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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., Vasculitis, inflammation of the blood vessels, takes many forms and can affect every organ system, potentially causing kidney failure, vision loss and death. This Review describes current knowledge on the global incidence and prevalence patterns for various types of vasculitis., Key points Vasculitis is a group of generally uncommon diseases of generally unknown aetiology.Vasculitis mainly occurs at the ends of the age spectrum, in young children and older adults.Kawasaki disease is most common in children aged 5 years or less and occurs most commonly in Japan and in children of Southeast Asian ancestry.Giant cell arteritis is the most common form of vasculitis in elderly individuals, particularly in those of Northern European ancestry.The three types of antineutrophil cytoplasmic antibody-associated vasculitis are rare; of the three types, granulomatosis with polyangiitis is the most prevalent.Behçet syndrome has the highest prevalence along the ancient silk road, which stretches from the Mediterranean through the Middle East to East Asia.

Objectives Rituximab (RTX) is an anti-CD20 antibody that selectively depletes B cells and has emerged as a therapy for ANCA-associated vasculitis (AAV) during the past decade. This study sought to quantify and determine potential risk factors for severe infections in AAV patients treated with RTX at rheumatology clinics in Mexico City, Mexico and Lund, Sweden. Methods The study consisted of a retrospective case-record review (2005–15) with standardized data collection related to the occurrence of severe infection in 46 patients with AAV in Mexico City (n = 20) and Lund (n = 26) treated with RTX during their disease course. Median duration of follow-up from first RTX dose to death or end of study was 26 months. Results Eleven (24%) patients suffered a total of 18 severe infections (infection rate of 11.5/100 patient-years). Thirteen of the 18 infections (72%) occurred within the first year of treatment. Risk factors for severe infection were older age at RTX initiation and absence of ENT involvement at diagnosis. In multivariate analyses, age at RTX infusion was the only independent factor predicting severe infection. Four patients (9%) died during follow-up, all as a result of infection. Conclusion Severe infections are common following RTX treatment, and mortality due to infection is a major concern. Most severe infections occur within the first year of RTX treatment. The negative correlation of ENT involvement with severe infection might reflect granulomatosis with polyangiitis phenotype heterogeneity. Older age at time of RTX treatment independently predicts severe infections.

Objective To characterize the epidemiology of temporal artery biopsy-positive (TAB+) GCA, including trends in incidence, seasonal variation and prevalence in Skåne, the southernmost region of Sweden. Methods All histopathology reports of TABs from 1997 through 2019 were reviewed to identify patients diagnosed with TAB+ GCA. Incidence rates based on the 23-year period and the point-prevalence at 31 December 2014 were determined. An alternative prevalence calculation included only TAB+ GCA patients living in the study area and receiving immunosuppressant therapy on the point-prevalence date. Results One thousand three hundred and sixty patients were diagnosed with TAB+ GCA (71% female). The average annual incidence 1997–2019 was 13.3 (95% CI: 12.6, 14.0) per 100 000 inhabitants aged ≥50 years and was higher in females (17.8; 95% CI: 16.7, 18.9) than in males (8.2; 95% CI: 7.4, 9.0). The age- and sex-standardized incidence declined from 17.3 in 1997 to 8.7 in 2019, with incidence ratio (IR) of 0.98 per year (95% CI: 0.98, 0.99). A seasonal variation was observed with higher incidence during spring than winter [IR = 1.19 (95% CI: 1.03, 1.39)]. The overall point-prevalence of TAB+ GCA was 127.1/100 000 (95% CI: 117, 137.3) and was 75.5 (95% CI: 67.7, 83.3) when including only patients receiving immunosuppressants. Conclusion Over the past 2 decades, the incidence of biopsy-confirmed GCA has decreased by ∼2% per year. Still, a high prevalence of GCA on current treatment was observed. More cases are diagnosed during spring and summer than in the winter.

An international consensus on antineutrophil cytoplasm antibodies (ANCA) testing in eosinophilic granulomatosis with polyangiitis (EGPA) is presented. ANCA, specific for myeloperoxidase (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. A positive 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 identify whether a patient should be subclassified as having "vasculitic" or eosinophilic" EGPA. At present, ANCA status cannot guide treatment decisions, that is, whether cyclophosphamide, rituximab, or mepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset.

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.

Background Giant cell arteritis (GCA; sometimes referred to as temporal arteritis) and polymyalgia rheumatica (PMR) are common and interrelated inflammatory conditions that almost exclusively affect adults older than 50 years. There is a need for updated information on the epidemiology of these diseases. Objective This systematic literature review (SLR) aims to summarize current evidence regarding the global incidence and prevalence of GCA and PMR. Methodology A systematic search of PubMed and Google Scholar databases from their inception dates to July 30, 2019 for relevant publications was performed. Studies that reported incidence and/or prevalence estimates for GCA and/or PMR were identified. When there were multiple studies of the same population, the most recent estimates were used. Details on source populations and case validation were systematically reviewed. Results were tabulated per region in the world. Results Screening by 2 authors resulted in 2643 abstracts, of which 77 articles met the inclusion criteria. There were more studies on GCA compared to PMR, and more on incidence than on prevalence. Wide variations were found in study design and populations studied. Studies that included a thorough case validation tended to give lower estimates, in particular for PMR. The highest incidence per 100 000 aged ≥50 years of GCA was observed in studies from Scandinavia and the UK (14.6 to 43.6), and in Minnesota, USA (19.8 per 100 000). Corresponding estimates for Southern Europe were lower (1.1 to 11.1). Limited evidence indicates that GCA and PMR is less common in non-Caucasian populations. Prevalence estimates for PMR were ≥ 3 times higher than that of GCA in Caucasians. Conclusion This SLR provides up to date estimates of the occurrence of GCA and PMR in different populations around the world. The incidence of GCA is higher in populations of Northern European ancestry. Data on the epidemiology of PMR are more limited, with greater variation in incidence and prevalence estimates.

ObjectivesTo investigate metabolic features that may predispose to GCA in a nested case–control study.MethodsIndividuals who developed GCA after inclusion in a population-based health survey (the Malmö 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.ResultsA 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].ConclusionDevelopment 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.

Background and Aims Glucocorticoids (GC) and/or immunosuppressive agents are the mainstay of therapy for adult-onset IgA Vasculitis (IgAV), but their efficacy is often partial while their toxicity is relevant. Recently, rituximab (RTX) has been reported as a safe and effective option but only few data on renal outcome are available.1 RTX has also been used in a few cases of crescentic IgA Nephropathy (cIgAN), an IgAN subset with vasculitic lesions and poor response to conventional immunosuppressive regimens.2 We present the results of a multicentre cohort of patients with IgAV and cIgAN treated with RTX. Method The databases of 16 consorted European centres were investigated to screen for patients with adult-onset, biopsy-proven IgAV and cIgAN (crescents in ≥25% glomeruli and rapid eGFR worsening at presentation), who received RTX as induction therapy. We selected patients with active renal manifestations at the time of RTX. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS)=0 or Results We identified 38 patients with IgAV and 12 patients with cIgAN who received RTX and had active renal involvement at the time of treatment. The median age at onset was 40 years (interquartile range, IQR, 25-53) and more than two-thirds of patients were male (Table 1). The median follow-up after RTX was 41 months (IQR 18-60). Renal outcomes are reported in Table 2. At the time of treatment, 24 patients (48%) had eGFR ≥60 mL/min/1.73 m2. All had IgAV and their median BVAS was 17 (IQR 10-22). Furthermore, all had microhaematuria and proteinuria. Renal histology showed mesangial or focal endocapillary proliferation in 12/17 (71%) patients who underwent biopsy (class II-IIIA according to Pillebout3). Twenty patients (83%) achieved remission; after a median of 12 months (range 9-14), four experienced a minor relapse and one had a major relapse with significant renal disease progression. Renal function remained stable in all but two patients who developed end-stage renal disease (ESRD). Micro-haematuria subsided in 14/24 (58%) and median 24h proteinuria decreased from 1750 mg (IQR 865-3275) to 175 mg (IQR 100-800) at last follow-up (p=0.029). Of the 26 patients with eGFR Remission rate and ESRD-free survival were respectively 86% and 92% in patients with IgAV, while they were respectively 42% and 42% in cIgAN patients. Furthermore, 21/24 (87%) patients who received RTX alone or combined to glucocorticoids but not to immunosuppressive agents achieved remission and 22/24 (92%) were ESRD-free at last follow-up. Of the 26 patients receiving immunosuppressive agents, 17 (65%) obtained remission and 18 (69%) were ESRD-free at last assessment. Over the whole follow-up, only one patient reported a severe adverse effect related to RTX (pneumonia). Conclusion Renal involvement in adult-onset IgAV and cIgAN is frequently severe. RTX, combined or not with other immunosuppressive agents, may improve renal manifestations and is well tolerated. IgAV patients show higher remission rates and a longer ESRD-free survival as compared to cIgAN patients.

Objective.Patients with ANCA-associated vasculitides (AAV) exhibit higher rates of malignancy than the general population. We assessed whether the cancer risk is increased in a well-characterized population-based cohort of AAV in southern Sweden, followed for a median time of 8 years.Methods.With case record review, the outcomes and malignancy development in a cohort of 195 patients with AAV [granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA] diagnosed between 1997 and 2010 were assessed. The patients were followed until death or December 31, 2015. The age- and sex-standardized incidence ratios (SIR) were estimated using the Swedish population data as a reference.Results.During the observation period of about 1500 person-years, we found 60 cancers in 52 of the 195 patients. SIR (95% CI) was 2.8 (2.1–3.6) for cancers at all sites, 1.8 (1.3–2.5) for all cancers excluding squamous cell carcinoma (SCC), 12.9 (8.4–18.8) for SCC, 4.3 (1.4–10.0) for bladder cancer, and 7.0 (1.4–20.5) for pancreatic cancer. Cumulative doses of cyclophosphamide (CYC) < 10 g were not associated with higher incidence of cancers other than SCC (SIR 1.63, 95% CI 0.8–2.9).Conclusion.In contrast to previous publications assessing malignancy risk in patients with AAV, we show in this population-based cohort of patients a persistent increased risk for overall malignancy, bladder cancer, and pancreatic cancer as well as a markedly increased risk for SCC. There was no increase in incidence of cancers other than SCC for those treated with < 10 g CYC.

ObjectiveTo 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 75.3 yrs, 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% CI were calculated compared to the background population.Results.One hundred seven 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.

ObjectiveTo 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.

Background: Giant cell arteritis (GCA) is a systemic disease with extensive vascular involvement. There is limited and conflicting information on the relation between patient characteristics at diagnosis and future disease phenotypes. We aimed to investigate predictors of time dependent large vessel involvement (LVI) in a population-based cohort of patients with GCA. Methods: GCA patients with positive temporal artery biopsies (TAB) between 1997and 2010 were identified through a regional pathology register. A structured review of histopathology reports and relevant imaging studies was performed. Cases with LVI through July 2016 were identified. Patients were followed to first LVI, death, migration from the area or July 29, 2016. Event free survival by clinical and histopathologic features was estimated using the Kaplan-Meier method. Potential predictors of LVI were examined using Cox regression models.Results: A total of 274 patients were included. The mean age at GCA diagnosis was 75.7 years. Fifty-one patients (19 %) had documented LVI during the follow-up, corresponding to an incidence rate of 2.4/100 person-years. The median time from GCA diagnosis to the diagnosis of LVI was 4.5 years (interquartile range 0.6-7.4). Thirty-four patients had aortic involvement (67% of those with LVI; 12% of all GCA cases). Survival free of LVI was longer in patients with giant cells in the TAB (75th percentile 14.0 vs 6.7 years; p=0.014). In age-adjusted analysis, the presence of giant cells in the TAB was associated with reduced risk of LVI (hazard ratio 0.48; 95 % confidence interval 0.27-0.86). Conclusions: The negative association with giant cells in the TAB suggests that patients with LVI constitute a subset of GCA with particular disease mechanisms. This underlines the heterogeneity of GCA, which should be further explored in prospective studies.

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 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.

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.

Objective.To investigate the association between infections and the subsequent development of giant cell arteritis (GCA) in a large population-based cohort from a defined geographic area in Sweden.Methods.Patients diagnosed with biopsy-confirmed GCA between 2000 and 2016 were identified through the database of the Department of Pathology in Skåne, the southernmost region of Sweden. For each GCA case, 10 controls matched for age, sex, and area of residence were randomly selected from the general population. Using the Skåne Healthcare Register, we identified all infection events prior to patients’ date of GCA diagnosis and controls’ index date. With infection as exposure, a conditional logistic regression model was employed to estimate the OR for developing GCA. The types of infections contracted nearest in time to the GCA diagnosis/index date were identified.Results.A total of 1005 patients with biopsy-confirmed GCA (71% female) and 10,050 controls were included in the analysis. Infections were more common among patients subsequently diagnosed with GCA compared to controls (51% vs 41%, OR 1.78, 95% CI 1.53–2.07). Acute upper respiratory tract infection (OR 1.77, 95% CI 1.47–2.14), influenza and pneumonia (OR 1.72, 95 % CI 1.35–2.19), and unspecified infections (OR 5.35, 95 % CI 3.46–8.28) were associated with GCA. Neither skin nor gastrointestinal infections showed a correlation.Conclusion.Infections, especially those of the respiratory tract, were associated with subsequent development of biopsy-confirmed GCA. Our findings support the hypothesis that a range of infections may trigger GCA.

Objective To determine the incidence rate, predictors and outcome of severe infections in a population-based cohort of ANCA-associated vasculitis (AAV). Methods The study included 325 cases of AAV (152 female) diagnosed from 1997 through 2016 from a defined geographic area in Sweden. All severe infection events (requiring hospitalization and treatment with intravenous antimicrobials) were identified. The Birmingham vasculitis activity score (BVAS) was used to evaluate disease activity, and organ damage was assessed using the vasculitis damage index (VDI). Patients were followed from time of AAV diagnosis to death or December 2017. Results A total of 129 (40%) patients suffered at least one severe infection. In 2307 person-years (PY) of follow-up, 210 severe infections were diagnosed. The incidence rate of severe infections was 9.1/100 PY and was highest during the first year following AAV diagnosis at 22.1/100 PY (P Conclusion . Severe infection is a common problem in AAV, with the most important prognostic factors being older age and high disease activity at diagnosis. Severe infections are associated with permanent organ damage and high mortality.

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 ANCAand 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. Funding Agencies|Vasculitis foundation USA; Swedish Research CouncilSwedish Research CouncilEuropean Commission [K2013-52X-20307-07-3, 2018-02551]; King Gustaf Vs 80-Year Fund; Swedish Rheumatism Association; Umea University

To estimate the annual incidence rate of paediatric primary systemic vasculitis (PSV) in a defined geographical area in southern Sweden.Potential cases of PSV [IgA vasculitis (IgAV, Henoch-Schönlein purpura), Kawasaki disease (KD), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), polyarteritis nodosa (PAN), and Takayasu's arteritis (TAK)] were identified in a comprehensive regional healthcare register. The study area is Skåne, the southernmost county of Sweden (population 1.29 million; 21.4% aged18 years). Case records for children (0-17 years) assigned a diagnosis code between M300 and M319 and/or D690 were reviewed to ascertain diagnosis. Only patients diagnosed between 2004 and 2014 were included.In total, 556 patients with PSV were identified. The annual incidence rate per million children (95% confidence interval) was estimated to be 200 (183-217) for all PSV, 175.5 for IgAV (160-191), 20.1 for KD (14.9-25.4), 1.4 (0-2.8) for each of GPA and MPA, 0.7 (0-1.7) for PAN, and 0.4 (0-1.1) for each of EGPA and TAK. Among children aged10 years, 99.5% of cases were either IgAV or KD, both exhibiting a seasonal pattern paralleling infections. There were no deaths, but three cases of end-stage renal disease were noted, all in MPA.Vasculitis is relatively common during childhood. Mild cases associated with the infection season are most common in the youngest age groups, while during adolescence a substantial proportion has more severe forms of vasculitis.

Background:Evidence on the efficacy of Mepolizumab (MEPO) in Eosinophilic Granulomatosis with Polyangiitis (EGPA) is scarce [1].Objectives:To assess the efficacy and safety of MEPO in real-life clinical practice.Methods:We retrospectively included patients diagnosed with EGPA and treated with MEPO (100 or 300 mg/month). MEPO efficacy was evaluated in the first 12 months in terms of systemic disease and asthma control. The occurrence of any adverse event (AE) was recorded.Results:142 patients were included (38% males; median age 46.4 (IQR 36.7-54.4); 110 and 32 on MEPO 100 and 300 mg/month, respectively). General, ear-nose-throat, pulmonary, and neurological symptoms significantly decreased during treatment (table 1). MEPO accounted for a significant reduction in the BVAS (figure 1) and for a steroid sparing effect (figure 2). The proportion of patients with asthma attacks decreased by 90% at 12 months compared to t0, and asthma-related emergency accesses dropped from 17.4% to 2.3%. Overall, 21.1% of patients had a non-serious AE.Table 1.Control of clinical symptomsMEPO beginning (t0)3 monthsp-value(t3 vs t0)6 monthsp-value(t6 vs t0)12 monthsp-value(t12 vs t0)N obsN=142N=135N=123N=89General symptoms40 (28.2%)17 (12.6%)19 (15.5%)13 (14.6%)0.002Cutaneous manifestations13 (9.2%)6 (4.4%)0.0085 (4.1%)0.0254 (4.5%)0.180ENT manifestations106 (74.7%)52 (38.5%)44 (35.8%)29 (32.6%)Pulmonary manifestations130 (91.6%)59 (43.7%)39 (31.7%)28 (31.5%)Cardiac manifestations6 (4.2%)2 (1.5%)0.0832 (1.6%)0.08300.157Intestinal manifestations10 (7.0%)1 (0.7%)0.0054 (3.3%)0.0593 (3.4%)0.059Renal manifestations5 (3.5%)3 (2.2%)0.41400.0461 (1.1%)0.317Neurological manifestations36 (25.4%)22 (16.3%)0.01218 (14.6%)0.00310 (11.2%)0.035Figure 1.Changes in BVASFigure 2.Steroid treatmentConclusion:MEPO effectively controlled systemic and respiratory EGPA symptoms in a large European cohort, with no major safety concerns.References:[1]Wechsler et al. MEPO or Placebo for Eosinophilic Granulomatosis with Polyangiitis. NEJM. 2017Disclosure of Interests:Alessandra Bettiol: None declared, Maria Letizia Urban: None declared, Federico Alberici: None declared, Carlo Agostini: None declared, Chiara Baldini: None declared, Enrica Bozzolo: None declared, Paolo Cameli: None declared, Nunzio Crimi: None declared, Stefano Del Giacco: None declared, Allyson Egan: None declared, Georgina Espigol-Frigole Consultant of: Roche and Janssen, Mara Felicetti: None declared, Marco Folci: None declared, Paolo Fraticelli: None declared, Marcello Govoni: None declared, Anna Kernder Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Carlo Lombardi: None declared, Giuseppe Lopalco: None declared, Claudio Lunardi: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Frank Moosig: None declared, Simone Negrini: None declared, Thomas Neumann: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Giuseppe Paolazzi: None declared, paola parronchi: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Vito Racanelli: None declared, Carlo Salvarani: None declared, Maxime Samson: None declared, Jan Schroeder: None declared, Savino Sciascia: None declared, Renato A. Sinico: None declared, Benjamin Terrier: None declared, Paola Toniati: None declared, Domenico Prisco: None declared, Augusto Vaglio: None declared, Giacomo Emmi: None declared

Background:There is a paucity of information on the current phenotypes, ethnic and geographic differences of PAN. A global PAN study group has been working for clinical subphenotype and GWAS studies.Objectives:This study is aimed to look for target organ associations in PAN.Methods:PAN patients fulfilling the EMA vasculitis classification algorithm were recruited. In addition to baseline characteristics, treatment and outcome data, occurrence of any of the clinical manifestations related to PAN during disease course was recorded.Factor analysis was used to analyse target organ associations of 306 patients. Five factors were identified by factor analysis of variables sex, paediatric-onset, HBV, monogenic disease relationship, cutaneous features, musculoskeletal symptoms, constitutional symptoms and involved areas (abdominal, renal, neurologic, ENT, cardiac, pulmonary).Results:PAN cohort from 7 countries were used (Italy: n=59, Japan: n=39, Mexico: n=29, Slovenia: n=14, Sweden:11, TUR: n=106, UK: n=48). 306 (M/F: 171/135 and Caucasian 77.1%, Asian 13.4%, and Hispanic 9.5%) patients were included. 8 were HBV-related, and 22 of TUR patients had a monogenic form of disease (FMF n=15, DADA2 n=7). 21.8% of patients were cutaneous-only PAN patients. 48.4% of patients had radiologic, 64% had biopsy-proven PAN. Median age at disease onset was 40 (IQR 27.0-57.5) years. During a median 57 (16-120) months follow-up, 39 (13%) patients died.Factor analysis revealed 5 factors that explained 54.1% of the original information on the matrix as follows:Factor 1,represented the association between gastrointestinal and renal involvement, male gender and negatively associated with cutaneous features;Factor 2,the association between monogenic relationship with paediatric onset disease;Factor 3,any of musculoskeletal findings with positive constitutional symptoms;Factor 4any neurologic involvement was associated with ENT and pulmonary findings;Factor 5cardiac involvement in non-HBV patients (Table).The eigenvalues of the 5 factors were 2.034, 1.470, 1.427, 1.079 and 1.030, in decreasing order, i.e., the highest contribution to the overall variance in the matrix came from the togetherness of the 4 clinical and demographic characteristics that made up Factor 1.Conclusion:Target organ associations could support distinctive subphenotypes in PAN. Factor 1 seems the most severe form. Patients with FMF or DADA2 have distinct target organ associations. The jury is out to decide whether these patients should be classified as ‘vasculitis associated with probable etiology’ just as HBV-related-PAN. Factor 4 might define a different subphenotype (ANCA- medium vessel vasculitis?).Disclosure of Interests:Omer Karadag: None declared, Ertugrul Cagri Bolek: None declared, Shunsuke Furuta: None declared, Giacomo Emmi: None declared, ALOJZIJA HOCEVAR: None declared, Andrea Hinojosa-Azaola: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Serdal Ugurlu: None declared, Fatma Alibaz-Oner: None declared, Ayten Yazici: None declared, Luca Quartuccio: None declared, Enrica Bozzolo: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Giuseppe Alvise Ramirez: None declared, Luca Cantarini: None declared, Gina Gregorini: None declared, Jeannin Guido: None declared, Sara Monti: None declared, Eduardo Martin-Nares: None declared, Franco Schiavon: None declared, Roberto Padoan: None declared, Hajime Kono: None declared, Augusto Vaglio: None declared, Saadettin Kiliçkap: None declared, Ali İhsan Ertenli: None declared, Haner Direskeneli: None declared, Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim

ANCA-associated vasculitis (AAV) includes granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Epidemiological studies in AAV are important in understanding possible aetiologic mechanisms and facilitating healthcare planning. However, epidemiological studies present a number of challenges including clear definition of cases differentiated from other clinical disorders, and identification of cases due to the rarity of AAV. The aim of this review is to summarize different aspects on the epidemiology of ANCA-associated vasculitis from different geographical areas throughout the world. During the past three decades, development of classification criteria worldwide, including the ACR classification of 1990, the Chapel Hill consensus definitions updated in 2012 and the EMA algorithm has facilitated epidemiology studies in AAV. The available epidemiological studies reported in AAV suggest that incidence and prevalence may have increased over the past 30 years. Possible explanations for this increase may be a genuine increase in incidence, the evolution of classification criteria and the definition, and availability and wider use of ANCA serology to aid diagnosis, and greater physician awareness through education. The age-specific incidence for the whole group of AAV showed a clear increase with age. However, there has been a clear shift in the peak age at onset towards a higher age during the last 20–30 years. In addition, variation in incidence of AAV between men and women has been clearly evident in a number of epidemiological studies.

Objective.Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown.Methods.Consecutive patients from Sweden, the United Kingdom, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide (CYC), rituximab (RTX), and corticosteroids the first 3 months was registered. Outcomes up to 2 years from diagnosis included Vasculitis Damage Index (VDI), hospitalization, and cause of death.Results.Treatment data were available for 167 of 202 patients. At 2 years, 4% had no items of damage. There was a positive association between VDI score at 2 years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using CYC or RTX. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. Myeloperoxidase–antineutrophil cytoplasmic antibody positivity and lower creatinine levels decreased the odds of readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose.Conclusion.Immunosuppressive treatment with CYC or RTX in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first 3 months was associated with treatment-related damage and fatal infections.

Background: Few previous studies have examined the prevalence of giant cell arteritis (GCA). The main objective of this study is to investigate the prevalence of temporal artery positive GCA (TAB+GCA) in southern Sweden.Methods: The study area is the region of Skane in southern Sweden with a population of 1,3 million inhabitants (36% aged ⩾50 years). To be included in the study, patient should fulfil the following criteria: 1) diagnosed with TAB+GCA after 1997, 2) living in Skane at date of diagnosis and date of point prevalence (p.p.) on December 31st, 2014, and 3) on oral glucocorticosteroids (GCs) treatment at the date of p.p. (that redeemed at least one GC prescription during 12 months preceding the date of p.p.) The national Swedish prescribed drug register (SPDR) has been used to identify patients still on GC treatment. The SPDR include data on all the purchased prescriptions since July 2005 and data available through October 2015. Using the unique Swedish personal identification number (PIN), the GCA cohort has been linked to the SPDR. Accordingly, for the prevalence estimate, the numerator was all patients with TAB+GCA who fulfil the study criteria and the denominator was all people aged ⩾50 years living in Skane at date of p.p. The ATC-codes of Betamethasone, Dexamethasone, Prednisolone, Prednisone and Methylprednisolone were identified.Results: At the date of p.p. estimate a total of 631 patients were alive and living in the study area. Of them 359 patients were on GCs at date of p.p. according to the study definition. Accordingly, the p.p. of TAB+ GCA per 100 000 inhabitants aged ⩾50 years was 75.3 (95% CI 67.5-83.1); 40.5 (32.2-48.8) for men and 107 (94.2-119.9) for women. The median time of being on GCs (from time of diagnosis to date of p.p.) 2.23 years (IQR 0.96-4.40). The percentage of patients with positive TAB who were alive at date of p.p. without GC treatment was 43.1%.Conclusion: This is the first estimate of prevalence of TAB+GCA from Sweden. Our prevalence estimate takes into account that GCA may be cured with patients no longer regarded as prevalent cases.Disclosures: Lund University (Less)

Background: Infectious complications in ANCA associated vasculitis (AAV) are a major cause of morbidity and mortality. The aim of this study was to determine the incidence rates, predictors and outcome of severe infections in AAV. Methods: We conducted a population-based cohort study in Southern Sweden with 326 incident cases of AAV diagnosed between 1997 and 2016. Diagnosis of vasculitis was confirmed by case record review and patients were classified according to the European Medicines Agency algorithm. Demographics, clinical, andlaboratory data was collected from time of diagnosis and follow-up. All events of severe infection (required hospitalization and treated with intravenous antimicrobials) were identified. Vasculitis disease activity was evaluated using the Birmingham Vasculitis Activity Score (BVAS) and the extent of organ damage was assessed using the vasculitis damage index (VDI). Patients were followed from time of AAV-diagnosis to death or end of study, December 2017Results: Data on 262 patients (122 women) was collated and are presented in this report. Total time of follow-up was 1368 person-year. In total 104 (39.7%) patients experienced at least one severe infection during the follow-up, 33 (12.5%) suffered 2 infections and 14 (5%) suffered 3 severe infections or more. The incidence rate of severe infection was higher during the first year after diagnosis compared to that during the whole follow-up time (24.3/100 year vs. 7.6/100, p

Infections are associated with increased risk of MPO- but not PR3-ANCA-associated vasculitis - a population-based case-control study from southern sweden

IntroductionEosinophilic 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.MethodsEGPA 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.ResultsSixty-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.DiscussionRituximab 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.

Objective: To develop evidence-based guidelines for the management of giant cell arteritis (GCA) as a complement to guidelines in other areas of rheumatology, issued by the Swedish Society of Rheumatology. Methods: A working group selected key areas for recommendations, reviewed the available evidence, and wrote draft guidelines. These were discussed and revised according to standard procedures within the Swedish Society of Rheumatology, including a one-day meeting open to all members. For key recommendations, the quality of evidence was assessed according to GRADE. The final guidelines were approved by the Society board in March 2018. Results: The guidelines include recommendations on diagnostic procedures, pharmacological treatment, follow-up, and adjuvant treatment. Ultrasonography is complementary to temporal artery biopsy (TAB) in the diagnostic work-up. Other imaging techniques (magnetic resonance imaging and positron emission tomography/computed tomography) are important in evaluating large-vessel involvement. Glucocorticoids (oral, or intravenous in cases with ischaemic complications) remain the first line treatment for GCA. Addition of tocilizumab is recommended for patients with relapsing disease who meet five criteria, representing active disease that has been objectively verified by TAB or imaging. Tocilizumab may also be considered in patients with newly diagnosed GCA who are at major risk of severe glucocorticoid side effects. Based on current evidence, tocilizumab treatment for >1 year cannot be recommended. Conclusion: These guidelines are based on current evidence and consensus within Swedish rheumatology. Following major developments in diagnostics and treatment of GCA, such guidelines are important for clinical practice, and should be updated on a regular basis.

Giant cell arteritis (GCA) is a systemic disease with extensive vascular involvement. The aim of this study was to investigate the cumulative incidence of large vessel involvement (LVI) in GCA, the distribution of vessels involved, and predictors for LVI.Patients with biopsy-proven GCA in a defined area in southern Sweden, diagnosed between 1997 and 2010, were identified through the register of the regional Department of Clinical Pathology. A structured review of all medical records and imaging and histopathology reports was performed. Imaging studies for an age- and sex-matched reference cohort were also reviewed.A total of 164 patients with GCA were investigated, of whom 24 (15%) had LVI. LVI manifestations were detected a median of 3.7 [interquartile range (IQR) 0.7-7.5] years after GCA diagnosis. Aortic involvement was found in 16 patients (10%), mainly aneurysms/ectasias of the thoracic aorta. Two patients had aortic dissections. Fourteen patients had tributary involvement. In the reference population, the cumulative incidence of LVI overall was 10.8% and aortic involvement was found in 5.4%. The presence of giant cells in the biopsy was significantly less frequent among GCA patients with LVI (23% vs. 52%; p = 0.01), and a presentation with polymyalgia rheumatica (PMR) was more frequent (44% vs. 20%, p = 0.01).The estimated incidence of LVI, detected by imaging in a clinical setting, was higher among patients with GCA than the reference population. The aorta was the most commonly affected vascular territory. The negative association with giant cells may suggest particular mechanisms in this subset of GCA.

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.

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 Skåne, 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 β-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 β-adrenergic inhibitors compared with patients without visual complications.

Background:Etiology and pathogenesis of ANCA-associated vasculitis (AAV) is multifactorial and understanding of the processes leading from a healthy immune system to autoimmunity and on to debut of symptoms in AAV is rudimentary.Objectives:To identify inflammatory proteins related to the early processes preceding AAV development, and potential novel biomarkers, using large-scale protein analysesMethods:The Swedish National Patient Register of in-patient carevand the Swedish Cause of Death Register with discharge diagnosis from ICD-9 and-10 for AAV were co-analysed with the registers of 4 different blood biobanks to identify AAV individuals with available samples predating onset of symptom. Of the pre-AAV cases 86 (36 male, 50 female; mean age (SD); 51.9 (16.9) years) were identified with at least one plasma or serum sample (28 plasma, and 100 serum) pre-dating symptom onset (mean (SD); -4.3 (3.1) years), and 14 had 2-3 samples. Serum and plasma control samples matched for sex, age and sampling date were identified (n=198; 82 male, 116 female; mean age (SD); 51.9±15.9 years). The samples were analysed for levels of 92 proteins using proximity extension assay (OLINK inflammation panel, SciLifeLab, Uppsala, Sweden). Data were analysed using routine statistical methods, random forest and Partial Least square-discriminant analysis (PLS-DA).Results:As previously described for the assay significant difference between plasma and serum samples were observed both in pre-AAV individuals and controls. In pre-AAV plasma samples significantly increased concentrations of interleukin (IL)-2, chemokine ligand (CCL)-4, fibroblast growth factor (FGF)21, IL-4 and CCL20 were found closer to symptom onset, ( 5 years) and compared with controls. In serum tumor necrosis factor receptor superfamily member (TNFRSF)9, CXCL9, osteoprotegerin and vascular endothelial growth factor-A were significantly increased 5 years) and compared with controls. PLS-DA score scattered plot separated the pre-AAV individuals from healthy controls (R2=0.26), with significantly increased levels of CCL23, CXCL5, and matrix metalloproteinases-1 (MMP-1),transforming growth factor-ß, orosomucoid, en-rage (S100A12) and IL-7 and decreased FGF-19 level in serum. Binary logistic regression analyses comparing tertiles for these proteins confirmed significantly increased odds ratios for disease development of CCL23, CXCL5 and MMP-1. The findings were confirmed in random forest analysis where these factors were among the 20 most discriminatory factors between pre-symptomatic AAV and controls.Conclusion:In serum samples collected years before symptom onset of AAV, proteins involved in immune system activation were increased, suggesting that the inflammatory process is initiated long before clinical manifestations of the disease appear. These findings propose the elevated proteins as novel biomarkers for disease progression.References:[1]Watts et al. Ann Rheum Dis 2007;66:222-22Acknowledgments:Vasculitis Foundation, USADisclosure of Interests:Ewa Berglin: None declared, Anders Esberg: None declared, Johanna Dahlqvist: None declared, Johanna Sjöwall: None declared, Anders Lundquist: None declared, Kristina Lejon: None declared, Ingegerd Johansson: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Solbritt Rantapää Dahlqvist: None declared

Background:Presence of anti-neutrophil cytoplasmatic autoantibodies (ANCA) is important for the diagnosis of ANCA-associated vasculitis (AAV) and reflects on-going immune processes. The timing of the antibody development and its contribution to disease is not well established.Objectives:To investigate the presence of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA in blood samples collected from healthy individuals who subsequently developed AAV.Methods:The Swedish National Patient Register of inpatient care and the Swedish Cause of Death Register were used to identify individuals assigned ICD codes for AAV (1) in the discharge summary or cause of death, respectively. The resulted cohort was then linked to the registers of 4 different biobanks to identify those with available predating blood samples. Diagnoses of AAV were confirmed and time point for onset of symptoms was identified by reviewing all available case records (1); 68 were classified as granulomatosis with polyangiitis (GPA), 14 as microscopic polyangiitis (MPA), and 4 as eosinophilic GPA (EGPA). The 86 cases (36 males, 50 females) had a mean (SD) age of 51.9 (16.9) years at sampling, with ≥1 sample (26% plasma, 74% serum samples). The sampling time point before onset of symptoms was mean (SD); 4.4 (3.1) years. Serum and plasma control samples (n=198; 82 males, 116 females; mean age (SD); 52.0 (16.5) years) were identified and matched for sex, age and date of sampling. The samples were first screened for ANCA using high sensitive ELISA (ORGANTEC diagnostika, Germany) and samples close to or above cut-off level were further analysed for capture PR3- and capture MPO-ANCA (ELISA; SVAR Life Science, Sweden). For each case one control sample was included for the ANCA specificity tests. Statistical calculations were performed using SPSS software.Results:In ANCA-screen 36.0% of the cases and 2.6 % of controls tested positive (pConclusion:The production of both PR3 and MPO-ANCA starts already years before onset of symptoms of AAV. Presence of MPO-ANCA appeared closer to symptom onset and with more severe disease presentation. Differences in the disease phenotype and disease severity were evident between the two ANCA serotypes.References:[1]Watts et al. Ann Rheum Dis 2007;66:222-22Acknowledgments: :Vasculitis Foundation, USADisclosure of Interests:Ewa Berglin: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Johanna Dahlqvist: None declared, Catharina Eriksson: None declared, Johanna Sjöwall: None declared, Solbritt Rantapää Dahlqvist: None declared

Background:Giant cell arteritis (GCA) is the most common form of systemic vasculitis in adults. GCA is often associated with comorbidities related to the disease itself or caused by its treatment, here: mainly glucocorticosteroids. Since 2017, tocilizumab (TCZ) is approved for the treatment of GCA, but its uptake and treatment outcomes in clinical practice remain to be characterized.Objectives:To describe characteristics of GCA patients treated with tocilizumab (TCZ) in clinical practice, to evaluate the use of prednisolone up until and following TCZ treatment start, and to describe the TCZ treatment duration.Methods:We linked together the Swedish Rheumatology Quality Register (SRQ), the national Prescribed Drug register, and national Patient register, covering data from July 2009 until July 2019. Through these linkages, we identified GCA patients treated with TCZ including start and discontinuation, their comorbidities and use of other medications. TCZ treatment durations were evaluated through survival probability curves.Results:We identified 468 patients with GCA treated with TCZ, before and after its formal approval for GCA, Table 1. Over calendar time, the proportion who started TCZ as first ever bDMARD increased, as did the mean age at start of TCZ. The pattern of co-morbidities and health care utilisation demonstrated substantial burden from, e.g., diabetes and infections (Table). Patients starting treatment with TCZ were characterized by an increasing average dose of prednisolone during the last 1.5 years before TCZ start. Thereafter, prednisolone use declined substantially, from a mean of 15 mg/day in the six months before the start of TCZ to 6 mg/day 1 year after its start (Figure 1). Analysis of the duration of TCZ treatment (from start until discontinuation) suggested that at one year, two thirds of patients were still on treatment (Figure 2).Table.Swedish GCA patients starting treatment with tocilizumab July 2009 - Nov 2019.July 2009 -July 2015July 2016 - July 2017July 2017 -July 2018July 2018 - Nov 2019Patients8914014099Female64%77%73%71%Age, mean (sd)67 (7.9)68 (8.8)69 (8)70 (7.8)Previous use of bDMARDs27%21%11%11%Hospitalisations most recent 5 years, mean (sd)3.9 (4.2)3.2 (2.6)2.9 (2.5)3.3 (3)Co-morbidities, most recent 5 years:Chronic obstructive pulmonary disease6%2%4%3%Ischemic heart disease12%7%14%11%Diabetes mellitus, type 1&234%26%26%26%Fractures (any location)15%14%11%10%Knee/hip replacement7%10%7%8%Myocardial infarction2%1%4%3%Stroke2%4%2%5%Hospitalisation listing infection39%40%39%37%Figure 1.Average daily dose of prednisolone before and after* start of tocilizumab, based on cumulative dose every 6 months. *The average daily dose of prednisolone after the start of TCZ is calculated only among patients who were still on treatment at the end of each period (351 patients in the first 6 months, 251 in 6m-1y, 161 in 1 – 1.5 y, 95 in 1.5 – 2y).Figure 2.Kaplan-Meier curve for tocilizumab in GCA by time since treatment start.Conclusion:Patients treated with TCZ for GCA in clinical practice are characterized by a significant burden of co-morbidities, many of which may be related to prolonged use of glucocorticosteroids. This study confirms a marked reduction in the use of oral prednisolone following treatment with TCZ, and demonstrates that in a majority of patients in clinical practice, treatment with TCZ for GCA is extended beyond one year. Future analyses will evaluate the association of these observed treatment patterns with the level of GCA disease control, co-morbidities and quality of life, over time.Acknowledgments:These analyses was partly funded through an agreement between Roche and Karolinska Institutet.Disclosure of Interests:Daniela Di Giuseppe: None declared, Ann Knight: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Carl Turesson Grant/research support from: Unrestricted grant from Bristol-Myers Squibb, Consultant of: Roche, Speakers bureau: Abbvie, Bristol Myers-Squibb, Pfizer, Roche, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma

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

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.

The aim was to describe the clinical characteristics and epidemiology of hypocomplementaemic urticarial vasculitis (HUV; anti-C1q vasculitis) in two geographically defined areas of Sweden.In the health-care districts surrounding Skåne University Hospital (mean population 950 560) and Linköping University Hospital (mean population 428 503), all incident cases of HUV residing within the study areas at the onset of disease were identified during the years 2000-15. The diagnosis of HUV was confirmed by review of medical records. Only patients meeting the proposed diagnostic HUV criteria and/or the 2012 Chapel Hill consensus definitions in combination with an ever-positive anti-C1q antibody test were included.Sixteen patients (14 females) were identified during the study period. The median (interquartile range) age at diagnosis was 51 (40.7-56.7) years. Median (interquartile range) time of follow-up from diagnosis to 31 December 2015, or death, was 94 (46.5-136.2) months. The most frequent manifestations at diagnosis were urticaria (100%), arthritis (88%), followed by biopsy-proven glomerulonephritis (19%), episcleritis/scleritis (19%) and recurrent abdominal pain (13%). The annual incidence rate per million inhabitants was estimated as 0.7 (95% CI: 0.4, 1.1). Sixty-three per cent suffered from pulmonary disease at the last follow-up. Two patients died during the follow-up period. One patient underwent lung transplantation, and two patients proceeded to end-stage renal disease. The point prevalence on 31 December 2015 was 9.5/million (95% CI: 4.5, 14.5).Hypocomplementaemic urticarial vasculitis constitutes a rare, but not always benign condition. Renal and lung manifestations were severe in some cases, highlighting the need for careful screening and monitoring of this potentially serious condition.

Objective.To study the efficacy and safety of anti-CD52 antibody (alemtuzumab) in the treatment of refractory and relapsing Behçet disease (BD).Methods.Thirty-two patients (22 women) with BD received 60 courses of alemtuzumab between 1994 and 2013. Three-dose regimens were used: 134 mg in 21 courses (Group 1), 95 mg in 18 courses (Group 2), and 60 mg in 21 courses (Group 3). Immunosuppressive drugs were stopped at the time of alemtuzumab, and prednisolone was reduced according to clinical response. Treatment response was assessed by clinical status, inflammatory activity, prednisolone dose, and the need for subsequent immunosuppressive drugs and disease relapse.Results.After the first alemtuzumab course, 27 of 32 patients (84%) achieved partial or complete remission (CR). Fifty of 60 courses (83%) resulted in remission (66% CR) without differences in remission rates between dosing regimens. Profound lymphocyte depletion occurred after all courses. Relapse-free survival rates were 83.6% at 6 months and 52.8% at 12 months, and were higher among Group 1 patients (Group 1: 100% and 77.8%, Group 2: 81.3% and 37.5%, and Group 3: 65.0% and 37.1%, p < 0.001). Mild to moderate infusion reactions occurred after 16 courses (27%). Eight patients (25%) developed symptomatic thyroid disease.Conclusion.Alemtuzumab led to remission in the majority of patients with difficult-to-treat BD. Relapse was common and may be associated with lower dosing. Adverse events included infusion reactions and new autoimmunity. Achieving complete lymphocyte depletion did not affect the remission rate or duration.

It is now 25 years since the first European studies on vasculitis--the anti-neutrophil cytoplasmic antibody (ANCA) standardization project. Over that period of time, there have been major developments in the classification of the vasculitides, which has permitted the conduct of high-quality epidemiology studies. Studying the epidemiology of rare diseases such as the ANCA-associated vasculitides (AAV) poses considerable challenges to epidemiologists. The first is the need for a clear definition of a case with good differentiation from similar disorders. The second is case capture. The vasculitides are rare, and therefore, a large population is required to determine the incidence and prevalence, and this poses questions of feasibility. A large population increases the risk of incomplete case detection but permits a reasonable number of cases to be collected in a practicable time frame, whereas a smaller population requires a much longer time frame to collect the necessary cases, which may also not be feasible. Statistical methods of capture-recapture analysis enable estimates to be made of the number of missing cases. The third is case ascertainment. The AAV are virtually always managed in secondary care, and therefore, hospital-based case ascertainment may be appropriate. Fourthly, the rarity of the conditions makes prospective case-control studies investigating risk factors difficult to conduct because the population size required to achieve statistical confidence is in excess of that which is readily available. Thus, much of the data on risk factors are derived from retrospective studies with inherent potential bias.

Background Few studies have examined predictors of giant cell arteritis (GCA). A negative association between body mass index (BMI) and development of GCA has been reported (1, 2). There is limited information on the impact of smoking and socioeconomic factors on the risk of GCA. Objectives To further investigate the relation between BMI and GCA, and also assess the role of smoking and socioeconomic factors in this context. Methods Two population based health-surveys, The Malmo Preventive Medicine Program (MPMP) and the Malmo Diet Cancer Study (MDCS), performed in the same catchment area between 1974 and 1996. In the MPMP, 33346 subjects (33% women), and in the MDCS, 30447 subjects (60% women) were included. Both surveys included standard physical examinations and self-administered questionnaires. Subjects were classified as blue-collar workers or white-collar workers, using the Socioeconomic Index (SEI) based on self-reported job titles in the Swedish national censuses. Individuals who developed GCA after inclusion in the two health surveys were identified by linking the health survey databases to local and national patient registers. A structured review of the medical records was performed. Four controls for every validated case, matched for sex, year of birth and year of screening, were selected from the corresponding databases. Potential predictors of GCA were examined in conditional logistic regression models. This is an extension of a previous study, adding more incident cases (2). Results A total of 138 cases with a confirmed clinical diagnosis of GCA (median age at diagnosis 71 years; 72% female; 66% biopsy-positive; 94% fulfilled the ACR criteria for GCA) were included. The median time from screening to diagnosis was 15 years (range 0–32). The cases who subsequently developed GCA had significantly lower BMI at baseline (24.3 vs 25.3 kg/m2, odds ratio (OR) 0.91 per kg/m2; 95% confidence interval (CI) 0.86–0.97) and were less likely to be current smokers when entering the health survey (OR 0.56; 95% CI 0.33–0.94). There was no difference in the proportion with low level of formal education between cases and controls (OR 1.27; 95% CI 0.66–2.44). Blue-collar workers tended to be less likely to develop GCA than white-collar workers (OR 0.53; 95% CI 0.28–1.00). This association reached statistical significance in women (OR 0.32; 95% CI 0.13–0.81) but not in men (OR 0.87; 95% CI 0.35–2.16). In multivariate analysis, including both variables and the SEI, the impact of BMI (OR 0.85; 95% CI 0.74–0.96) and smoking (OR 0.26; 95% CI 0.12–0.60) remained significant. Conclusions In this study, the negative association between BMI and subsequent GCA was confirmed, and there was an independent protective effect of smoking. Socioeconomic status, reflected by occupation later in life rather than level of formal education, may also influence the risk of developing GCA. References Larsson K et al Ann Rheum Dis 2006; 65:529–532. Jakobsson K et al Rheumatology 2015; 54:433–440. Disclosure of Interest None declared

Background Giant cell arteritis (GCA) is the most common vasculitis among patients age >50 years in north European countries. Although ethnic factors and age clearly play a role, the etiology of the disease is largely unknown. Studies of predictors are therefore of major interest. A meta-analysis of observational studies demonstrated that patients with GCA have a significantly reduced prevalence of diabetes at the time of diagnosis (1). Objectives To investigate metabolic features prior to diagnosis of 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=33346) 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. Fasting blood samples had been obtained and analyzed using standard methods as part of the health survey. Potential predictors of GCA were examined in conditional logistic regression models. Results There were 76 cases with a confirmed clinical diagnosis of GCA (61% female; 65% biopsy positive; 95% fulfilled the ACR criteria for GCA). The mean age at diagnosis was 70 years, and the median time from screening to diagnosis was 20 years (range 2–32). The cases had significantly lower fasting blood glucose (fB-glucose) at baseline screening compared to controls [mean 4.7 vs 5.1 mmol/l, odds ratio (OR) 0.49 per mmol/l; 95% confidence interval (CI) 0.30–0.79]. Current smokers had a reduced risk of GCA (OR 0.35; 95% CI 0.18–0.70). The negative association between baseline fB-glucose and GCA remained significant in analysis adjusted for smoking (OR 0.46 per mmol/l; 95% CI 0.28–0.76). Both cholesterol (mean 5.6 vs 6.0 mmol/l) and triglyceride levels (median 1.0 vs 1.2 mmol/l) were lower among the cases at baseline screening, with significant negative associations with subsequent GCA in crude and smoking-adjusted (ORs with 95% CIs 0.66 per mmol/l; 0.46–0.94 for cholesterol, 0.33 per mmol/l; 0.16–0.69 for triglycerides) models. The effect of fB-glucose on the risk of GCA was stronger in men compared to women (smoking-adjusted ORs per mmol/l 0.11; 95% CI 0.03–0.37, and 0.77; 95% CI 0.50–1.18, respectively). Apart from this, results were similar in women and men. Conclusions Development of GCA was associated with lower fB-glucose, lower cholesterol and triglyceride levels at baseline, all adjusted for current smoking. These findings are in line with the previous findings of a reduced prevalence of diabetes mellitus at the time of diagnosis of GCA (1). This suggests that metabolic factors influence the development of GCA. References Ungprasert P et al Mod Rheumatol. 2016;26(3):410–414. Disclosure of Interest None declared

OBJECTIVE: Adult-onset IgA vasculitis (Henoch-Schönlein) (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. METHODS: In 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. RESULTS: Twenty-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 < 0.0001), CRP level (P = 0.0005), BVAS (P < 0.0001), and prednisone dose (P < 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. CONCLUSION: Our data suggest that RTX is an effective and safe therapeutic option for adult-onset IgAV.

Objective.To describe pulmonary involvement at time of diagnosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), as defined by computed tomography (CT).Methods.Patients with thoracic CT performed on or after the onset of AAV (n = 140; 75 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 nodular 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 occurs exclusively among patients with PR3-ANCA while UIP were mainly seen in those with MPO-ANCA. These findings may have important implications for the investigation, management, and pathogenesis of AAV.

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.

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 Skåne 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 Skåne 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.

Involvement of large arteries is well-documented in giant-cell arteritis (GCA), but the risk for cardiovascular events is not well-understood.To evaluate the risks for incident myocardial infarction (MI), cerebrovascular accident (CVA), and peripheral vascular disease (PVD) in individuals with incident GCA in a general population context.Observational cohort study.U.K. primary care database.3408 patients with incident GCA and 17 027 age- and sex-matched reference participants without baseline cardiovascular disease (MI, CVA, or PVD).Diagnoses of GCA, outcomes, and cardiovascular risk factors were identified from electronic medical records. One combined and 3 separate cohort analyses were conducted for the outcomes of MI, CVA, and PVD. The association of GCA with study outcomes is expressed with hazard ratios (HRs) with 95% CIs after adjustment for potential cardiovascular risk factors.Among 3408 patients with GCA (73% female; mean age, 73 years), the incidence rates of MI, CVA, and PVD were 10.0, 8.0, and 4.2 events per 1000 person-years, respectively, versus 4.9, 6.3, and 2.0 events per 1000 person-years, respectively, among reference participants. The HRs were 1.70 (95% CI, 1.51 to 1.91) for the combined outcome, 2.06 (CI, 1.72 to 2.46) for MI, 1.28 (CI, 1.06 to 1.54) for CVA, and 2.13 (CI, 1.61 to 2.81) for PVD. The HRs were more pronounced in the first month after GCA diagnosis (combined HR, 4.92 [CI, 2.59 to 9.34]; HR for MI, 11.89 [CI, 2.40 to 59.00]; HR for CVA, 3.93 [CI, 1.76 to 8.79]; HR for PVD, 3.86 [CI, 0.78 to 19.17]).Information on temporal arterial biopsies was not available, and there was a substantial amount of missing data on cardiovascular risk factors.Giant-cell arteritis is associated with increased risks for MI, CVA, and PVD.National Institute of Arthritis and Musculoskeletal and Skin Diseases.