occurs within the 30 days following diagnosis of GCA. Individuals with GCA have a moderately increased risk of MI compared with a reference population. Incident MI has a major impact on mortality in GCA.
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2.
  • Moiseev, Sergey, et al. (författare)
  • International consensus on antineutrophil cytoplasm antibodies testing in eosinophilic granulomatosis with polyangiitis
  • 2020
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 202:10, s. 1360-1372
  • Tidskriftsartikel (refereegranskat)abstract
    • An international consensus on antineutrophil cytoplasm antibodies (ANCA) testing in eosinophilic granulomatosiswith polyangiitis (EGPA) is presented.ANCA, specific formyeloperoxidase (MPO), can be detected in 30-35% of patients with EGPA. MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms; purpura; polyneuropathy; unexplained heart, gastrointestinal, or kidney disease; and/or pulmonary infiltrates or hemorrhage.Apositive MPO-ANCA result contributes to the diagnostic workup for EGPA. Patients with MPO-ANCA-associated EGPA have vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations, more frequently than patients with ANCA-negative EGPA. However, the presence of MPO-ANCA is neither sensitive nor specific enough to identifywhether a patient should be subclassified as having "vasculitic"or "eosinophilic"EGPA. At present, ANCA status cannot guide treatment decisions, that is,whether cyclophosphamide, rituximab, ormepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset.
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3.
  • Wadstrom, Karin, et al. (författare)
  • Associations between plasma metabolism-associated proteins and future development of giant cell arteritis: results from a prospective study
  • 2024
  • Ingår i: RHEUMATOLOGY. - : Oxford University Press. - 1462-0324 .- 1462-0332.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to investigate the relationship between biomarkers associated with metabolism and subsequent development of GCA. Method Participants in the population-based Malmo Diet Cancer Study (MDCS; N = 30 447) who were subsequently diagnosed with GCA were identified in a structured process. Matched: GCA-free controls were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics metabolism panel (92 metabolic proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explained the variance in the proteome. Results: There were 95 cases with a confirmed incident diagnosis of GCA (median 12.0 years after inclusion). Among biomarkers with a priori hypotheses, adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated [odds ratio (OR) per S.D. 1.67; 95% CI 1.08-2.57], and fructose-1,6-bisphosphatase 1 (FBP1) was negatively associated (OR per S.D. 0.59; 95% CI 0.35-0.99) with GCA. In particular, ADGRE2 levels were associated with subsequent GCA in the subset sampled <8.5 years before diagnosis. For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those patients sampled closest to diagnosis, with a decreasing trend with longer time to GCA (P = 0.03). In the hypothesis-generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA. Conclusion: Biomarkers identified years before clinical diagnosis indicated a protective role of gluconeogenesis (FBP1) and an association with macrophage activation (ADGRE2 and Metrnl) and proinflammatory signals (ROR1) for development of GCA.
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4.
  • Wadström, Karin, et al. (författare)
  • Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis: a prospective study
  • 2023
  • Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 62:6, s. 2304-2311
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the relation between biomarkers of inflammation and subsequent development of GCA. Method: Participants in the population-based Malmo Diet Cancer Study (MDCS; N=30 447), established 1991-96, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth and year of screening were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on eigenvalues, proteins with a factor loading of >0.50 were investigated. Results: Ninety-four cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-gamma was positively associated with GCA [odds ratio (OR) per S.D. 1.52; 95% CI 1.00, 2.30]. Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-gamma (OR 2.37; 95% CI 1.14, 4.92) and monocyte chemotactic protein 3 (MCP3) (OR 4.27; 95% CI 1.26, 14.53) were particularly associated with increased risk of GCA in the subset sampled <8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25. Conclusion: Elevated IFN-gamma levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.
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5.
  • Wadström, Karin, et al. (författare)
  • Apolipoproteins and the risk of giant cell arteritis-a nested case-control study
  • 2024
  • Ingår i: ARTHRITIS RESEARCH & THERAPY. - 1478-6354 .- 1478-6362. ; 26:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe etiology of giant cell arteritis (GCA) and its predictors are incompletely understood. Previous studies have indicated reduced risk of future development of GCA in individuals with obesity and/or diabetes mellitus. There is limited information on blood lipids before the onset of GCA. The objective of the study was to investigate the relation between apolipoprotein levels and future diagnosis of GCA in a nested case-control analysis.MethodsIndividuals who developed GCA after inclusion in a population-based health survey (the Malmo Diet Cancer Study; N = 30,447) were identified by linking the health survey database to the local patient administrative register and the national patient register. A structured review of medical records was performed. Four controls for every validated case, matched for sex, year of birth, and year of screening, were selected from the database. Anthropometric measures, self-reported physical activity, based on a comprehensive, validated questionnaire, and non-fasting blood samples had been obtained at health survey screening. Concentrations of apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) in stored serum were measured using an immunonephelometric assay. Potential predictors of GCA were examined in conditional logistic regression models.ResultsThere were 100 cases with a confirmed clinical diagnosis of GCA (81% female; mean age at diagnosis 73.6 years). The median time from screening to diagnosis was 12 years (range 0.3-19.1). The cases had significantly higher ApoA-I at baseline screening compared to controls (mean 168.7 vs 160.9 mg/dL, odds ratio [OR] 1.57 per standard deviation (SD); 95% confidence interval [CI] 1.18-2.10) (SD 25.5 mg/dL). ApoB levels were similar between cases and controls (mean 109.3 vs 110.4 mg/dL, OR 0.99 per SD; 95% CI 0.74-1.32) (SD 27.1 mg/dL). The ApoB/ApoA1 ratio tended to be lower in cases than in controls, but the difference did not reach significance. The association between ApoA-I and GCA development remained significant in analysis adjusted for body mass index and physical activity (OR 1.48 per SD; 95% CI 1.09-1.99).ConclusionSubsequent development of GCA was associated with significantly higher levels of ApoA-I. These findings suggest that a metabolic profile associated with lower risk of cardiovascular disease may predispose to GCA.
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7.
  • Wadström, Karin, et al. (författare)
  • Negative associations for fasting blood glucose, cholesterol and triglyceride levels with the development of giant cell arteritis
  • 2020
  • Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332 .- 1310-0505. ; 59:11, s. 3229-3236
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. To investigate metabolic features that may predispose to GCA in a nested case-control study. Methods. Individuals who developed GCA after inclusion in a population-based health survey (the Malmo Preventive Medicine Project; N = 33 346) were identified and validated through a structured review of medical records. Four controls for every validated case were selected from the database. Results. A total of 76 cases with a confirmed incident diagnosis of GCA (61 % female, 65% biopsy positive, mean age at diagnosis 70 years) were identified. The median time from screening to diagnosis was 20.7 years (range 3.0-32.1). Cases had significantly lower fasting blood glucose (FBG) at baseline screening compared with controls [mean 4.7 vs 5.1 mmol/l (s.D. overall 1.5), odds ratio (OR) 0.35 per mmol/l (95% CI 0.17, 0.71)] and the association remained significant when adjusted for smoking [OR 0.33 per mmol/l (95% CI 0.16, 0.68)]. Current smokers had a reduced risk of GCA [OR 0.35 (95% CI 0.18, 0.70)]. Both cholesterol [mean 5.6 vs 6.0 mmol/l (s.D. overall 1.0)] and triglyceride levels [median 1.0 vs 1.2 mmol/l (s.D. overall 0.8)] were lower among the cases at baseline screening, with significant negative associations with subsequent GCA in crude and smoking-adjusted models [OR 0.62 per mmol/l (95% CI 0.43, 0.90) for cholesterol; 0.46 per mmol/l (95% CI 0.27, 0.81) for triglycerides]. Conclusion. Development of GCA was associated with lower FBG and lower cholesterol and triglyceride levels at baseline, all adjusted for current smoking, suggesting that metabolic features predispose to GCA.
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8.
  • Weiner, Maria, et al. (författare)
  • Proteinase-3 and myeloperoxidase serotype in relation to demographic factors and geographic distribution in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis
  • 2019
  • Ingår i: Nephrology, Dialysis and Transplantation. - : OXFORD UNIV PRESS. - 0931-0509 .- 1460-2385. ; 34:2, s. 301-308
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. In anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, antigen specificity varies between myeloperoxidase (MPO) and proteinase 3 (PR3). This has been reported to vary in relation to age, gender, geography and extrarenal manifestations. However, studies are difficult to compare as criteria for inclusion vary. The aim of this study was to investigate the relationship between ANCA serotype, latitude, ultraviolet (UV) radiation levels, age, gender and renal function at diagnosis in a large study with uniform inclusion criteria. Methods. Patients with biopsy-proven ANCA-associated glomerulonephritis were identified from regional or nationwide registries in 14 centres in Norway, Sweden, the UK, the Czech Republic, Croatia, Italy and the USA during the period 2000-13. UV radiation levels for 2000-13 in Europe were obtained from the Swedish Meteorological and Hydrological Institute. Results. A total of 1408 patients (45.2% PR3-ANCA) were included in the study. In univariable analysis, PR3-ANCA was significantly associated with male gender {odds ratio [OR] 2.12 [95% confidence interval (CI) 1.71-2.62]}, younger age [OR per year 0.97 (95% CI 0.96-0.98)] and higher glomerular filtration rate [OR per mL/min 1.01 (95% CI 1.01-1.02); Pamp;lt;0.001] at diagnosis but not with latitude or UV radiation. In multivariable logistic regression analysis, latitude and UV radiation also became significant, with higher odds for PR3-ANCA positivity at northern latitudes/lower UV radiation levels. However, the latitudinal difference in MPO: PR3 ratio is smaller than differences previously reported concerning microscopic polyangiitis and granulomatosis with polyangiitis. Conclusions. The ratio between PR3-ANCA and MPO-ANCA varies in glomerulonephritis with respect to age, gender, renal function and geographic latitude/UV radiation levels.
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9.
  • Baldwin, Corisande, et al. (författare)
  • Long-term outcomes of patients with Takayasu arteritis and renal artery involvement : A cohort study
  • 2018
  • Ingår i: Rheumatology Advances in Practice. - : Oxford University Press (OUP). - 2514-1775. ; 2:2, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To describe the long-term outcomes of patients with Takayasu arteritis (TAK) and renal artery involvement (RAI). Methods. A retrospective review of 122 patients with TAK at three tertiary centres in Canada, Sweden and the UK. Data on demographics, laboratory and clinical parameters, medications and angiography findings were collected. Non-renal and renal parameters were compared at baseline and follow- up. Results. A total of 37 patients (30%) with RAI were identified: 18 (49%) with unilateral and 19 (51%) with bilateral RAI. Patients were predominantly female (89%). The median age at diagnosis was 27 years [interquartile range (IQR) 16-38]. The median follow-up time was 7 years (IQR 2-12). Hypertension was seen in 27 patients (73%) at presentation and 25 (68%) at follow-up. The median estimated glomerular filtration (eGFR) at presentation was 94 and 98 ml/min/1.73 m 2 in those with unilateral and bilateral RAI, respectively. The corresponding median eGFR at follow-up was 101.5 and 104 ml/min/1.73 m 2 , respectively. Three patients at presentation and two at follow-up had an eGFR of < 60 ml/min/1.73 m 2 . Five underwent endovascular intervention and three required surgical interventions. Among the 33 patients with radiologic follow-up, 23 (69%) had persistent RAI and 10 (30%) had resolution of RAI. One (6%) patient with unilateral RAI developed bilateral RAI and three (19%) with bilateral RAI regressed to unilateral RAI. Over time, 23 (62%) patients had stable renal function, 7 (19%) had improvement and 4 had a decline in renal function; no patient developed end-stage renal disease (ESRD). Conclusion. In this series of TAK patients with RAI, long-term non-renal and renal outcomes were favourable. No patient experienced ESRD or died.
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10.
  • Berglin, Ewa, MD, PhD, 1955-, et al. (författare)
  • Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis : a case-control study
  • 2021
  • Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 117
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed.Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities.Results: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p < 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3–7.7) years and MPO-ANCA+ 2.0 (0.9–3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P < 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p < 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p < 0.01 and p < 0.05, respectively).Conclusion: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.
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11.
  • Brink, Mikael, et al. (författare)
  • Protein Profiling in Presymptomatic Individuals Separates Myeloperoxidase-Antineutrophil Cytoplasmic Antibody and Proteinase 3-Antineutrophil Cytoplasmic Antibody Vasculitides
  • 2023
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:6, s. 996-1006
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a chronic relapsing condition with unknown etiology. To gain insight into the molecular processes underlying the disease, we examined biomarkers in blood samples collected prior to symptom onset. Methods. The National Patient Register and Cause of Death register were searched for AAV-related International Classification of Diseases, Ninth Revision and Tenth Revision codes and linked to the registers from 5 biobanks. Eighty-five AAV patients with samples predating symptom onset of AAV were identified. For each case of AAV, 2 matched controls were included. Proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA expression levels were analyzed using enzyme-linked immunosorbent assays. Using an Olink Inflammation panel, 73 of 92 proteins were included after quality control. Data were replicated in a second cohort of 48 presymptomatic individuals and 96 controls. Results. Of the 20 proteins with the lowest P values in the original cohort, 7 were replicated in the second cohort and 5 proteins were found to be significant between the groups in a meta-analysis. Eleven different pathways were identified in network enrichment analyses and were found to be significant in both cohorts. Stratification of samples obtained <= 5 years before symptom onset showed significant levels of CCL23, vascular endothelial growth factor A, and hepatocyte growth factor, which were also increased at borderline significant levels in the replication cohort (interleukin-6 was found to be significantly increased in the replication cohort). In presymptomatic AAV patients, 6 proteins were associated with MPO-ANCA positivity, and 7 proteins were associated with PR3-ANCA positivity. Conclusion. To our knowledge, this is the first study to identify protein markers preceding symptom onset in AAV patients. These findings set the stage for further research into the underlying cellular and molecular mechanisms in the pathogenesis of AAV and the diversification of patients into PR3-ANCA+ and MPO-ANCA+ subphenotypes.
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12.
  • Dahlqvist, Johanna, 1979-, et al. (författare)
  • Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
  • 2022
  • Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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13.
  • Egan, Allyson C, et al. (författare)
  • The Sound of Interconnectivity; The European Vasculitis Society 2022 Report
  • 2022
  • Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:8, s. 1745-1757
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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14.
  • Ekman, Diana, et al. (författare)
  • Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
  • 2023
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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15.
  • Englund, Martin, et al. (författare)
  • Comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis versus the general population
  • 2016
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:8, s. 1553-1558
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To evaluate the consultation rates of selected comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) compared with the general population in southern Sweden. Methods. We used data from a population-based cohort of patients with AAV diagnosed between 1998 and 2010 in Southern Sweden (701,000 inhabitants). For each patient we identified 4 reference subjects randomly sampled from the general population and matched for year of birth, sex, area of residence, and index year. Using the population-based Skåne Healthcare Register, we identified relevant diagnostic codes, registered between 1998 and 2011, for selected comorbidities assigned after the date of diagnosis of AAV or the index date for the reference subjects. We calculated rate ratios for comorbidities (AAV:reference subjects). Results. There were 186 patients with AAV (95 women, mean age 64.5 yrs) and 744 reference persons included in the analysis. The highest rate ratios (AAV:reference) were obtained for osteoporosis (4.6, 95% CI 3.0-7.0), followed by venous thromboembolism (4.0, 95% CI 1.9-8.3), thyroid diseases (2.1, 95% CI 1.3-3.3), and diabetes mellitus (2.0, 95% CI 1.3-2.9). For ischemic heart disease, the rate ratio of 1.5 (95% CI 1.0-2.3) did not reach statistical significance. No statistically significant differences were found for cerebrovascular accidents. Conclusion. AAV is associated with increased consultation rates of several comorbidities including osteoporosis and thromboembolic and endocrine disorders. Comorbid conditions should be taken into consideration when planning and providing care for patients with AAV.
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16.
  • Esberg, Anders, et al. (författare)
  • Oral Microbiota Profile in Patients with Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis
  • 2022
  • Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 10:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbiota has been associated with autoimmune diseases, with nasal Staphylococcus aureus being implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV). Little is known about the role of oral microbiota in AAV. In this study, levels of IgG antibodies to 53 oral bacterial species/subspecies were screened using immunoblotting in plasma/serum in pre-symptomatic AAV-individuals (n = 85), matched controls, and established AAV-patients (n = 78). Saliva microbiota from acute-AAV and controls was sequenced from 16s rDNA amplicons. Information on dental status was extracted from a national register. IgG levels against oral bacteria were lower in established AAV versus pre-AAV and controls. Specifically, pre-AAV samples had, compared to controls, a higher abundance of periodontitis-associated species paralleling more signs of periodontitis in established AAV-patients than controls. Saliva microbiota in acute-AAV showed higher within-sample diversity but fewer detectable amplicon-sequence variants and taxa in their core microbiota than controls. Acute-AAV was not associated with increased abundance of periodontal bacteria but species in, e.g., Arthrospira, Staphylococcus, Lactobacillus, and Scardovia. In conclusion, the IgG profiles against oral bacteria differed between pre-AAV, established AAV, and controls, and microbiota profiles between acute AAV and controls. The IgG shift from a pre-symptomatic stage to established disease cooccurred with treatment of immunosuppression and/or antibiotics.
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17.
  • Gisslander, Karl, et al. (författare)
  • Data quality and patient characteristics in European ANCA-associated vasculitis registries : data retrieval by federated querying
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - 0003-4967. ; 83:1, s. 112-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. Methods Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. Results A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. Conclusions In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.
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18.
  • Gisslander, Karl, et al. (författare)
  • The Role of Sural Nerve Biopsy in the Diagnosis of Vasculitis
  • 2022
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 49:9, s. 1031-1036
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The diagnostic yield of sural nerve biopsy (SNB) in vasculitis is uncertain. Our aim was to document relevant characteristics of patients undergoing SNB in the investigation of vasculitis; determine the diagnostic yield; relate positive biopsy findings to patient demographic, laboratory, and clinical variables; and to calculate the rate of surgical complications. Methods. Patients with suspected vasculitis that underwent SNB as part of diagnostic evaluation at academic medical centers in Sweden and the United Kingdom were identified by searching local pathology databases and clinic registers. A structured review of medical case records and pathology reports was conducted. Histological findings were categorized as definite, probable, or no vasculitis in accordance with the 2015 Brighton Collaboration reinterpretation and update of the Peripheral Nerve Society guidelines for vasculitic neuropathy. Definite and probable findings were considered positive for vasculitis. Results. Ninety-one patients that underwent SNB were identified (45% female). Forty (44%) patients showed histological evidence of vasculitis: 14 definite and 26 probable. A concomitant muscle biopsy conducted in 10 patients did not contribute to the diagnostic yield. Positive antineutrophil cytoplasmic antibody test, organ involvement other than the nervous system, and a longer biopsy sample were associated with a positive biopsy. The reported surgical complication rate was 15%. Conclusion. SNB of sufficient length is a useful procedure to confirm a diagnosis of vasculitis.
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19.
  • Heijl, Caroline, et al. (författare)
  • Long-term patient survival in a Swedish population-based cohort of patients with ANCA-associated vasculitis
  • 2017
  • Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Patients with antineutrophil cytoplasmatic antibodies-associated vasculitides (AAV) exhibit higher mortality than the general population. In the current study, we assessed whether cluster affiliation based on clinical presentation might predict mortality. Methods: With case record review, the outcomes for a population-based cohort of patients diagnosed with AAV in southern Sweden (catchment area of 0.7 million inhabitants) between 1997 and 2010 were assessed. Based on organ involvement at presentation, the cohort was stratified into the following clusters: gastrointestinal, cardiovascular, non-renal, renal with proteinase 3 (PR3) and renal without PR3. Cluster affiliation, demographics, clinical and laboratory values at entry were tested as prognostic factors for survival in multivariable models. Results: 195 patients (98 female) with a median age of 69 years (IQR 55-77) at diagnosis were included in the cohort. The median time of follow-up was 4 years for the 98 patients (50%) who died during follow-up and 11 years for those alive at end of follow-up. The 1-year, 2-year, 5-year and 10-year survival was 87%, 82%, 70% and 55%, respectively. Prognostic factors for survival were sex, age, renal function and cluster affiliation. The mortality of patients with AAV was significantly increased compared with the general population except in the non-renal cluster. The cardiovascular and gastrointestinal clusters showed the highest mortality. Conclusion: Even though the mortality in patients with AAV is increased compared with the general population this does not apply to patients without gastrointestinal, cardiovascular or renal involvement at diagnosis. We suggest that the initial clinical presentation is an important predictor for survival.
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20.
  • Hellmich, Bernhard, et al. (författare)
  • EULAR recommendations for the management of ANCA-associated vasculitis : 2022 update
  • 2024
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 83:1, s. 30-47
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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21.
  • Jakobsson, Karin, et al. (författare)
  • The effect of clinical features and glucocorticoids on biopsy findings in giant cell arteritis
  • 2016
  • Ingår i: Bmc Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To investigate the effect of baseline clinical characteristics and glucocorticoid treatment on temporal artery biopsy (TAB) findings in patients with giant cell arteritis (GCA). Methods: Individuals who developed GCA after inclusion in two population-based health surveys were identified through linkage to the local and the national patient registers. In addition, other patients diagnosed with GCA at the Departments of Internal Medicine and Rheumatology at an area hospital were included. A structured review of medical records and TAB pathology reports was performed. The presence or absence of giant cells, granuloma, fragmented internal elastic lamina, fibrosis and grade of inflammatory infiltrates were recorded. Results: In 183 cases with a confirmed clinical diagnosis of GCA, 139 were biopsied after start of glucocorticoids (median treatment duration 3 days; interquartile range 2-5). Patients with a positive TAB (77 %) had significantly higher C-reactive protein (CRP; p = 0.007) and erythrocyte sedimentation rate (ESR; p = 0.03) at the time of clinical diagnosis. A positive TAB tended to more common in women, but there was no difference in the proportion of patients with polymyalgia rheumatica or visual symptoms. Patients biopsied before or on the same day as initial treatment where more likely than those biopsied 1-3 days after treatment start to have positive biopsy [odds ratio (OR) 2.86; 95 % CI 1.06-7.70] as well as inflammatory infiltrates (OR 3.30; 95 % CI 1.15-9.49). There was no significant difference in the proportions of a fragmented internal lamina (p = 0.86), giant cells (p = 0. 10), granuloma (p = 0.19), minor inflammatory infiltrates (p = 0.47), major inflammatory infiltrates (p = 0.09), or overall positive biopsy (p = 0.17) report by treatment duration comparing: <= 0 days, 1-3 days, 4-6 days, 7-28 days. Among those biopsied 7-28 days after start of treatment, 80 % of TABs were positive, and histopathology features were not substantially different from those biopsied after shorter glucocorticoid treatment. Conclusion: Biopsies were more likely to be positive and have characteristic histopathologic features in patients with high CRP and ESR, and prior to start of corticosteroid treatment TABs taken 1-4 weeks after initiation of glucocorticoid treatment reveal changes consistent with GCA and therefore still yields clinically useful information for the diagnosis.
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22.
  • Kiadaliri, Aliasghar A, et al. (författare)
  • Hospitalizations due to systemic connective tissue diseases: : Secular trends and regional disparities in Sweden, 1998-2016
  • 2018
  • Ingår i: International Journal of Rheumatic Diseases. - 1756-185X. ; 21:11, s. 1900-1906
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To investigate secular trends and regional disparities in hospitalizations due to systemic connective tissue diseases (SCTD) in Sweden from 1998 to 2016.METHOD: We identified all hospital admissions with a principal diagnosis of SCTD (ICD-10 codes: M30-M36) from the Swedish National Patient Register. Joinpoint regression was used to assess secular trends in age-standardized hospitalization rates (ASHR) and proportions of SCTD from all and musculoskeletal disorders hospitalizations. We also assessed the secular trends in the absolute and relative regional disparities of SCTD hospitalizations.RESULTS: We identified 89 333 SCTD hospitalizations (0.3% of all hospitalizations), of these about 69% were for women and 49% of patients were aged 15-64 years. Polyarteritis nodosa and related conditions (PANRC) and systemic lupus erythematosus (SLE) were the most frequent SCTD among those aged <10 years and 10-54 years, respectively. Joinpoint regression suggested that both rates and proportions of SCTD hospitalizations declined over time. These trends persisted among sex, age and diagnosis subgroups except for PANRC in patients aged 0-19 years who observed an average annual increase of 3.4% (95% CI: 1.8, 5.1) over the study period. There were 2.4-fold (95% CI: 2.3-2.5) difference between the regions with the highest and lowest mean ASHR. There was no statistically significant secular trend in the relative regional disparities, whereas the absolute regional disparity declined over time.CONCLUSION: There were substantial decreases in the absolute and relative burden of SCTD hospitalizations reflecting possible improvements in disease management in Sweden. The rising trend in PANRC among the youngest children warrants further investigation.
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23.
  • Liapi, Matina, et al. (författare)
  • Venous thromboembolism in ANCA-associated vasculitis : A population-based cohort study
  • 2021
  • Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:10, s. 4616-4623
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To determine incidence rate and predictors of venous thromboembolic events (VTE) in a population-based cohort with ANCA-associated vasculitis (AAV). Methods: The study comprised 325 patients diagnosed with AAV from 1997 to 2016. All cases of VTE from prior to vasculitis diagnosis to the end of the study period were identified. The BVAS was used to assess disease activity at diagnosis. Venous thromboembolisms occurring in a period beginning 3 months prior to AAV diagnosis were considered to be AAV-related. The standardized incidence ratio (SIR) and 95% CI of VTE were calculated using the incidence rate in the general population. Results: Fifty-nine patients (18%) suffered 64 VTE events. Of these, 48 (81%) suffered AAV-related VTE [deep vein thrombosis (n = 23), pulmonary embolism (n = 18) and other (n = 9)]. The incidence rate of AAV-related VTE was 2.4 per 100 person-years (95% CI 1.7, 3.0) during 2039 person-years of follow-up. The incidence during the first 3 months post-AAV diagnosis was 20.4 per 100 person-years (95% CI 11.5, 29.4), decreasing to 8.9 (95% CI 0.2, 17.6) and 1.5 (95% CI 0.0, 3.5) in months 4-6 and months 7-12 post-AAV diagnosis, respectively. The SIR was 34.2 (95% CI 20.2, 48.1) for deep vein thrombosis and 10.4 (95% CI 5.6, 15.1) for pulmonary embolism. In multivariate Cox regression analyses, only age and BVAS were predictive of VTE. Conclusions: The incidence rate and SIR of AAV-related VTE is high, and higher early in the course of the disease. Vasculitis activity and age are positively associated with VTE.
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24.
  • Lundberg, Ingrid E., et al. (författare)
  • An update on polymyalgia rheumatica
  • 2022
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 292:5, s. 717-732
  • Forskningsöversikt (refereegranskat)abstract
    • Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2–3 times more common in women. The most common symptoms are pain and morning stiffness in the shoulder and pelvic girdle and the onset may be acute or develop over a few days to weeks. General symptoms such as fatigue, fever and weight loss may occur, likely driven by systemic IL-6 signalling. The pathology includes synovial and periarticular inflammation and muscular vasculopathy. A new observation is that PMR may appear as a side effect of cancer treatment with checkpoint inhibitors. The diagnosis of PMR relies mainly on symptoms and signs combined with laboratory markers of inflammation. Imaging modalities including ultrasound, magnetic resonance imaging and positron emission tomography with computed tomography are promising new tools in the investigation of suspected PMR. However, they are still limited by availability, high cost and unclear performance in the diagnostic workup. Glucocorticoid (GC) therapy is effective in PMR, with most patients responding promptly to 15–25 mg prednisolone per day. There are challenges in the management of patients with PMR as relapses do occur and patients with PMR may need to stay on GC for extended periods. This is associated with high rates of GC-related comorbidities, such as diabetes and osteoporosis, and there are limited data on the use of disease-modifying antirheumatic drugs and biologics as GC sparing agents. Finally, PMR is associated with giant cell arteritis that may complicate the disease course and require more intense and prolonged treatment.
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25.
  • Lundtoft, Christian, et al. (författare)
  • The HLA region in ANCA-associated vasculitis : characterisation of genetic associations in a Scandinavian patient population
  • 2024
  • Ingår i: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 10:2, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV.METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively.RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.
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26.
  • Maritati, Federica, et al. (författare)
  • Brief Report: Rituximab for the Treatment of Adult-Onset IgA Vasculitis (Henoch-Schonlein)
  • 2018
  • Ingår i: Arthritis & Rheumatology. - : WILEY. - 2326-5191 .- 2326-5205. ; 70:1, s. 109-114
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveAdult-onset IgA vasculitis (Henoch-Schonlein) (IgAV) is a rare systemic vasculitis characterized by IgA1-dominant deposits. The treatment of adult-onset IgAV is controversial and is based on the combination of glucocorticoids and immunosuppressive agents, but many patients have refractory or relapsing disease despite treatment. Rituximab (RTX) is a B cell-depleting antibody of proven efficacy in antineutrophil cytoplasmic antibody-associated vasculitis. We undertook this study to test the efficacy and safety of RTX in a multicenter cohort of patients with adult-onset IgAV. MethodsIn this multicenter observational study, we included patients with adult-onset IgAV who had received RTX either for refractory/relapsing disease or because they had contraindications to conventional glucocorticoid/immunosuppressive therapy. We analyzed the rates of remission (defined on the basis of the Birmingham Vasculitis Activity Score [BVAS]) and relapse as well as the variations over time in estimated glomerular filtration rate (GFR), proteinuria, C-reactive protein (CRP) level, BVAS, and prednisone dose. ResultsTwenty-two patients were included; their median duration of follow-up was 24 months (interquartile range 18-48 months). Sixteen patients received RTX as add-on therapy and 6 as monotherapy. Twenty patients (90.9%) achieved remission, and 7 of those 20 patients (35%) had subsequent relapse of disease. There were significant reductions in 24-hour proteinuria (P amp;lt; 0.0001), CRP level (P = 0.0005), BVAS (P amp;lt; 0.0001), and prednisone dose (P amp;lt; 0.0001) from RTX initiation through the last follow-up visit; estimated GFR remained stable. RTX was generally well tolerated. One patient died after 60 months of follow-up. ConclusionOur data suggest that RTX is an effective and safe therapeutic option for adult-onset IgAV.
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27.
  • Mohammad, Aladdin J, et al. (författare)
  • Incidence and disease severity of anti-neutrophil cytoplasmic antibody-associated nephritis are higher than in lupus nephritis in Sweden.
  • 2015
  • Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 30, s. i23-i30
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives :The objectives of this study were to compare incidence rates, renal and patient survival between lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody-associated nephritis (AAN) during a 12-year period in two geographically defined populations in Sweden.METHODS: In the health care districts surrounding the Skåne University Hospital in Lund [mean population ≥18 years (1997-2008), 188 400] and the University Hospital in Linköping [mean population ≥18 years (1997-2008), 328 900] all patients with biopsy-proven LN and AAN during the period 1997-2008 were included in the study if they (i) were residing within the study areas at the time of onset of nephritis, (ii) had a clinical diagnosis of either SLE or ANCA-associated vasculitis (AAV) and (iii) experienced a first flare of biopsy-proven nephritis during the study period.RESULTS: Eighty-two patients (Lund 44 + Linköping 38) with biopsy-proven AAN were identified and 27 patients with LN (Lund 13 + Linköping 14). The annual incidence rate per million inhabitants aged ≥18 years in both study areas was estimated to be 13.2 (95% CI 10.4-16.1) for AAN and 4.3 (95% CI 2.7-6.0) for LN, P < 0.001. The patients were followed until January 2013. During the follow-up time 38 patients died (AAN 36, LN 2; P = 0.001), and 20 patients went into end-stage renal disease (AAN 19 and LN 1), P = 0.020.CONCLUSIONS: In Sweden, AAN was three times more common than LN, and the outcome was considerably worse. SLE is often diagnosed before the onset of nephritis leading to earlier treatment, while AAN is still often diagnosed at a later stage.
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28.
  • Mohammad, Aladdin J., et al. (författare)
  • Pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis : The influence of ANCA subtype
  • 2017
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 44:10, s. 1458-1467
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To describe pulmonary involvement at time of diagnos is in a ntineutrophil cytoplasm ic antibodies (ANCA)-associated vasculitis (AAV), as defined by computed tomography (CT). Methods. Pati ents w ith thoracic CT perfor med on or after the onset of AAV (n = 140; 7 5 women; granulomatosis with polyangiitis, n = 79; microscopic polyangiitis MPA, n = 61) followed at a tertiary referral center vasculitis clinic were studied. Radiological patterns of pulmonary involvement were evaluated from the CT studies using a predefined protocol, and compared to proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA specificity. Results. Of the patients, 77% had an abnormal thoracic CT study. The most common abnormality was nodular disease (24%), of which the majority were peribronchial nodules, followed by bronchiectasis and pleural effusion (19%, each), pulmonary hemorrhage and lymph node enlargement (14%, each), emphysema (13%), and cavitating lesions (11%). Central airways disease and a n odular pattern of pulmonary involvement were more common in PR3-ANCA-positive patients (p < 0.05). Usual interstitial pneumonitis (UIP) and bronchiectasis were more prevalent in MPO-ANCA-positive patients (p < 0.05). Alveolar hemorrhage, pleural effusion, lymph node enlargement, and pulmonary venous congestion were more frequent in MPO-ANCA-positive patients. Conclusion. Pulmonary involvement is frequent and among 140 patients with AAV who underwent a thoracic CT study, almost 80% have pulmonary abnormalities on thoracic CT. Central airway disease oc curs exclusively among patients with PR3-ANCA while UIP were mainl y seen in those wit h MPO-ANCA. These findings may have important implications for the investigation, ma nagement, and pathogenesis of AAV.
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29.
  • Mohammad, Aladdin J., et al. (författare)
  • Rate of comorbidities in giant cell arteritis : A population-based study
  • 2017
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 44:1, s. 84-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare the rate of occurrence of comorbidities, including severe infections, in a population-based cohort of patients with biopsy-proven giant cell arteritis (GCA) with a reference population in Southern Sweden. Methods. The study included a population-based cohort of biopsy-proven GCA cases diagnosed between 1998 and 2010 from the Skane region in Southern Sweden (population: 1.2 million). For each patient, 4 reference subjects were identified from the general population and matched for age, sex, area of residence, and date of diagnosis of GCA. Using the Skane Healthcare Register, comorbidities and severe infections (requiring hospitalization) diagnosed after GCA onset were identified. The rate of the first occurrence of each comorbidity was the result of dividing the number of subjects with a given comorbidity by the person-years of followup. The rate ratio (RR; GCA:reference population) was also calculated. Results. There were 768 patients (571 women) with GCA and 3066 reference persons included in the study. The RR were significantly elevated for osteoporosis (2.81, 95% CI 2.33-3.37), followed by venous thromboembolic diseases (2.36, 95% CI 1.61-3.40), severe infections (1.85, 95% CI 1.57-2.18), thyroid diseases (1.55, 95% CI 1.25-1.91), cerebrovascular accidents (1.40, 95% CI 1.12-1.74), and diabetes mellitus (1.29, 95% CI 1.05-1.56). The RR for ischemic heart disease was elevated, but did not reach statistical significance (1.20, 95% CI 1.00-1.44). Conclusion. Patients with GCA have higher rates of selected comorbidities, including severe infections, compared with a reference population. Several of these comorbidities may be related to treatment with glucocorticosteroids, emphasizing the unmet need to find alternative treatments for GCA.
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30.
  • Mohammad, Aladdin J., et al. (författare)
  • Severe infection in antineutrophil cytoplasmic antibody-associated vasculitis
  • 2017
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 44:10, s. 1468-1475
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare the rate of severe infections after the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with the rate in the background population, and to identify predictors of severe infections among patients with AAV. Methods. The study cohort was 186 patients with AAV diagnosed from 1998 to 2010, consisting of all known cases in a defined population in southern Sweden. For each patient, 4 age- and sex-matched reference subjects were randomly chosen from the background population. Using the Skåne Healthcare Register, all International Classification of Diseases codes of infections assigned from 1998 to 2011 were identified. Severe infections were defined as infectious episodes requiring hospitalization. Rate ratios were calculated by dividing the rate in AAV by the rate among the reference subjects. Results. The rate ratio for all severe infections was 4.53 (95% CI 3.39-6.00). The highest rate ratios were found for upper respiratory tract: 8.88 (3.54-25.9), Clostridium difficile: 5.35 (1.54-23.8), nonspecific septicemia 4.55 (1.60-13.8), and skin 5.35 (1.69-19.8). Of the severe infections, 38.4% occurred within 6 months of diagnosis, 30.2% from 7-24 months, and 31.4% after 24 months. High serum creatinine and older age at diagnosis were associated with severe infection (p < 0.001). Of those with severe infection, 46.5% died during followup compared to 26% of patients without severe infection (p = 0.004). Conclusion. Patients with AAV have markedly higher rates of severe infection compared with the background population, especially patients with older age and impaired renal function. The risk of severe infection is particularly high in the first 6 months following the diagnosis of vasculitis.
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31.
  • Mohammad, Aladdin J., et al. (författare)
  • Trajectory of Healthcare Resources Utilization in Giant Cell Arteritis – A Population-Based Study
  • 2021
  • Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:8, s. 1307-1313
  • Tidskriftsartikel (refereegranskat)abstract
    • To estimate the healthcare resource utilization (HRU) in patients with giant cell arteritis (GCA) compared with the general population in southern Sweden.MethodsThe study sample comprised 653 patients with GCA along with 10 age-, sex-, and residency area–matched reference subjects per patient. Data on public and private healthcare consultations and hospitalizations were extracted from the Skåne Healthcare Register. We assessed trajectories of primary and specialist healthcare visits, as well as hospital admissions and inpatient days from 3 years before through 5 years after the date of GCA diagnosis for patients and matched references. HRU was analyzed using generalized estimating equations adjusted for sex, age at the index year, calendar year of diagnosis, education, income, marital status, place of birth, and Charlson Comorbidity Index. Inverse probability weighting was used to account for dropout during study.ResultsPatients with GCA had higher rates of healthcare visits than the references from the year before GCA diagnosis and up to 4 years after diagnosis, with the largest relative (rate ratio 1.85, 95% CI 1.68–2.05) and absolute (mean difference 10.2, 95% CI 8.1–12.3 visits per person) differences in the year of diagnosis. Similar trajectories were observed for primary and specialist healthcare visits. For hospital admissions and inpatient days, the differences disappeared 1 year after diagnosis date.ConclusionPatients with GCA utilized healthcare services at a significantly higher rate than the reference population. The increased utilization among Swedish patients with GCA was evident 1 year before and prolonged up to 4 years after diagnosis date.
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32.
  • Mohammad, Aladdin, et al. (författare)
  • Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss).
  • 2016
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 75:2, s. 396-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Conventional treatment of eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss) with glucocorticoids, with or without additional immunosuppressive drugs, is limited by partial efficacy, frequent toxicity and a high relapse rate. Rituximab is a licensed treatment for granulomatosis with polyangiitis and microscopic polyangiitis and is of potential benefit to patients with EGPA.
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33.
  • Moiseev, Sergey, et al. (författare)
  • Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis : A multinational study
  • 2021
  • Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 60:10, s. 4654-4661
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. Methods: Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. Results: Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15-60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. Conclusion: Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.
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34.
  • Moiseev, Sergey, et al. (författare)
  • Traditional and Disease-Specific Risk Factors for Cardiovascular Events in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis : A Multinational Retrospective Study
  • 2023
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 50:9, s. 1145-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To investigate the occurrence of cardiovascular events (CVEs) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-Associated vasculitis (AAV) across the European Union, China, Turkey, Russia, the United Kingdom, and the USA. Methods. Patients with a definite diagnosis of AAV who were followed for ? 3 months and had sufficient documentation were included. Data on myocardial infarction (MI) and stroke were collected retrospectively from tertiary vasculitis centers. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. Results. Over a median follow-up of 62.0 months (IQR 22.6-100.0), CVEs (mostly MIs) occurred in 245 (10.7%) of 2286 patients with AAV, with a higher frequency in China and the UK. On multivariate regression analysis, older age (55-64.9 yrs, HR 2.93, 95% CI 1.99-4.31), smoking (HR 1.98, 95% CI 1.48-2.64), Chinese origin (HR 4.24, 95% CI 3.07-5.85), and pulmonary (HR 1.50, 95% CI 1.09-2.06) and kidney (HR 3.02, 95% CI 2.08-4.37) involvement were independent variables associated with a higher occurrence of CVEs. Conclusion. We showed that geographic region and both traditional and disease-specific (kidney involvement in particular) factors were independently associated with CVEs. Proper assessment and management of modifiable cardiovascular (CV) risk factors are essential for prevention of CV morbidity in patients with AAV.
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35.
  • Mossberg, Maria, et al. (författare)
  • High risk of coronary artery aneurysm in Kawasaki disease
  • 2021
  • Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 60:4, s. 1910-1914
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Kawasaki disease (KD) is a vasculitis of unknown aetiology with a high risk of coronary aneurysms if untreated. Timely treatment with intravenous immunoglobulin decreases the risk for coronary artery aneurysms (CAA). In this study, we set out to elucidate the factors associated with the risk of developing CAA. METHODS: Records of all KD-diagnosed children in Skåne between 2004 and 2014 were collected and clinical and demographic data were compiled. KD is defined according to the revised American Heart Association diagnostic criteria and classified as either complete KD (cKD) or incomplete KD (iKD). RESULTS: KD was diagnosed in 77 children and CAA was found in 31% (n = 24). Children with CAA were younger compared with children without (median; 20 vs 34 months) and intravenous immunoglobulin treatment within 10 days was less likely to be received (75% vs 91%). In children presenting with iKD, 47% developed CAA compared with 21% in cKD patients. Using multivariate analysis, an association between the risk of CAA with low age in children with iKD was observed. CONCLUSION: The risk of CAA development is disturbingly high in young children with iKD. This highlights the importance of rapid intense treatment and vigilance in infants, who are the most difficult to diagnose, in order to reduce the frequency of CAA.
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36.
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37.
  • Nakagomi, Daiki, et al. (författare)
  • Development of a score for assessment of radiologic damage in large-vessel vasculitis (Combined Arteritis Damage Score, CARDS)
  • 2017
  • Ingår i: Clinical and Experimental Rheumatology. - 0392-856X. ; 35:1, s. 139-145
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Outcome assessment in large-vessel vasculitis (LVV) remains challenging and this impairs patient management and the conduct of clinical studies. Previous proposals for outcome tools have not included imaging. This study aimed to develop an imaging score to quantify damage in LVV and to assess the difference between Takayasu (TAK) and giant cell arteritis (GCA).METHODS: Ninety-six patients (41 TAK, 55 GCA) were identified from local registries at two University Hospitals in the UK. Radiologic lesions including stenosis, occlusion and aneurysm were evaluated in 25 arterial regions by enhanced computed tomography or magnetic resonance angiography. Lesion correlation with combined damage assessment scores was employed in a multiple regression analysis to define the weight of individual lesions and develop a damage index.RESULTS: A numerical damage index was developed: the "Combined Arteritis Damage Score (CARDS)". The index was derived from a formula: number of regions with mild stenosis × 0.6 + number of regions with moderate to severe stenosis × 1.2 + number with occlusions × 1.6 + number with aneurysms × 0.8 in 25 arterial regions. The median CARDS was higher in TAK than GCA (4.1 and 0.6, interquartile range 1.3-5.7 and 0-3, p<0.001).CONCLUSIONS: We have developed a damage assessment tool, CARDS, based on imaging in LVV of potential value to clinical studies and patient management. TAK and GCA differ in the radiologic severity of disease.
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38.
  • Saleh, Muna Atallah, et al. (författare)
  • Visual complications in patients with biopsy-proven giant cell arteritis : A population-based study
  • 2016
  • Ingår i: Journal of Rheumatology. - Lund : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:8, s. 1559-1565
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To study the clinical and laboratory characteristics of patients with biopsy-proven giant cell arteritis (GCA) with visual complications, and to evaluate the incidence rate of visual complications in GCA compared to the background population. Methods. Data from 840 patients with GCA in the county of Skane, Sweden, diagnosed between 1997 and 2010, were used for this analysis. Cases with visual complications were identified from a diagnosis registry and confirmed by a review of medical records. The rate of visual complications in patients with GCA was compared with an age-and sex-matched reference population. Results. There were 85 patients (10%) who developed ≥ 1 visual complication after the onset of GCA. Of the patients, 18 (21%) developed unilateral or bilateral complete visual loss. The mean age at diagnosis was 78 years (± 7.3); 69% were women. Compared with patients without visual complications, those with visual complication had lower C-reactive protein levels at diagnosis and were less likely to have headache, fever, and palpable abnormal temporal artery. The use of-adrenergic inhibitors was associated with visual complications. The incidence of visual complications among patients with GCA was 20.9/1000 person-years of followup compared to 6.9/1000 person-years in the reference population, resulting in a rate ratio of 3.0 (95% CI 2.3.3.8). Conclusion. Ten percent of patients with GCA developed visual complications, a rate substantially higher than that of the general population. Patients with GCA who had visual complications had lower inflammatory responses and were more likely to have been treated with 1β-adrenergic inhibitors compared with patients without visual complications.
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39.
  • Sjöwall, Christopher, et al. (författare)
  • HUVS [Hypocomplementemic Urticarial Vasculitis Syndrome] : sällsynt men inte ofarlig vaskulit associerad med urtikaria [A Rare but Not Always Benign Condition]]
  • 2019
  • Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 116
  • Tidskriftsartikel (refereegranskat)abstract
    • Although more than 45 years have passed since hypocomplementemic urticarial vasculitis (HUVS) was first described by McDuffie and colleagues at the Mayo clinic, data on epidemiology, disease outcomes, prognosis and clinical features are scarce. Recently, we published the first epidemiological study of HUVS including data on incidence, prevalence, disease outcomes, prognosis and clinical features using data from two separate Swedish regions during a period of 16 years. The estimation of incidence and prevalence rates indicates that HUVS is rare but not always benign. Renal and lung manifestations were severe in some cases, highlighting the need for careful screening and monitoring of this potentially serious condition. It is reasonable to suspect HUVS in patients with unexplained systemic inflammation combined with >6 months of urticaria. Special attention should be paid to patients with recent-onset dyspnea and proteinuria.
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40.
  • Stamatis, Pavlos, et al. (författare)
  • Malignancies In Giant Cell Arteritis : A Population-Based Cohort Study
  • 2020
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 47:7, s. 400-406
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate the risk of cancer in patients with biopsy-proven giant cell arteritis (GCA) from a defined population in southern Sweden.METHODS: The study cohort consisted of 830 patients (mean age at GCA diagnosis was 76.3 years, 74 % women) diagnosed with biopsy-proven GCA between 1997 and 2010. Temporal artery biopsy results were retrieved from a regional database and reviewed to ascertain GCA diagnosis. The cohort was linked to the Swedish Cancer Registry. The patients were followed from GCA diagnosis until death or December 31, 2013. Incident malignancies registered after GCA diagnosis were studied. Based on data on the first malignancy in each organ system, age- and sex standardized incidence ratios (SIR) with 95 % confidence intervals (CI) were calculated compared to the background population.RESULTS: 107 patients (13%) were diagnosed with a total of 118 new malignancies after the onset of GCA. The overall risk for cancer after the GCA diagnosis was not increased (SIR 0.98; 95% CI 0.81 - 1.17). However, there was an increased risk for myeloid leukemia (2.31; 95% CI 1.06 - 4.39) and a reduced risk for breast cancer (0.33; 95% CI 0.12 - 0.72) and upper gastrointestinal tract cancer (0.16; 95% 0.004- 0.91). Rates of other site-specific cancers were not different from expected.CONCLUSION: In this Swedish population-based cohort of GCA, the overall risk for cancer was not increased compared to the background population. However, there was an increased risk for leukemia and a decreased risk for breast and upper gastrointestinal tract cancer.
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41.
  • Stamatis, Pavlos, et al. (författare)
  • Pathogenesis of giant cell arteritis with focus on cellular populations
  • 2022
  • Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Giant cell arteritis (GCA), the most common non-infectious vasculitis, mainly affects elderly individuals. The disease usually affects the aorta and its main supra-aortic branches causing both general symptoms of inflammation and specific ischemic symptoms because of the limited blood flow due to arterial structural changes in the inflamed arteries. The pathogenesis of the GCA is complex and includes a dysregulated immune response that affects both the innate and the adaptive immunity. During the last two decades several studies have investigated interactions among antigen-presenting cells and lymphocytes, which contribute to the formation of the inflammatory infiltrate in the affected arteries. Toll-like receptor signaling and interactions through the VEGF-Notch-Jagged1 pathway are emerging as crucial events of the aberrant inflammatory response, facilitating among others the migration of inflammatory cells to the inflamed arteries and their interactions with the local stromal milieu. The increased use of checkpoint inhibitors in cancer immunotherapy and their immune-related adverse events has fed interest in the role of checkpoint dysfunction in GCA, and recent studies suggest a dysregulated check point system which is unable to suppress the inflammation in the previously immune-privileged arteries, leading to vasculitis. The role of B-cells is currently reevaluated because of new reports of considerable numbers of plasma cells in inflamed arteries as well as the formation of artery tertiary lymphoid organs. There is emerging evidence on previously less studied cell populations, such as the neutrophils, CD8+ T-cells, T regulatory cells and tissue residing memory cells as well as for stromal cells which were previously considered as innocent bystanders. The aim of this review is to summarize the evidence in the literature regarding the cell populations involved in the pathogenesis of GCA and especially in the context of an aged, immune system.
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42.
  • Tabakovic, Dennis, et al. (författare)
  • High risk of stroke in ANCA-Associated vasculitis-a population-based study
  • 2023
  • Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 62:8, s. 2806-2812
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To determine the incidence rate, predictors and outcome of stroke in a population-based cohort of individuals with ANCA-Associated vasculitis (AAV). Methods: The study included 325 patients diagnosed with AAV from 1997 through 2016 in a defined geographic area of Sweden. Patients who suffered a stroke were identified from Riksstroke, a national Swedish stroke register established in 1994, and the Skåne Healthcare Register (SHR), which includes data for all inhabitants of Skåne since 1998. Case record review was carried out to confirm the diagnosis of stroke in AAV patients identified in the SHR. The incidence rate of stroke was calculated per 1000 person-years of follow-up. Using data from the Swedish general population, the standardized incidence ratio (SIR) of stroke was estimated. Cox regression analysis was utilized to investigate survival and predictors of stroke. Results: Twenty-five subjects (8%) suffered a stroke during 2206 person-years of follow-up. The incidence rate of stroke in AAV was 11.3/1000 person-years (95% CI 6.9, 15.8). Patients with AAV showed an increased risk of stroke compared with the general population [SIR 1.85 (95% CI 1.27, 2.59)], with a greater risk for those <65 years of age [SIR 3.19 (95% CI 1.53, 5.88)]. Higher platelet count at AAV diagnosis was an independent predictor of stroke [hazard ratio 1.14 (95% CI 1.00, 1.29)]. There were no differences in survival or other outcome measures between AAV patients with and without stroke. Conclusions: The incidence rate of stroke in AAV is higher than in the general population. High platelet count at AAV diagnosis was associated with an increased risk of stroke.
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43.
  • Teixeira, Vitor, et al. (författare)
  • Efficacy and safety of rituximab in the treatment of eosinophilic granulomatosis with polyangiitis
  • 2019
  • Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Eosinophilic granulomatosis with polyangiitis (EGPA) is a subset of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis with distinct pathophysiological mechanisms, clinical features and treatment responses. Rituximab is a licensed therapy for granulomatosis with polyangiitis and microscopic polyangiitis but there is limited experience of rituximab in EGPA. Methods EGPA patients from a tertiary centre who received rituximab for mostly refractory EGPA or in whom cyclophosphamide was contra indicated were studied. A standardised dataset was collected at time of initial treatment and every 3 months for 24 months. Response was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and partial response as ≥50% reduction in BVAS from baseline. Remission was defined as a BVAS of 0 on prednisolone dose ≤5 mg. Results Sixty-nine patients (44 female) received rituximab between 2003 and 2017. Improvement (response and partial response) was observed in 76.8% of patients at 6 months, 82.8% at 12 months and in 93.2% by 24 months, while relapses occurred in 54% by 24 months, with asthma being the most frequent manifestation. The median BVAS decreased from 6 at baseline to 1 at 6 months, and 0 at 12 and 24 months. Prednisolone dose (mg/day, median) decreased from 12.5 to 7, 7.5 and 5 at 6, 12 and 24 months, respectively. ANCA positive patients had a longer asthma/ear, nose and throat (ENT) relapse-free survival time and a shorter time to remission. Discussion Rituximab demonstrated some efficacy in EGPA and led to a reduction in prednisolone requirement, but asthma and ENT relapse rates were high despite continued treatment. The ANCA positive subset appeared to have a more sustained response on isolated asthma/ENT exacerbations.
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44.
  • Thalen, Michaela, et al. (författare)
  • Epidemiology and clinical characteristics of biopsy-confirmed adult-onset IgA vasculitis in southern Sweden
  • 2024
  • Ingår i: RMD Open. - 2056-5933. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Immunoglobulin A vasculitis (IgAV) is the most prevalent primary childhood vasculitis in Sweden, but is considerably rarer in adults. This study aims to describe the epidemiology, clinical characteristics and renal outcome of adult-onset IgAV in Skåne, Sweden. Methods The study area consisted of Skåne, the southernmost region of Sweden, with a population ≥18 years of 990 464 on 31 December 2010. Adult patients assigned the International Classification of Diseases-10 code for IgAV (D69.0) from 2000 through 2019 were retrospectively identified in a population-based database. Medical records were reviewed to validate the diagnosis of IgAV and extract data. Only patients with clinical manifestations of IgAV and biopsy-confirmed disease were included. The annual incidence and point prevalence of biopsy-confirmed IgAV were estimated. Results Fifty-nine patients (19 women) were classified as having adult-onset IgAV. The incidence was 3 per 1 000 000 and was higher among men than women (4 vs 2/1 000 000, p=0.004). Ninety-seven per cent of patients presented with non-thrombocytopenic purpura, 78% with renal involvement, 59% with arthritis/arthralgia and 39% with gastrointestinal symptoms. Fifteen per cent developed chronic kidney disease stage ≥G3 a and one patient progressed to end-stage kidney disease during follow-up. Conclusion Adult-onset IgAV is rare in southern Sweden with the incidence higher in men than in women. IgAV frequently affects the kidneys and leads to chronic kidney disease in adults, although the long-term renal outcome appears favourable compared with other small-vessel vasculitides affecting the kidneys.
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45.
  • Turkiewicz, Aleksandra, et al. (författare)
  • Cardiovascular drug treatment, statins and biopsy-confirmed giant cell arteritis : a population-based case-control study
  • 2020
  • Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 6:2
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine whether exposure to cardiovascular medications and statins is associated with increased risk of giant cell arteritis (GCA). DESIGN: The population-based case-control study comprised a cohort of patients with biopsy-confirmed GCA linked to the Swedish Prescribed Drug Register to identify all exposure to drugs prior to diagnosis of GCA. Ten controls per GCA case, matched for age, sex and residential area, were included. Using corresponding Anatomical Therapeutic Chemical codes, ACE inhibitors, angiotensin II receptor blockers, beta-blocking agents, calcium antagonists, diuretics, statins and cardiac therapy drugs were investigated from July 1, 2005 to the diagnosis/index date. A conditional logistic regression model was fitted adjusted for income, education level and marital status. We repeated the analyses including only new drug users excluding those with any prescription during the year from July 1, 2005 to July 1, 2006. RESULTS: 574 cases (29% men) of diagnosed GCA and 5740 controls (29% men) were included. The mean age at diagnosis is 75 years (SD 8). Of the GCA cases, 71% had at least one dispensation of a cardiovascular drug prior to the index date, compared to 74% of controls. The ORs for the association of target drug exposure with GCA were <1 for most drugs, but close to 1 in the analysis of new users. Statins were consistently associated with lower risk of GCA, OR 0.74 (95% CI 0.61 to 0.90). CONCLUSION: Statins may be associated with lower risk of incident biopsy-confirmed GCA. No association was evident for other studied drugs.
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46.
  • Watts, Richard A., et al. (författare)
  • Global epidemiology of vasculitis
  • 2022
  • Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4790 .- 1759-4804. ; 18:1, s. 22-34
  • Forskningsöversikt (refereegranskat)abstract
    • The many forms of vasculitis are characterized by inflammation of blood vessels, leading to potentially long-term sequelae including vision loss, aneurysm formation and kidney failure. Accurate estimation of the incidence and prevalence has been hampered by the absence of reliable diagnostic criteria and the rarity of these conditions; however, much progress has been made over the past two decades, although data are still lacking from many parts of the world including the Indian subcontinent, China, Africa and South America. Giant cell arteritis occurs in those aged 50 years and over and seems to mainly affect persons of northern European ancestry, whereas Takayasu arteritis occurs mainly in those aged under 40 years. By contrast, Kawasaki disease mainly occurs in children aged under 5 years and is most common in children of Asian ancestry, and IgA vasculitis occurs in children and adolescents. Although much less common than giant cell arteritis, the different forms of antineutrophil cytoplasmic antibody-associated vasculitis are being increasingly recognized in most populations and occur more frequently with increasing age. Behçet syndrome occurs most commonly along the ancient silk road between Europe and China. Much work needs to be done to better understand the influence of ethnicity, geographical location, environment and social factors on the development of vasculitis.
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47.
  • Wiberg, Frans, et al. (författare)
  • Evaluation of revised classification criteria for giant cell arteritis and its clinical phenotypes
  • 2022
  • Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:1, s. 383-387
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: GCA is a systemic vasculitis of the elderly, viewed by many as a disease with multiple and overlapping clinical phenotypes. Retrospective studies have shown differences in clinical presentation between these phenotypes. To reflect the heterogeneity of GCA and novel diagnostic methods, new classification criteria have been proposed. Methods: This is a retrospective study of newly diagnosed patients with GCA at the outpatient rheumatology clinics at Skåne University Hospital (Malmö and Lund) between 2012 and 2018. All patients were evaluated using two sets of classification criteria, the ACR classification criteria from 1990 and a proposed revision of these criteria requiring objective findings (positive biopsy or imaging) for classification. Patients were further classified as one of four widely used clinical phenotypes. Results: A total of 183 patients with a new diagnosis of GCA were identified. The diagnosis was confirmed by one or two experienced rheumatologists in 116 of these patients during a review of medical records. The ACR criteria were more sensitive than the revised criteria (93.1% vs 72.4%), but the revised criteria had higher specificity (94.0% vs 28.4%). The revised criteria tended to have higher sensitivity in the phenotype with constitutional symptoms compared with cranial GCA (P = 0.08). Conclusion: The specificity of the ACR classification criteria for GCA can be improved by using revised criteria requiring objective findings of vasculitis. In addition, the wider symptoms covered by the revised criteria may improve classification of patients with a phenotype characterized by constitutional symptoms.
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48.
  • Wilding, Anna, et al. (författare)
  • Thyroid disease in ANCA-associated vasculitis : a clinical and epidemiological study
  • 2024
  • Ingår i: RMD Open. - 2056-5933. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To describe clinical and laboratory characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and thyroid disease (TD). We also aimed to calculate incidence and identify predictors of TD in two large cohorts of patients with AAV. Methods The study comprised 644 patients with AAV in a population-based cohort from southern Sweden (n=325) and a cohort from a specialised vasculitis centre in Cambridge, UK (n=319). Diagnosis and classification of AAV and TD were confirmed by medical record review. Person-years (PY) of follow-up were calculated from AAV diagnosis to the earliest of TD, death or the end of study. Cox-regression analysis was employed to study predictors of TD. Results At AAV diagnosis, 100 individuals (15.5%, 77 females) had TD, 59 had myeloperoxidase (MPO)ANCA+ and 34 had proteinase-3 (PR3)-ANCA+. Patients with TD tended to have lower C reactive protein, lower haemoglobin and fewer constitutional symptoms. Survival and renal survival was greater in those patients with AAV with pre-existing TD. During 4522 PY of follow-up, a further 29 subjects developed TD, yielding an incidence rate of 641/100 000 PY. No analysed factor predicted de novo TD in AAV. The prevalence of TD among patients with AAV in southern Sweden was 18%. Conclusion TD is a common comorbidity in AAV, affecting nearly one in five. While TD diagnosis is more common in females and MPO-ANCA+, these factors do not predict de novo TD after initiation of AAV treatment, necessitating monitoring of all patients with AAV with respect to this comorbidity.
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