Rheumatoid Arthritis: Jacobsson LT

Theander E, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, Lund University, 20502 Malmö, Sweden. · Rheum Dis Clin North Am. · Pubmed #18984413 No free full text.

Abstract: Sjögren's syndrome is a systemic autoimmune disease that frequently presents concomitantly with other systemic connective tissue or organ-specific autoimmune diseases. This association is well described for systemic lupus erythematosus and rheumatoid arthritis. The presence of Sjögren's syndrome influences the expression of the other autoimmune disease to some degree, for instance by increasing fatigue and lymphoma risk. The etiopathogenic mechanism for the simultaneous or sequential development of multiple autoimmune diseases in one individual is not well understood. Common genetic backgrounds and additional immunogenetic, environmental, or hormonal factors may be responsible for the formation of subsets of autoimmune disease clustering. While the most currently accepted classification criteria (American European Consensus Criteria) designate these cases as secondary Sjögrens syndrome, the terms overlapping or associated Sjögren's syndrome are frequently used in the literature to describe these cases.

Turesson C, Jacobsson LT, Matteson EL. · Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. · Vasc Health Risk Manag. · Pubmed #18827910 links to  free full text

Abstract: Patients with rheumatic disorders have an increased risk of cardiovascular disease (CVD). This excess co-morbidity is not fully explained by traditional risk factors. Disease severity is a major risk factor for CVD in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Shared disease mechanisms in atherosclerosis and rheumatic disorders include immune dysregulation and inflammatory pathways, which are potential targets for therapy. Lessons from RA and SLE may have implications for future research on the pathogenesis of atherosclerotic vascular disease in general. Recent data indicate that suppression of inflammation reduces the risk of CVD morbidity and mortality in patients with severe RA. The modest, but clinically relevant, efficacy of atorvastatin treatment in RA adds to the evidence for important anti-inflammatory properties for statins. There is increased recognition of the need for structured preventive strategies to reduce the risk of CVD in patients with rheumatic disease. Such strategies should be based on insights into the role of inflammation in CVD, as well as optimal management of life style related risk factors. In this review, the research agenda for understanding and preventing CVD co-morbidity in patients with rheumatic disorders is discussed.

Strömbeck B, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. · Curr Opin Rheumatol. · Pubmed #17278938 No free full text.

Abstract: PURPOSE OF REVIEW: The purpose of this review is to present an update on the evidence-based effects of exercise in systemic lupus erythematosus and in primary Sjögren's syndrome. RECENT FINDINGS: Physical capacity is reduced in both systemic lupus erythematosus and primary Sjögren's syndrome and fatigue is a dominating and disabling symptom in both conditions. The documentation on the effect of exercise on the rehabilitation of patients with systemic lupus erythematosus and primary Sjögren's syndrome is sparse; the studies are few and the sample sizes often small. The available studies indicate that patients with systemic lupus erythematosus of mild to moderate disease activity as well as patients with primary Sjögren's syndrome benefit from exercise of moderate to high intensity. Positive effects can be expected with regard to aerobic capacity, fatigue, physical function and depression. SUMMARY: There is reason to believe that exercise should be included in the rehabilitation of patients with mild to moderate systemic lupus erythematosus and patients with primary Sjögren's syndrome. Further research is needed and should aim to evaluate the effect of exercise on groups with varying degree of disease severity and to document the long-term impact on the disease.

Askling J, Fored CM, Geborek P, Jacobsson LT, van Vollenhoven R, Feltelius N, Lindblad S, Klareskog L. · Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden. · Ann Rheum Dis. · Pubmed #16414975 links to  free full text

Abstract: Data from several different monitoring systems are examined. The potential for registers based on data obtained from clinical practice, and linkage of such data to national health and population registers, is discussed. The approach described is a possible prototype for long term surveillance systems needed for the safe introduction of new treatments.

Turesson C, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, Lund University, Sweden. · Scand J Rheumatol. · Pubmed #15163106 No free full text.

Abstract: Extra-articular RA (ExRA) includes a wide variety of disease manifestations. Although rheumatologists in general are aware that such events are clinically important, the heterogeneity of available data, including discrepancies in case definitions, has complicated constructive discussions on this aspect of the RA disease phenotype. In recent years, there has been a growing recognition of the importance of co-morbidity in patients with RA. ExRA manifestations are not uncommon, explain excess mortality in RA and are predicted by smoking and autoantibodies. Further studies of the mechanisms underlying these associations are likely to be important in improving our understanding of the systemic nature of RA. This article discusses the methodological issues involved in the study of ExRA manifestations, presents suggested criteria that have been used in clinical studies, and reviews important surveys of the epidemiology of extra-articular RA.

Wikström I, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, Sweden. · Scand J Rheumatol. · Pubmed #16296568 No free full text.

Abstract: OBJECTIVE: To describe factors associated with leisure activities, changes in leisure activities over time, and predictors of such changes among persons with rheumatoid arthritis (RA). METHODS: A prospective study was conducted of 80 consecutive persons with RA, recruited while participating in a 3-week, rehabilitation day-care programme. The number of leisure activities was assessed through a structured interview. Sociodemographic variables, measures of disease activity [pain, patient's global assessment, C-reactive protein (CRP)], disability [Health Assessment Questionnaire (HAQ), Signals of Functional Impairment (SOFI), grip strength], quality of life at baseline, as well as disease activity [mean erythrocyte sedimentation rate (ESR)] and treatment (proportion of follow-up time on anti-rheumatic drugs during follow-up) were evaluated as possible predictors of change in leisure activities. RESULTS: Active leisure activities increased, while 'not obviously active or passive' leisure activities were unchanged during the follow-up period. The change in active leisure activities did not correlate with the predictors evaluated. CONCLUSION: The increase in active leisure activities was not predicted to a substantial degree by disease activity, disability, or medication. The results suggest that factors other than those evaluated influence changes in leisure activities.

Theander E, Horrobin DF, Jacobsson LT, Manthorpe R. · Sjögren's Syndrome Research Centre, Department of Rheumatology, Malmö University Hospital, Sweden. · Scand J Rheumatol. · Pubmed #12109650 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of the essential omega-6 fatty acid Gammalinolenic acid (GLA) on fatigue associated with primary Sjögren's syndrome. METHODS: Ninety patients with primary Sjögren's syndrome (with or without signs of autoimmunity) entered a 6-month double blind placebo-controlled randomised trial with high dose GLA (extracted from Evening Primrose Oil) or corn oil. The primary outcome parameter was fatigue; secondary endpoints were eye dryness, mouth dryness, muscle and joint pain. RESULTS: No statistically significant improvement was found in fatigue assessed by Visual Analogue Scale (VAS) or in the time needed for sleeping/resting during a 24-hour period. No differences were found between the treatment and placebo group. The same applies to the secondary endpoints: no differences in VAS for eye and mouth dryness or pain, no significant changes in Schirmer-1-test, van Bijsterveld score, unstimulated whole sialometry (UWS), or use of artificial tears or analgesics. Only mild side effects were observed. CONCLUSION: According to our study results GLA (Evening Primrose oil) treatment for fatigue in primary Sjögren's syndrome is ineffective.

Söderlin MK, Jacobsson LT, Petersson IF, Englund M, Saxne T, Geborek P. · Spenshult Rheumatology Hospital, SE-313 92, Oskarström, Sweden. · J Rheumatol. · Pubmed #19411397 No free full text.

Abstract: OBJECTIVE: Studies on patients not answering postal questionnaires are scarce. We assessed the demographics and longitudinal disease and treatment characteristics of patients with rheumatoid arthritis (RA) in a Swedish biologics register who replied and who did not reply to a postal questionnaire. METHODS: In the South Swedish Arthritis Treatment Group register, we have detailed disease severity characteristics at baseline and at followup for rheumatology patients taking biologic drugs. In 2005 a questionnaire on smoking, comorbidities, education, and ethnicity was sent to 1234 RA patients who had started their first biologic drug. RESULTS: In total, 989 subjects (80%) answered the questionnaire. The 245 (20%) who did not answer generally had more severe RA [higher Disease Activity Score, worse Health Assessment Questionnaire score, higher visual analog scale scores for general health and pain at baseline and at followup, and stopped the drug treatment more frequently (72% vs 53%; p=0.0001)]. There were no statistically significant differences in gender and disease duration between those who replied and those who did not reply, but in general the patients who did not reply were younger. CONCLUSION: Patients with RA in a Swedish biologics register not replying to a postal questionnaire had more severe RA and stopped biological drug treatment more frequently. Thus a detailed analysis of prospectively collected data can clarify selection bias introduced by subjects who do not answer a postal questionnaire, which may influence the validity and interpretation of results from postal survey studies.

Nyhäll-Wåhlin BM, Petersson IF, Nilsson JA, Jacobsson LT, Turesson C, Anonymous00073. · Department of Rheumatology, Falun Hospital, Falun, Sweden. · Rheumatology (Oxford). · Pubmed #19213849 No free full text.

Abstract: OBJECTIVES: To identify patients with severe extra-articular RA (ExRA) in an early RA cohort and to investigate potential risk factors. METHODS: From a cohort (n = 2900) in a structured programme for newly diagnosed RA, 40 patients with severe ExRA after RA diagnosis were identified. Disease activity score (DAS28), functional disability (HAQ) and treatment with glucocorticosteroids (GCs) and DMARDs were assessed regularly. Cases with ExRA were compared with RA controls from the same cohort matched for age, sex and duration of symptoms at inclusion. RESULTS: Patients who developed severe ExRA were more often current smokers and had higher mean DAS28, HAQ and CRP at baseline. Among the ExRA cases, 93% had a positive RF vs 59% of the controls. The area under the curve (AUC) of DAS28 odds ratio (OR) 7.79/S.D.; 95% CI 3.04, 19.95, HAQ (OR 2.30/S.D.; 95% CI 1.37, 3.88) and CRP (OR 3.05/S.D.; 95% CI 1.77, 5.26) during the first 2 years of follow-up were strong predictors of subsequent development of ExRA. The most frequently used DMARDs were MTX and SSZ, with similar frequency and duration of treatment among cases and controls. The cases were treated with GC before onset of ExRA more frequently (73 vs 47%; P = 0.005) and with higher mean cumulative dose (3667 vs 2037 mg, P = 0.015). CONCLUSIONS: High levels of disease activity and disability during the first 2 years after RA diagnosis, smoking and RF predict the development of severe extra-articular RA.

Askling J, Baecklund E, Granath F, Geborek P, Fored M, Backlin C, Bertilsson L, Cöster L, Jacobsson LT, Lindblad S, Lysholm J, Rantapää-Dahlqvist S, Saxne T, van Vollenhoven R, Klareskog L, Feltelius N. · Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Ann Rheum Dis. · Pubmed #18467516 No free full text.

Abstract: 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.

Mandl T, Granberg V, Apelqvist J, Wollmer P, Manthorpe R, Jacobsson LT. · Department of Rheumatology, Ing 25 plan 2, Malmö University Hospital, S-205 02 Malmö, Sweden. · Rheumatology (Oxford). · Pubmed #18411214 No free full text.

Abstract: OBJECTIVES: Objective signs of autonomic dysfunction (AD) have been reported in patients with primary SS (pSS) while the presence of associated symptoms has not been systematically studied. Therefore, the aims of this study were (i) to assess the presence and severity of various AD symptoms in pSS patients and (ii) to relate AD symptoms to other clinical features of pSS. METHODS: Thirty-eight pSS patients and 200 population-based controls were studied for presence and severity of AD symptoms using the Autonomic Symptom Profile (ASP), a validated self-completed questionnaire evaluating various AD symptoms. In addition, patients were investigated by three different objective autonomic nervous function tests. RESULTS: pSS patients scored significantly higher in the parasympathetic [secretomotor disorder, urinary disorder, gastroparesis (females only) and pupillomotor disorder] as well as sympathetic (orthostatic intolerance and vasomotor disorder) ASP domains compared with controls. Consequently, the standardized ASP total score was significantly increased in pSS patients [1.77 (0.57, 3.15) vs - 0.21 (-0.82, 0.72); P = 0.00] and 45% of pSS patients had an ASP total score >/=2 s.d. Furthermore, the autonomic nervous function tests showed signs of objective parasympathetic and sympathetic dysfunction as well. However, the ASP domain and total scores showed limited associations with the objective autonomic nervous function test parameters as well as clinical and serological factors of pSS. CONCLUSIONS: pSS patients showed subjective and objective signs of both a parasympathetic and a sympathetic dysfunction. However, AD symptoms showed limited associations with objective autonomic nervous function as well as other clinical features of the disease.

Mandl T, Ekberg O, Wollmer P, Manthorpe R, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. · Scand J Rheumatol. · Pubmed #17963171 No free full text.

Abstract: OBJECTIVES: To assess the prevalence of pharyngeal and oesophageal symptoms and dysmotility in patients with primary Sjögren's syndrome (pSS) and relate these to autonomic nervous function. METHODS: Twenty consecutive pSS patients, according to the American-European Consensus Criteria (AECC), and 30 age- and sex-matched controls from the Swedish general population registry were studied. All subjects completed a pharyngeal and oesophageal symptoms questionnaire and were examined by pharyngeal and oesophageal video radiography. In addition, the pSS patients were examined by two different autonomic nervous function tests, the deep breathing test [calculating the expiration/inspiration (E/I) ratio] and the finger skin blood flow test [the vasoconstriction (VAC) index]. RESULTS: pSS patients experienced significantly more dysphagia compared with controls (65% vs. 3%; p<0.001). Pharyngeal (45% vs. 7%; p<0.01), oesophageal (80% vs. 7%; p<0.001) and gastro-oesophageal reflux symptoms (60% vs. 23%; p<0.01) were also more prevalent in pSS patients compared with controls while pharyngeal (15% vs. 17%; p = NS) and oesophageal dysmotility (40% vs. 30%; p = NS) were not. Dysphagia was not associated with dysmotility but was found to be associated with a decreased E/I ratio [-1.05 (-1.51 to -0.40) in patients with dysphagia vs. -0.21 (-0.39 to 0.65) in patients without dysphagia; p<0.01]. CONCLUSION: Subjective swallowing difficulties were more common in pSS patients than in controls while objective signs of pharyngeal and oesophageal dysmotility were not. Dysphagia in pSS patients does not seem to be related to video radiographical signs of dysmotility but may be related to an impaired parasympathetic function.

Mandl T, Wollmer P, Manthorpe R, Jacobsson LT. · Departments of Rheumatology and Clinical Physiology, Malmö University Hospital, and the Sjögren's Syndrome Research Centre, Malmö, Sweden. · J Rheumatol. · Pubmed #17659755 No free full text.

Abstract: OBJECTIVE: Exocrine function always is and autonomic nervous function may be impaired in primary Sjögren's syndrome (pSS). Since autonomic nervous signaling is a prerequisite for exocrine secretion we wanted to assess autonomic nervous function in pSS and relate it to diagnostic measures of exocrine function. METHODS: Autonomic nervous function was determined in 46 patients with pSS using the deep breathing test [expiration/inspiration (E/I) ratio], orthostatic test [acceleration index (AI), orthostatic systolic and diastolic blood pressure response (lSBP ratio and lDBP ratio)], and finger skin blood flow test [vasoconstrictory (VAC) score]. The results were corrected for age and expressed as z-scores by comparison with 3 control groups (E/I ratio and AI, n = 56; lSBP ratio and lDBP ratio, n = 238; and VAC score, n = 80). Exocrine gland function was determined in patients with pSS using the objective functional Schirmer-I test and rose-bengal staining (van Bijsterveld score) for the lacrimal glands and unstimulated whole sialometry for the salivary glands. RESULTS: The E/I ratio and orthostatic systolic and diastolic blood pressures were significantly decreased and the VAC score was significantly increased in patients with pSS compared to controls, indicating both parasympathetic and sympathetic dysfunction. Autonomic and exocrine function measures were found to associate poorly. CONCLUSION: Patients with pSS showed signs of both parasympathetic and sympathetic dysfunction. However, an association between cardiovascular autonomic and exocrine function in pSS was not detected.

Jacobsson LT, Lindroth Y, Marsal L, Juran E, Bergström U, Kobelt G. · Department of Rheumatology, Malmö University Hospital, Sweden. · Scand J Rheumatol. · Pubmed #17657670 No free full text.

Abstract: OBJECTIVE: We sought to investigate the cost of living with rheumatoid arthritis (RA) and evaluate the influence of both demographics and specific disease characteristics on these costs. METHODS: We used a population-based questionnaire to survey 895 patients living in the city of Malmö, Sweden, during 2002. Data were obtained on direct resource consumption, investments, informal care and work capacity, as well as utility, function and patients' assessment of disease severity and pain. RESULTS: The survey was completed by 613 patients (68%). Their mean age was 66 years, 74% were female and the mean duration of disease was 16.7 years. The total mean annual cost per patient was 108,370 SEK (12,020 EUR). Direct costs represented 41% of that amount and were predominantly for drugs [14% of the participants were receiving treatment with tumour necrosis factor (TNF) blockers], community services and hospitalisation. Function measured with the Health Assessment Questionnaire (HAQ) was the main statistical predictor for all types of costs except sick leave, which was most strongly associated with patients' perception of global health. CONCLUSION: This is the first study in Sweden to include all costs incurred by a group representative of RA in the community. In comparison with previous studies, total costs had increased by more than 40%. Furthermore, direct costs were higher and constituted a great proportion of total costs because of more intensive treatments (i.e. the use of TNF blockers). Future comparisons will enable health economic evaluations on a community level.

Söderlin MK, Lindroth Y, Jacobsson LT. · Consultant Rheumatologist, Spenshult Rheumatology Hospital, 313 92, Oskarström, Sweden. · Rheumatology (Oxford). · Pubmed #17567634 links to  free full text

Abstract: OBJECTIVES: To study trends in treatment, health status and health-related quality of life (HRQL) in two cross-sectional surveys over a 5-yr period and in an observational follow-up sub-cohort based on a population-based rheumatoid arthritis (RA) register in Malmö, Sweden. MATERIAL AND METHODS: A continuously updated population-based RA register was established in Malmö city in southern Sweden in 1997. Patient-administered questionnaires in 1997 and 2002 were used to collect information on demographics, medication and health status. Cross-sectional comparisons were made between 1997 and 2002. A longitudinal analysis was also performed in the RA patients participating in both surveys. RESULTS: Increased proportions of patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) (69 vs 52%), corticosteroids (30 vs 23%), methotrexate (52 vs 29%) and biologics (14 vs 0%) in 2002 compared with 1997. In the cross-sectional analysis, the visual analogue scores (VAS) for pain and general health and the short form 36 (SF-36) domains were slightly better in 2002 than in 1997. In the observational sub-cohort, patients treated with biologics improved significantly in several measures of health status, whereas those starting on methotrexate or undergoing other or no changes in DMARD therapy did not. CONCLUSIONS: In this population-based RA cohort, patients were more actively treated in 2002. Small improvements were seen in health status and these improvements were exclusively attributable to treatment with biologics.

Strömbeck BE, Theander E, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, SE-205 02 Malmö, Sweden. · Rheumatology (Oxford). · Pubmed #17308315 links to  free full text

Abstract: OBJECTIVE: To investigate the effect of a moderate to high intensive exercise program on two primary outcomes (aerobic capacity, fatigue), and three secondary outcomes [anxiety, depression and health-related quality of life (HRQoL)] in women with primary Sjögren's syndrome (primary SS). METHODS: Twenty-one women with primary SS were ranked according to degree of fatigue and allocated to an exercise group (TG; n = 11) or a control group (CG; n = 10). The exercise method was Nordic walking for 45 min three times a week for 12 weeks. Outcome measures assessed at baseline and after 12 weeks were aerobic capacity, fatigue, ratings of perceived exertion (RPE), anxiety, depression and HRQoL. RESULTS: Nine women in the TG and 10 women in the CG completed the study. Analysis showed significant differences between the groups regarding aerobic capacity (P = 0.03), fatigue (P = 0.03), RPE (P = 0.03), and depression (P = 0.02) with the better values for the TG. There were no differences in anxiety or HRQoL. CONCLUSION: Our findings support the use of appropriate aerobic exercise in the treatment of primary SS.

Askling J, Fored CM, Brandt L, Baecklund E, Bertilsson L, Feltelius N, Cöster L, Geborek P, Jacobsson LT, Lindblad S, Lysholm J, Rantapää-Dahlqvist S, Saxne T, van Vollenhoven RF, Klareskog L. · Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. · Ann Rheum Dis. · Pubmed #17261532 No free full text.

Abstract: OBJECTIVES: The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers. METHODS: First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account. RESULTS: Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years. CONCLUSION: Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.

Jacobsson LT, Turesson C, Nilsson JA, Petersson IF, Lindqvist E, Saxne T, Geborek P. · Department of Rheumatology, Malmö University Hospital, S-205 02 Malmö, Sweden. · Ann Rheum Dis. · Pubmed #17158824 No free full text.

Abstract: OBJECTIVE: To assess mortality in patients with rheumatoid arthritis (RA) treated with tumour necrosis factor (TNF) inhibitors, compared with a standard RA population. METHODS: Patients were recruited from a regional register, which includes over 90% of patients with RA treated with TNF blockers in the area in 1999 or later, and a local community-based cohort of patients with RA, established in 1997. Of a total of 1430 patients in the combined cohort <80 years old, 921 received treatment with TNF inhibitors during the study period. The total cohort was linked with the national register for cause of death. Overall mortality in those treated versus those not treated with TNF blockers was estimated using standardised mortality ratios and time-dependent Cox proportional hazards. RESULTS: There were 188 deaths per 7077 person-years at risk in the total cohort. Controlling for age, sex, disability and baseline comorbidity, the adjusted HR for death was 0.65 (95% CI 0.46 to 0.93) in those treated with anti-TNF versus those not treated. The effect was significant in women (HR = 0.52, 95% CI 0.33 to 0.82) but not in men (HR = 0.95, 95% CI 0.52 to 1.71). CONCLUSION: After adjusting for disease severity, treatment with TNF inhibitors was found to be associated with a reduced mortality in women but not men with RA. These findings are compatible with a critical role for inflammation in RA-associated premature mortality.

Wikström I, Jacobsson LT, Arvidsson B. · Department of Rheumatology, Malmö University Hospital, Sweden. · Musculoskeletal Care. · Pubmed #17041996 No free full text.

Abstract: OBJECTIVE: To explore how people with rheumatoid arthritis (RA) perceive leisure activities. METHOD: A phenomenographic approach using semi-structured interviews to explore the impact of RA on leisure pursuits was used. RESULTS: Three descriptive categories containing 11 conceptions emerged: (1) Experiencing constraints included four conceptions: seeing limitations, needing time, finding balance, being dependent. (2) Experiencing coherence included four conceptions: accepting feelings participating in a social context, being active, having insight. (3) Finding solutions included three conceptions: choosing, planning, and adapting. CONCLUSIONS: This study emphasizes the limited choices and problems people with RA had participating in leisure activities, as well as its impact on self-esteem.

Turesson C, Schaid DJ, Weyand CM, Jacobsson LT, Goronzy JJ, Petersson IF, Dechant SA, Nyähll-Wåhlin BM, Truedsson L, Sturfelt G, Matteson EL. · Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. · Arthritis Rheum. · Pubmed #16947780 links to  free full text

Abstract: OBJECTIVE: To compare HLA-C genotypes and smoking habits in patients with vasculitis or other severe extraarticular manifestations of rheumatoid arthritis (ExRA) with those in RA patients without extraarticular disease. METHODS: Patients were recruited from a large research database of patients with RA at the Mayo Clinic, from 2 Swedish cohorts of prevalent RA cases, and from a regional Swedish early RA cohort. Patients with severe ExRA (n = 159) and control patients with RA but no history of ExRA (non-ExRA controls) (n = 178) were matched for duration of RA and for clinical center. Data on smoking at RA onset, rheumatoid factor (RF) status, and antinuclear antibodies (ANAs) were extracted from the medical records. Polymerase chain reaction-based HLA-C genotyping was performed using a sequence-specific primer kit. RESULTS: The distribution of HLA-C alleles was significantly different between patients with RA-associated vasculitis and non-ExRA controls (P = 0.014). This was mainly due to a positive association of the HLA-C3 allele with vasculitis (allele frequency 0.411 in vasculitis patients versus 0.199 in non-ExRA controls; P < 0.001) and a decreased frequency of HLA-C7 (0.122 and 0.243, respectively; P = 0.018). The association between HLA-C3 and vasculitis was not due to linkage disequilibrium with HLA-DRB1. Smoking (P = 0.001), RF positivity (P < 0.0001), and presence of ANAs (P < 0.0001) were all associated with ExRA. HLA-C3 and smoking were both significant predictors of vasculitis in a multivariate model. CONCLUSION: Vasculitis in RA is associated with HLA-C3. Smoking is an independent predictor of vasculitis and other types of severe ExRA. Our results suggest that these variables are among the genetic and environmental factors that contribute significantly to the pathomechanisms of systemic RA.

Turesson C, Jacobsson LT, Sturfelt G, Matteson EL, Mathsson L, Rönnelid J. · Department of Rheumatology, Malmö University Hospital, Södra Förstadsgatan 101, S-205 02 Malmö, Sweden. · Ann Rheum Dis. · Pubmed #16901955 No free full text.

Abstract: OBJECTIVE: To study antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor in patients with active, severe extra-articular rheumatoid arthritis (ExRA) compared with controls without ExRA. METHODS: 35 consecutive patients with severe ExRA manifestations according to predefined criteria were studied. 70 patients with rheumatoid arthritis, but no ExRA manifestations, individually matched for age, sex and disease duration, served as controls. Patients were included when ExRA was diagnosed, before any new treatment was started. Anti-CCPs were detected with ELISA, rheumatoid factor was quantified using nephelometry and anti-nuclear antibodies (ANA) were investigated using indirect immune fluorescence. RESULTS: Anti-CCPs were detected in 77% of patients with ExRA versus 56% of controls without ExRA (p = 0.03). Anti-CCP levels also tended to be higher in patients with ExRA (p = 0.09). Rheumatoid factor was detected in 94% v 71% of patients and controls, respectively (p = 0.006), and rheumatoid factor levels were higher in patients with ExRA (median interquartile range (IQR) 245 IU/ml (94-604) v 73 IU/ml (not detected-165); p = 0.001). Levels and occurrence of ANA did not differ between patients with ExRA and controls. Patients with ExRA had higher swollen joint counts and C reactive protein levels, but no correlations were found between anti-CCP or rheumatoid factor levels and these measures within the ExRA group. CONCLUSION: Rheumatoid factor is strongly associated with severe ExRA manifestations in patients with rheumatoid arthritis, and a similar but weaker association exists for anti-CCPs. This suggests a role for rheumatoid factor and anti-CCP in the pathogenesis of ExRA.

Wikström I, Book C, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, S. Förstadsgatan 101, S-205 02 Malmö, Sweden. · Rheumatology (Oxford). · Pubmed #16531435 links to  free full text

Abstract: OBJECTIVE: To compare leisure activities and associated factors in a group with recent onset RA and matched community derived controls, to examine whether leisure activities are altered during the early years of disease and to seek predictors. METHODS: One hundred and forty-seven consecutive persons with early RA were followed for 0.9-5.9 yr. One hundred and forty-four RA patients were compared cross-sectionally at baseline with community-derived controls matched for age, gender and residential area. Leisure activities were evaluated with an interest checklist (20 domains). Socio-demographic variables, disease activity (DAS) and disability (HAQ) were evaluated as possible predictors for loss of participation in leisure activities at baseline and longitudinally (using area under the curve analyses). RESULTS: At baseline (mean disease duration 7 months) RA patients performed less (8.2 vs 9.9 domains, P < 0.001) but did not have significantly less interest (10.9 vs 11.4 domains, P = 0.15) in leisure activities compared with controls. Decrease in performed leisure activities was only significant in those with a low level of education. At baseline, in RA patients, low education (P = 0.035), age (P = 0.019) and HAQ (P < 0.001) significantly predicted performed leisure activity. No loss in performed leisure activities was seen during follow-up and no significant predictors were found for individual change. CONCLUSION: Loss of performed leisure activities occurs early in RA and chiefly in those with low formal education. Disability was associated with early loss, but not with change during follow-up. Other factors, possibly related to individual personality and resources, may be more important for predicting changes in leisure activities.

Strömbeck B, Theander E, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. · Scand J Rheumatol. · Pubmed #16393768 No free full text.

Abstract: OBJECTIVE: To translate the disease-specific Profile of Fatigue (ProF) into Swedish and to evaluate the reliability and validity of the Swedish version. METHODS: Forward and back translations were performed. Seventy patients with primary Sjögren's syndrome (PSS), 48 control persons, and two rheumatologists participated. Test-retest reliability, internal consistency, content, construct and discriminant validity were investigated. RESULTS: The translation was accepted without modifications. The test-retest reliability varied between moderate and good (weighted Kappa = 0.51-0.63). Internal consistency was high (Cronbach's alpha = 0.97). Construct validity was proved by significant correlations of the questionnaire items with the Visual Analogue Scale (VAS) for fatigue (r(s) = 0.55-0.70), and the Physical Function (PF) (r(s) = -0.20 to -0.41) and Vitality (VT) scales (r(s) = -0.60 to -0.77) of the MOS 36-Item Short-Form Health Survey (SF-36). Content validity was mainly judged as good. A significant difference between the scorings of the patients and the scorings of the control group was seen (mean difference 1.6, p<0.005). CONCLUSION: The Swedish version of the ProF is a relatively reliable and valid instrument for the measurement of fatigue in patients with PSS.

Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, S-20502 Malmö, Sweden. · Ann Rheum Dis. · Pubmed #16284097 links to  free full text

Abstract: OBJECTIVES: To assess the risk of lymphoproliferative disease or other malignancy (standardised incidence ratios (SIRs)), in patients with primary Sjögren's syndrome according to the American-European Consensus Criteria (AECC), compared with patients with sicca syndrome (non-AECC) and the background population. To identify predictors of malignancy and describe lymphoma types and survival probabilities. METHODS: A linked register study using information from the Malmö Primary SS Register, Swedish Cancer Register, and Cause-of-Death Register for calculation of SIRs was carried out. Detected lymphomas were reclassified according to the WHO classification. Cox regression analysis was used to study the predictive value of clinical, laboratory, and histological findings at the time of diagnosis. RESULTS: 507 patients with a median follow up of 8 years (range 1 month to 19 years) were included. SIRs (95% confidence interval (CI)) for malignancies in total and for non-Hodgkin's lymphomas (NHL) were 1.42 (0.98 to 2.00) and 15.57 (7.77 to 27.85), respectively, in those fulfilling the AECC (n = 286). In non-AECC sicca patients (n = 221) SIR for malignancy of any kind was 0.77 (0.41 to 1.32); no lymphoproliferative neoplasms were detected. Significant predictors of lymphoproliferative disease were purpura/skin vasculitis (hazard ratio (HR) = 4.64, 95% CI 1.13 to 16.45), low complement factor C3 (HR = 6.18, 95% CI 1.57 to 24.22), low C4 (HR = 9.49, 95% CI 1.94 to 46.54), CD4+ T lymphocytopenia (HR = 8.14, 95% CI 2.10 to 31.53), and a low CD4+/CD8+ T cell ratio < or = 0.8 (HR = 10.92, 95% CI 2.80 to 41.83). 7/12 (58%) NHLs were diffuse large B cell lymphomas. CONCLUSION: A 16-fold increased risk for development of NHL was found. CD4+ T lymphocytopenia is an additional strong risk factor for developing lymphoma.

Turesson C, Schaid DJ, Weyand CM, Jacobsson LT, Goronzy JJ, Petersson IF, Sturfelt G, Nyhäll-Wåhlin BM, Truedsson L, Dechant SA, Matteson EL. · Department of Rheumatology, Malmö University Hospital, Södra Förstadsgatan 101, 205 02 Malmö, Sweden. · Arthritis Res Ther. · Pubmed #16277691 links to  free full text

Abstract: The objective of this study was to examine HLA-DRB1 and HLA-DQB1 genotypes in patients with severe extra-articular rheumatoid arthritis (ExRA) and to compare them with the genotypes of rheumatoid arthritis (RA) patients without extra-articular manifestations. Patients with severe ExRA were recruited from a large research database of patients with RA, from two cohorts of prevalent RA cases, and from a regional multicenter early RA cohort. Cases with ExRA manifestations (n = 159) were classified according to predefined criteria. Controls (n = 178) with RA but no ExRA were selected from the same sources. Cases and controls were matched for duration of RA and for clinical center. PCR based HLA-DRB1 and HLA-DQB1 genotyping was performed using the Biotest SSP kit, with additional sequencing in order to distinguish DRB1*04 subtypes. Associations between alleles and disease phenotypes were tested using multiple simulations of random distributions of alleles. There was no difference in global distribution of HLA-DRB1 and HLA-DQB1 alleles between patients with ExRA and controls. DRB1*0401 (P = 0.003) and 0401/0401 homozygosity (P = 0.002) were more frequent in Felty's syndrome than in controls. The presence of two HLA-DRB1*04 alleles encoding the shared epitope (SE) was associated with ExRA (overall odds ratio 1.79, 95% confidence interval 1.04-3.08) and with rheumatoid vasculitis (odds ratio 2.44, 95% confidence interval 1.22-4.89). In this large sample of patients with ExRA, Felty's syndrome was the only manifestation that was clearly associated with HLA-DRB1*0401. Other ExRA manifestations were not associated with individual alleles but with DRB1*04 SE double dose genotypes. This confirms that SE genes contribute to RA disease severity and ExRA. Other genetic and environmental factors may have a more specific impact on individual ExRA manifestations.