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Item does not contain fulltext OBJECTIVE: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. METHODS: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. RESULTS: The PRS was associated with earlier age at gout onset in men (β = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; β = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; β = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (β = 0.07 [95% CI -2.32, 2.45] in European women; β = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; β -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (β = -2.42 [95% CI -3.37, -1.46] and β = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (β = -1.79 [95% CI -4.74, 1.16]). CONCLUSION: Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.

This study aimed to describe the incidence and prevalence of gout, describe the use of allopurinol among prevalent gout cases, and determine persistence with allopurinol and degree of compliance with treat-to-target recommendations before and after the publication of Swedish national guidelines in 2016.Prospectively registered data on gout diagnoses and allopurinol prescriptions were used to calculate incidence and prevalence, and the proportion of prevalent patients on allopurinol. Gout patients starting allopurinol during 2013-2015 versus 2016-2018 were compared regarding persistence and compliance with treat-to-target principles.The incidence of gout was 221-247 per 100 000 person-years during 2014-2019, prevalence in 2018 was 2.45%. Among prevalent cases, the proportion on allopurinol ranged from 21% to 25%. Allopurinol persistence was better for individuals starting therapy during 2016-2018 compared with 2013-2015 (45% vs 39%, p = 0.031), as were several outcomes related to treat-to-target principles, e.g. measuring baseline serum urate (SU) (84% vs 77%, p 0.001), follow-up SU (50% vs 36%, p 0.001), and the proportion of patients reaching an SU level 360 µmol/L (45% vs 30%, p 0.001).Incidence and prevalence were slightly higher than in previous Swedish reports. Allopurinol use among prevalent gout patients did not increase during 2014-2019. Only a minor improvement in persistence was seen, and a moderate increase in compliance with guidelines, suggesting a need for improved management and extended patient involvement to increase and optimize the use of urate lowering therapy.

Objectives In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). Methods Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009–2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with ≥3, ≥4 or ≥5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with ≥3 b/tsDMARDs stratified by calendar-period (2009–2011, 2012–2013, 2014–2015, 2016–2018). In the subgroup of patients starting a first b/tsDMARD 2009–2015, baseline characteristics associated with multi-switching (within 3 years’ follow-up) were explored using multiple logistic regression analyses. Results Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009–2015, whereof proportions treated with ≥3, ≥4 or ≥5 b/tsDMARDs within 3 years’ follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (≥3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. Conclusion In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group.

Objectives Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis. Methods Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP Results Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P Conclusion This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy.

ObjectivesTo estimate the incidence of non-vertebral fractures in ankylosing spondylitis (AS) compared with the general population.MethodsNationwide register-based cohort study including patients with AS (n=11 611, 65% men, mean age 48 years), and matched general population controls (n=58 050). Five prespecified fracture outcomes: (1) non-vertebral; (2) fracture of the proximal humerus, distal forearm or hip; (3) proximal humerus; (4) distal forearm and (5) hip) were identified through register linkages with follow-up 2007–2016. We used Poisson regression to calculate incidence rates (IRs), number of fractures per 1000 person-years at risk and IR ratios (IRRs), overall and by sex and age. IRRs were adjusted for history of any prior fracture.ResultsIRs (men/women) for non-vertebral fracture in AS were 11.9 (95% CI 11.0 to 12.9)/14.5 (95% CI 13.1 to 16.1) and in controls 10.0 (95% CI 9.7 to 10.4)/11.8 (95% CI 11.1 to 12.4), IRR (men/women) 1.2 (95% CI 1.1 to 1.3)/1.2 (95% CI 1.1 to 1.4). IRs (men/women) for fractures of the humerus, forearm or hip in AS were 4.0 (95% CI 3.5 to 4.6)/6.3 (95% CI 5.4 to 7.3) and in controls 2.7 (95% CI 2.5 to 2.9)/5.5 (95% CI 5.1 to 6.0), IRR (men/women) 1.5 (95% CI 1.3 to 1.7)/1.1 (95% CI 0.9 to 1.3). IRRs were statistically significantly elevated in men with AS versus controls for forearm fracture (1.4 (95% CI 1.1 to 1.7)) and hip fracture (1.8 (95% CI 1.4 to 2.3)), whereas not in women with AS where the IRRs were 1.1 (95% CI 0.9 to 1.4) and 1.0 (95% CI 0.6 to 1.4). For humerus fracture, IRRs were 1.4 (95% CI 0.99 to 1.9) in men with AS versus controls and 1.1 (95% CI 0.8 to 1.6) in women.ConclusionsBoth men and women with AS have a slightly higher risk of non-vertebral fractures than the general population. A statistically significantly higher risk of fractures of the proximal humerus, distal forearm or hip was found in men with AS in comparison to general population, where the relative risk was especially pronounced for hip fracture.

Hyperuricemia is defined by a blood urate level405 µmol/L, the cut-off value at which urate forms crystals in vivo. In 15-20% these individuals develop gout, clinically characterized by attacks of acute arthritis, initially and most commonly affecting MTP 1 or other joints, tendons and soft tissues of the foot. These attacks usually subside within 1 to 2 weeks. Over time attacks occur more frequently and can transform into chronic arthritis characterized by tophi. The gold standard for diagnosis relies on identification of urate crystals by polarization microscopy in aspirated joint fluid. This procedure is rarely performed in primary care where the majority of patients are seen, and gout is usually diagnosed by clinical criteria. New imaging technologies (ultrasound, dual-energy CT) can be helpful when aspiration is not available and when the diagnosis is unclear. Gout has a prevalence of 1.7% and incidence rate of approximately 200 per 100000 person-years in Sweden, figures that increase over time.

Urate lowering therapy (ULT) should, according to recent guidelines, be initiated in the majority of cases already after the first attack of gout. Allopurinol is the first line choice of ULT and should be started with low dose, which is increased until the treatment target is reached. The treatment target should be a blood urate of360 µmol/l or300 µmol/l (in the presence of topfi), which should be maintained until topfi have resolved. NSAID/cox-inhibitors, colchicine and glucocorticoids are all valid short-term treatments of gout attacks. ULT should not be paused/terminated during attacks and can be initiated during an attack that is adequately treated. Recent RCTs of ULT treatment have demonstrated the importance of thorough and adequate information to the patient and regular follow-up until treatment targets are reached. Such a strategy improve both compliance and outcomes of ULT treatment.

Background: A recent study in German chronic back pain (CBP) patients (pts) with a suspicion of axial spondyloarthritis (axSpA) report on the performance of, among others, the ASAS inflammatory back pain (IBP) criteria and the individual IBP parameters. Pts were diagnosed by a rheumatologist blinded for all clinical features but IBP and by a rheumatologist with all diagnostic tests available as in daily practice (reference standard). Data show high sensitivity but low specificity of the ASAS IBP criteria and individual IBP parameters(1). Performance of IBP in other countries is less studied. Objectives: What is the diagnostic utility of IBP and the individual IBPpar according to the ASAS IBP criteria in several rheumatology settings in West- and Northern-Europe? Methods: Data of the multicentre, observational Be-Giant and SPondyloArthritis Cause Early (SPACE) cohorts were used. The Be-Giant cohort included ≥18 years old, newly diagnosed axSpA pts who were diagnosed by a rheumatologist and fulfilled the ASAS axSpA criteria. SPACE cohort included pts, ≥16 years, with (almost) daily CBP for ≥3 months and ≤2 years, with a symptom onset Results: IBPpar data was available in 661 pts (SPACE) and 228 pts (Be-Giant); 36.0% and 49.6% were male, mean age 30.8±8.2 and 34.7±9.7 years, respectively. The figure shows a majority of axSpA pts with >2 IBPpar, but this is also seen in the no axSpA pts. IBPpar show high sensitivity but very low specificity with ‘pain at night’ as exception with a slightly better specificity. LR+ were, in both cohorts, much lower (figure) than the LR+ of 3.1 for IBP previously reported as diagnostic estimate in routine practice. Conclusion: IBP and the individual IBPpar. are commonly seen in patients with and without an axSpA diagnosis. Our data confirm results from Germany, showing that the diagnostic utility of IBP in a rheumatology setting is lower than previously assumed with a (very) low specificity and LR+. It seems the distinctive impact of IBP is expressed when physicians refer their patient to the rheumatologist. Reference [1] Poddubnyy D, et al. RMD Open2018;4:e000825 Disclosure of Interests: Manouk de Hooge: None declared, Floris A. van Gaalen: None declared, Marleen van de Sande Grant/research support from: Research support from Janssen, Novartis, Eli Lily, Consultant for: Received consultation fees from Abbvie and Novartis, Karen Fagerli: None declared, Lennart Jacobsson Consultant for: Eli-Lily, Janssen, Novartis, Pfizer, Speakers bureau: Abbvie., Dirk Elewaut: None declared, Desiree van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB.

Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21

Background The role of environmental exposures in the pathogenesis of ankylosing spondylitis (AS) remains unclear. In particular, two types of exposures have been suspected to play a role: mechanical stress and infections. The objective of this case-control study was to determine if childhood infections are associated with later development of AS. Methods The cases with AS were identified through the Swedish national outpatient specialised-care register, based on having been given at least one AS diagnosis in the register between 2001 and 2010. Five controls per case were identified in the Swedish population register, matched at the time-point of the index case’s first spondyloarthritis diagnosis on sex, birth year, and county. All cases/controls matched prior to the age of 17 years were excluded, as well as all cases/controls given a diagnosis of reactive arthritis or juvenile arthritis at any time point, or any other diagnosis of a rheumatic disease, psoriasis, iridocyclitis, or inflammatory bowel disease before the time-point of matching. All events of hospitalisation with an infection before the age of 17 years were retrieved from the register, and categorised according to the focus of the infection. Odds ratios (ORs) and confidence intervals (CIs) were determined through conditional logistic regression analyses. Results Of the 2453 cases with AS and 10,257 controls, 17.4 % of the cases and 16.3 % of the controls had been hospitalised with an infection before the age of 17 years (OR 1.08, 95 % CI 0.96–1.22). Appendicitis (1.5 % cases; 2.5 % controls; OR 0.59, 95 % CI 0.41–0.83), respiratory tract infections (cases 11.2 %; controls 9.2 %; OR 1.24, 95 % CI 1.07–1.44) and, in particular, tonsillitis (cases 3.7 %; controls 2.8 %; OR 1.31, 95 % CI 1.03–1.67) were associated with AS. There were no associations between AS and any other type of infection, and the point estimates were similar in several sensitivity analyses. Conclusions Childhood appendicitis was associated with a decreased risk, whereas respiratory tract infections were associated with an increased risk for later development of AS. These findings support a possible relationship between childhood infections and later development of AS, although the study is limited to infections resulting in inpatient care. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1141-8) contains supplementary material, which is available to authorized users.

The presence of 2 M-components in single patients (double gammopathy) was studied retrospectively by means of the electrophoresis files in Umeå (serving a population of approximately 150 000 inhabitants). During the 11-year period 1974-1984, 109 000 electrophoreses were performed, among which 1034 patients with gammopathy were found. Of these, 20 (2%) had double gammopathy; 3 were associated with lymphoma, 7 with myelomatosis, 9 with monoclonal gammopathy of undetermined significance (MGUS), and 1 with lupus erythematosus disseminatus. It is suggested that one subgroup of double gammopathy (6 patients) had a neoplastic cell clone combined with a normally regulated cell line, the latter marked by a transient M-component. Another subgroup (14 patients) seems to have 2 coexisting different neoplastic cell lines, with persistent double gammopathy.

Blood and bone marrow changes induced by continuous low-dose hydroxyurea treatment are described. A linear increase in mean red cell volume was observed after onset of therapy. The entire normocyte population was replaced by abnormally large erythrocytes within 150 days. The bone marrow morphology changed in megaloblastic direction. Bone marrow iron stores and number of sideroblasts increased, findings compatible with ineffective erythropoiesis. Serum folate and cobalamin levels remained normal. These morphologic changes might cause confusion when examining blood or bone marrow samples from patients treated with hydroxyurea.

Mortality rates for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) have decreased after the introduction of cyclophosphamide. Standardized mortality ratio (SMR) expresses the overall mortality of patients compared with the general population. The aims of this study were to compare survival in an old and a recent cohort of patients with WG and MPA using SMR and to determine predictors for death in both groups combined. Survival analyses were performed by Kaplan-Meier survival curves, SMR and proportional hazards regression models. The nephrology and rheumatology clinics at Linkoping University Hospital, Sweden. All patients diagnosed with WG or MPA in the catchment area during 1978-2005 were divided into two cohorts; patients diagnosed before (n = 32, old cohort) and after (n = 63, recent cohort) December 31, 1996. The two cohorts differed regarding the proportion of WG (75% vs. 56%, P = 0.03) and a tendency for more pronounced kidney involvement in the old cohort: 266 mu mol L-1 (16% dialysis-dependent) vs. 192 mu mol L-1 (5% dialysis-dependent), but were comparable regarding disease severity. SMR at 1 and 5 years were 2.1 (95% CI: 0.43-6.09) and 1.6 (95% CI: 0.6-3.2) in the recent cohort and 5.2 (95% CI: 1.07-15.14) and 2.5 (95% CI: 0.93-5.52) in the old cohort. Five-year survival was 87% and 81%. Serum creatinine, age, end-stage renal disease, diagnosis before 1997 and first relapse were independent predictors for death. Patient survival in WG and MPA analysed with SMR may be better than previously believed. Severe renal disease and disease relapse were the major predictors of reduced survival. (Less)

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 ¼ 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.

Objectives: Osteoporosis is a known complication of rheumatoid arthritis (RA). This prospective study aimed to evaluate whether disease activity, disability, and glucocorticoid (GC) treatment in early RA were risk factors for loss of bone mineral density (BMD). Methods: We followed 97 women (mean age 58 years), for 24 months, with a history of RA of less than 12 months. At baseline, 77 women were receiving standard treatment with disease-modifying antirheumatic drugs (DMARDs) and 20 were receiving no treatment. Risk factors for osteoporosis were recorded. Disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, and medications were registered at baseline and every 6 months and calculated as areas under the curve (AUCs). Femoral neck and lumbar spine BMD were measured at baseline and after 2 years and compared to BMD in age- and gender-matched controls. Risk factors were analysed by linear regression models. Results: BMD loss was comparable to that of age-matched women in both the lumbar spine and the femoral neck, although neither was significantly different from baseline. In multivariate analyses the AUC for DAS28 was an independent predictor of changes in lumbar spine BMD (p=0.003) and that for HAQ of changes in femoral neck BMD (p=0.018). GC use was not an overall predictor of BMD loss. Conclusion: BMD loss was predicted by high disease activity and disability but not by GC treatment. With the DMARD, GC, hormone replacement therapy (HRT), and bisphosphonate treatment strategies used during the study period, the general outcome seems favourable concerning loss of BMD in patients with early RA.

Introduction Stockholm County Council is the largest health care provider in Sweden with an annual budget of US$ 5 billion and catering the needs of a metropolitan population of 2 million people. About 10% of health care costs are used on drugs. In 1996 Stockholm County Council decided to address the main problems associated with the process and the quality of drug prescribing. Methods A multiyear strategy was designed, including the establishment of a strong evidence-based organisation, Drug and Therapeutics Committees and editorial resources to adapt information to the IT-media and the development of the IT-architecture. The development and implementation of computerized tools such as a physician drug order entry system including decision support, a drug information website and electronic transmission of prescriptions were started in 1996. Results The implementation was slow at the point-of-care units. It took about 6 years before the implementation process gained speed. In September 2005 almost 1000 doctors could use the decision support system for prescribing drugs and more than 70% of all prescriptions were transmitted electronically in our region. Conclusions The work with the strategy has shown that improvements in drug use can be accomplished by providing access to simple, rapid and safe electronic tools, but the information provided has to be associated with well-recognized regional and national expert organisations.

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.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.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.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.

OBJECTIVE To investigate the impact of overweight and obesity on the risk of RA. METHODS From two large population-based health surveys (30 447 and 33 346 participants), individuals who developed RA after inclusion were identified by linkage to four different registers and a structured review of the medical records. Matched controls were selected from the corresponding health survey database. The impact of overweight or obesity (BMI > 25 kg/m(2)) compared with normal BMI (18.5-25 kg/m(2)) on the risk of RA was examined in conditional logistic regression models, stratified by sex. RESULTS A total of 172 (36 men/136 women) and 290 (151 men/139 women) individuals were diagnosed with RA after inclusion in the two health surveys. The median time from inclusion to RA diagnosis was 5 years and 12 years, respectively. In men, being overweight or obese at inclusion in the health survey was associated with a reduced risk of subsequent development of RA in both cohorts [odds ratio (OR) = 0.33; 95% CI: 0.14, 0.76, and 0.60; 95% CI: 0.39, 0.91]. There was no such association in women (OR = 1.01; 95% CI: 0.65, 1.54, and 1.37; 95% CI: 0.86, 2.18). Estimates were similar in analyses adjusted for potential confounders, including smoking. CONCLUSION A high BMI was associated with a reduced risk of future RA in men, but not in women. Factors related to adipose tissue may contribute to mechanisms that are protective from RA in men.

The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS.

Osteoarthritis (OA) is a complex process affecting many different joint areas in the body. From a pathophysiological point of view some features are crucial for the diagnosis, such as cartilage fibrillation and thinning, subchondral sclerosis and the presence of osteophytes. From a clinical perspective, OA is the most prevalent rheumatic joint disorder, causing pain and stiffness of the joints and, for the individual, impaired function and health status. The aim of this chapter is to present current knowledge of definitions of OA, its presence in different populations and in different joint areas (the back excluded). Furthermore, methods of diagnosing and delineating clinically relevant forms of OA, now and in the future, are presented as well as current knowledge of the risk factors for developing and the factors for preventing OA.

Objective: To evaluate the eYcacy of the essential omega-6 fatty acid Gammalinolenic acid (GLA) on fatigue associated with primary Sjo¨ gren’s syndrome. Methods: Ninety patients with primary Sjo¨ gren’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 signiŽ cant 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 diVerences were found between the treatment and placebo group. The same applies to the secondary endpoints: no diVerences in VAS for eye and mouth dryness or pain, no signiŽ cant changes in Schirmer-1-test, van Bijsterveld score, unstimulated whole sialometry (UWS), or use of artiŽ cial tears or analgesics. Only mild side eVects were observed. Conclusion: According to our study results GLA (Evening Primrose oil ) treatment for fatigue in primary Sjo¨gren’s syndrome is ineVective. (Less)

The diagnostic difficulties and the potential serious course of Mycobacterium marinum synovitis are illustrated in a patient in whom treatment with local steroid injections and immunosuppressive therapy resulted in local destruction of the wrist and systemic reactions. Healing was achieved after correct medical and surgical treatment was initiated.

Objectives: To investigate the importance of birth characteristics and early life infections on the risk of later rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Methods: A nationwide register-based case–control study was performed based on prospectively recorded data on individuals born in 1973 or later. Using the Swedish inpatient register and the early arthritis register, cases with RA aged 16 years or above (n = 333) and JIA (n = 3334) were identified. From the Swedish medical birth register (MBR), four controls per case, matched by sex, year and delivery unit were randomly selected. Through linkage to the MBR and to the Swedish inpatient register information on maternal, pregnancy and birth characteristics and infections during the first year of life was identified. Univariate and multivariate odds ratios (OR) were calculated using conditional logistic regression. Results: Overall, infections during the first year of life were associated with increased risks for seronegative (OR 2.6, 95% CI 1.0 to 7.0) but not seropositive (OR 1.2) RA and for JIA (OR 1.9, 95% CI 1.7 to 2.1). Low birth weight (OR 0.7) and being small for gestational age (OR 0.5) were associated with reduced risks of RA of borderline statistical significance. Preterm birth (gestational age ⩽258 days) was associated with a non-significantly decreased risk of RA (OR 0.6). Large for gestational age (OR 1.6) and having more than three older siblings (OR 1.4) were non-significantly associated with the risk of RA. Conclusion: Infections during the first year of life, and possibly also factors related to fetal growth and timing of birth, may be important in the aetiologies of adult RA and JIA.

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 Sjogren's syndrome. Recent findings: Physical capacity is reduced in both systemic lupus erythematosus and primary Sjogren'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 Sjogren'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 Sjogren'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 Sjogren'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. (Less)

Objective. Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA. Methods. Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004. Results. During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment. Conclusion. Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.

Nine patients with spondylarthropathy (SpA) (6 with ankylosing spondylitis and 3 with psoriatic arthritis) who had not responded properly to conventional DMARD therapy were treated with 3 infusions (at 0, 2 and 6 weeks) of the TNF alpha inhibitor infliximab (3 mg/kg), in combination with methotrexate. To measure the effect of treatment, patients were evaluated before as well as 8 and 12 weeks after treatment with respect to disease activity (BASDAI), function (BASFI), mobility (BASMI) and global well-being in the past week (BASG1) as well as the past 6 months (BASG2). BASDAI, BASFI, BASMI and BASG1 improved significantly, with the most pronounced effect during the first 8 weeks. Also, ESR and CRP decreased significantly from baseline to 12 weeks after treatment. We conclude that infliximab is an effective therapy in SpA which does not respond sufficiently to conventional DMARD therapy. Best response to treatment was found after the first treatment regimen with regard to both effect and effect duration. Most patients responding to and tolerating anti-TNF alpha treatment needed one infliximab infusion every 8th week (3 mg/kg) to control disease activity and symptoms. Further studies are warranted to evaluate long-term outcome of anti-TNF alpha treatment in patients with SpA.

BACKGROUND: Ankylosing spondylitis (AS) is associated with several extra-articular manifestations. Nephrolithiasis (NL) has not been recognized as one of those, however, several factors known to increase the risk of NL are at play in AS patients. The objective was to estimate rates and predictors of NL in Swedish patients with AS compared to the general population. METHODS AND FINDINGS: We performed a prospective population-based nationwide cohort study based on linkage of data from Swedish registries. 8,572 AS patients were followed for 49,258 person-years (py) and 39,639 matched general population comparators were followed for 223,985 py. Patients were followed prospectively together with comparator subjects from January 2001 through December 2009. The first occurrence of NL during follow-up was the primary outcome. Hazard Ratios (HR) were used to compare these rates adjusting for comorbidities and treatment, and to assess predictors for NL. Mean age at study entry was 46 years (inter quartile range 36-56 years), 65% were males. Based on 250 vs. 466 NL events, the adjusted HR of NL in AS patients was 2.1 (95%CI 1.8 to 2.4). Predictors of NL within the AS group included prior diagnosis of inflammatory bowel disease (IBD) (HR 2.3; 95%CI 1.7 to 3.3), prior diagnosis of NL (HR 16.4; 95%CI 11.5 to 23.4), and patients receiving anti-TNF treatment (HR 1.6; 95%CI 1.2 to 2.1). Male sex was a risk factor for NL both in AS patients and in the general population. LIMITATIONS: The risk for residual confounding and inability to study the chemical nature of NL were considered the main limitations of the study. CONCLUSIONS: Patients with AS are at increased risk of NL, which may be considered a novel extra-articular manifestation. Previous history of NL, IBD, AS disease severity and male sex were identified as predictors of NL in AS.

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.

A convenient method for the determination of inulin in diabetics and in subjects with advanced renal failure is presented. The interfering substances of small molecular size are eliminated by gel filtration on cross-linked dextran (Sephadex G-25).

Cystic puncture was performed percutaneously in 18 patients with solitary renal cysts and in 22 with multiple, congenital renal cysts. With the aid of tritiated water it was possible to estimate the fluid turnover in the cysts and compare it with their volume, pressure and potassium and creatinine levels. Fluid turnover was rapid in all the renal cysts. Two to five hours after i.v. injection of tritium, the tritium concentration in cystic fluid averaged 88% of the concentration in plasma fluid in patients with polycystic kidneys and 73 percent in patients with solitary cysts. Fluid turnover was more rapid in small than in large cysts, but there was no such difference between cysts with high and low pressure. It is possible that the fluid turnover was slightly faster in cysts with high potassium and creatinine levels than in those with low levels. The results show that the fluid turnover in a renal cyst of 10 ml is considerable--probably more than 100 ml/24 hours. This indicates that fluid inflow to the cyst comes mainly from cells in the cyst wall and not from a single glomerule. Fluid probably leaves the cyst actively via cells in the cyst wall, since the fluid turnover does not increase with high cyst pressure. The fluid turnover is probably secondary to the active solute transportation, which is performed by the cyst cells. This means that these cells have a tubular cell-like function and should respond to pharmacotherapy.

Background Ankylosing Spondylitis (AS) is a chronic inflammatory disease with onset in young adults, but little is known about the prevalence in older age groups. Furthermore, there is very limited information of health status of elderly patients with AS. Our objective was to estimate the prevalence of moderate to severe radiographic sacroiliitis in elderly men and its impact on health. Methods A cross-sectional, population-based survey, that included 1005 men aged 69-81 years old, with the primary aim to study risk factors for osteoporosis (MrOS), was used. X-rays of the pelvis and spine were done for the whole population and then examined by two readers. The prevalences of grade 3-4 sacroiliitis, syndesmophytes and spondylophytes were ascertained. Using a self-administered questionnaire, information was obtained on physical activity (PASE), functional status (IADL items), health related quality of life - QoL (SF-12) and back pain (pain question, Quebec Pain Disability Scale items). Results Fourteen cases with grade 3-4 sacroiliitis were identified, corresponding to a prevalence of 1.4% (95%CI: 0.7-2.4). Eight of the patients with sacroiliitis had both AS-typical and degenerative changes in the spine, 4 had only degenerative changes and 2 had only AS-related changes. There were no statistically significant differences between those with and without radiographic sacroiliitis regarding demographics, anthropometric measures, smoking status or health status, reflected by measures on physical activity, functional status, health related QoL and back pain. Conclusions The prevalence of moderate to severe radiographic sacroiliitis was estimated to be 1.4% among elderly men in Sweden. Self-reported health was only slightly different in those with sacroiliitis, suggesting that the relative impact of AS is modest in this age group.