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  • 1. Almehed, K
    et al.
    Carlsten, H
    Forsblad-d'Elia, Helena
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Health-related quality of life in systemic lupus erythematosus and its association with disease and work disability.2010Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 39, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To determine the health-related quality of life (HRQOL) and its relationship to disease variables, vertebral fractures, and employment status in female patients with systemic lupus erythematosus (SLE).

    METHODS: HRQOL was assessed with the Swedish version of the Medical Outcomes Study (MOS) 36-Item Short Form Survey (SF-36) in female patients (n=163) and in age- and sex-matched controls (n=1045). Associations between the SF-36 score and demographics, disease variables, prevalent vertebral fractures, and employment status were analysed.

    RESULTS: The SLE patients, aged 20 to 82 years, scored significantly lower than the controls on all SF-36 subscales. Patients with vertebral fractures were older, had greater disease damage, and lower physical functioning (PF) than patients without fractures. Of the SLE patients of working age (n=142), 54% worked full or part time. These patients scored their HRQOL significantly higher (better) than patients not working. Being able to work was significantly associated with low age and high scores in PF and role physical (RP): the area under the receiver operating characteristic (ROC) curve for these variables was 0.82, confidence interval 0.75-0.89.

    CONCLUSIONS: HRQOL is substantially lower in SLE than in the general population but working ability indicates better health. We encourage further research regarding the effects on HRQOL by preventive actions taken against work disability in SLE.

  • 2. Almehed, K
    et al.
    Forsblad d'Elia, Helena
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Kvist, G
    Ohlsson, C
    Carlsten, H
    Prevalence and risk factors of osteoporosis in female SLE patients-extended report.2007Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 46, nr 7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To determine the frequency of osteoporosis and possible risk factors of low bone mineral density (BMD) in women with systemic lupus erythematous (SLE) in western Sweden. In addition, to evaluate if adequate anti-osteoporotic treatment was provided.

    METHODS: BMD was measured at radius, lumbar spine and hip by dual X-ray absorptiometry (DXA). An 'expected' control BMD was calculated for each patient. Simple and multiple linear regression analyses were performed to determine associations between BMD and demographic and disease-related variables.

    RESULTS: One hundred and sixty-three women were included. Median age was 47 (20-82) yrs, 89 (55%) were post-menopausal and 85 (52%) were taking glucocorticosteroids. BMD was significantly reduced in all measured sites compared with expected BMD. Thirty-seven (23%), 18 (11%) and 6 (4%) of the patients were osteoporotic in at least one, two and three or more measured locations. Bisphosphonates were used by 23 (27%) of patients taking glucocorticosteroids and 13 (35%) with osteoporosis. High age and low weight or BMI were associated with low BMD in all measured sites. In total hip, high SLICC/American Collage of Rheumatology (ACR), ESR and 'combinations of DMARD' were additional markers of low BMD. High S-creatinine was associated with low BMD in lumbal spine whereas high S-creatinine and CRP were markers in radius.

    CONCLUSION: Women with SLE are at greater risk of osteoporosis compared with controls and few are treated adequately. Factors associated with low BMD in SLE are high age and low weight but also markers of inflammation, impaired kidney function and disease damage, however glucocorticosteroids were not associated.

  • 3. Almehed, Katarina
    et al.
    d'Elia, Helena Forsblad
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Bokarewa, Maria
    Carlsten, Hans
    Role of resistin as a marker of inflammation in systemic lupus erythematosus.2008Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 10, nr 1, s. R15-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Resistin is a cystein-rich secretory adipokine. It is proposed to have proinflammatory properties in humans. The aim of this study was to determine associations between serum levels of resistin and markers of inflammation and bone mineral density (BMD) in female patients with systemic lupus erythematosus (SLE).

    METHODS: One hundred sixty-three female patients with SLE (20 to 82 years old) were examined in a cross-sectional study. Venous blood samples were analyzed for resistin, erythrocyte sedimentation rate (ESR), C-reactive protein, creatinine, fasting lipids, complements, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, sIL-6R (soluble IL-6 receptor), ICTP (C-terminal telopeptide of type I collagen), and PINP (N-terminal propeptide of type I procollagen). Simple and multiple regression analyses as well as logistic regression analyses were performed. Resistin in serum was compared with 42 healthy female controls with respect to age.

    RESULTS: Serum resistin levels in controls were similar to those of patients with SLE. Markers of inflammation and current dose of glucocorticosteroids correlated positively to resistin in serum. Markers of renal function, number of prevalent vertebral fractures, and BMD were also significantly associated with resistin. In a multiple regression model, ESR, creatinine, C3, current glucocorticosteroid dose, high-density lipoprotein, and BMD radius remained significantly associated with resistin. In logistic regression analyses with resistin as the independent variable, a significant association was found with ESR (normal or elevated) but not with S-creatinine or z score for hip and radius total.

    CONCLUSION: Although resistin measurements did not differ between patients and controls, resistin was clearly associated with general inflammation, renal disease, treatment with glucocorticosteroids, and bone loss. We hypothesize that resistin has proinflammatory and disease-promoting properties in SLE. Further studies are needed to elucidate the mechanism behind these associations.

  • 4. Almehed, Katarina
    et al.
    Hetényi, Szabolcs
    Ohlsson, Claes
    Carlsten, Hans
    Forsblad-d'Elia, Helena
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Prevalence and risk factors of vertebral compression fractures in female SLE patients.2010Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 12, nr 4, s. R153-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Our objective was to determine the frequency of and factors associated with prevalent vertebral compression fractures in female systemic lupus erythematosus (SLE) patients attending rheumatologists in western Sweden.

    METHODS: In this cross sectional study 150 women were included. They were examined with x-ray of thoracic and lumbar spine (Th4 to L4). A reduction of at least 20% of any vertebral height, assessed by Genant's semiquantitative method, was defined as a fracture. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA).

    RESULTS: Median patient age was 47 years (20 to 82) and disease duration 11 years (1 to 41). Only 6 (4%) women had a history of clinical compressions whereas 43 (29%) had at least one radiological fracture each. The patients with at least one fracture at any site were characterized by older age (P < 0.001), being postmenopausal (P < 0.01), higher Systemic Lupus International Collaborative Clinics Damage Index (P < 0.05), lower BMD total hip and femoral neck (P < 0.05), more peripheral fractures (P < 0.01), medication with bisphosphonates (P <0.05) and calcium and vitamin D3 (P < 0.05). There were no significant differences regarding current or cumulative glucocorticosteroid dose between the groups. In logistic regression analyses high age remained as a risk factor of at least one vertebral fracture at any site whereas low BMD in total hip was associated with vertebral fracture in the lumbar spine.

    CONCLUSIONS: Radiological compression fractures are common but seldom diagnosed in SLE patients. High age and low BMD in total hip, but not in spine, was associated with vertebral fractures.

  • 5. Andersson, K.
    et al.
    Pullerits, R.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Dept Rheumatology and inflammation research, Inst Medicine, Göteborg university, Göteborg.
    Erlandsson, M.
    Silfversward, T.
    Bokarewa, M.
    Oestrogen dependent regulation of micro-rna in rheumatoid arthritis2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 236-237Artikel i tidskrift (Övrigt vetenskapligt)
  • 6. Bengtsson, K.
    et al.
    Klingberg, E.
    Deminger, A.
    Jacobsson, L. T.
    Bergfeldt, L.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Göteborg.
    Ankylosing spondylitis related factors predict the presence of cardiac conduction disturbances: a swedish longitudinal cohort study2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 337-338Artikel i tidskrift (Övrigt vetenskapligt)
  • 7. Bengtsson, K.
    et al.
    Klingberg, E.
    Deminger, A.
    Jacobsson, L. T. H.
    Bergfeldt, L.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    CARDIAC CONDUCTION DISTURBANCES IN PATIENTS WITH ANKYLOSING SPONDYLITIS - A SWEDISH LONGITUDINAL COHORT STUDY2018Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, nr 4, s. 714-714Artikel i tidskrift (Övrigt vetenskapligt)
  • 8. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Department of Rheumatology and Inflammation Research, Göteborg, Sweden.
    Klingberg, Eva
    Lindstrom, Ulf
    Dehlin, Mats
    Exarchou, Sofia
    Deminger, Anna
    Askling, Johan
    Jacobsson, Lennart T. H.
    Incidence of extra-articular manifestations in ankylosing spondylitis, proriatic arthritis and undifferentiated spondyloarthritis - results from a national register-based cohort study2019Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, s. 1237-1237Artikel i tidskrift (Övrigt vetenskapligt)
  • 9. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lie, Elisabeth
    Klingberg, Eva
    Dehlin, Mats
    Exarchou, Sofia
    Lindstrom, Ulf
    Askling, Johan
    Jacobsson, Lennart T. H.
    Are Ankylosing Spondylitis, Psoriatic Arthritis and Undifferentiated Spondylarthritis Associated with an Increased Risk of Cardiovascular Disease?2015Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, artikel-id 1057Artikel i tidskrift (Övrigt vetenskapligt)
  • 10. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Box 480405 30 Gothenburg, Sweden.
    Lie, Elisabeth
    Klingberg, Eva
    Dehlin, Mats
    Exarchou, Sofia
    Lindstrom, Ulf
    Askling, Johan
    Jacobsson, Lennart T. H.
    Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events?: A prospective nationwide population-based cohort study2017Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, artikel-id 102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP).

    Methods: This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001–2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively.

    Results: Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31–1.82)), PsA (1.76 (1.59–1.95)) and uSpA (1.36 (1.05–1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37–0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06–1.48)) and PsA (1.34 (1.22–1.48)), and nonsignificantly increased in uSpA (1.16 (0.91–1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP.

    Conclusions: Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.

  • 11. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lie, Elisabeth
    Klingberg, Eva
    Dehlin, Mats
    Exarchou, Sofia
    Lindstrom, Ulf
    Askling, Johan
    Jacobsson, Lennart T. H.
    Increased Risk of Atrioventricular Block, Atrial Fibrillation and Pacemaker Implantation in Ankylosing Spondylitis, Undifferentiated Spondylarthritis and Psoriatic Arthritis Compared to the General Population2015Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, nr 10, artikel-id 1059Artikel i tidskrift (Övrigt vetenskapligt)
  • 12. Bengtsson, Karin
    et al.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden .
    Lie, Elisabeth
    Klingberg, Eva
    Dehlin, Mats
    Exarchou, Sofia
    Lindstrom, Ulf
    Askling, Johan
    Jacobsson, Lennart T. H.
    Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population: a register-based study from Sweden2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr 4, s. 541-548Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To describe the incidence of atrioventricular (AV) block II-III, atrial fibrillation (AF), pacemaker implantation (PM) and aortic regurgitation in patients with ankylosing spondylitis (AS), undifferentiated spondyloarthritis (uSpA) and psoriatic arthritis (PsA) compared with the general population (GP) and with each other. Methods: A prospective nationwide study with cohorts of patients with AS (n=6448), PsA (n=16063) and uSpA (n=5190) and a GP (n=266435) cohort, identified in 2001-2009 in the Swedish National Patient and Population registers. Follow-up began on 1 January 2006 and ended at event, death, emigration or 31 December 2012. Age-standardised and sex-standardised incidence rates and hazard ratios (HRs) were calculated. Results: The highest incidence rates were noted for AF (5.5-7.4 events per 1000 person-years), followed by PM (1.0-2.0 events per 1000 person-years). HRs for AV block, AF, PM and aortic regurgitation were significantly increased in AS (HRs 2.3, 1.3, 2.1 and 1.9), uSpA (HRs 2.9, 1.3, 1.9 and 2.0) and PsA (HRs 1.5, 1.5, 1.6 and 1.8) compared with the GP cohort. The highest HRs were seen for AV block in male uSpA (HR 4.2) and AS (HR 2.5) compared with GP. Compared with PsA, significantly increased HRs were noted for PM (HR 1.5) in AS and for AV block (HR 1.8) in uSpA. Conclusions: Patients with SpA are at increased risk of aortic regurgitation, cardiac rhythm disturbances and, as a probable consequence, also PM. Particularly for AF, the most common arrhythmia, increased caution is warranted, whereas AV block should be looked for especially in men with AS or uSpA.

  • 13. Bengtsson, Karin
    et al.
    Jacobsson, Lennart T H
    Rydberg, Barbro
    Kvist, Göran
    Torstenson, Tomas
    Dehlin, Mats
    Hilme, Elisabet
    Lindhé, Anna
    Wallerstedt, Susanna Maria
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden..
    Comparisons between comorbid conditions and health care consumption in rheumatoid arthritis patients with or without biological disease-modifying antirheumatic drugs: a register-based study2016Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, nr 1, artikel-id 499Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Symptoms and prognosis of patients with rheumatoid arthritis (RA) have improved with more intensive therapy, including the biological disease-modifying anti-rheumatic drugs (bDMARDs). Real life data concerning how comorbidities are distributed among patients treated or not treated with bDMARDs are scarce. Our objective was to investigate differences in comorbidity and health care consumption in RA patients, with and without bDMARDs.

    METHODS: This cross-sectional study was performed in the Southwestern part of Sweden. Patients, aged ≥ 18 years and diagnosed with RA in secondary health care during 2009-2010, were identified in the regional health care database. Aggregated data of comorbidity and health care consumption were retrieved between 2006 and 2010. RA patients treated with bDMARDs on 31st December 2010 were identified in the Swedish Rheumatology Quality Register (SRQ), which includes the biologics register Anti-Rheumatic Therapy in Sweden (ARTIS). Descriptive, comparative, univariate and multiple logistic regression analyses were used to identify factors associated with bDMARDs.

    RESULTS: Seven thousand seven hundred and twelve (7712) RA patients were identified (age 64.8 ± 14.9 years, women 74.3%), of whom 1137 (14.7%) were treated with bDMARDs. Overall, the most common comorbidities were infections (69.2%), hypertension (41.1%), chronic respiratory disease (15.3%), ischemic heart disease (14.0%) and malignancy (13.7%). Patients without bDMARDs were older and had more comorbidity. In the multiple logistic regression analysis, older age, cerebrovascular and chronic respiratory disease, heart failure, depression and malignancy were all associated with no present bDMARDs. Infections were associated with bDMARDs. Patients treated with bDMARDs consumed more secondary outpatient care but less visits in primary health care compared to patients without bDMARDs.

    CONCLUSIONS: Patients treated with bDMARDs versus no bDMARDs were younger and had significantly lower period prevalence for most common comorbidities, with the exception of infections. Differences in comorbidities between RA patients with or without bDMARDs should be taken into consideration when evaluating effectiveness and safety of bDMARDs in ordinary care.

  • 14. Bertilsson, L
    et al.
    Andersson-Gäre, B
    Fasth, A
    Forsblad-d'Elia, Helena
    Department of Rheumatology and Inflammation Research, University of Gothenburg.
    A 5-year prospective population-based study of juvenile chronic arthritis: onset, disease process, and outcome.2012Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 41, nr 5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To investigate, in a population-based cohort of patients with juvenile chronic arthritis (JCA), onset characteristics, progression, outcome, and prognostic factors longitudinally for 5 years.

    METHODS: This cohort consisted of 132 incidence cases identified between 1984 and 1986 in southwestern Sweden followed for 5 years with annual reports of subgroup, joint assessment, disease activity, eye examinations, laboratory measurements, and medication. At the 5-year follow-up, the Childhood Health Assessment Questionnaire (Child-HAQ) was evaluated. European League Against Rheumatism (EULAR) criteria for diagnosis and disease activity were used.

    RESULTS: During the 5 years only four patients were lost to follow-up, 34% changed subgroup and 8% developed uveitis. At the 5-year follow-up the disease was active in 12% of the patients, stable in 28%, inactive in 25%, and in remission in 34%. Among those examined, 24% had radiological changes, of whom half had advanced changes. The Child-HAQ median score at the 5-year follow-up was 0.13 (range 0.0-1.9). The number of involved joints at inclusion correlated positively with active disease at the 5-year follow-up. Age at disease onset, the number of involved joints, and the number of joints with arthritis correlated positively with continuous disease and Child-HAQ score. CONCLUSION. Our study shows a diverse disease course during the first 5 years of JCA where one-third changed subgroup and two-thirds did not reach remission. Age of disease onset, the number of involved joints, and the number of joints with arthritis at inclusion were associated with poor outcome at the 5-year follow-up.

  • 15. Bertilsson, Lennart
    et al.
    Andersson-Gäre, Boel
    Fasth, Anders
    Petersson, Ingemar F
    Forsblad-D'elia, Helena
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Disease course, outcome, and predictors of outcome in a population-based juvenile chronic arthritis cohort followed for 17 years.2013Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 40, nr 5, s. 715-24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate disease course, outcome, and predictors of outcome in an unselected population-based cohort of individuals diagnosed with juvenile chronic arthritis (JCA) followed for 17 years.

    METHODS: The cohort consisted of 132 incidence JCA cases identified 1984-1986 according to EULAR criteria. At 5-year followup, 129 individuals underwent joint assessment, laboratory measurements, radiographic examination, and medication and functional assessment. At 17-year followup, 86 were examined with joint assessment, laboratory measurements, medication assessment, Health Assessment Questionnaire (HAQ), Keitel functional test (KFT), and Medical Outcomes Study Short Form-36 (SF-36).

    RESULTS: At 17-year followup, 40% were in remission, 44% changed subgroups, median HAQ score was 0.0 (range 0.0-1.5), and median KFT was 100 (range 54-100). SF-36 scores were significantly lower compared to a reference group. Thirty-nine percent of those in remission at 5-year followup were not in remission at 17-year followup. In multivariate analyses of variables from the 17-year followup: remission was predicted by remission at 5-year followup (OR 4.8); HAQ > 0 by rheumatoid factor (RF)-positivity at 5-year followup (OR 3.6); KFT < 100 by nonremission (OR 11.3); and RF-positivity (OR 5.6) at 5-year followup; and the SF-36 physical component summary score above average of the reference group by remission at 5-year followup (OR 5.8).

    CONCLUSION: This longterm study of 86 individuals with JCA showed large variability of disease courses and of impaired health-related quality of life. Sixty percent were not in remission at 17-year followup. Longterm outcome was best predicted by and associated with characteristics at 5-year followup rather than those at onset.

  • 16. Björk, Albin
    et al.
    Mofors, Johannes
    Kvarnström, Marika
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Bucher, Sara Magnusson
    Hillert, Jan
    Eriksson, Per
    Mandl, Thomas
    Nordmark, Gunnel
    Alfredsson, Lars
    Wahren-Herlenius, Marie
    Cigarette smoking is a risk factor for developing primary Sjögren's syndrome with Ro/SSA and La/SSB autoantibodies2018Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, nr 3, s. S330-S330Artikel i tidskrift (Övrigt vetenskapligt)
  • 17. Boström, Elisabeth Almer
    et al.
    d'Elia, Helena Forsblad
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Dahlgren, Ulf
    Simark-Mattsson, Charlotte
    Hasséus, Bengt
    Carlsten, Hans
    Tarkowski, Andrej
    Bokarewa, Maria
    Salivary resistin reflects local inflammation in Sjögren's syndrome.2008Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 35, nr 10, s. 2005-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To assess the role of resistin in primary Sjögren's syndrome (pSS) and its relation to local inflammation.

    METHODS: Blood and saliva were collected from 37 patients with pSS (duration of symptoms 12.6+/-1 yrs) and 32 healthy controls. Expression of resistin in salivary glands was visualized immunohistologically, and levels of resistin were detected by ELISA. Levels of resistin were evaluated at baseline and following oral dehydroepiandrosterone (DHEA) treatment (50 mg/day). The effect of DHEA treatment on the secretion of resistin was assessed in vitro in human leukocytes after challenge with insulin and lipopolysaccharide.

    RESULTS: Levels of resistin in saliva were significantly higher in patients with pSS than in controls, while circulating levels of resistin were similar in both groups. Resistin was expressed in the epithelial cells of striated ducts and in the lymphocytic foci. Resistin levels in saliva were related to the intensity of inflammation in the minor salivary glands of pSS patients. No changes of the levels of resistin in blood or saliva were observed during DHEA treatment. Exposure of naive leukocytes to DHEA in vitro induced significant expression of resistin compared to nonstimulated peripheral blood mononuclear cells (p=0.031).

    CONCLUSION: We showed that levels of resistin are upregulated locally in the salivary glands of patients with pSS; and that the levels of resistin correspond to the intensity of lymphocytic inflammation in patients with pSS. We suggest that resistin is expressed in the salivary glands of patients with pSS and may be a driving factor of local inflammation.

  • 18. Dehlin, M. I.
    et al.
    Drivelegka, P.
    Sigurdardottir, V.
    Angeras, O.
    Jacobsson, L. T.
    Forsblad-D'elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hyperuricemia is associated with increased coronary artery calcification in men but not women2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 375-375Artikel i tidskrift (Övrigt vetenskapligt)
  • 19. Dehlin, M. I.
    et al.
    Drivelegka, P.
    Sigurdardottir, V.
    Angerås, O.
    Jacobsson, L. T.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Urate correlates to coronary artery calcification but not to intima media thickness2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 655-656Artikel i tidskrift (Övrigt vetenskapligt)
  • 20.
    d'Elia, Helena Forsblad
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Carlsten, H
    The impact of hormone replacement therapy on humoral and cell-mediated immune responses in vivo in post-menopausal women with rheumatoid arthritis.2008Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 68, nr 6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is well known that oestrogen has immunomodulatory properties. We have previously shown disease ameliorating effects of hormone replacement therapy (HRT) in post-menopausal women with rheumatoid arthritis (RA). The aim of this study was to investigate the effects of HRT and the patients inflammatory state on humoral and cell-mediated immune responses. Eighty-eight post-menopausal RA women were allocated to receive HRT (oestradiol and noretisterone acetate), vitamin D3 and calcium or vitamin D3 and calcium alone in a 2-year randomized controlled trial. Immunoglobulins (IgM, IgG and IgA) in serum were measured by nephelometry and rheumatoid factor (RF) concentration by enzyme-linked immunosorbent assay. Immunization with influenza vaccine was performed to quantitate humoral response to recall antigen and tuberculin skin test with purified protein derivative (PPD) to test T-cell-mediated immune response. These immune related measures were correlated with demographic and disease-related variables. HRT during 2 years did not alter concentrations of Ig, RF, IgM response to influenza vaccine or the PPD reaction. The increase in IgM against influenza vaccine was significantly positively correlated with signs of disease activity; C-reactive protein, disease activity score 28 and inversely with haemoglobin. In contrast, PPD reactivity was inversely associated with disease activity. In conclusion, long-term HRT in RA does not influence Ig or autoantibody concentrations in serum and has no significant impact on humoral and cell-mediated immune responses to recall antigens. Interestingly, high disease activity was associated to increased humoral but decreased cell-mediated immune responses irrespectively of hormone treatment.

  • 21.
    d'Elia, Helena Forsblad
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Bjurman, C
    Rehnberg, E
    Kvist, G
    Konttinen, Y T
    Interleukin 6 and its soluble receptor in a central role at the neuroimmunoendocrine interface in Sjogren syndrome: an explanatory interventional study.2009Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, nr 2Artikel i tidskrift (Refereegranskat)
  • 22.
    D'Elia, Helena Forsblad
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Larsen, Arvi
    Mattsson, Lars-Ake
    Waltbrand, Eva
    Kvist, Göran
    Mellström, Dan
    Saxne, Tore
    Ohlsson, Claes
    Nordborg, Elisabeth
    Carlsten, Hans
    Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis.2003Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 30, nr 7, s. 1456-63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Hormone replacement therapy (HRT) is known to exert a positive effect in preventing bone loss and a beneficial effect on the disease activity in rheumatoid arthritis (RA). We evaluated the effects of HRT on bone mineral density (BMD) and on the course of established RA.

    METHODS: Eighty-eight postmenopausal women with RA were randomly allocated to receive HRT, vitamin D3, and calcium supplementation or vitamin D3 and calcium supplementation alone for 2 years. The effects of additional HRT on laboratory and clinical measures of disease activity, quality of life, and BMD and on radiographic joint damage were investigated.

    RESULTS: Treatment with HRT suppressed signs of inflammation as shown by reduction in erythrocyte sedimentation rate (ESR) (p = 0.025) and an elevation in hemoglobin concentration (p = 0.007), a better clinical outcome assessed by response on the Disease Activity Score 28 (DAS28) (p = 0.036), increased BMD in the forearm, proximal femur and spine (p < 0.01), and retarded (p = 0.026) progression of joint destruction among patients with radiological progressive disease. No significant effect on quality of life was seen.

    CONCLUSION: Two years of HRT in women with active RA had significant ameliorating effects on inflammation, DAS28 response, and BMD and was associated with slower progression of radiological joint destruction. The mechanisms by which HRT exerts its effects remain to be elucidated. We suggest HRT can be used in addition to conventional therapy in the management of postmenopausal patients with RA.

  • 23.
    D'Elia, Helena Forsblad
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Mattsson, Lars-Ake
    Ohlsson, Claes
    Nordborg, Elisabeth
    Carlsten, Hans
    Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1.2003Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 5, nr 4, s. R202-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hormone replacement therapy (HRT) modulates the imbalance in bone remodeling, thereby decreasing bone loss. Sex hormones are known to influence rheumatic diseases. The aim of this study was to investigate the effects of HRT on the serum levels of hormones and cytokines regulating bone turnover in 88 postmenopausal women with active rheumatoid arthritis (RA) randomly allocated to receive HRT plus calcium and vitamin D3 or calcium and vitamin D3 alone for 2 years. An increase in estradiol (E2) correlated strongly with improvement of bone mineral density in the hip (P < 0.001) and lumbar spine (P < 0.001). Both baseline levels and changes during the study of IL-6 and erythrocyte sedimentation rate were correlated positively (P < 0.001). HRT for 2 years resulted in an increase of the bone anabolic factor, insulin-like growth factor 1 (IGF-1) (P < 0.05) and a decrease of serum levels of soluble IL-6 receptor (sIL-6R) (P < 0.05), which is known to enhance the biological activity of IL-6, an osteoclast-stimulating and proinflammatory cytokine. Baseline levels of IL-6 and IGF-1 were inversely associated (P < 0.05), and elevation of IGF-1 was connected with decrease in erythrocyte sedimentation rate (P < 0.05) after 2 years. Interestingly, increase in serum levels of E2 was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05). The latter association was however not significant after adjusting for the effect of E2 (P = 0.075). The influences of IGF-1 and the IL-6/sIL-6R pathways suggest possible mechanisms whereby HRT may exert beneficial effects in RA. However, to confirm this hypothesis future and larger studies are needed.

  • 24. Deminger, A.
    et al.
    Klingberg, E.
    Lorentzon, M.
    Carlsten, H.
    Jacobsson, L. T.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Changes in volumetric bone mineral density and bone microarchitecture in patients with ankylosing spondylitis. a five-year prospective study using hrpqct2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 916-916Artikel i tidskrift (Övrigt vetenskapligt)
  • 25. Deminger, A.
    et al.
    Klingberg, E.
    Lorentzon, M.
    Carlsten, H.
    Jacobsson, L. T. H.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    FACTORS ASSOCIATED WITH CHANGES IN VOLUMETRIC BONE MINERAL DENSITY IN PATIENTS WITH ANKYLOSING SPONDYLITIS: A FIVE-YEAR PROSPECTIVE STUDY USING HRpQCT2018Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, nr 4, s. 706-706Artikel i tidskrift (Övrigt vetenskapligt)
  • 26. Deminger, Anna
    et al.
    Klingberg, Eva
    Geijer, Mats
    Gothlin, Jan
    Hedberg, Martin
    Rehnberg, Eva
    Carlsten, Hans
    Jacobsson, Lennart T.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis2018Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 20, artikel-id 162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Knowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex. Methods: Swedish patients with AS, age (mean +/- SD) 50 +/- 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples. Results: Of 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 +/- 2.8 vs. 1.2 +/- 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression >= 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women. Conclusion: This first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men.

  • 27. Deminger, Anna
    et al.
    Klingberg, Eva
    Lorentzon, Mattias
    Geijer, Mats
    Gothlin, Jan
    Hedberg, Martin
    Rehnberg, Eva
    Carlsten, Hans
    Jacobsson, Lennart T.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Which measuring site in ankylosing spondylitis is best to detect bone loss and what predicts the decline: results from a 5-year prospective study2017Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, artikel-id 273Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes.

    Methods: In a longitudinal study, BMD in Swedish AS patients, 50 +/- 13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes.

    Results: Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, beta = -0.15, p = 0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p < 0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (beta = 3.15, p = 0.012).

    Conclusion: The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients.

  • 28. Deminger, Anna
    et al.
    Klingberg, Eva
    Nurkkala, Merja
    Carlsten, Hans
    Jacobsson, Lennart T. H.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Sahlgrenska Academy at University of Gothenburg, Department of Rheumatology and Inflammation Research, Göteborg, Sweden.
    Hepatocyte growth factor is a predictor of development of new syndesmophytes in men with ankylosing spondylitis. A five year prospective study2019Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, s. 1240-1240Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Patients with ankylosing spondylitis (AS) have an increased risk of spinal new bone formation characterized by the development of syndesmophytes. Knowledge of predictors for development of syndesmophytes is limited. Hepatocyte growth factor (HGF) has regulatory effects on a variety of cells in many different organs. HGF signaling can affect both osteoclast and osteoblast lineages and has been shown to promote osteogenesis. Cross-sectional association between increased HGF and increased modified Stoke Ankylosing Spine Score (mSASSS) has previously been shown [1], whereas knowledge of HGF as a predictor for new bone formation is lacking.

    Objectives: To study serum HGF as a predictor for development of new syndesmophytes in patients with AS followed for five years.

    Methods: Serum levels of HGF was analyzed using ELISA in patients with AS (modified NY-criteria) and in healthy controls (HC) at baseline. Spinal lateral radiographs were obtained at baseline and at the 5-year follow-up and assessed for development of new syndesmophytes using mSASSS. Univariate and multivariable logistic regression analyses were used to assess predictors for development of ≥ 1 new syndesmophyte.

    Results: Serum HGF and radiographs at baseline and follow-up were available for 163 patients, 88 men and 75 women, baseline mean age 50±12 years. AS patients had higher serum HGF than HC (n=80), p=0.050. In the AS group, 36 patients (22%) developed ≥ 1 syndesmophyte, 27 men and 9 women. In the total AS group, neither did baseline serum HGF differ between those who developed ≥ 1 new syndesmophyte and those who did not progress, nor did it predict development of ≥ 1 new syndesmophyte in the univariate analysis, p=0.25. Interestingly, men who developed ≥1 new syndesmophyte had higher serum HGF than the non-progressors (1706±454 vs 1420±338 pg/mL, p=0.001) and increased serum HGF at baseline predicted development of ≥ 1 syndesmophyte (OR per 1 SD HGF 2.39, 95% CI 1.31 to 4.36) in the univariate analysis. Serum HGF did not predict new syndesmophytes in women, p=0.13. Multivariable analysis for men including age, smoking, baseline syndesmophyte and serum HGF showed high HGF (OR per 1SD 1.90, 95% CI 1.01 to 3.59) and ≥1 baseline syndesmophyte (OR 3.48, 95% CI 1.09 to 11.07) to independently predict development of ≥ 1 new syndesmophyte. If baseline CRP was included in the multivariable model, serum HGF and baseline syndesmophytes remained the significant predictors.

    Conclusion: High baseline serum HGF was shown to independently predict the development of at least one new syndesmophyte over five years in men with AS.

  • 29. Di Giuseppe, D.
    et al.
    Frisell, T.
    Ernestam, S.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lindqvist, E.
    Lindstrom, U.
    Sjowall, C.
    Askling, J.
    Assessment of biosimilars using real world data: the complexity of choosing a comparator and understanding uptake2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 452-453Artikel i tidskrift (Övrigt vetenskapligt)
  • 30. Di Giuseppe, Daniela
    et al.
    Frisell, Thomas
    Ernestam, Sofia
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lindqvist, Elisabet
    Lindström, Ulf
    Sjöwall, Christopher
    Askling, Johan
    Uptake of rheumatology biosimilars in the absence of forced switching2018Ingår i: Expert Opinion on Biological Therapy, ISSN 1471-2598, E-ISSN 1744-7682, Vol. 18, nr 5, s. 499-504Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To describe the uptake and system-level effects of the introduction of biosimilars in a setting without forced switching.Research design and methods: We used data from the Swedish Rheumatology Quality register from start of marketing of infliximab (Remsima (R) and Inflectra (R)) and etanercept (Benepali (R)) biosimilars until 31 December 2016. We compared users of each originator-product and its biosimilar(s) by line of treatment: bDMARD-naive patients, non-medical switchers (vs. matched patients remaining on originator), and patients switching from a previous bDMARD of another type.Results: From the start of marketing 1343 patients started an infliximab biosimilar (22 months) and 2691 started etanercept (9months). Overall, the introduction of these biosimilars resulted in an increase of the total number of ongoing infliximab and etanercept treatments (originator + biosimilar) . At the end of the study period, biosimilars accounted for 31% of all infliximab treatments and 31% of all etanercept-treated patients. For each line of therapy, we noted only small differences in patient characteristics between those starting the originator product vs. its biosimilar(s).Conclusions: Introduction of biosimilars have effects beyond replacement of the originator product, in terms of an increased rate of bDMARD initiation. Selection to non-medical switching displayed no particular disease- or patient-characteristics.

  • 31. Engdahl, C.
    et al.
    Raufer, J.
    Harre, U.
    Bondt, A.
    Pfeifle, R.
    Kroenke, G.
    Scherer, H. U.
    Forsblad, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rhemtology and Inflammation reserch, CBAR, Institue of Medicine, Gothenburg, Sweden.
    Schett, G.
    Estrogen influences the sialylation profile and inflammatory properties of antibodies – a potential explanation for the sex differences and increased risk for ra in postmenopausal women2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 775-775Artikel i tidskrift (Övrigt vetenskapligt)
  • 32. Engdahl, Cecilia
    et al.
    Bondt, Albert
    Harre, Ulrike
    Raufer, Jasmin
    Pfeifle, René
    Camponeschi, Alessandro
    Wuhrer, Manfred
    Seeling, Michaela
    Mårtensson, Inga-Lill
    Nimmerjahn, Falk
    Krönke, Gerhard
    Scherer, Hans U.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Schett, Georg
    Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: a potential explanation for the increased risk of rheumatoid arthritis in postmenopausal women2018Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 20, artikel-id 84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Rheumatoid arthritis (RA) preferentially affects women, with the peak incidence coinciding with estrogen decrease in menopause. Estrogen (E2) may therefore have intrinsic immune-regulatory properties that vanish with menopause. Fc sialylation is a crucial factor determining the inflammatory effector function of antibodies. We therefore analyzed whether E2 affects immunoglobulin G (IgG) sialylation.

    Methods: Postmenopausal (ovariectomized) mice were immunized with ovalbumin and treated with E2 or vehicle. Total and ovalbumin-specific IgG concentrations, sialylation, and Fc. receptor expression were analyzed. Postmenopausal women with RA receiving hormone replacement therapy, including E2, or no treatment were analyzed for IgG sialylation. Furthermore, effects of E2 on the expression of the sialylation enzyme beta-galactoside a2,6-sialyltransferase 1 (St6Gal1) were studied in mouse and human antibody-producing cells.

    Results: E2 treatment significantly increased Fc sialylation of total and ovalbumin-specific IgG in postmenopausal mice. Furthermore, E2 led to increased expression of inhibitory Fc. receptor IIb on bone marrow leukocytes. Treatment with E2 also increased St6Gal1 expression in mouse and human antibody-producing cells, providing a mechanistic explanation for the increase in IgG-Fc sialylation. In postmenopausal women with RA, treatment with E2 significantly increased the Fc sialylation of IgG.

    Conclusions: E2 induces anti-inflammatory effector functions in IgG by inducing St6Gal1 expression in antibodyproducing cells and by increasing Fc sialylation. These observations provide a mechanistic explanation for the increased risk of RA in conditions with low estrogen levels such as menopause.

  • 33. Engdahl, Cecilia
    et al.
    Lagerquist, Marie K
    Stubelius, Alexandra
    Andersson, Annica
    Studer, Erik
    Ohlsson, Claes
    Westberg, Lars
    Carlsten, Hans
    Forsblad-d'Elia, Helena
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Role of androgen and estrogen receptors for the action of dehydroepiandrosterone (DHEA).2014Ingår i: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 155, nr 3, s. 889-96Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dehydroepiandrosterone (DHEA) is an abundant steroid hormone, and its mechanism of action is yet to be determined. The aim of this study was to elucidate the importance of androgen receptors (ARs) and estrogen receptors (ERs) for DHEA function. Orchidectomized C57BL/6 mice were treated with DHEA, DHT, 17β-estradiol-3-benzoate (E2), or vehicle. Orchidectomized AR-deficient (ARKO) mice and wild-type (WT) littermates were treated with DHEA or vehicle for 2.5 weeks. At termination, bone mineral density (BMD) was evaluated, thymus and seminal vesicles were weighted, and submandibular glands (SMGs) were histologically examined. To evaluate the in vivo ER activation of the classical estrogen signaling pathway, estrogen response element reporter mice were treated with DHEA, DHT, E2, or vehicle, and a reporter gene was investigated in different sex steroid-sensitive organs after 24 hours. DHEA treatment increased trabecular BMD and thymic atrophy in both WT and ARKO mice. In WT mice, DHEA induced enlargement of glands in the SMGs, whereas this effect was absent in ARKO mice. Furthermore, DHEA was able to induce activation of classical estrogen signaling in bone, thymus, and seminal vesicles but not in the SMGs. In summary, the DHEA effects on trabecular BMD and thymus do not require signaling via AR and DHEA can activate the classical estrogen signaling in these organs. In contrast, DHEA induction of gland size in the SMGs is dependent on AR and does not involve classical estrogen signaling. Thus, both ERs and ARs are involved in mediating the effects of DHEA in an organ-dependent manner.

  • 34. Exarchou, Sofia
    et al.
    Lie, Elisabeth
    Lindström, Ulf
    Askling, Johan
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Turesson, Carl
    Kristensen, Lars Erik
    Jacobsson, Lennart Th
    Mortality in ankylosing spondylitis: results from a nationwide population-based study2016Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, nr 8, s. 1466-1472Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Information on mortality in ankylosing spondylitis (AS) is scarce. Our study therefore aimed to assess: (1) mortality in AS versus the general population, and (2) predictors of death in the AS population. Methods: Nationwide cohorts of patients with AS diagnosed at rheumatology or internal medicine outpatient clinics (n=8600) and age-matched, sex-matched and county-matched general population comparators (n=40 460) were identified from the National Patient Register and the census register, respectively. The follow-up period began on 1 January 2006 or at the first date of registered diagnosis thereafter and extended until death, emigration or 31 December 2012, whichever occurred first. Socioeconomic variables, AS-related clinical manifestations, joint surgery, comorbidities and medication were identified from other national registers. Cox regression models were used to determine mortality and predictors for death in the AS cohort. Results: There were 496 deaths in the AS cohort and 1533 deaths in the control cohort resulting in an age-adjusted and sex-adjusted HR of 1.60 (95% CI 1.44 to 1.77), with increased mortality for men (age-adjusted HR=1.53, 95% CI 1.36 to 1.72) and women (ageadjusted HR=1.83, 95% CI 1.50 to 2.22). Within the AS cohort, statistically significant predictors for death were a lower level of education, general comorbidities (diabetes, infections, cardiovascular, pulmonary and malignant diseases) and previous hip replacement surgery. Conclusions: Mortality was increased for male and female patients with AS. Predictors of death within the AS cohort included socioeconomic status, general comorbidities and hip replacement surgery.

  • 35. Exarchou, Sofia
    et al.
    Lindström, Ulf
    Askling, Johan
    Eriksson, Jonas K
    Forsblad-d'Elia, Helena
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Neovius, Martin
    Turesson, Carl
    Kristensen, Lars Erik
    Jacobsson, Lennart Th
    The prevalence of clinically diagnosed ankylosing spondylitis and its clinical manifestations: a nationwide register study2015Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, nr 1, artikel-id 118Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Prevalence estimates of ankylosing spondylitis vary considerably, and there are few nationwide estimates. The present study aimed to describe the national prevalence of clinically diagnosed ankylosing spondylitis in Sweden, stratified according to age, sex, geographical, and socio-economic factors, and according to subgroups with ankylosing spondylitis-related clinical manifestations and pharmacological treatment.

    METHODS: All individuals diagnosed with ankylosing spondylitis according to the World Health Organization International Classification of Disease codes, between 1967 and 2009, were identified from the National Patient Register. Data regarding disease manifestations, patient demographics, level of education, pharmacological treatment, and geographical region were retrieved from the National Patient Register and other national registers.

    RESULTS: A total of 11,030 cases with an ankylosing spondylitis diagnosis (alive, living in Sweden, and 16 to 64 years old in December 2009) were identified in the National Patient Register, giving a point prevalence of 0.18% in 2009. The prevalence was higher in northern Sweden, and lower in those with a higher level of education. Men had a higher prevalence of ankylosing spondylitis (0.23% versus 0.14%, P < 0.001), a higher frequency of anterior uveitis (25.5% versus 20.0%, P < 0.001) and were more likely to receive tumor necrosis factor inhibitors than women (15.6% versus 11.8% in 2009, P < 0.001). Women were more likely than men to have peripheral arthritis (21.7% versus 15.3%, P < 0.001), psoriasis (8.0% versus 6.9%, P = 0.03), and treatment with oral corticosteroids (14.0% versus 10.4% in 2009, P < 0.001).

    CONCLUSION: This nationwide, register-based study demonstrated a prevalence of clinically diagnosed ankylosing spondylitis of 0.18%. It revealed phenotypical and treatment differences between the sexes, as well as geographical and socio-economic differences in disease prevalence.

  • 36. Feldthusen, Caroline
    et al.
    Björk, Mathilda
    Forsblad-d'Elia, Helena
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Mannerkorpi, Kaisa
    Perception, consequences, communication, and strategies for handling fatigue in persons with rheumatoid arthritis of working age--a focus group study.2013Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 32, nr 5, s. 557-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to describe how persons with rheumatoid arthritis (RA) of working age experience and handle their fatigue in everyday life. Six focus group discussions were conducted focusing on experiences of fatigue in 25 persons with RA (19 women, 6 men), aged 20-60 years. The discussions were recorded, transcribed verbatim, and analyzed according to qualitative content analysis. The analyses resulted in four categories. (1) Perception of fatigue: Fatigue was experienced different from normal tiredness, unpredictable, and overwhelming. It was associated with negative emotions, changed self-image, and fears. Feelings of frustration and shame were central when the persons were forced to omit valued life activities. (2) Consequences due to fatigue: The fatigue caused changes in cognitive ability, ability to act, and overall activity pattern where the increased need for rest and sleep caused an imbalance in daily life. The participants struggled not to let the fatigue interfere with work. The fatigue also brought negative consequences for their significant others. (3) Communicating fatigue: Fatigue was difficult to gain understanding for, and the participants adjusted their communication accordingly; it was important to keep up appearances. During medical consultation, fatigue was perceived as a factor not given much consideration, and the participants expressed taking responsibility for managing their fatigue symptoms themselves. (4) Strategies to handle fatigue: Strategies comprised conscious self-care, mental strategies, planning, and prioritizing. Fatigue caused considerable health problems for persons with RA of working age: negative emotions, imbalance in daily life due to increased need for rest, and difficulties gaining understanding. This draws attention to the importance of developing new modes of care to address fatigue in RA. Person-centered care to improve balance in life may be one approach needing further investigations.

  • 37. Feldthusen, Caroline
    et al.
    Dean, Elizabeth
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Mannerkorpi, Kaisa
    Effects of Person-Centered Physical Therapy on Fatigue-Related Variables in Persons With Rheumatoid Arthritis: A Randomized Controlled Trial2016Ingår i: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 97, nr 1, s. 26-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine effects of person-centered physical therapy on fatigue and related variables in persons with rheumatoid arthritis (RA).

    DESIGN: Randomized controlled trial.

    SETTING: Hospital outpatient rheumatology clinic.

    PARTICIPANTS: Persons with RA aged 20-65y (n=70); intervention-group (n=36) and reference-group (n=34).

    INTERVENTION: The 12-week intervention, with 6-month follow-up, focused on partnership between participant and physical therapist, and tailored health-enhancing physical activity and balancing life activities. The reference-group continued with regular activities; both groups received usual healthcare.

    MAIN OUTCOME MEASURES: Primary outcome was general fatigue (Visual Analogue Scale, VAS). Secondary outcomes included multidimensional fatigue (Bristol Rheumatoid Arthritis Fatigue - Multi-Dimensional Questionnaire, BRAF-MDQ), and fatigue-related variables, i.e., disease, health and function.

    RESULTS: At posttest, general fatigue improved more in the intervention-group than reference-group (p=0.042). Improvement in median general fatigue reached minimal clinically important difference between and within groups at posttest and follow-up. Improvement was also observed for anxiety (p=0.0099) and trends toward improvements was observed for most multidimensional aspects of fatigue (p=0.023-p=0.048), leg strength/endurance (p=0.024) and physical activity (p=0.023). Compared with the reference-group at follow-up, intervention-group improvement was observed for leg strength/endurance (p=0.001) and the trends toward improvements persisted for physical (p=0.041) and living-related (p=0.031) aspects of fatigue, physical activity (p=0.019) and anxiety (p=0.015) and self-rated health (p=0.010) and self-efficacy (p=0.046).

    CONCLUSIONS: Person-centered physical therapy focused on health-enhancing physical activity and balancing life activities, showed significant benefits on fatigue in persons with RA.

  • 38. Feldthusen, Caroline
    et al.
    Grimby-Ekman, Anna
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Jacobsson, Lennart
    Mannerkorpi, Kaisa
    Explanatory factors and predictors of fatigue in persons with rheumatoid arthritis: a longitudinal study2016Ingår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 48, nr 5, s. 469-476Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the impact of disease-related aspects on long-term variations in fatigue in persons with rheumatoid arthritis.

    DESIGN: Observational longitudinal study.

    METHODS: Sixty-five persons with rheumatoid arthritis, age range 20-65 years, were invited to a clinical examination at 4 time-points during the 4 seasons. Outcome measures were: general fatigue rated on visual analogue scale (0-100) and aspects of fatigue assessed by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire. Disease-related variables were: disease activity (erythrocyte sedimentation rate), pain threshold (pressure algometer), physical capacity (six-minute walk test), pain (visual analogue scale (0-100)), depressive mood (Hospital Anxiety and Depression scale, depression subscale), personal factors (age, sex, body mass index) and season. Multivariable regression analysis, linear mixed effects models were applied.

    RESULTS: The strongest explanatory factors for all fatigue outcomes, when recorded at the same time-point as fatigue, were pain threshold and depressive mood. Self-reported pain was an explanatory factor for physical aspects of fatigue and body mass index contributed to explaining the consequences of fatigue on everyday living. For predicting later fatigue pain threshold and depressive mood were the strongest predictors.

    CONCLUSION: Pain threshold and depressive mood were the most important factors for fatigue in persons with rheumatoid arthritis.

  • 39. Feldthusen, Caroline
    et al.
    Grimby-Ekman, Anna
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Jacobsson, Lennart
    Mannerkorpi, Kaisa
    Seasonal variations in fatigue in persons with rheumatoid arthritis: a longitudinal study2016Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, artikel-id 59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fatigue is a prominent symptom in persons with rheumatoid arthritis (RA). Although this symptom has been described to vary in duration and frequency little is known about fluctuations in fatigue over time and season. The aim of this study was to describe monthly and seasonal variations in fatigue, in persons with RA of working age.

    Methods: Sixty-five participants diagnosed with RA and aged 20-65 years were recruited from a rheumatology clinic in Sweden. The participants provided self-assessments of their fatigue at seven time points during the four seasons using a 0-100 mm visual analogue scale (VAS) and the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). Multiple regression analysis using mixed models was used to analyze changes in fatigue over time.

    Results: The mean +/- SD of fatigue rated on the VAS was 51 +/- 13, indicating substantial fatigue. Analysis of monthly variation showed statistically significant variation in fatigue ratings concerning VAS fatigue score (p < 0.01) as well as the BRAF-MDQ total score and Living, Cognition (p < 0.001), and Physical (p < 0.05) sub-scores, but not the BRAF-MDQ Emotional sub-score. The greatest variations were seen from January to September, with higher fatigue ratings in January. The changes in VAS fatigue scores over time were considered to be of clinical importance. Analysis of seasonal variation revealed a statistically significant seasonal variation in fatigue levels, with higher fatigue values during the winter as measured by VAS fatigue score (p < 0.01) as well as BRAF-MDQ total score (p < 0.01) and Physical and Living sub-scores (both p < 0.01). The greatest variation was seen between winter and autumn for VAS fatigue and between winter and summer for BRAF-MDQ total score and Physical and Living sub-scores. There were no statistical differences in fatigue levels, monthly or seasonal, between sexes or age groups.

    Conclusions: The majority of rating scales used in this study showed fluctuations in fatigue, general and physical fatigue being significantly greater during the winter. As fatigue is a substantial symptom in many persons with RA, this information is important for rheumatology professionals when dealing with persons with RA in routine care.

  • 40.
    Forsblad d'Elia, Helena
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Christgau, Stephan
    Mattsson, Lars-Ake
    Saxne, Tore
    Ohlsson, Claes
    Nordborg, Elisabeth
    Carlsten, Hans
    Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456].2004Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 6, nr 5, s. R457-68Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.

  • 41.
    Forsblad D'Elia, Helena
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Larsen, A
    Waltbrand, E
    Kvist, G
    Mellström, D
    Saxne, T
    Ohlsson, C
    Nordborg, E
    Carlsten, H
    Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis.2003Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 62, nr 7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To investigate determinants of joint destruction and reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) not treated with bisphosphonates or hormone replacement therapy and to evaluate if there are common markers of erosive disease and bone loss.

    METHODS: BMD was measured using dual x ray absorptiometry and joint damage was examined by x ray examination according to the Larsen method in 88 patients with RA. Associations between BMD and Larsen score, and between demographic and disease related variables, including proinflammatory cytokines, HLA-DR4 epitopes, and markers of bone and cartilage turnover, were examined bivariately by simple and multiple linear regression analyses.

    RESULTS: 49/88 (56%) patients had osteoporosis in at least one site. Reduced BMD and increased joint destruction were associated with: at the forearm and femoral neck, high Larsen score, low weight, and old age (R(2)=0.381, p<0.001; R(2)=0.372, p<0.001, respectively); at the total hip, low weight, high Larsen score, and dose of injected glucocorticosteroids (R(2)=0.435, p<0.001); at the lumbar spine, low weight, reduced cartilage oligomeric matrix protein, and increased carboxyterminal propeptide of type I procollagen (R(2)=0.248, p<0.001). Larsen score was associated with long disease duration and increased C reactive protein (CRP) (R(2)=0.545, p<0.001).

    CONCLUSIONS: Osteoporosis is common in postmenopausal patients with RA. Low weight and high Larsen score were strongly associated with BMD reduction. Increased CRP and long disease duration were determinants of erosive disease in postmenopausal women with RA. These findings indicate common mechanisms of local and generalised bone loss in RA.

  • 42.
    Forsblad d'Elia, Helena
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Pullerits, R
    Carlsten, H
    Bokarewa, M
    Resistin in serum is associated with higher levels of IL-1Ra in post-menopausal women with rheumatoid arthritis.2008Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 47, nr 7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: The aim of this study was to investigate associations between serum levels of resistin, an adipokine and markers of inflammation, bone metabolism, plasma lipids and kidney function in post-menopausal RA patients and to evaluate if HRT during 2 yrs affected resistin levels.

    METHODS: Eighty-eight women were randomly allocated to receive HRT, vitamin D(3) and calcium or vitamin D(3) and calcium alone. Serum levels of resistin, IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-6 soluble receptor, TNF-alpha were measured by ELISA, markers of bone metabolism, carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen by RIA, ESR, CRP, Hb, creatinine and lipids by standard laboratory techniques, BMD and total lean mass (TLM) by DXA and joint destruction by Larsen score. Resistin was also measured in 42 healthy control women.

    RESULTS: There was no difference in resistin concentration between patients and healthy controls. Resistin was significantly correlated with IL-1Ra, CRP, TNF-alpha, ICTP, glucocorticosteroids and Larsen score and inversely with BMD, hip and with TLM. In multiple regression analysis, IL-1Ra, TLM and use of corticosteroids remained determinants of resistin. Patients treated with HRT displayed significant increase in resistin compared with controls in the first but not the second year.

    CONCLUSIONS: Resistin was associated with increased inflammation, particularly by the acute-phase reactant IL-1Ra antagonizing IL-1beta, joint destruction, glucocorticosteroids and with reduced BMD and TLM. These findings suggest resistin being a significant mediator in the inflammatory process in RA. Further studies examining the mechanisms behind the relation between resistin and IL-1Ra are encouraged. HRT does not seem to have important long-term effect on resistin.

  • 43.
    Forsblad d'Elia, Helena
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Rehnberg, E
    Kvist, G
    Ericsson, A
    Konttinen, Yt
    Mannerkorpi, K
    Fatigue and blood pressure in primary Sjogren's syndrome2008Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 37, nr 4, s. 284-292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Primary Sjogren's syndrome (SS) is an autoimmune disease characterized by fatigue. Little is known about the genesis of fatigue. Fatigue is thought to represent a multidimensional concept and it is important to be able to measure it confidently. The aims were to evaluate the reliability and validity of the 20-item Multidimensional Fatigue Inventory (MFI-20) in SS and to search for factors associated with this disabling symptom.

    METHODS: Forty-eight women with primary SS completed the MFI-20 questionnaire. The results were compared with age-matched women with fibromyalgia (FM) and healthy controls. Convergent construct validity was assessed by correlations to a Visual Analogue Scale (VAS) for global fatigue by Spearman's correlation (r(s)). Test-retest reliability was analysed by the intraclass correlation coefficient (ICC) in 28 women. Associations between clinical variables and subscales of the MFI-20 were analysed.

    RESULTS: The SS women scored significantly higher in all subscales of the MFI-20 compared to controls but similar to FM. The ICCs were satisfactory, ranging from 0.66 for general fatigue to 0.85 for the total score of MFI-20. All subscales correlated significantly to VAS for global fatigue, general fatigue showing the highest correlation (r(s) = 0.70). The estimated number of hours of sleep/day was significantly associated with many of the fatigue dimensions. All five subscales of the MFI-20 were inversely associated with diastolic blood pressure (BP) and two with systolic BP.

    CONCLUSIONS: The MFI-20 was found to be a reliable and valid tool for the measurement of fatigue in primary SS. High levels of fatigue were correlated with low BP, suggesting an associated involvement of the autonomic nervous system.

  • 44.
    Forsblad-d'Elia, Helena
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Bengtsson, Karin
    Kristensen, Lars Erik
    Jacobsson, Lennart T H
    Drug adherence, response and predictors thereof for tocilizumab in patients with rheumatoid arthritis: results from the Swedish biologics register.2014Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To evaluate drug adherence, clinical response and predictors thereof for tocilizumab in patients with RA in routine care based on prospectively collected data from the Swedish biologics register, Anti-Rheumatic Therapies in Sweden.

    METHODS: RA patients who had started with tocilizumab from September 2008 until March 2012 were identified. Cox regression and logistic regression models were used.

    RESULTS: A total of 530 RA patients were included, of whom 80.6% were female, 64.7% were on concomitant DMARDs, of which 300 were on MTX and 12% were biologic naive. The overall 6 month, 1 and 2 year estimated drug continuations were 79%, 64% and 50%, respectively. In the multivariate analyses, a low initial level of CRP [hazard ratio (HR) 0.76/1s.d. (95% CI 0.63, 0.91)], high HAQ score [HR 1.23/1s.d. (95% CI 1.06, 1.44)] and prior exposure to different biologics [HR 1.43 (95% CI 1.12, 1.83)] were predictors for drug termination, whereas concomitant DMARD therapy was not. European League Against Rheumatism (EULAR) good, moderate, and no response were achieved by 184 (46.7%), 133 (33.8%) and 77 (19.5%) patients, respectively. Predictors for EULAR good response vs no response (at 2.5-8 months) were low HAQ [odds ratio (OR) 0.56/1s.d. (95% CI 0.40, 0.78)], high 28-joint DAS [OR 2.0/1s.d. (95% CI 1.44, 2.78)] and not being on prednisolone [OR 0.47 (95% CI 0.25, 0.88)] at baseline.

    CONCLUSION: In this RA cohort treated with tocilizumab, the estimated 1 year drug continuation was 64% and 80% of the patients achieved a EULAR response. Drug discontinuation was not predicted by no concomitant DMARD, but by low CRP, high HAQ and prior exposure to biologics.

  • 45.
    Forsblad-d'Elia, Helena
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Carlsten, Hans
    Bone mineral density by digital X-ray radiogrammetry is strongly decreased and associated with joint destruction in long-standing rheumatoid arthritis: a cross-sectional study.2011Ingår i: BMC musculoskeletal disorders, ISSN 1471-2474, Vol. 12, s. 242-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The aims were to explore bone mineral density (BMD) by digital X-ray radiogrammetry (DXR) in postmenopausal women with long-lasting rheumatoid arthritis (RA) in relation to dual x-ray absorptiometry (DXA)-BMD, joint destruction by conventional radiographs and disease related variables in a cross-sectional study.

    METHODS: Seventy-five postmenopausal women with RA were examined by DXA measuring DXA-BMD of the forearm, total hip and lumbar spine, by scoring joint destruction on plain radiographs by the method of Larsen and by DXR-BMD in metacarpals two to four. The DXR-BMD results of the RA women were compared with an age and sex-matched reference database. A function of DXR-BMD in relation to age and disease duration was created. Associations were investigated by bivariate and multiple linear regression analyses.

    RESULTS: DXR-BMD was strongly decreased in RA patients compared to the reference database (p < 0.001). Calculations showed that DXR-BMD was not markedly influenced the first years after diagnosis of RA, but between approximately 5-10 years of disease there was a steep decline in DXR-BMD which subsequently levelled off. In multiple regression analyses disease duration, CRP and DXR-BMD were independent variables associated with Larsen score (R2= 0.64). Larsen score and BMD forearm were independent determinants of DXR-BMD (R2 = 0.79).

    CONCLUSIONS: DXR-BMD was strongly reduced and associated with both Larsen score and DXA-BMD forearm in these postmenopausal women with RA implying that DXR-BMD is a technique that reflects both the erosive process and bone loss adjacent to affected joints.

  • 46.
    Forsblad-d'Elia, Helena
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Carlsten, Hans
    Hormone replacement therapy in postmenopausal women with rheumatoid arthritis stabilises bone mineral density by digital x-ray radiogrammetry in a randomised controlled trial.2011Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 70, nr 6, s. 1167-8Artikel i tidskrift (Refereegranskat)
  • 47.
    Forsblad-d'Elia, Helena
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Carlsten, Hans
    Labrie, Fernand
    Konttinen, Yrjö T
    Ohlsson, Claes
    Low serum levels of sex steroids are associated with disease characteristics in primary Sjogren's syndrome; supplementation with dehydroepiandrosterone restores the concentrations.2009Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, nr 6, s. 2044-51Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Serum levels of the sex steroid prohormones dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) decline upon aging and are reduced in primary Sjogren's syndrome.

    OBJECTIVE: Our aim was to investigate: 1) effects of 50 mg oral DHEA/day on changes in serum levels of DHEA and 12 of its metabolites; 2) relationships between steroid levels and disease characteristics; and 3) whether these parameters were influenced by DHEA.

    DESIGN: Twenty-three postmenopausal women with primary Sjogren's syndrome and subnormal levels of DHEA-S were included in a randomized, 9-month, controlled, double blind crossover study. Liquid chromatography/mass spectrometry (MS)/MS and gas chromatography/MS were used to measure the sex steroids. Anti-SS-A/Ro and/or anti-SS-B/La, salivary gland focus score, salivary flow rates, dry mouth and eye symptoms, and routine laboratory tests were assessed.

    RESULTS: Baseline erythrocyte sedimentation rate was inversely correlated with testosterone (Testo), dihydrotestosterone, and DHEA-S (rs = -0.42, -0.45, and -0.58, respectively). Dry mouth symptoms correlated with low Testo and androstenedione, whereas dry eyes correlated with low estrogens, most strongly estrone (rs = -0.63). Presence of anti-SS-A and/or anti-SS-B was independently associated with low estradiol (area under the receiver operating characteristic curve, 0.82). All metabolites increased during DHEA but not during placebo. The relative increases were less for estrogens and Testo compared to dihydrotestosterone and glucuronidated androgen metabolites. Dry mouth symptoms decreased during DHEA therapy.

    CONCLUSIONS: Disease manifestations in primary Sjogren's syndrome were associated with low sex hormone levels, dry mouth symptoms with low androgens, and dry eyes with low estrogens. Exogenous DHEA was preferentially transformed into androgens rather than into estrogens.

  • 48.
    Forsblad-d'Elia, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Law, Lucy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Beckman Rehnman, Jeannette
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Deminger, A.
    Klingberg, E.
    Jacobsson, L. T. H.
    High disease activity, reduced physical function, long disease duration, fatigue and living without a partner are factors related to worse health related quality of life in ankylosing spondylitis2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 347-347Artikel i tidskrift (Övrigt vetenskapligt)
  • 49.
    Forsblad-d'Elia, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Law, Lucy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Bengtsson, Karin
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Educed strain and increased stiffness of common carotid arteries in patients with ankylogin spondylitis2019Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, s. 1241-1241Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Ankylosing spondylitis (AS) is associated with an increased risk of cardiovascular disease (CVD) which also contributes to the increased mortality observed in AS. It is therefore important to develop non-invasive, accurate methods for early detection of atherosclerotic vascular changes. Studies, in other populations, have demonstrated associations between arterial stiffness and atherosclerotic burden and incident cardiovascular events. The arterial stiffness can be examined by ultrasound providing the β stiffness index that evaluates mechanical deformation properties. Technological advancements in ultrasound have developed a method assessing strain, using speckle tracking technique, which measures deformation mechanics in more dimensions. The speckle tracking method assessing arterial wall motion might permit earlier detection of subclinical CVD.

    Objectives: To study, for the first time, bilateral common carotid arterial (CCA) circumferential strain and β stiffness index in patients with AS and 1) compare the results with age and sex-matched controls and 2) explore relationships between circumferential strain and β stiffness index with disease activity, physical function and traditional risk factors for CVD in patients with AS.

    Methods: A cohort of 149 patients with AS from Northern Sweden (Modif NY, mean age 55.3±11.2 years, 102(68.5%) men, 146(98%) HLAB27) were assessed with spinal radiographs for mSASSS, clinical examination and BASMI, BASFI, ASDAS-CRP and BASDAI. Forty-six patients with AS (50.4±8.7 years, 31(67%) men) and 46 age- and sex-matched controls (49.8±9.2 years, 31(67%) men) with no known hypertension, diabetes or previous CV events were compared. Bilateral CCA ultrasound was carried out on all patients and controls. The circumferential systolic strain was measured and the β stiffness index was calculated. To analyze factors associated with strain and β stiffness index univariate and standard multivariable linear regression analyses were used. Variables with a univariate p-value ≤ 0.1 were considered for the multivariable models. For dichotomous variables, yes was coded 1 and no was coded 0.

    Results: The mean strain was significantly lower in AS patients compared with controls, 7.9±2.6% vs 10.3±1.9%, p<0.001 and the mean β stiffness index was significantly higher in AS compared to controls, 13.1±1.6 mmHg/mm vs 12.3±1.3 mmHg/mm, p=0.018.

  • 50.
    Forsblad-d'Elia, Helena
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Wallberg, Hanna
    Klingberg, Eva
    Carlsten, Hans
    Bergfeldt, Lennart
    Cardiac conduction system abnormalities in ankylosing spondylitis: a cross-sectional study.2013Ingår i: BMC musculoskeletal disorders, ISSN 1471-2474, Vol. 14, s. 237-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Cardiac conduction disturbances are common in spondyloarthropathies such as ankylosing spondylitis (AS). Whether their occurrence can be linked to signs and symptoms of rheumatic disease activity is an unsettled issue addressed in this study.

    METHODS: In this cross-sectional study patients with AS according to modified New York criteria but without psoriasis, inflammatory bowel disease, dementia, pregnancy, other severe diseases such as malignancy and difficulties in answering questionnaires were invited; and 210 participated (120 men), mean age 49 years (SD 13; range: 16-77). Questionnaires, physical examination, ECG, and laboratory tests were performed at the same visit.

    RESULTS: Cardiac conduction disturbances were common and diagnosed in 10-33%, depending on if conservative or less conservative predefined criteria were applied. They consisted mostly of 1st degree atrio-ventricular block and prolonged QRS duration, but one patient had a pacemaker and 7 more had complete bundle branch blocks. Conduction abnormalities were associated mainly with age, male gender and body weight, and not with laboratory measures of inflammation or with Bath Ankylosing Spondylitis Disease Activity Index. Neither were they associated with the presence of HLA B27, which was found in 87% of all patients; the subtype B270502 dominated in all patients.

    CONCLUSIONS: Cardiac conduction abnormalities are common in AS, but not associated with markers of disease activity or specific B27 subtypes. Even relatively mild conduction system abnormalities might, however, indirectly affect morbidity and mortality.

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