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  • 51.
    Arkema, Elizabeth V.
    et al.
    Karolinska Institute, Sweden.
    Svenungsson, Elisabet
    Karolinska Institute, Sweden.
    Von Euler, Mia
    Karolinska Institute, Sweden.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Simard, Julia F.
    Karolinska Institute, Sweden; Stanford School Med, CA USA; Stanford School Med, CA USA.
    Stroke in systemic lupus erythematosus: a Swedish population-based cohort study2017Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, nr 9, s. 1544-1549Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To study the occurrence of ischaemic and haemorrhagic stroke in systemic lupus erythematosus (SLE) compared with the general population by age, sex and time since SLE diagnosis Methods Adults with incident SLE were identified from the Swedish National Patient Register (NPR, n=3390) and general population comparators from the Total Population Register were matched on age, sex and county (n=16730). Individuals were followed prospectively until first of death, December 2013, emigration or incident stroke (identified from the NPR, Cause of Death Register and the Stroke Register). Incidence rates, rate differences and HR were estimated comparing SLE with non-SLE. Estimates were stratified by sex, age and time since diagnosis. Results We observed 126 strokes in SLE and 304 in the general population. Individuals with SLE had a twofold increased rate of ischaemic stroke compared with the general population (HR 2.2; 95% CI 1.7 to 2.8). The HR for intracerebral haemorrhage was 1.4 (95% CI 0.7 to 2.8). There was effect modification by sex and age, with the highest HRs for females and individuals amp;lt;50 years old. The HR for ischaemic stroke was highest in the first year of follow-up (3.7; 95% CI 2.1 to 6.5). Conclusions The relative risk of ischaemic stroke in SLE was more than doubled compared with the general population, and importantly, the highest relative risks were observed within the first year after SLE diagnosis. Thus, the first encounter with patients presents an opportunity for rheumatologists to screen for risk factors and intervene.

  • 52. Arkema, Elizabeth V
    et al.
    van Vollenhoven, Ronald F
    Askling, Johan
    Incidence of progressive multifocal leukoencephalopathy in patients with rheumatoid arthritis: a national population-based study2012Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, nr 11, s. 1865-1867Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cases of progressive multifocal leukoencephalopathy (PML), a rare but serious disease, have been reported in patients with rheumatoid arthritis (RA) in association with biological therapy, but little is known about the incidence of PML in patients with RA in the absence of treatment exposure.

    OBJECTIVE: To estimate the incidence rate of PML in patients with RA compared with the general population, with and without exposure to biological agents.

    METHODS: Patients with adult onset RA, exposure to biological agents and a diagnosis of PML from 1999 through 2009 were identified from national registries and linked using each Swedish resident's unique personal identification number. General population comparators matched on age, sex and county were also identified. Crude and age- and sex-standardised incidence rates (cases per 100 000 person-years) were calculated with 95% CI.

    RESULTS: 66 278 patients with RA and 286 949 general population comparators were included in the study. The incidence rate of PML in the overall RA population was 1.0 (95% CI 0.3 to 2.5) compared with 0.3 (95% CI 0.1 to 0.6) in the general population. The difference in incidence rate was 0.7 (95% CI -0.3 to 17). Among all patients exposed to biological agents, only one patient was diagnosed with PML.

    CONCLUSION: Data from this national population-based cohort study suggest that patients with RA may have an increased rate of PML compared with the general population.

  • 53.
    Arnaud, Laurent
    et al.
    Univ Strasbourg, Ctr Natl Reference Malad Syst & Autoimmunes Rares, INSERM, UMR S 1109, Strasbourg, Sweden.;Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden..
    Nordin, Annica
    Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden..
    Lundholm, Hannes
    Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden..
    Hellbacher, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Wikner, Johan
    Karolinska Inst, Stockholm, Sweden.;Soder Sjukhuset, Stockholm, Sweden..
    Zickert, Agneta
    Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden..
    Gunnarsson, Iva
    Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden..
    Effect of Corticosteroids and Cyclophosphamide on Sex Hormone Profiles in Male Patients With Systemic Lupus Erythematosus or Systemic Sclerosis2017Inngår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, nr 6, s. 1272-1279Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are autoimmune diseases that predominantly affect female patients, and therefore fewer investigations have been conducted in men. The aim of this study was to analyze sex hormone levels in male patients with SLE and those with SSc, compared to matched controls, in relation to the use of corticosteroids and cyclophosphamide (CYC).

    Methods: Sex hormone levels were measured in fasting blood samples from male patients with SLE (n=71) and those with SSc (n=29) and compared to population-based, age-matched male controls. Relevant hormone profiles were identified using cluster analysis.

    Results: Male SLE patients had higher levels of luteinizing hormone (LH) (P<0.0001) and more frequent bioactive testosterone deficiency (P=0.02) than their matched controls. The current dosage of prednisolone correlated inversely with the levels of bioactive testosterone (r=-0.36, P=0.03). Cluster analysis identified a subset of SLE patients with increased levels of follicle-stimulating hormone, LH, and prolactin as well as lower levels of bioactive testosterone (P<0.0001) in relation to higher daily doses of prednisolone. In male SSc patients, levels of testosterone (P=0.03) and bioactive testosterone (P=0.02) were significantly lower than those in matched controls. Use of CYC during the previous year was associated with lower bioactive testosterone levels in both SLE patients (P=0.02) and SSc patients (P=0.01), after adjustment for age.

    Conclusion: The results of this study highlight the negative impact of corticosteroids on gonadal function in men with SLE. Furthermore, use of CYC during the year prior to study inclusion impaired bioactive testosterone levels in male patients with either SLE or SSc. Physicians should be more aware of the possibility of hypogonadism in male patients with autoimmune diseases. The need for hormonal supplementation remains to be formally evaluated in these patients.

  • 54.
    Arnstad, Ellen Dalen
    et al.
    Nord Trondelag Hosp Trust, Levanger Hosp, Levanger, Norway;Norwegian Univ Sci & Technol, Trondheim, Norway.
    Rypdal, Veronika
    Univ Hosp North Norway, Tromso, Norway;Arctic Univ Norway, Tromso, Norway.
    Peltoniemi, Suvi
    Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland.
    Herlin, Troels
    Aarhus Univ Hosp, Aarhus, Denmark.
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Fasth, Anders
    Univ Gothenburg, Gothenburg, Sweden.
    Nielsen, Susan
    Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    Glerup, Mia
    Ekelund, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning. Ryhov Cty Hosp, Jonkoping, Sweden.
    Zak, Marek
    Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    Aalto, Kristiina
    Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland.
    Nordal, Ellen
    Univ Hosp North Norway, Tromso, Norway;Arctic Univ Norway, Tromso, Norway.
    Romundstad, Pal Richard
    Norwegian Univ Sci & Technol, Trondheim, Norway.
    Rygg, Marite
    Norwegian Univ Sci & Technol, Trondheim, Norway;St Olavs Hosp, Trondheim, Norway.
    Marhaug, Gudmund
    Anderson-Gare, Boel
    Pedersen, Freddy Karup
    Lahdenne, Pekka
    Pelkonen, Pirkko
    Early Self-Reported Pain in Juvenile Idiopathic Arthritis as Related to Long-Term Outcomes: Results From the Nordic Juvenile Idiopathic Arthritis Cohort Study2019Inngår i: Arthritis care & research, ISSN 2151-464X, E-ISSN 2151-4658, Vol. 71, nr 7, s. 961-969Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To study self-reported pain early in the disease course of juvenile idiopathic arthritis (JIA) as a predictor of long-term disease outcomes. Methods Consecutive cases of JIA with disease onset from 1997 to 2000 from defined geographical areas of Norway, Sweden, Finland, and Denmark were prospectively enrolled in this population-based cohort study. Self-reported, disease-related pain was measured on a 10-cm visual analog scale (VAS pain). Inclusion criteria were a baseline visit with a pain score 6 months after disease onset, followed by an 8-year study visit. Remission was defined according to Wallace et al (2004) preliminary criteria. Functional disability was measured by the Childhood Health Assessment Questionnaire and the Child Health Questionnaire Parent Form if the child was age <18 years and by the Health Assessment Questionnaire if age >= 18 years. Damage was scored using the Juvenile Arthritis Damage Index. Results The final study cohort consisted of 243 participants, and 120 participants (49%) had oligoarticular onset. At baseline, 76% reported a VAS pain score >0 compared to 57% reporting at 8 years. Half of those who reported baseline pain also reported pain at 8 years but at a lower intensity. Compared to no pain, higher pain intensity at baseline predicted more pain at 8 years, more functional disability, more damage, and less remission without medication. Baseline pain predicted more use of disease-modifying antirheumatic drugs/biologics during the disease course. Participants with oligoarticular JIA reporting pain at baseline were more likely to develop extended oligoarticular JIA or other JIA categories with an unfavorable prognosis. Conclusion Early self-reported, disease-related pain among children and adolescents with JIA is common and seems to predict persistent pain and unfavorable long-term disease outcomes.

  • 55.
    Arvonen, Miika
    et al.
    Kuopio Univ Hosp, Dept Pediat, Kuopio, Finland.;Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland..
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Pokka, Tytti
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland..
    Karttunen, Tuomo J.
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, Canc & Translat Med Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Pathol, Oulu, Finland..
    Vahasalo, Paula
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland..
    Stoll, Matthew L.
    Univ Alabama Birmingham, Dept Pediat, CPP N 210 M,1600 7th Ave South, Birmingham, AL 35233 USA..
    Gut microbiota-host interactions and juvenile idiopathic arthritis2016Inngår i: Pediatric Rheumatology, ISSN 1546-0096, E-ISSN 1546-0096, Vol. 14, artikkel-id 44Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Background: Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease. Main body: Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself. Conclusions: The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.

  • 56.
    Askling, J
    et al.
    Karolinska University Hospital, Stockholm, Sweden.
    Baecklund, E
    Uppsala University Hospital, Uppsala, Sweden.
    Granath, F
    Karolinska University Hospital, Stockholm, Sweden.
    Geborek, P
    Lund University Hospital, Lund, Sweden.
    Fored, M
    Karolinska University Hospital, Stockholm, Sweden.
    Backlin, C
    Uppsala University, Uppsala, Sweden.
    Bertilsson, L
    Sahlgrens University Hospital, Gothenburg, Sweden.
    Cöster, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Jacobsson, L T
    Malmö University Hospital, Malmö, Sweden.
    Lindblad, S
    Karolinska University Hospital, Stockholm, Sweden.
    Lysholm, J
    Falu County Hospital, Falun, Sweden.
    Rantapaa-Dahlqvist, S
    Umeå University Hospital, Umeå, Sweden.
    Saxne, T
    University of Lund Hospital, Lund, Sweden.
    van Vollenhoven, R
    Karolinska University Hospital, Stockholm, Sweden.
    Klareskog, L
    Karolinska University Hospital, Stockholm, Sweden.
    Feltelius, N
    Medical Products Agency, Uppsala, Sweden.
    Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register2009Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, nr 5, s. 648-653Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis ( RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.

    Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 ( n = 6604) were identified. A general population comparator ( n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.

    Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients ( 336 lymphomas during 365 026 person-years) and 2.72 ( 95% CI 1.82 to 4.08) versus the general population comparator ( 1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.

    Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.

  • 57. Askling, J
    et al.
    Fored, C M
    Brandt, L
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Bertilsson, L
    Feltelius, N
    Medical Products Agency, Uppsala, Sweden .
    Cöster, L
    Geborek, P
    Jacobsson, L T
    Lindblad, S
    Lysholm, J
    Rantapää-Dahlqvist, S
    Saxne, T
    Klareskog, L
    Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists2005Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, nr 10, s. 1421-1426Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s.

    OBJECTIVE:

    To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials.

    METHODS:

    A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53,067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003.

    RESULTS:

    With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA.

    CONCLUSION:

    The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.

  • 58. Askling, J
    et al.
    Klareskog, L
    Hjalgrim, H
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Björkholm, M
    Ekbom, A
    Do steroids increase lymphoma risk? A case-control study of lymphoma risk in polymyalgia rheumatica/giant cell arteritis2005Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, nr 12, s. 1765-1768Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Recent studies indicate increased risks of malignant lymphomas among individuals treated with corticosteroids, but have not taken into account the underlying reasons for steroid use, so the increased risks might be attributable to the underlying disease or concomitant treatments other than steroids. Polymyalgia rheumatica (PMR) and temporal arteritis (giant cell arteritis, GCA) are common inflammatory conditions treated with steroids as single immunosuppressive therapy, but data on lymphoma risk in GCA/PMR are limited.

    OBJECTIVE:

    To assess the risk of lymphoma associated with steroid treatment of GCA/PMR.

    METHODS:

    The association between GCA/PMR and malignant lymphomas (overall, and separately for non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic lymphatic leukaemia) was examined in a nationwide, population based, case-control study of 42,676 lymphoma cases and 78,487 matched population controls, using prospectively recorded data on lymphomas from the Swedish cancer register 1964-2000 and data on pre-lymphoma hospital admissions for GCA/PMR from the Swedish inpatient register 1964-2000. Odds ratios (OR) associated with a pre-lymphoma hospital admission for GCA/PMR were calculated using conditional logistic regression.

    RESULTS:

    153 lymphoma cases and 345 population controls had a history of GCA/PMR, resulting in an overall OR for malignant lymphomas of 0.81 (95% confidence interval, 0.67 to 0.98). The OR varied little with lymphoma type, sex, age, and calendar period. The OR for GCA was 0.67 (0.48 to 0.98) and for PMR, 0.83 (0.67 to 1.04).

    CONCLUSIONS:

    Treated GCA is not associated with increased lymphoma risks, which suggests that even at considerable cumulative doses, steroids may not appreciably increase lymphoma risk.

  • 59. Askling, Johan
    et al.
    Holmqvist, Marie
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Is Rheumatoid Arthritis a Mortal Disease?2017Inngår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, nr 8, s. 1509-1511Artikkel i tidsskrift (Annet vitenskapelig)
  • 60.
    Askling, Johan
    et al.
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    van Vollenhoven, Ronald F
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Granath, Fredrik
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Raaschou, Pauline
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Fored, C Michael
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Baecklund, Eva
    Uppsala University Hospital, Uppsala, Sweden.
    Dackhammar, Christina
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Feltelius, Nils
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Cöster, Lars
    Linköping University Hospital, Linköping, Sweden.
    Geborek, Pierre
    Lund University Hospital, Lund, Sweden.
    Jacobsson, Lennart T
    Malmö University Hospital, Malmö, Sweden.
    Lindblad, Staffan
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Saxne, Tore
    Lund University Hospital, Lund, Sweden.
    Klareskog, Lars
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor α therapies: does the risk change with the time since start of treatment?2009Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, nr 11, s. 3180-3189Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions. METHODS: By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. RESULTS: During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. CONCLUSION: During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.

  • 61.
    Axén, Iben
    et al.
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, The Karolinska Institutet, Stockholm, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, The Karolinska Institutet, Stockholm, Sweden.
    Bergström, Gunnar
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, The Karolinska Institutet, Stockholm, Sweden.
    Halasz, Laszlo
    Private practise, Lund, Sweden.
    Lange, Fredrik
    Private practise, Stockholm, Sweden.
    Lövgren, Peter W.
    Private practise, Stockholm, Sweden.
    Rosenbaum, Annika
    Private practise, Linköping, Sweden.
    Leboeuf-Yde, Charlotte
    Institute of Regional Health Research, Spine Centre of Southern Denmark, Hospital Lillebælt, University of Southern Denmark, Kolding, Denmark.
    Jensen, Irene
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, The Karolinska Institutet, Stockholm, Sweden.
    Clustering patients on the basis of their individual course of low back pain over a six month period2011Inngår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 12, artikkel-id 99Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Several researchers have searched for subgroups in the heterogeneous population of patients with non-specific low back pain (LBP). To date, subgroups have been identified based on psychological profiles and the variation of pain.

    Methods: This multicentre prospective observational study explored the 6- month clinical course with measurements of bothersomeness that were collected from weekly text messages that were sent by 176 patients with LBP. A hierarchical cluster analysis, Ward's method, was used to cluster patients according to the development of their pain.

    Results: Four clusters with distinctly different clinical courses were described and further validated against clinical baseline variables and outcomes. Cluster 1, a "stable" cluster, where the course was relatively unchanged over time, contained young patients with good self- rated health. Cluster 2, a group of "fast improvers" who were very bothered initially but rapidly improved, consisted of patients who rated their health as relatively poor but experienced the fewest number of days with bothersome pain of all the clusters. Cluster 3 was the "typical patient" group, with medium bothersomeness at baseline and an average improvement over the first 4-5 weeks. Finally, cluster 4 contained the "slow improvers", a group of patients who improved over 12 weeks. This group contained older individuals who had more LBP the previous year and who also experienced most days with bothersome pain of all the clusters.

    Conclusions: It is possible to define clinically meaningful clusters of patients based on their individual course of LBP over time. Future research should aim to reproduce these clusters in different populations, add further clinical variables to distinguish the clusters and test different treatment strategies for them.

  • 62.
    Baecklund, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Toes, R
    Huizinga, Twj
    Åhlin, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Askling, J
    Hochberg, F H
    Klareskog, L
    Kay, J
    Smedby, K E
    Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and smoking as risk factors for lymphoma in patients with rheumatoid arthritis2018Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, nr 4, s. 270-275Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA.

    METHOD: subclasses of anti-CCP antibodies and for 15 antinuclear antibody (ANA)-associated specific autoantibodies. Relative risks were estimated as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs) using logistic regression.

    RESULTS: We found no association between anti-CCP IgG ≥ 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG ≥ 500 units/mL (adjOR 1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1, 95% CI 0.5-2.2) and lymphoma risk among patients with RA.

    CONCLUSION: In this study, neither anti-CCP antibodies (IgG, IgG1–4, IgM, or IgA), nor other common autoantibodies, nor smoking predicted lymphoma risk in RA

  • 63.
    Bala, Sidona-Valentina
    et al.
    Department of Health Sciences, Lund University, Lund, Sweden.
    Forslind, Kristina
    Section of Rheumatology, Department of Medicine, Helsingborg Hospital, Helsingborg, Sweden.
    Fridlund, Bengt
    Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för omvårdnad. Högskolan i Jönköping, Hälsohögskolan, HHJ. ADULT.
    Hagell, Peter
    The PRO-CARE Group, School of Health & Society, Kristianstad University, Kristianstad, Sweden.
    Measuring person-centred care in nurse-led outpatient rheumatology clinics2018Inngår i: Musculoskeletal Care, ISSN 1478-2189, E-ISSN 1557-0681, Vol. 16, nr 2, s. 296-304Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Measurement of person-centred care (PCC) outcomes is underdeveloped owing to the complexity of the concept and lack of conceptual clarity. A framework conceptualizing outpatient PCC in rheumatology nurse-led clinics has therefore been suggested and operationalized into the PCC instrument for outpatient care in rheumatology (PCCoc/rheum).

    Objective: The aim of the present study was to test the extent to which the PCCoc/rheum represents the underpinning conceptual outpatient PCC framework, and to assess its measurement properties as applied in nurse-led outpatient rheumatology clinics.

    Methods: The 24-item PCCoc/rheum was administered to 343 persons with rheumatoid arthritis from six nurse-led outpatient rheumatology clinics. Its measurement properties were tested by Rasch measurement theory.

    Results: Ninety-two per cent of individuals (n = 316) answered the PCCoc/rheum. Items successfully operationalized a quantitative continuum from lower to higher degrees of perceived PCC. Model fit was generally good, including lack of differential item functioning (DIF), and the PCCoc/rheum was able to separate individuals with a reliability of 0.88. The four response categories worked as intended, with the exception of one item. Item ordering provided general empirical support of a priori expectations, with the exception of three items that were omitted owing to multidimensionality, dysfunctional response categories and unexpected ordering. The 21-item PCCoc/rheum showed good accordance with the conceptual framework, improved fit, functioning response categories and no DIF, and its reliability was 0.86.

    Conclusion: We found general support for the appropriateness of the PCCoc/rheum as an outcome measure of patient-perceived PCC in nurse-led outpatient rheumatology clinics. While in need of further testing, the 21-item PCCoc/rheum has the potential to evaluate outpatient PCC from a patient perspective.

  • 64.
    Bala, Sidona-Valentina
    et al.
    Department of Health Sciences, Lund University, Lund, Sweden.
    Forslind, Kristina
    Department of Clinical Science, Section of Rheumatology, Faculty of Medicine Lund University, Lund, Sweden.
    Fridlund, Bengt
    Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för omvårdnad. Högskolan i Jönköping, Hälsohögskolan, HHJ. ADULT.
    Samuelson, Karin
    Department of Health Sciences, Lund University, Lund, Sweden.
    Svensson, Björn
    Department of Clinical Science, Section of Rheumatology, Faculty of Medicine Lund University, Lund, Sweden.
    Hagell, Peter
    The PRO-CARE Group, School of Health & Society, Kristianstad University, Kristianstad, Sweden.
    Person-centred care in nurse-led outpatient rheumatology clinics: Conceptualization and initial development of a measurement instrument2018Inngår i: Musculoskeletal Care, ISSN 1478-2189, E-ISSN 1557-0681, Vol. 16, nr 2, s. 287-295Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Person-centred care (PCC) is considered a key component of effective illness management and high-quality care. However, the PCC concept is underdeveloped in outpatient care. In rheumatology, PCC is considered an unmet need and its further development and evaluation is of high priority. The aim of the present study was to conceptualize and operationalize PCC, in order to develop an instrument for measuring patient-perceived PCC in nurse-led outpatient rheumatology clinics.

    METHODS: A conceptual outpatient PCC framework was developed, based on the experiences of people with rheumatoid arthritis (RA), person-centredness principles and existing PCC frameworks. The resulting framework was operationalized into the PCC instrument for outpatient care in rheumatology (PCCoc/rheum), which was tested for acceptability and content validity among 50 individuals with RA attending a nurse-led outpatient clinic.

    RESULTS: The conceptual framework focuses on the meeting between the person with RA and the nurse, and comprises five interrelated domains: social environment, personalization, shared decision-making, empowerment and communication. Operationalization of the domains into a pool of items generated a preliminary PCCoc/rheum version, which was completed in a mean (standard deviation) of 5.3 (2.5) min. Respondents found items easy to understand (77%) and relevant (93%). The Content Validity Index of the PCCoc/rheum was 0.94 (item level range, 0.87-1.0). About 80% of respondents considered some items redundant. Based on these results, the PCCoc/rheum was revised into a 24-item questionnaire.

    CONCLUSIONS: A conceptual outpatient PCC framework and a 24-item questionnaire intended to measure PCC in nurse-led outpatient rheumatology clinics were developed. The extent to which the questionnaire represents a measurement instrument remains to be tested.

  • 65.
    Bala, Sidona-Valentina
    et al.
    Department of Health Sciences, Lund University, Lund, Sweden.
    Samuelson, Karin
    Department of Health Sciences, Lund University, Lund, Sweden .
    Hagell, Peter
    The PRO-CARE Group, School of Health and Society, Kristianstad University, Kristianstad, Sweden.
    Fridlund, Bengt
    Högskolan i Jönköping, Hälsohögskolan, HHJ. ADULT. Department of Health Sciences, Lund University, Lund, Sweden .
    Forslind, Kristina
    Section of Rheumatology, Department of Medicine, Helsingborg Hospital, Helsingborg, Sweden.
    Svensson, Björn
    Section of Rheumatology at the Institution of Clinical Science, Lund University, Lund, Sweden.
    Thomé, Bibbi
    Department of Health Sciences, Lund University, Lund, Sweden .
    Living with persistent rheumatoid arthritis: A BARFOT study2017Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 26, nr 17-18, s. 2646-2656Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim and objective: To describe and understand the meaning of living with persistent rheumatoid arthritis.

    Background: A considerable number of patients with rheumatoid arthritis live with an ongoing active and symptomatic illness despite access to potent antirheumatic treatment. There is, however, a lack of knowledge about the meaning of living with this severe long-term illness, defined as persistent rheumatoid arthritis.

    Design: A descriptive design based on a hermeneutic phenomenological method was used.

    Methods: Ten adults with persistent rheumatoid arthritis and at least five years disease duration were interviewed. The interviews were analysed according to van Manen's method.

    Results: Living with persistent rheumatoid arthritis revealed four overall themes: an existence dominated by painful symptoms and treatment, radical changes and limitations in one's life, a continual struggle to cope with one's life and to master the illness, and a dependency on those who are close by and the world around. The lifeworld was affected to a varying extent and in various ways by the illness but also by the dependence on its treatment and care that was not experienced as sufficiently meeting needs in terms of security, access to and coordination of care as well as team and rehabilitation services.

    Conclusions: Persistent rheumatoid arthritis and its treatment entail a radical effect on the person's life and quality of life. Current ordinary rheumatology care does not seem to meet the individual needs of the person with persistent rheumatoid arthritis in an optimal way.

    Relevance to clinical practice: A greater knowledge about and understanding of the person who lives with persistent rheumatoid arthritis is important for facilitating the development of care and the relief of suffering. A holistic alternative to conventional clinical practice, such as person-centred care, could be tested as an innovative model of care. Our findings might serve as material for educational and counselling purposes for healthcare professionals. 

  • 66. Balboni, Imelda
    et al.
    Niewold, Timothy B
    Morgan, Gabrielle
    Limb, Cindy
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Utz, Paul J
    Pachman, Lauren M
    Brief Report: Interferon-α Induction and Detection of Anti-Ro, Anti-La, Anti-Sm, and Anti-RNP Autoantibodies by Autoantigen Microarray Analysis in Juvenile Dermatomyositis2013Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr 9, s. 2424-2429Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective:

    To evaluate serum interferon- (IFN) activity in the context of autoantibody profiles in patients with juvenile dermatomyositis (JDM). 

    Methods:

    Sera from 36 patients with JDM were analyzed. Autoantibody profiles were determined by probing microarrays, which were fabricated with approximate to 80 distinct autoantigens, with serum and a Cy3-conjugated secondary antibody. Arrays were scanned and analyzed to determine antigen reactivity. Serum IFN activity was measured using a functional reporter cell assay. Sera were assayed alone or in combination with cellular material released from necrotic U937 cells to stimulate peripheral blood mononuclear cells from healthy donors in vitro, and IFN production in culture was measured by a dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). 

    Results:

    Reactivity against at least 1 of 41 autoantigens on the microarray, including Ro 52, Ro 60, La, Sm, and RNP, was observed in 75% of the serum samples from patients with JDM. IFN activity was detected in 7 samples by reporter cell assay. The reporter cell assay showed a significant association of reactivity against Ro, La, Sm, and proliferating cell nuclear antigen with serum IFN activity (P = 0.005). Significance Analysis of Microarrays (SAM) identified increased reactivity against Sm, RNP, Ro 52, U1-C, and Mi-2 in these sera. Sixteen samples induced IFN production as measured by DELFIA, and there was a significant association of reactivity against Ro, La, Sm, and RNP with the induction of IFN by serum and necrotic cell material (P = 0.034). SAM identified increased reactivity against Ro 60 in these sera. 

    Conclusion:

    These data support the hypothesis that nucleic acid-associated autoantibodies, including the Ro/La and Sm/RNP complexes, may stimulate the production of active IFN in children with JDM.

  • 67.
    Barbe, MF
    et al.
    Department of Anatomy and Cell biology, Temple University, Philadelphia, USA.
    Xin, DL
    Department of Surgery, University of Pennsylvania, USA.
    Hadrevi, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Elliott, ME
    Department of Neurosurgery, Thomas Jefferson University, USA.
    Barr-Gillespie, A
    College of Health Professions, Pacific University, USA.
    Sickness behaviors (reduced social interaction and pain behaviors) are linked to inflammatory mechanisms in a rat model of work-related musculoskeletal disorders2016Inngår i: Proceedings of the Human Factors and Ergonomics Society Annual Meeting, ISSN 1541-9312, Vol. 60, nr 1, s. 975-979Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We sought to determine if sickness behaviors (decreased social interaction and pain) are induced in a rat model of work-related overuse and effectiveness of anti-inflammatory treatments. Rats first trained to learn a high force reaching task (15 min/week day for 6 wks), with subsets treated prophylactically with ibuprofen or anti-TNFalpha. Others performed a high repetition high force (HRHF) task for 6 or 12 weeks (2 hrs/day, 3 days/wk) untreated, or with ibuprofen, anti-TNFalpha or rest treatments beginning task week 5. Untreated HRHF rats had increased IL-1beta, IL-6 and TNFalpha in serum and brain, increased Substance P in spinal cord, decreased social interaction and increased forepaw allodynia. Secondary antiinflammatory treatments attenuated social interaction and brain changes, but not allodynia or spinal cord changes; rest provided partial attenuation. Prophylactic treatments prevented all changes. Thus, inflammatory mechanisms mediate the development of sickness behaviors induced by work-related overuse, but not maintenance of allodynia.

  • 68.
    Bejerot, Susanne
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Faculty of Medicine and Health, University Health Care Research Centre, Örebro University, Örebro, Sweden.
    Hesselmark, Eva
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Mobarrez, Fariborz
    Unit of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Wallén, Håkan
    Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden.
    Hietala, Max Albert
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nybom, Rolf
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Wetterberg, Lennart
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Neuromyelitis optica spectrum disorder with increased aquaporin-4 microparticles prior to autoantibodies in cerebrospinal fluid: a case report2019Inngår i: Journal of Medical Case Reports, ISSN 1752-1947, E-ISSN 1752-1947, Vol. 13, nr 1, artikkel-id 27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Neuromyelitis optica spectrum disorders are severe autoimmune inflammatory diseases of the central nervous system associated with the presence of immunoglobulin G antibodies against the water channel protein aquaporin-4. During exacerbation, specific aquaporin-4 immunoglobulin G may be produced intrathecally. We measured extracellular aquaporin-4 microparticles in the cerebrospinal fluid of a patient who later developed the typical symptoms and signs of a neuromyelitis optica spectrum disorder.

    CASE PRESENTATION: A 17-year-old South American girl developed acute severe motor and vocal tics and difficulties in walking, peripheral numbness, muscle pain, and bilateral headache. At age 22, she had a multitude of motor and psychiatric symptoms. Over the years, she fulfilled the diagnostic criteria for anorexia nervosa, depression, sleep disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, agoraphobia, social anxiety disorder, development coordination disorder, attention-deficit/hyperactivity disorder, hypomania, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, conversion disorder, psychosis, and schizotypal personality syndrome. At age 24, she was found to have elevated titers of aquaporin-4 antibodies in serum, suggestive of probable neuromyelitis optica. She subsequently developed visual impairment, and swollen optic nerves were verified by magnetic resonance imaging. She was thus treated with a chimeric monoclonal antibody targeted against the pan-B-cell marker CD20 (rituximab), and almost all symptoms, including the psychiatric symptoms, rapidly decreased. We found a significant increase of extracellular microparticles of aquaporin-4 in cerebrospinal fluid sampled from our patient when she was 22 years old, 2 years before the full clinical development of neuromyelitis optica.

    CONCLUSIONS: Microparticles of aquaporin-4 represent subcellular arrangements that may influence the pathogenesis of neuromyelitis optica spectrum disorders and may serve as biomarkers for the underlying cellular disturbances. The increase of aquaporin-4 microparticles in cerebrospinal fluid may be used for early diagnostic purposes; for prevention; and for evaluation of effective treatment, long-term follow-up studies, and elucidating the pathophysiology in neuromyelitis optica spectrum disorders. Further studies of aquaporin-4 microparticles in cerebrospinal fluid of patients with neuromyelitis optica and similar neuropsychiatric disorders are thus called for.

  • 69.
    Bengtsson, A. A.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Systemic lupus erythematosus: still a challenge for physicians2017Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, nr 1, s. 52-64Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Systemic lupus erythematosus (SLE) has a complex clinical picture, and a number of defects in the immune system have been described in patients with the disease. Most organs can be involved in SLE, and in addition to the typical major organ manifestations (e.g. from kidneys and the central nervous system), early cardiovascular disease is a major determinant of prognosis. Several important findings during the last decade have increased the understanding of the mechanisms behind the disease characteristics and the underlying autoimmune process. Amongst, these are defects in the handling of apoptotic cells, increased expression of type I interferon-regulated genes and activation of autoreactive B cells, with both the type I interferon system and the B lymphocyte stimulator (BLyS) having key roles. In addition, a large number of genes have been identified that contribute to these abnormalities. It has also become clear that certain SLE risk genes are associated with some organ manifestations, such as STAT4 with nephritis and IRF8 with myocardial infarction. Furthermore, environmental factors that can induce SLE or trigger a disease flare have been identified. As a consequence of this increased knowledge, new treatments for SLE have been developed. The most recently approved drug for SLE is belimumab, which blocks BLyS, and several new therapies and therapeutic strategies are in the pipeline for clinical application.

  • 70.
    Bengtsson, Anders A.
    et al.
    Lund Univ, Skdne Univ Hosp, Dept Clin Sci Lund, Rheumatol, S-22185 Lund, Sweden..
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Role of interferons in SLE2017Inngår i: Baillière's Best Practice & Research: Clinical Rheumatology, ISSN 1521-6942, E-ISSN 1532-1770, Vol. 31, nr 3, s. 415-428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects many different organ systems, with excessive production of type I interferons (IFNs) and auto antibodies against nucleic acids as hallmarks. Activation of the type I IFN system in SLE is due to continuous stimulation of plasmacytoid dendritic cells by endogenous nucleic acids, leading to sustained type I IFN production. This is reflected by an over expression of type I IFN-regulated genes or an IFN signature. Type I IFNs have effects on both the innate and adaptive immune systems, which contribute to both loss of tolerance and the autoimmune disease process. In this review, we discuss the current understanding of IFNs in SLE, focusing on their regulation, the influence of genetic background, and environmental factors and therapies that are under development aiming to inhibit the type I IFN system in SLE.

  • 71. Bengtsson, Anders A
    et al.
    Sturfelt, Gunnar
    Lood, Christian
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    van Vollenhoven, Ronald F
    Axelsson, Bengt
    Sparre, Birgitta
    Tuvesson, Helén
    Wallén Öhman, Marie
    Leanderson, Tomas
    Pharmacokinetics, tolerability, and preliminary efficacy of ABR-215757, a new quinoline-3-carboxamide derivative, in murine and human SLE2012Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr 5, s. 1579-1588Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To assess the efficacy of ABR-215757, a new immunomodulatory small molecule in a murine SLE model, to evaluate the pharmacokinetics and tolerability in SLE patients at doses predicted to be efficacious and safe, and to determine the maximum tolerated dose (MTD).

    METHODS: The efficacy of ABR-215757 was studied in lupus prone MRLlpr/lpr mice and compared with established SLE treatments. Dose response data of ABR-215757 were together with pharmacokinetic data used to calculate effective and safe clinical doses. The pharmacokinetics and tolerance of ABR-215757 were evaluated in a Phase Ib double-blind, placebo controlled, dose-escalation study where cohorts of SLE patients received daily oral treatment for 12 weeks.

    RESULTS: Disease inhibition in MRLlpr/lpr mice, comparable to that of prednisolone and mycophenolate mofetil, was obtained with ABR-215757. Prominent effects on disease manifestations, serological markers and a steroid sparing effect were seen for ABR-215757. The pharmacokinetic properties in SLE patients were linear and well suitable for once daily oral treatment. The majority of the adverse events (AEs) were mild or moderate and transient. The most frequent AEs were arthralgia and myalgia, reported at the highest (4.5 and 6 mg/day) dose levels. At 4.5 mg and higher some AEs of severe intensity and serious adverse events (SAEs) were reported.

    CONCLUSION: ABR-215757 effectively inhibited disease and had a steroid sparing effect in experimental lupus. Clinical doses up to 3 mg/day, dose levels predicted from pre-clinical studies to be efficacious and safe, were well tolerated in the SLE patients. The MTD was concluded to be 4.5 mg/day.

  • 72.
    Bengtsson, C.
    et al.
    Department of Rheumatology, Östersund Hospital, Sweden .
    Bengtsson, A. A.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Costenbader, K. H.
    Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA .
    Jönsen, A.
    2Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sturfelt, G.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Nived, O.
    Department of Rheumatology, Institute of Clinical Sciences, Lund University Hospital, Sweden .
    Systemic lupus erythematosus and cardiac risk factors: medical record documentation and patient adherence2011Inngår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 20, nr 10, s. 1057-1062Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study explores patients' knowledge of cardiac risk factors (CRFs), analyses how information and advice about CRFs are documented in clinical practice, and assesses patient adherence to received instructions to decrease CRFs. Systemic lupus erythematosus (SLE) patients with >= 4 ACR criteria participated through completing a validated cardiovascular health questionnaire (CHQ). Kappa statistics were used to compare medical records with the self-reported CHQ (agreement) and to evaluate adherence. Two hundred and eleven (72%) of the known patients with SLE participated. The mean age of the patients was 55 years. More than 70% of the SLE patients considered hypertension, obesity, smoking and hypercholesterolaemia to be very important CRFs. The agreement between medical record documentation and patients' reports was moderate for hypertension, overweight and hypercholesterolaemia (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). Patients' self-reported adherence to advice they had received regarding medication was substantial to perfect (kappa 0.65-1.0). For lifestyle changes in patients with hypertension and overweight, adherence was only fair to moderate (kappa 0.13-0.47). Swedish SLE patients' awareness of traditional CRFs was good in this study. However, the agreement between patients' self-reports and medical record documentation of CRF profiles, and patients' adherence to medical advice to CRF profiles, could be improved. Lupus (2011) 20, 1057-1062.

  • 73.
    Bengtsson, C.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wahlin, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Braune, A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Jonsson, E.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hydroxychloroquine improves the blood lipid profile in rheumatoid arthritis and systemic lupus erythematosus after four and eight weeks of treatment: a randomized interventional study2018Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, s. 29-29Artikkel i tidsskrift (Annet vitenskapelig)
  • 74. Bengtsson, C
    et al.
    Öhman, Marie-Louise
    Nived, O
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Cardiovascular event in Systemic Lupus Erythematosus in northern Sweden: incidence and predictors in a 7-year follow up study2012Inngår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 21, nr 4, s. 452-459Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction. An increased rate of cardiovascular disease (CVD) has been suggested in patients with systemic lupus erythematosus (SLE). The risk for myocardial infarction (MI), coronary artery disease and stroke has been reported as particularly prevalent in younger females compared with the reference population. This study was performed to analyse the standard incidence ratio (SIR) of and predictors for cardiovascular events (CVEs) in patients with SLE from northern Sweden, with a fairly homogenous population.

    Methods. In 2000 all prevalent patients with SLE (≥4 American College of Rheumatology [ACR] criteria; n = 277) from the four northern-most counties of Sweden were assessed with clinical and laboratory analyses. Seven years follow-up data concerning MI and stroke were extracted from the national registers of hospitalization and death in Sweden. The incidence ratio among the patients was compared with that for the general population from the same catchment area using data from the same register and Statistics Sweden. To identify time to event and CVE predictors, two matched controls for each patient were used and disease related variables as CVD predictors.

    Results. The SIR for a CVE was 1.27 (95% CI 0.82-1.87) and for females separately aged 40-49 years was 8.00 (95% CI 1.65-23.38). The overall SIR for MI was 2.31 (95% CI 1.34-3.7), for females overall was 1.75 (95% CI 0.84-3.22) and for females aged between 40 and 49 years was 8.7 (95% CI 1.1-31.4). The time to an event was significantly shorter among SLE patients (p < 0.001) and was predicted by hypertension adjusted for smoking and disease. High SLEDAI and anti-cardiolipin IgG antibodies predicted an event in Cox proportional hazards regression models adjusted for age and previous MI. Diabetes, smoking ever and sex did not affect the prediction models.

    Conclusion. The risk of a CVE, or MI, was eight- or nine-fold greater among middle-aged female SLE patients. Time to event was significantly shorter and CVE was associated with SLE-related factors including hypertension and age.

  • 75. Bengtsson, Christine
    et al.
    Öhman, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Prediction of cardiovascular event in systemic lupus erythematosus in northern Sweden: a 7-year follow up study2010Inngår i: Scandinavian Journal of Rheumatology. Supplement, ISSN 0301-3847, E-ISSN 1502-7740, Vol. 39, nr Suppl.124, s. S28-Artikkel i tidsskrift (Fagfellevurdert)
  • 76. 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 study2018Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 337-338Artikkel i tidsskrift (Annet vitenskapelig)
  • 77. 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 STUDY2018Inngår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, nr 4, s. 714-714Artikkel i tidsskrift (Annet vitenskapelig)
  • 78. 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?2015Inngår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, artikkel-id 1057Artikkel i tidsskrift (Annet vitenskapelig)
  • 79. 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 Population2015Inngår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, nr 10, artikkel-id 1059Artikkel i tidsskrift (Annet vitenskapelig)
  • 80. 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 study2016Inngår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, nr 1, artikkel-id 499Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 81.
    Bentow, C.
    et al.
    Inova Diagnost, CA USA.
    Lakos, G.
    Inova Diagnost, CA USA.
    Martis, P.
    Inova Diagnost, CA USA.
    Wahl, E.
    Inova Diagnost, CA USA.
    Garcia, M.
    Hospital Clin Barcelona, Spain.
    Vinas, O.
    Hospital Clin Barcelona, Spain.
    Espinosa, G.
    Hospital Clin Barcelona, Spain.
    Cervera, R.
    Hospital Clin Barcelona, Spain.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Carmona-Fernandes, D.
    University of Lisbon, Portugal.
    Santos, M. J.
    University of Lisbon, Portugal.
    Hanly, J. G.
    Dalhousie University, Canada.
    Mahler, M.
    Inova Diagnost, CA USA.
    International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies2016Inngår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 25, nr 8, s. 864-872Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Patients and methods: A total of 1431 samples (SLE, n=843; disease controls, n=588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n=566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off ofamp;gt;4 was used to define active disease. Results: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (pamp;lt;0.0001) in active SLE (SLEDAI-2Kamp;gt;4; n=232; median value 83.0IU/mL) versus the inactive patients (n=573; median value 22.3IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearmans rho=0.44, pamp;lt;0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. Conclusions: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.

  • 82.
    Berg, L.
    et al.
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Sundström, Y.
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Aftab, Obaid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Bergqvist, F.
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Gustafsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Sundström, M.
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Ossipova, E.
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Lengqvist, J.
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Jakobsson, P-J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Rubin, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Characterizing the effects of epigenetic regulation in assays using peripheral blood mononuclear cells from patients with inflammatory diseases2016Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 45, s. 44-45Artikkel i tidsskrift (Annet vitenskapelig)
  • 83.
    Berggren, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Regulation of Type I Interferon Production in Plasmacytoid Dendritic Cells: Effect of Genetic Factors and Interactions with NK Cells and B Cells2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The type I interferon (IFN) system plays a central role in the etiopathogenesis of many autoimmune diseases, e.g. systemic lupus erythematosus (SLE). Activation of the type I IFN system in SLE is promoted by endogenous nucleic acid-containing immune complexes (ICs) which stimulate plasmacytoid dendritic cells (pDCs). This thesis focuses on the regulation of IFN-α production in pDCs, by interactions with B cells and natural killer (NK) cells, and by genetic factors.

    In Study I, RNA-IC-stimulated CD56dim NK cells were found to be activated via FcγRIIIa and enhanced the IFN-α production by pDCs. The enhancing effect of the NK cells was mediated via both soluble factors, such as the cytokine MIP-1β, and in a cell-cell contact mediated manner via the adhesion molecule LFA-1. In Study II, B cells enhanced the IFN-α production by pDCs via cell-cell contact or soluble factors, depending on the stimuli. The cell-cell contact-mediated enhancement, when the cells were stimulated with RNA-IC, was abolished by blocking the cell adhesion molecule CD31. B cells stimulated with the oligonucleotide ODN2216 enhanced the IFN-α production via soluble factors. In Study III, gene variants related to autoimmune or inflammatory diseases were analyzed for the association to the IFN-α production by pDCs, alone or in coculture with NK or B cells. Depending on cell combination, 18-86 SNPs (p < 0.001) were associated with the IFN-α production. Several of the SNPs showed novel associations to the type I IFN system, while some loci have been described earlier for their association with SLE, e.g. IL10 and PXK. In Study IV, several B cell populations were affected by cocultivation with pDCs and stimulation with RNA-IC. The frequency of CD24hiCD38hi B cells of regulatory character was increased in the pDC-B cell cocultures. However, RNA-IC-stimulation only induced modest levels of IL-10. A remarkably increased frequency of double negative CD27-IgD- B cells was found in the RNA-IC-stimulated cocultures of pDCs and B cells.

    In conclusion, the findings in the present thesis reveal novel mechanisms behind the regulation of the type I IFN system which could be important targets in autoimmune diseases with constantly activated pDCs.

  • 84.
    Berggren, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Alexsson, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Morris, David
    King’s College London School of Medicine, Guy’s Hospital, London.
    Tandre, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Weber, Gert
    Free University of Berlin.
    Vyse, Timothy
    King’s College London School of Medicine, Guy’s Hospital, London.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    IFN-α production by plasmacytoid dendritic cell associations with polymorphisms in gene loci related to autoimmune and inflammatory diseases2015Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 12, s. 3571-3581Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The type I interferon (IFN) system is persistently activated in systemic lupus erythematosus (SLE) and many other systemic autoimmune diseases. Studies have shown an association between SLE and several gene variants within the type I IFN system. We investigated whether single nucleotide polymorphisms (SNPs) associated with SLE and other autoimmune diseases affect the IFN-α production in healthy individuals. Plasmacytoid dendritic cells (pDCs), B and NK cells were isolated from peripheral blood of healthy individuals and stimulated with RNA-containing immune complexes (IC), herpes simplex virus (HSV) or the oligonucleotide ODN2216. IFN-α production by pDCs alone or in cocultures with B or NK cells was measured by an immunoassay. All donors were genotyped with the 200K ImmunoChip and a 5bp CGGGG length polymorphism in the IFN regulatory factor 5 gene (IRF5) was genotyped by PCR. We found associations between IFN-α production and 18-86 SNPs (p ≤ 0.001), depending on the combination of the stimulated cell types. However, only three of these associated SNPs were shared between the cell type combinations. Several SNPs showed novel associations to the type I IFN system among all the associated SNPs, while some loci have been described earlier for their association with SLE. Furthermore, we found that the SLE-risk variant of the IRF5 CGGGG-indel was associated with lower IFN-α production. We conclude that the genetic variants affecting the IFN-α production highlight the intricate regulation of the type I IFN system and the importance of understanding the mechanisms behind the dysregulated type I IFN system in SLE.

  • 85.
    Berggren, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Alexsson, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Tandre, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Syvanen, A-C
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Effect of single-nucleotide polymorphisms on type I interferon production by plasmacytoid dendritic cells stimulated with SLE-associated immune complexes2014Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr S127, s. 92-92Artikkel i tidsskrift (Annet vitenskapelig)
  • 86.
    Berggren, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Activated plasmacytoid dendritic cells alter the composition of peripheral blood B cell subsetsManuskript (preprint) (Annet vitenskapelig)
  • 87.
    Berggren, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Activated Plasmacytoid Dendritic Cells (PDCS) Alter The Composition of The Blood B Cell Subsets2016Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 179-179Artikkel i tidsskrift (Annet vitenskapelig)
  • 88.
    Berggren, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    The effect of PTPN22 Gene Variant R620W on the Type I Interferon Production Stimulated by Different TLR7 Agonists: Comment on Article by Wang et al (pages 2403-2414)2016Inngår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 68, nr 4, s. 1045-1045Artikkel i tidsskrift (Fagfellevurdert)
  • 89.
    Berglin, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lorentzon, Ronnie
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Nordmark, L
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nilsson-Sojka, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Predictors of radiological progression and changes in hand bone density in early rheumatoid arthritis2003Inngår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 42, nr 2, s. 268-275Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To identify predictors for radiological and functional outcome and bone loss in the hands in early rheumatoid arthritis (RA) during the first 2 yr of disease and to study the relationship between these variables.

    METHODS: An inception cohort of consecutively recruited patients was examined at baseline and after 12 and 24 months using X-rays of hands and feet, clinical [28-joint count, Health Assessment Questionnaire (HAQ), global visual analogue scale (VAS), grip strength] and laboratory (erythrocyte sedimentation rate, C-reactive protein, markers of bone formation and resorption) measurements and dual-energy X-ray absorptiometry measurements of the hands.

    RESULTS: Joint destruction increased significantly during the study, with the Larsen score at baseline as the strongest predictor. Radiological progression and bone loss over 24 months were significantly retarded in patients responding to therapy. The effects of the shared epitope and initial high inflammatory activity on radiological progression were overridden by the therapeutic response. Radiological progression correlated significantly with bone loss. Global VAS, Larsen score and HAQ at inclusion significantly predicted change in HAQ over time.

    CONCLUSIONS: Radiological progression and bone loss were retarded by early therapeutic response. Bone loss was related to radiological progression.

  • 90.
    Berglin, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Carlsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Effect of hydrogen sulfide on the mutagenicity of hydrogen peroxide in Salmonella typhimurium strain TA1021986Inngår i: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 175, nr 1, s. 5-9Artikkel i tidsskrift (Fagfellevurdert)
  • 91.
    Berglin, Ewa H.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Does Evaluation Of Hand Bone Loss By Digital x-Ray Radiogrammetry Within The First 3 Months After Diagnosis Of Rheumatoid Arthrits Identify Patients At Risk For Radiological Progression?2013Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S834-S834, Meeting Abstract: 1958Artikkel i tidsskrift (Annet vitenskapelig)
  • 92.
    Berglin, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Johansson, T.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sundin, U.
    Jidell, Erik
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hallmans, Göran
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset2006Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, nr 4, s. 453-458Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression. METHODS: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified. RESULTS: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis. CONCLUSIONS: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.

  • 93.
    Berglin, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Padyukov, Leonid
    Sundin, Ulf
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Van Venrooij, Walther J
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis2004Inngår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 6, nr 4, s. R303-R308Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis (RA) by years. A nested case–control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of shared epitope (SE) genes, defined as HLA-DRB1*0404 or DRB1*0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified from among blood donors whose samples had been collected years before the onset of symptoms. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified as blood donors, with a median antedating time of 2.0 years (interquartile range 0.9–3.9 years) before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17–42% and 94%, respectively. In a logistic regression analysis, SE (odds ratio [OR] = 2.35), anti-CCP antibodies (OR = 15.9), and IgA-RF (OR = 6.8) significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR (66.8, 95% confidence interval 8.3–539.4) in predicting RA, compared with anti-CCP antibodies without SE (OR = 25.01, 95% confidence interval 2.8–222.2) or SE without anti-CCP antibodies (OR = 1.9, 95% confidence interval 0.9–4.2). This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA.

  • 94.
    Berglin, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Comparison of the 1987 ACR and 2010 ACR/EULAR classification criteria for rheumatoid arthritis in clinical practice: a prospective cohort study2013Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, nr 5, s. 362-368Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To compare application of the 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for diagnosing rheumatoid arthritis (RA) in clinical practice. Method: The medical records of patients with early arthritis attending the Rheumatology Department, Umea University Hospital (n = 1026) were analysed. Patients with synovitis in at least one joint, no diagnosis other than RA being better for explaining the synovitis, and duration of symptoms less than 1 year at first visit, and at least 1 year of follow-up were included consecutively. Fulfilment of the 1987 and 2010 criteria at baseline was evaluated. Sensitivity and specificity for each criterion set, where estimated by using the outcome measures: initiation of methotrexate (MTX) therapy during the first year, and a clinical diagnosis of RA at the 1-year follow-up. Radiographs of hands and feet were evaluated using the Larsen score. Results: The study included 313 patients, of whom 56% fulfilled the 1987 ACR criteria, 74% the 2010 ACR/EULAR criteria, and 53% both sets of criteria at baseline. The sensitivity/specificity for the 1987 and 2010 criteria with MTX within the first year as the outcome measure was 0.68/0.79 and 0.84/0.54, respectively, and with a diagnosis of RA at follow-up 0.72/0.83 and 0.91/0.65, respectively. Older patients (i.e. >= 60 years) more often fulfilled the 2010 criteria. Patients who fulfilled the 2010 ACR/EULAR but not the 1987 ACR criteria had a lower Larsen score at inclusion and after 2 years. Conclusions: Compared with the 1987 ACR criteria, the 2010 ACR/EULAR criteria have higher sensitivity but lower specificity, especially in patients aged >= 60 years. The 1987 ACR criteria are suggested to predict a more erosive disease.

  • 95.
    Berglin, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Comparison of the 1987 ACR and 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis in Clinical Practice2011Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 63, nr 10, s. S117-S117Artikkel i tidsskrift (Fagfellevurdert)
  • 96.
    Berglund, Britta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Pettersson, Carina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Pigg, Maritta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Kristiansson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Self-reported quality of life, anxiety and depression in individuals with Ehlers-Danlos syndrome (EDS): a questionnaire study2015Inngår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 16, artikkel-id 89Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Many individuals with Ehlers-Danlos Syndrome (EDS) are hypermobile, suffer from long term pain, and have complex health problems. Since these sometimes have no objective physical signs, individuals with EDS sometimes are referred for psychiatric evaluation. The aim was therefore to identify the level of anxiety and quality of life in a Swedish group of individuals with EDS. Methods: A postal survey in 2008 was distributed to 365 members over 18 years of the Swedish National EDS Association and 250 with EDS diagnosis responded. Two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and SF-36, were used. A Swedish population study was used to compare results from SF-36. Independent Student's t-test was used to compare differences between groups, possible relationships were tested using Spearman's correlation coefficient and the General Linear Model was used for regression analyses. Higher scores on HADS represent higher levels of anxiety and depression and higher scores on SF-36 represent higher quality of health. Results: Of the respondents 74.8% scored high on anxiety and 22.4% scored high on depression on the HADS. Age, tiredness and back pain was independently associated with the HAD anxiety score in a multiple regression analysis, When comparing the SF-36 scores from the EDS group and a Swedish population group, the EDS group scored significantly lower, indicating lower health-related quality of health than the general population (p < 0.001). Conclusions: In comparison with a Swedish population group, a lower health-related quality of life was found in the EDS group. Also, higher levels of anxiety and depression were detected in individuals with EDS. The importance to explore the factors behind these results and what initiatives can be taken to alleviate the situation for this group is emphasized.

  • 97. Berglund, S
    et al.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine: a six-year follow-up study2009Inngår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 27, nr 5, s. 822-825Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate whether homocysteine is linked to atherothrombotic (AT) events in patients with rheumatoid arthritis (RA). METHODS: Analysis of homocysteine (Hcy) levels was carried out in 235 consecutive RA patients. They were followed-up for 6.5 years or until death, with analysis of AT risk factors and the type and length of DMARD and corticosteroid treatment. The disease history before inclusion was collected. Six categories of AT events were defined. In addition, the diagnosis of the patients at follow-up was co-analyzed with the nationwide population-based Swedish Inpatient Register and Death Register to certify all events. RESULTS: The Hcy level was found to be higher in males (p<0.05) and increased with age (p<0.001). Patients with folic acid supplementation had significantly lower levels, while those on corticosteroids had higher levels. High Hcy levels predicted AT events (n=48) during a 6.5-year follow-up adjusted for age and male sex in a logistic regression analysis. CONCLUSION: In this study, RA patients on folic acid had lower Hcy levels. High Hcy levels (in addition to age, sex and diabetes) predicted AT event prospectively.

  • 98.
    Bergman, Stefan
    Spenshult Hospital, Oskarström, Sweden.
    Management of musculoskeletal pain2007Inngår i: Baillière's Best Practice & Research: Clinical Rheumatology, ISSN 1521-6942, E-ISSN 1532-1770, Vol. 21, nr 1, s. 153-166Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic musculoskeletal pain is a major public health problem affecting about one third of the adult population. Pain is often present without any specific findings in the musculoskeletal system and a strictly biomedical approach could be inadequate. A biopsychosocial model could give a better understanding of symptoms and new targets for management. Identification of risk factors for chronicity is important for prevention and early intervention. The cornerstones in management of chronic non-specific, and often widespread, musculoskeletal pain are non-pharmacological. Physical exercise and cognitive behavioral therapy, ideally in combination, are first line treatments in e.g. chronic low back pain and fibromyalgia. Analgesics are useful when there is a specific nociceptive component, but are often of limited usefulness in non-specific or chronic widespread pain (including fibromyalgia). Antidepressants and anticonvulsants could be of value in some patients but there is a need for more knowledge in order to give general recommendations.

  • 99.
    Bergman, Stefan
    Spenshult Hospital, Oskarström, Sweden.
    Public health perspective - how to improve the musculoskeletal health of the population2007Inngår i: Baillière's Best Practice & Research: Clinical Rheumatology, ISSN 1521-6942, E-ISSN 1532-1770, Vol. 21, nr 1, s. 191-204Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Musculoskeletal disorders are the most common cause of long-term sick leave in several western countries and individuals with chronic musculoskeletal pain score very low on health status measurements. Musculoskeletal health is multidimensional and is best understood from a biopsychosocial perspective. Body structure and function interacts with personal and environmental factors, affecting the ability to perform activities and participate in society. Interventions aimed at the whole population must attend to the underlying causes of musculoskeletal disorders and promote a healthy lifestyle. Safe environments and activities could reduce the risk of traumatic events and also make participation possible for those with a disability. Public beliefs about musculoskeletal symptoms and consequences need to be changed in order to minimise fear and avoidance, which, together with other psychosocial factors, could lead to chronicity. Public awareness and identification of those at risk for the development of musculoskeletal problems could lead to early and properly timed management.

  • 100.
    Bergman, Stefan
    et al.
    Primary Care Centre Hertig Knut, Halmstad, Sweden.
    Herrström, Per
    Jacobsson, Lennart T
    Petersson, Ingemar F
    Chronic widespread pain: a three year followup of pain distribution and risk factors2002Inngår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 29, nr 4, s. 818-825Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To describe the change of pain reports over time in 3 cohorts derived from the general population: (1) no chronic pain (NCP; n = 1156); (2) chronic regional pain (CRP; n = 502); and (3) chronic widespread pain (CWP; n = 242). To identify risk factors that predict the development or persistence of chronic widespread pain.

    METHODS: A 3-year followup from 1995 to 1998 with postal questionnaire to 2425 subjects of both sexes aged 20-74 years on the west coast of Sweden.

    RESULTS: At followup, a larger proportion of subjects with initial CRP compared to initial NCP reported CWP (16.4 and 2.2%, respectively; p < 0.001). The majority of subjects (56.9%) who primarily reported CWP remained in that group at followup, but 26.8% had changed status to CRP and 16.3% to NCP. The number of painful regions (7-12 vs 0 regions) reported at baseline was the strongest predictor for the development of CWP with an odds ratio (OR) of 12.13 (95% CI 4.47-32.88). The development of CWP was also predicted by higher age (OR = 3.13, 95% CI 1.47-6.69, age-group 59-74 years vs age-group 20-34 years), and a family history of chronic pain (OR = 1.87, 95% CI 1.14-3.07). A habit of drinking alcohol weekly (OR = 0.42, 95% CI 0.21-0.85) compared to the habit of never or seldom drinking alcohol was protective, as well as having personal social support (OR = 0.49, 95% CI 0.28-0.85). The persistence of CWP was predicted by the number of painful regions (13-18 vs 1-6 regions) at baseline (OR = 7.56, 95% CI 2.17-26.30), and being an immigrant (OR = 3.22, 95% CI 1.33-7.77).

    CONCLUSION: Although the overall prevalence of CWP was stable over a 3-year period there was a considerable variation on an individual basis. This variability in expressing CWP was moderately predicted by a combination of risk factors, the most important being the number of painful regions at baseline. Future research will need to show how useful the identified factors are in clinical practice and whether intervention aimed at changing these factors will improve pain outcome. 

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