The one-year infection risk among patients diagnosed with giant cell arteritis: use of antibiotics and hospitalisations.

OBJECTIVES: Patients with giant cell arteritis (GCA) primarily have their infections managed by primary care providers and hospitalisation is rarely necessary. Existing studies in GCA focus on infection-related hospitalisations only, whereas the use of antibiotic prescriptions is largely unknown. This study aims to examine the one-year overall infection risk among patients with GCA. METHODS: This nationwide observational cohort study included patients aged ≥50 years with a first-time GCA diagnosis in the Danish National Patient Registry (1996-2022). Patients with GCA were matched 1:10 by sex and date of birth with general population individuals and followed from date of diagnosis. Overall infections were defined as redeemed antibiotic prescriptions or infection-related hospitalisations. Utilising a pseudo-observation approach, we assessed 1-year cumulative incidence proportions (CIP), risk differences (RD), and relative risks (RR) of infections. RESULTS: The study included 17 773 incident patients with GCA and 177 730 reference individuals. Patients with GCA had a 1-year CIP of 52.4% (95% CI: 51.7-53.2) for overall infections and 17.6% (95% CI: 17.1-18.2) for infection-related hospitalisations. Compared with the reference cohort, patients with GCA had a RR of 1.40 (95% CI: 1.38-1.42) for overall infections and 2.71 (95% CI: 2.61-2.82) for infection-related hospitalisations. Additionally, higher cumulative glucocorticoid doses, advanced age (≥70 years), and higher comorbidity were associated with an increased risk of infections among patients with GCA. CONCLUSIONS: The use of antibiotic prescriptions and infection-related hospitalisations in the first year after a GCA diagnosis is high compared with the background population. The cumulative glucocorticoid dose is associated with the infection risk.

Long-term risk of heart failure and other adverse cardiovascular outcomes in primary Sjögren's syndrome.

BACKGROUND: Data on long-term cardiovascular outcomes in primary Sjögren's syndrome (PSS) are scarce. OBJECTIVES: We aim to investigate the long-term rate of incident heart failure (HF) and other adverse cardiovascular endpoints in patients with PSS compared with the general population and to investigate mortality in individuals with incident HF with or without a history of PSS. METHODS: Using Danish nationwide registries, PSS patients (diagnosed 1996-2018) without a history of other autoimmune diseases were each matched with four individuals from the general population by sex, age, and comorbidities. Multivariable Cox regression was used to estimate the rate of cardiovascular outcomes. In addition, the rate of death from any cause was compared between PSS patients with incident HF and four age- and sex-matched HF patients without PSS. RESULTS: In total, 5092 patients with newly diagnosed PSS were matched with 20,368 individuals from the general population (median age 57 years, 87.3% women, median follow-up 7.4 years). The cumulative incidence of HF at 10 years was 4.0% for PSS patients and 2.8% for matched individuals. After adjustment, patients with PSS had a higher associated rate of incident HF (hazard ratios [HR] 1.42 [95% CI, 1.20-1.68]) and other cardiovascular outcomes, compared with the background population. PSS patients with incident HF had a similar rate of death from all-cause mortality compared with HF patients without PSS (HR 0.94 [0.74-1.19]). CONCLUSIONS: Patients with PSS had a higher associated rate of incident HF and other cardiovascular outcomes compared with the general population. In individuals with incident HF, a history of PSS was not associated with increased mortality.

Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis.

BACKGROUND: Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV, conducting several prospective randomized controlled trials (RCTs). The aim for the present study was to further evaluate the long-term survival of patients with AAV included in seven RCTs conducted by the EUVAS as well as to identify potential prognostic factors. METHODS: Long-term follow-up data were collected from questionnaires sent to the principal investigators of the original RCTs (1995-2012): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC, comprising 848 patients, all newly diagnosed with AAV. Relative survival estimates are presented for the study cohorts. Demographic, clinical and laboratory characteristics at trial entry were studied as potential prognostic factors in multivariable models. RESULTS: A total of 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (44%) had microscopic polyangiitis (MPA) with a mean age at diagnosis of 58 ± 14 years. The median follow-up time was 8 years (interquartile range 2.9-13.6). During the observation period there were 305 deaths and the main causes were infections (26%), cardiovascular disease (14%) and malignancies (13%). When compared with a matched cohort (regarding country, age group and sex) from the background population there were 14.2% more deaths among our cohort of AAV patients at 5 years, 19.9% at 10 years, 28.8% at 15 years and 36.3% at 20 years. The excess mortality occurred in all age groups. The estimated median survival time (from diagnosis) was 17.8 years (95% confidence interval 15.7-20). Among variables measured at baseline, advanced age, male sex, low estimated glomerular filtration rate and low platelet count were identified as predictors of death in a multivariate Cox model. CONCLUSIONS: Patients with AAV still have an increased risk of mortality compared with the general population despite newer therapeutic regimens. Treatment complications and organ damage are the main causes of limited survival and infections remain the leading cause of mortality among patients with AAV.

Gender- and age-specific rates of heart failure and other adverse cardiovascular outcomes in systemic sclerosis.

OBJECTIVE: To investigate the long-term rates of heart failure (HF) and other adverse cardiovascular outcomes, including arrhythmias, myocardial infarction, ischaemic stroke, venous thromboembolism, pulmonary hypertension and pericarditis, in SSc patients according to gender and age. METHODS: Using Danish nationwide registries, SSc patients (diagnosed from 1996 to 2018) were matched with four controls from the background population by gender, age and comorbidities. Cox regression was used to compare the rates of cardiovascular outcomes between SSc patients and controls and the rate of mortality between SSc patients developing HF and HF patients without SSc, according to gender and age (above/below median). RESULTS: In total, 1569 SSc patients were matched with 6276 non-SSc controls (median age 55 years, 80.4% women, median follow-up 7.3 years). SSc had a higher rate of HF in both women [HR 2.99 (95% CI 2.18, 4.09)] and men [HR 3.01 (1.83, 4.95)] (Pinteraction = 0.88), with similar trends for other cardiovascular outcomes. SSc had a higher rate of HF in patients <55 years of age [HR 4.14 (95% CI 2.54, 6.74)] and ≥55 years [HR 2.74 (1.98, 3.78)] (Pinteraction = 0.22), with similar trends for other cardiovascular outcomes. SSc patients with new-onset HF had a higher rate of mortality than HF patients without a history of SSc, irrespective of gender (Pinteraction = 0.53) and age (Pinteraction = 0.43). CONCLUSIONS: SSc was associated with higher rates of HF and other cardiovascular outcomes than matched controls, irrespective of gender and age. Among patients with new-onset HF, a history of SSc was associated with higher mortality.

Distinct patterns of comorbidity prior to diagnosis of incident systemic lupus erythematosus in the Danish population.

The objective of this study was to assess the cumulative prevalence of pre-existing comorbidities among patients diagnosed with systemic lupus erythematosus (SLE) in Denmark. The study included patients aged ≥18 years at the index date set to the date of first registration of SLE in the Danish National Patient Registry (DNPR) between 1996 and 2018. Up to 19 age- and sex-matched general population comparators per case were selected. Comorbidity diagnoses were retrieved from the DNPR based on International Classification of Diseases codes. We estimated cumulative prevalence of various comorbidities among cases and comparators, prevalence differences (PDs), and prevalence ratios (PRs), with PDs and PRs adjusted for age and sex, at the index date and 1, 2, 5, and 10 years before the index date. We identified 3,010 SLE cases and 57,046 comparators (mean age at index date: 47.3 years). Most comorbidities occurred more often in SLE patients versus comparators at the index date and up to 10 years before. Overrepresented comorbidities in SLE patients 10 years before SLE diagnosis included neuropsychiatric, cardiovascular, and venous thromboembolic diseases; PDs (95% CI) were 2.3% (1.4-3.3%), 1.3% (0.6-1.9%), and 1.1% (0.6-1.5%), respectively; corresponding PRs (95% CI) were 1.5 (1.3-1.8), 1.7 (1.4-2.1), and 4.3 (3.1-6.1). We found a higher prevalence of multiple comorbidities-not only at the time of SLE diagnosis but likewise during the 10-year pre-diagnosis period-among individuals with SLE. These findings underscore the importance of early clinical vigilance toward comorbidities starting in the diagnostic phase of SLE.

Mortality and cardiovascular morbidity among patients diagnosed with Takayasu's arteritis: a Danish nationwide cohort study.

OBJECTIVES: To assess the long-term mortality and risk of cardiovascular events (CVE) among Danish patients with Takayasu's arteritis (TAK). METHODS: Administrative registers with nationwide coverage were used to identify patients diagnosed with TAK in Denmark during 1994-2014 and construct an age- and gender-matched cohort of population-controls. CVE were identified by means of hospital discharge diagnoses and categorised as major or minor, based on severity. Cox regression analyses were used to calculate hazard ratios (HRs) for death and first-time hospitalisations for CVE as a measure of relative risk. RESULTS: 79 patients with TAK were identified, corresponding to an incidence rate of 0.7 (95% confidence interval (CI): 0.6-0.9)/million/year. Median duration of follow-up in the TAK cohort was 6.4 (IQR: 3.7-11) years. Mortality was significantly higher among the TAK patients than among the population controls during the first 3 years of follow-up [HR for death: 8.0 (95% CI: 3.0-21)], but not after >3 years [HR for death: 0.5 (95% CI: 0.1-3.5)]. Risk of CVE was significantly increased among TAK patients after ≤3 years [HR for major CVE: 12 (95% CI: 3.8-37), HR for minor CVE: 19 (95% CI: 7.5-50)] as well as after >3 years [HR for major CVE: 7.6 (95% CI: 2.8-21), HR for minor CVE: 3.0 (95% CI: 1.01-9.0)]. CONCLUSIONS: Compared to the general population, patients with TAK experience markedly increased mortality during early follow-up periods. The long-term risk of CVE is high among patients affected by the disease.

Atherosclerosis and renal disease involvement in patients with systemic lupus erythematosus: a cross-sectional cohort study.

Objective: To investigate the association between LN, renal function and atherosclerosis measured by coronary artery calcium (CAC) and carotid plaque in a cross-sectional study of patients with SLE. Methods: Presence of CAC and carotid plaque was measured in 147 SLE patients with and without LN. The patients were divided into four groups according to LN and renal function [by first quartile of estimated glomerular filtration rate (eGFR): 70 ml/min/1.73 m2]. Impaired renal function was defined by an eGFR <70 ml/min/1.73 m2. We used multivariate logistic regression models to explore the association between LN, renal function, CAC and carotid plaque. Results: Of the 147 SLE patients, 74 had LN. Median age of the study cohort was 46 years, 89% were women and median eGFR was 89 ml/min/1.73 m2. CAC score >0 was present in 57 (39%) and carotid plaque in 29 (20%) of the SLE patients. The presence of CAC and/or carotid plaque was highest in SLE patients with impaired renal function. Regression analyses showed that compared with SLE patients without LN and eGFR ⩾70 ml/min/1.73 m2 (reference group), only the combination of LN and impaired renal function was associated with the presence of CAC (odds ratio: 6.82, 95% CI: 1.59, 29; P = 0.01) and carotid plaque (odds ratio: 5.60, 95% CI: 1.19, 26; P = 0.03). Conclusion: Our findings indicate that LN in combination with impaired renal function defined by an eGFR <70 ml/min/1.73 m2 is strongly associated with the presence of atherosclerosis in SLE.

The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study.

Objective: . To assess the role of LN as a risk factor for myocardial infarction (MI), stroke and cardiovascular mortality (CVM) in patients with SLE. Methods: . The study was conducted using individual-level data from multiple nationwide registers. We identified a cohort of patients diagnosed with SLE and further determined if they had a diagnosis of LN during 1995-2011. Each SLE patient was matched with five population controls. Hazard ratios (HRs) were calculated to measure the risk of MI, stroke and CVM in SLE patients relative to population controls and in SLE patients with relative to without LN. Results: . We identified 1644 SLE patients with incident SLE; 233 of these patients had a diagnosis of incident LN during follow-up. The number of events in the SLE cohort was: 42 (MI), 74 (stroke) and 56 (CVM). For MI, the HR was 2.2 (95% CI: 1.4, 3.4) in SLE without LN and 18.3 (95% CI: 5.1, 65) in SLE with LN. The HR for LN was 8.5 (95% CI: 2.2, 33; P = 0.002). For stroke, HRs were 2.1 (95% CI: 1.5, 2.9) and 4.1 (95% CI: 1.9, 8.7) in SLE without and with LN, respectively, and we found no significant association with LN (P = 0.115). For CVM, the respective HRs were 1.6 (95% CI: 1.1, 2.4) and 7.8 (95% CI: 3.0, 20). The corresponding HR for LN was 4.9 (95% CI: 1.8, 13.7; P = 0.002). Conclusion: . The risk of MI and CVM, but not of stroke, is significantly higher in SLE patients with LN than SLE patients without LN.

Anti-B cell antibody therapies for inflammatory rheumatic diseases.

Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated vasculitis, polymyositis/dermatomyositis, and primary Sjögren's syndrome. For some anti-B cell agents, clinical benefits have been convincingly demonstrated, while other B cell-targeted therapies failed to improve outcomes when added to standard-of-care treatment or were associated with increased rates of adverse events. Although the risk-benefit balance seems to be acceptable for currently licensed anti-B cell agents, additional studies are required to fully assess the safety of treatment regimens involving prolonged interference with B cell counts and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies.

Impact of pre-existing co-morbidities on mortality in granulomatosis with polyangiitis: a cohort study.

OBJECTIVE: To assess the impact of pre-existing co-morbidities on mortality among patients affected by granulomatosis with polyangiitis (GPA). METHODS: By means of the Danish National Hospital Register, we identified a cohort of patients hospitalized for GPA during 1994-2010 (n = 308). The burden of pre-existing co-morbidities among the patients was quantified according to the Charlson Comorbidity Index (CCI). Each patient was matched with five age- and gender-matched population controls with no pre-existing co-morbidities captured by the CCI (CCI score = 0). The study subjects were followed throughout 2010. Cox regression analyses were used to calculate mortality rate ratios (MRRs). RESULTS: The median duration of follow-up in the GPA cohort was 5.8 years (interquartile range 2.3-10.0). Compared with their matched population controls, the MRR for patients presenting with a CCI score of 0 (n = 246) was 3.9 (95% CI 2.0, 7.5) during years 0-2 and 1.4 (95% CI 0.9, 2.0) from the second year of follow-up onwards. The corresponding MRRs were 13.3 (95% CI 5.8, 31) and 1.9 (95% CI 1.1, 3.6) for patients with a CCI score ⩾1 (n = 62). In a direct comparison, GPA patients with a CCI score ⩾1 were found to have significantly higher mortality than GPA patients with a CCI score of 0 during years 0-2 [adjusted MRR 3.4 (95% CI 1.6, 7.0)] but not after >2 years of follow-up [adjusted MRR 1.3 (95% CI 0.7, 2.6)]. CONCLUSION: During early follow-up periods, the mortality among GPA patients with pre-existing co-morbidities is markedly higher than that among GPA patients with no pre-existing illnesses. Our analyses identify an increased CCI score for pre-existing co-morbidities as an important risk factor for a fatal outcome in GPA.

Mortality in patients with giant cell arteritis.

OBJECTIVE: The aim of this study was to examine whether GCA is associated with increased mortality. METHODS: We conducted a nationwide population-based cohort study including all individuals who between 1993 and 2011 were registered in the Danish National Hospital Register and the Danish Pathology Register with a biopsy-proven diagnosis of GCA (n = 1787). Through the Danish Civil Registration System we identified a comparison cohort of 33 953 persons from the background population, individually matched on age and sex. Data on causes of death were obtained from the Danish Registry of Causes of Death. We used Poisson regression to determine mortality rate ratios as estimates of relative risk of death and specific causes of death. RESULTS: Compared with the general population, the relative risk (RR) of death in patients diagnosed with GCA was 1.17 (95% CI 1.01, 1.36) and 1.22 (95% CI 1.05, 1.41) 0-2 years and >10 years after diagnosis, respectively, whereas we observed no increased mortality during the follow-up period of 2-10 years [RR 0.96 (95% CI 0.88, 1.05)]. The increased mortality during the first 2 years of follow-up was mainly due to diseases of the circulatory system, including aortic aneurisms. CONCLUSION: GCA is associated with slightly increased early and late mortality.

Prolonged risk of specific malignancies following cyclophosphamide therapy among patients with granulomatosis with polyangiitis.

OBJECTIVE: The long-term cancer risk for patients treated for granulomatosis with polyangiitis (GPA) is not well characterized. We assessed the risk of early and late-occurring cancers among 293 patients diagnosed with GPA from 1973 to 1999 and followed throughout 2010. METHODS: Cancer incidence in the cohort was determined by linkage with the Danish Cancer Registry and compared with that in the general population by calculation of standardized incidence ratios (SIRs). RESULTS: The median duration of follow-up was 9.7 years (range 0-36). Seventy-three cancers occurred, of which 30 were non-melanoma skin cancers (NMSCs) and 11 were bladder carcinomas. A high occurrence of NMSC was observed from the second year of follow-up onwards, with a SIR of 7.0 (95% CI 2.3, 16) for cases diagnosed ≥20 years after GPA. The incidence of bladder cancer increased after 5-9, 10-14 and 15-19 years of follow-up, with SIR estimates for these latency periods of 5.3 (95% CI 1.1, 15), 14.4 (95% CI 5.3, 31) and 10.5 (95% CI 1.2, 38), respectively. The incidence of myeloid leukaemia was significantly increased during years 5-9 [SIR 23.9 (95% CI 2.7, 86)]. Increased incidence of NMSC, bladder cancer and myeloid leukaemia was observed among patients exposed to cumulative CYC doses >36 g, while the only malignancy type observed in excess among those treated with lower CYC doses was NMSC. The cancer risk among CYC-naive patients was not significantly increased. CONCLUSION: GPA patients experience a greater than expected number of specific malignancies following conventional therapies. Our analyses demonstrate a substantially increased risk of very late-occurring NMSC and bladder cancer in this patient group.

Long-term Rate of Ventricular Arrhythmia in Autoimmune Disease.

AIMS: Although selected autoimmune diseases (AIDs) have been linked to an increased risk of ventricular arrhythmias (VAs), data on the long-term rate of VAs across the spectrum of AIDs are lacking. The aim of our study was to investigate the long-term rate of VAs (a composite of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest) in individuals with a history of 28 different AIDs. METHODS: Individuals diagnosed with an AID (2005-2018) were identified through Danish nationwide registries. Each patient with AID was matched with four individuals from the background population by age and sex. Multivariable Cox regression was used to compare the rate of VAs between the AIDs and background population, overall and according to individual AIDs. RESULTS: In total, 186,733 patients diagnosed with AIDs were matched with 746,932 individuals without AIDs (median age 55 years; 63% female; median follow-up 6.0 years). The 5-year cumulative incidence of VAs was 0.5% for patients with AIDs and 0.3% for matched individuals. Patients with any AIDs had a higher associated rate of VAs than matched individuals (HR 1.39 [95% CI, 1.29-1.49]). The highest HR was observed in patients with systemic sclerosis (3.86 [95% CI, 1.92-7.75]). The higher rate of VAs in patients with AIDs, compared with individuals from the background population, was more pronounced in patients without ischemic heart disease or heart failure/cardiomyopathy compared to those with these conditions (Pinteraction < 0.05). CONCLUSIONS: Despite a low cumulative incidence, patients with a history of AIDs had a higher relative rate of VAs than matched individuals.

In a large Danish nationwide study, we examined the risk of ventricular arrhythmias, which are serious and potentially life-threatening conditions, in patients with and without a history of autoimmune diseases. Patients with a history of any autoimmune disease had a higher risk of experiencing ventricular arrhythmias compared with age- and sex-matched individuals from the background population. This association was observed for most of the autoimmune diseases when examined individually. The higher rate of ventricular arrhythmias in patients with autoimmune diseases, compared with individuals from the background population, was relatively more pronounced in patients without a history of ischemic heart disease or heart failure/cardiomyopathy compared with individuals with a history of these conditions.

Brief Report: long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: The NORAM (Nonrenal Wegener's Granulomatosis Treated Alternatively with Methotrexate [MTX]) trial demonstrated that MTX can replace cyclophosphamide (CYC) as remission-inducing treatment for patients with newly diagnosed early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Duration of relapse-free survival was longer among CYC-treated patients than among MTX-treated patients during short-term followup. The aim of the present study was to describe the long-term outcome in patients enrolled in the randomized clinical trial. METHODS: Outcome questionnaires were sent to investigators who had recruited patients for the NORAM trial. Patients treated with MTX for induction of remission (n = 49) were compared to CYC-treated patients (n = 46) with respect to immunosuppressive therapy during followup, relapse-free survival, mortality, and occurrence of other clinical events. RESULTS: The median duration of followup was 6 years (range 0.1-10.8 years). One patient developed end-stage renal disease, and 11 died. The number of patients affected by serious infection, malignancy, or severe organ failure did not differ between treatment groups, and no difference in survival rate was observed. The duration of corticosteroid therapy was longer in the MTX group during the 18 months of the trial (P = 0.005). During subsequent followup, patients who were in the MTX group in the NORAM trial received corticosteroids, CYC, and other immunosuppressive agents (azathioprine, MTX, and/or mycophenolate mofetil) for longer periods than those who were in the CYC group (P = 0.004, P = 0.037, and P = 0.031, respectively). The cumulative relapse-free survival tended to be lower in the MTX group (P = 0.056). CONCLUSION: In the NORAM cohort, no difference in occurrence of major adverse events was observed between treatment groups during long-term followup. However, first-line treatment with MTX was associated with less effective disease control than CYC-based induction therapy.

Risk of End-Stage Renal Disease in Patients With Systemic Lupus Erythematosus and Diabetes Mellitus: A Danish Nationwide Cohort Study.

OBJECTIVE: The risk of end-stage renal disease (ESRD) is increased in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine whether diabetes mellitus (DM) increases ESRD risk in a large inception cohort of SLE patients. METHODS: By means of the Danish National Patient Registry, we identified 3,178 adult patients diagnosed as having SLE between January 1, 1996, and July 31, 2018. DM was defined as the date of first hospital contact for DM or date of a first prescription of an antidiabetic drug. ESRD was defined as first registration of dialysis, renal transplant, or terminal renal insufficiency in the Danish National Patient Registry. ESRD incidence was compared between SLE patients with DM (SLE-DM) and those without DM (SLE-non-DM). Hazard ratios (HRs), adjusted for sex, age, educational level, and occupational status at baseline were calculated for sex, age, educational level, and hypertension (at baseline or during follow-up) strata. The overall hazard ratio (HR) was also adjusted for hypertension. RESULTS: The SLE-DM group included 290 patients, of whom 77% were female, compared with 85% of the 2,859 patients in the SLE-non-DM group. SLE-DM patients had a 3 times higher risk of ESRD compared with SLE-non-DM patients (multivariable-adjusted HR 3.3 [95% confidence interval 1.8-6.1]). In stratified multivariable-adjusted analyses, DM increased the rate of ESRD in women and men, patients ≥50 years old at baseline, those with low educational level at baseline, and those with concomitant hypertension. CONCLUSION: Our findings indicate that SLE patients with DM have a markedly higher risk of developing ESRD compared with SLE patients without DM.

Mortality in heart failure with and without autoimmune disease.

AIMS: Autoimmune diseases (AIDs) are associated with a higher risk of heart failure (HF). However, data on the prognosis of HF patients with a history of AID are limited. The aim was to investigate the rates of all-cause mortality and HF hospitalization in a large, nationwide cohort of patient with HF according to a history of 29 AIDs. METHODS AND RESULTS: Using Danish nationwide registries, each HF patient (diagnosed 2000-18) with a history of AID was matched with four HF patients without AID by age, sex, and year of HF diagnosis. Rates of outcomes were compared by Cox regression models. The prevalence of AID in patients with HF was 10.7%. In total, 21 256 HF patients with a history of AID were matched with 85 024 HF patients without AID (median age 77 years; 58.9% female). During a median follow-up of 3.2 years, the incidence rates per 100 person-years for all-cause mortality were 17.1 (95% confidence interval, 16.9-17.4) and 14.4 (14.3-14.6) in patients with and without AID, respectively. The corresponding rates for HF hospitalization were 5.0 (4.9-5.1) and 5.2 (5.1-5.4), respectively. A history of AID was associated with higher rate of all-cause mortality [hazard ratio (HR) 1.14 (1.12-1.17)], but not HF hospitalization [HR 1.00 (0.96-1.04)] compared with no AID. CONCLUSIONS: In a nationwide cohort study, patients with HF and a history of AID had a higher associated rate of mortality than those without a history of AID.

This study examined the rates of all-cause mortality and hazard ratio (HF) hospitalization in a large, nationwide cohort of patient with HF with and without a history of 29 autoimmune diseases (AIDs). Among HF patients, a history of AID was associated with higher mortality. Further research elucidating the explanations for the observed excess mortality is needed. Among HF patients, a history of AID was not associated with higher HF hospitalization.

Treatment of orbital inflammation with rituximab in Wegener's granulomatosis.

OBJECTIVES: To study the efficacy of rituximab therapy for the treatment of orbital inflammation in patients with Wegener's granulomatosis (WG). METHODS: Ten WG patients with orbital inflammation were included in this case-series. None had symptoms suggestive of extra-orbital disease activity. Immunosuppressive medication (mycophenolate and prednisolone) was administered to 3 patients at the time of rituximab therapy. Three patients had previously been treated with anti-tumour-necrosis-factor-alpha antibodies, and one of these patients had also received cyclophosphamide as treatment for orbital inflammation. All patients were treated with 1000 mg of rituximab administered twice with an interval of 14 days between the infusions. Six months after therapy, a physical examination and a control computerised tomography (CT) scan was performed. RESULTS: All patients had orbital inflammation demonstrated by CT-scan before treatment (3 had bilateral and 7 unilateral orbital involvement). Orbital symptoms at study baseline included pain, pressure sensation behind the eyes, epiphora, diplopia, and affection of the visual acuity. Nine out of ten patients experienced subjective improvement. Four patients (seven eyes) with visual impairment responded to therapy, and the improvement in visual acuity was sustained throughout follow-up (median duration of follow-up: 17 months; range: 6-18 months). At the time of the control CT-scan, size-reduction of the orbital mass was observed in two patients, while the size of the orbital mass was unchanged in eight patients. CONCLUSIONS: Rituximab therapy has positive effects on symptoms, visual acuity and/or granuloma size in some WG patients with orbital inflammation. Treatment with rituximab should be considered in WG patients with this serious manifestation of the disease.

High incidence of potentially virus-induced malignancies in systemic lupus erythematosus: a long-term followup study in a Danish cohort.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus-associated malignancies, defined as malignancies potentially caused by virus infection. METHODS: A hospital-based cohort of 576 SLE patients was linked to the Danish Cancer Registry. The cohort was followed up for malignancies from the date of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for various forms of cancer. RESULTS: The median duration of followup was 13.2 years. Compared to the general population, the patients experienced an increased overall risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2-2.0). We observed an increased risk of virus-associated cancers combined (SIR 2.9 [95% CI 2.0-4.1]). Among human papillomavirus (HPV)-associated malignant and premalignant conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7-83.4]), vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3-36.5]), epithelial dysplasia/carcinoma in situ of the uterine cervix (SIR 1.8 [95% CI 1.2-2.7]), and nonmelanoma skin cancer (SIR 2.0 [95% CI 1.2-3.6]). Increased SIRs were also found for other potentially virus-induced cancer types (liver cancer SIR 9.9 [95% CI 2.5-39.8], bladder cancer SIR 3.6 [95% CI 1.4-9.7], and non-Hodgkin's lymphoma SIR 5.0 [95% CI 1.9-13.3]). CONCLUSION: The patients in this SLE cohort experienced an increased risk of HPV-associated tumors and other potentially virus-induced cancers during long-term followup. Our findings call for clinical alertness to oncogenic virus infections in SLE patients.

Risk of Cancer Among Sarcoidosis Patients With Biopsy-verified Nonnecrotizing Granulomatous Inflammation: Population-based Cohort Study.

OBJECTIVE: To assess the long-term risk of hematologic cancers, invasive solid tumors, and nonmelanoma skin cancer (NMSC) among sarcoidosis patients with biopsy-verified nonnecrotizing granulomatous inflammation. METHODS: We used Danish administrative registers with nationwide coverage to construct a cohort of 3892 patients with sarcoidosis and an age- and sex-matched comparison cohort of 38,920 population controls. For all patients, a biopsy demonstrating nonnecrotizing granulomatous inflammation had been obtained from the lower respiratory tract at the time of diagnosis. Study outcome was time to diagnosis of cancer. Follow-up began at time of sarcoidosis diagnosis and continued for up to 10 years. We calculated hazard ratios (HRs) as estimates of the cancer risk among the patients with sarcoidosis relative to that among the population controls and used cumulative incidence functions to calculate absolute 10-year risk estimates. RESULTS: We observed an increased long-term risk of hematologic cancers (HR during the first 2 years of follow-up: 2.71 [95% CI 1.18-6.25]; HR after > 2 years of follow-up: 2.12 [95% CI 1.29-3.47]) and NMSC (HR after > 2 years of follow-up: 1.82 [95% CI 1.43-2.32]) among the patients with sarcoidosis. An increased risk of invasive solid tumors was only observed during the first 2 years (HR 1.55, 95% CI 1.18-2.04). Compared with the population controls, the patients with sarcoidosis had an increased absolute 10-year risk of hematologic cancers (risk difference 0.56%, 95% CI 0.11-1.01%) and NMSC (risk difference 1.58%, 95% CI 0.70-2.47%). CONCLUSION: Sarcoidosis patients with biopsy-verified nonnecrotizing granulomatous inflammation have an increased long-term risk of hematologic cancers and NMSC compared with the general population.

A nationwide study of ocular manifestations leading to hospital contacts among patients with giant cell arteritis.

OBJECTIVES: To investigate the risk of ocular manifestations leading to hospital contacts among patients with giant cell arteritis (GCA). METHODS: A Danish, nationwide, register-based cohort study including 14,574 GCA patients diagnosed 1996-2018 and 145,740 general population referents, matched on sex and date of birth. Cumulative incidence proportions (CIPs) and relative risks (RRs) of ocular manifestations with 95% confidence intervals (CIs) were calculated using a pseudo-observation approach. RESULTS: A total of 1026/14,574 (7.0%) GCA patients were registered with ocular manifestations within ±1 year of the diagnosis; 392/1026 (38%) being before and 634/1026 (62%) after the GCA diagnosis, and 744/1026 (73%) were registered within ±1 month of the diagnosis. The diagnoses were 336/1026 (33%) retinal vascular occlusions, 300/1026 (29%) disorders of the optic nerve, 177/1026 (17%) visual impairment, 90/1026 (9%) diplopia, and 123/1026 (12%) amaurosis fugax. The CIP for ocular manifestations among GCA patients after 3, 6, and 12 months following the diagnosis were 4.0% (95% CI: 3.6-4.3), 4.2% (95% CI: 3.9-4.6), and 4.6% (95% CI: 4.2-4.9). The 1-year RR of ocular manifestations among GCA patients was 28.0 (95% CI: 24.0-32.7), with age above 70 years, male sex, and a positive temporal artery biopsy being risk factors. Treatment with low-dose aspirin was not associated with a reduced 1-year RR of incident ocular manifestations. CONCLUSIONS: In GCA, most cases of ocular manifestations leading to hospital contacts occur close to the time of diagnosis, with over one-third of cases occurring before the diagnosis, emphasizing the need for early recognition and treatment.