Bakgrund: Smärta vid Reumatoid artrit (RA) ärett välkänt symtom som orsakar lidande ochaktivitetsbegränsning. Traditionellt mäts smärtainom reumatologin som smärtintensitet på enVisuell Analog Skala (VAS). Kunskapen kring hurpatienter med RA upplever smärta och dess konsekvenser är begränsad. Patientens egenbeskrivning behövs som underlag för behandlingsplanering och för att utveckla nya metoderför att beskriva problematiken.Syfte: Syftet med studien är att beskriva smärtavid RA ur ett patientperspektiv med fokus på hursmärtan påverkar dagliga aktiviteter.Metod: Patienter med diagnostiserad RA i syd-östra Sverige identifierades via Svenska Reumatologiregistret. Urvalet baserades på minst 5 årssjukdomsduration och minst 40 mm smärtintensitet på VAS vid de två senaste besöken på reumatologklinik. Sammanlagt 33 patienter, 7 män och26 kvinnor, deltog i sju fokusgrupper. Gruppernaformades utifrån kön och ålder. Intervjuguideninnehöll frågor som: Hur beskriver patienter medRA sin smärta? Vad påverkar smärtan? Vilkakonsekvenser har smärtan för aktivitetsutförande,aktivitetsbalans och undvikande av aktivitet? Enkvalitativ innehållsanalys görs.Resultat/förväntat resultat: Analyser hittills visar patienternas frustration över att inteklara det man vill eller behöver göra, beroendeav andra, minskade möjligheter till delaktigheti sociala sammanhang. Och närståendes betydelse. Analyserna visar att smärtan är relaterad till Göteborg6-8 april 201134trötthet, stress och sinnesstämning och att arbeteeller andra aktiviteter medverkar till att glömmabort smärtan och uppehålla förmåga. Analysenslutförs under hösten.Konklusion: Denna studie förväntas genererany angelägen kunskap om och förståelse försmärta.

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Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.

Background Primary Sjogrens syndrome (pSS) is characterised by a chronic inflammation of exocrine glands. Salivary gland infiltrates, however, do not correlate well with disease symptoms, and a primary role for the salivary gland parenchyma in disease development has been suggested. Specifically, dysfunction of exocrine pathways involving the muscarinic receptor 3 (CHRM3) has been indicated. Objective To investigate possible genetic divergence in the CHRM3 gene in patients with pSS. Methods 530 patients with pSS and 532 controls from a combined Swedish and Norwegian cohort were genotyped for 84 single nucleotide polymorphisms (SNPs) distributed throughout CHRM3. Results Genetic association was observed with five SNPs localised in intron 3 and 4 of CHRM3, the strongest being rs7548522 (minor allele frequency = 0.06, OR=1.93, 95% CI (1.24 to 3.01); p=0.0033). In addition, clinical parameters, including focus score, abnormal Schirmers test and presence of autoantibodies, were associated with different SNPs in CHRM3. Conclusion The study demonstrates a novel association of CHRM3 polymorphisms with pSS, suggesting a functional role for CHRM3 and the salivary gland parenchyma in the pathogenesis of pSS.

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.

Objective. To determine the short-term and medium-term risks of cancer in patients receiving antitumor necrosis factor alpha (anti-TNF alpha) 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.

Objective: Atherosclerosis is characterized by a chronic inflammatory response involving activated T cells and impairment of natural killer (NK) cells. An increased T cell activity has been associated with plaque instability and risk of acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate the immune status. However, peripheral blood contains only a minor proportion of lymphocytes. In this study, we hypothesized that thoracic lymph nodes from patients with stable angina (SA) and acute coronary syndrome (ACS) might add information to peripheral blood analyses. less thanbrgreater than less thanbrgreater thanMethods: Peripheral blood and lymph nodes were collected during coronary by-pass surgery in 13 patients with SA and 13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR, IL-18 receptor (R) and CCR4. less thanbrgreater than less thanbrgreater thanResults: Lymph nodes revealed a lymphocyte subpopulation profile substantially differing from that in blood including a higher proportion of B cells, lower proportions of CD8(+) T cells and NK cells and a 2-fold higher CD4/CD8 ratio. CD4(+)CD69(+) cells as well as Foxp3(+) regulatory T cells were markedly enriched in lymph nodes (p andlt; 0.001) while T helper 1-like (CD4(+)IL-18R(+)) cells were more frequent in blood (p andlt; 0.001). The only significant differences between ACS and SA patients involved NK cells that were reduced in the ACS group. However, despite being reduced, the NK cell fraction in ACS patients contained a significantly higher proportion of IL-18R(+) cells compared with SA patients (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: There were several differences in lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte perturbations in peripheral blood of ACS patients compared with SA patients were not mirrored in lymph nodes. The findings indicate that lymph node analyses in multivessel coronary artery disease may not reveal any major changes in the immune response that are not detectable in blood.

Objectives: This study analyses the relationships between pain intensity and other aspects of health commonly used to assess disease activity and disability in early rheumatoid arthritis and examines whether such relationships were different between women and men.

Subjects and methods: This study included the 189 patients (69% women) with early RA (symptoms <12 months at diagnosis) still remaining in the Swedish TIRA cohort 5 years after inclusion. Disease activity and disability was assessed 3, 6, 12, 18, 24, 36, 48, and 60 months (M0-M60) after inclusion by erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), number of swollen and tender joints, physicians global assessment of disease activity (PGA), grip force average over 10 seconds (Grippit), Grip Ability Test (GAT), Signals of Functional Impairment (SOFI) in hand, lower limb and upper limb, Health Assessment Questionnaire (HAQ), and pain intensity measured with a visual analogue scale (VAS). The variables were divided into meaningful blocks according to the correlation structure in a principal component analysis (PCA) at M60. Using hierarchical partial least squares (PLS) analyses, this study investigated the blocks cross-sectionally to test for correlations with pain intensity at M0 and M60. The blocks at M0 were also used as predictors of pain intensity at M60 in a hierarchical PLS.

Results: The strongest relationship was found between pain intensity and the second block, consisting of HAQ and SOFI-lower limb at the cross-sectional analyses in both women and men. The block representing disease activity (i.e., ESR, CRP, PGA, and swollen and tender joints) had the weakest relation to pain intensity. According to the longitudinal analyses, the disease activity variables (block 1) at M0 had the strongest relationship to pain intensity at M60 in men. In contrast, HAQ and SOFI-lower limb (block 2) at M0 had a strong relation to pain intensity in women.

Objective. Our study describes sick leave during 3 years before and 3 years after diagnosis of rheumatoid arthritis (RA) in relation to referents and identifies predictors for sick leave during the third year after diagnosis of RA.

Methods. One hundred twenty patients (76% women) from the Swedish early RA study TIRA were included. Disease activity and disability were registered regularly during 3 years in TIRA. Referents were matched for sex, age, and home town. Sick leave data were obtained for patients 3 years before and 3 years after diagnosis and for the referents for the corresponding 6 years.

Results. No differences were seen between patients and referents regarding sick leave during the first 2 years, whereas sick leave increased in patients 6 months before diagnosis, from 30% to 53%. During the 3 years after diagnosis, sick leave among patients was rather stable, varying between 50% and 60%, even though disability pension increased and sickness benefit decreased. Sick leave before diagnosis, disability 1 year after diagnosis, and type of work were identified as predictors for sick leave during the third year after diagnosis.

Conclusion. Not surprisingly, sick leave in patients increased the year before diagnosis. Although disease activity and disability diminished after diagnosis, the patients’ sick leave remained essentially unchanged. Sick leave 3 years after diagnosis was foremost predicted by earlier sick leave, disability, and type of work.

Background: Neutrophils are key-players in the innate host defense and their programmed cell death and removal are essential for efficient resolution of inflammation. These cells recognize a variety of pathogens, and the NOD-like receptors (NLRs) have been suggested as intracellular sensors of microbial components and cell injury/stress. Some NLR will upon activation form multi-protein complexes termed inflammasomes that result in IL-1 beta production. NLR mutations are associated with auto-inflammatory syndromes, and our previous data propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk and severity of inflammatory disease by acting as genetic susceptibility factors. These gene products are components of the NALP3 inflammasome, and approximately 6.5% of the Swedish population are heterozygote carriers of these combined gene variants. Since patients carrying the Q705K/C10X polymorphisms display leukocytosis, the aim of the present study was to find out whether the inflammatory phenotype was related to dysfunctional apoptosis and impaired clearance of neutrophils by macrophages. less thanbrgreater than less thanbrgreater thanMethods and Findings: Patients carrying the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well as microbe-induced apoptosis compared to matched controls. Western blotting revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients neutrophils. In contrast to macrophages from healthy controls, macrophages from the patients produced lower amounts of TNF; suggesting impaired macrophage clearance response. less thanbrgreater than less thanbrgreater thanConclusions: The Q705K/C10X polymorphisms are associated with delayed apoptosis of neutrophils. These findings are explained by altered involvement of different regulators of apoptosis, resulting in an anti-apoptotic profile. Moreover, the macrophage response to ingestion of microbe-induced apoptotic neutrophils is altered in the patients. Taken together, the patients display impaired turnover and clearance of apoptotic neutrophils, pointing towards a dysregulated innate immune response that influences the resolution of inflammation. The future challenge is to understand how microbes affect the activation of inflammasomes, and why this interaction will develop into severe inflammatory disease in certain individuals.

Resistin is a cysteine-rich protein, which is abundantly expressed at the site of inflammation, and acts as a regulator of the NF-kB-dependent cytokine cascade. The aim of this study was to evaluate resistin levels in relation to inflammatory mediators, disease phenotype and autoantibody status in a spectrum of pathological conditions of the gastrointestinal tract. Resistin levels were measured with an ELISA in sera originated from 227 patients and 40 healthy controls (HC). Fifty patients diagnosed with non-alcoholic fatty liver disease (NAFLD), 53 ulcerative colitis (UC), 51 Crohns disease (CD), 46 autoimmune hepatitis (AIH) and 27 primary sclerosing cholangitis (PSC) were included. The sera were analysed with respect to biochemical parameters of systemic inflammation and liver function and to the presence of antibodies to nuclear antigens (ANA), mitochondria (AMA) and smooth muscle (SMA). Compared with HC, resistin levels were raised in AIH (P = 0.017) and PSC (P = 0.03); compared with NAFLD, levels were elevated in CD (P = 0.041), AIH (P andlt; 0.001) and PSC (P andlt; 0.001). Patients with elevated levels of resistin were more often treated with corticosteroids, but no difference was found between active disease and clinical remission. Resistin levels were significantly higher in ANA-positive individuals compared with ANA-negative (P = 0.025). Resistin levels were directly correlated with IL-6 (r = 0.30, P = 0.02) and IL-8 (r = 0.51, P andlt; 0.001). Elevated levels of resistin were prominent in patients with hepatobiliary inflammation and were associated with breach of self-tolerance, i.e. ANA positivity. Thus, we propose that resistin may be an important marker of disease severity in autoantibody-mediated gastrointestinal inflammatory diseases.

The polymorphonuclear neutrophil granulocytes (neutrophils) are gaining renewed interest regarding their involvement in chronic inflammatory disorders, including rheumatoid arthritis (RA). Besides phagocytic and destructive capabilities, neutrophils have regulatory roles, e.g. by influencing responses from dendritic cells and lymphocytes. Several animal models have revealed that neutrophils are crucial for the initiation and maintenance of chronic inflammatory diseases. Neutrophil function is highly dependent on their ability to produce superoxide, an oxygen radical which can be further metabolized to other free radicals. Whether or not neutrophils are capable of producing the oxygen radical nitric oxide (NO˙) has been a matter of debate.

In this thesis it was shown that freshly isolated neutrophils from the joint cavity of patients with RA, but not from other arthritis patients, had ongoing intracellular production of superoxide, indicating the processing of ingested material.

The finding that joint neutrophils, but seemingly not circulating cells, expressed the NO-inducing enzyme iNOS, led to a series of experiments aimed to elucidate where in the exudative process this enzyme could first be detected. We could finally, for the first time, present evidence that human neutrophils actually express iNOS constitutively. Our data also suggest that neutrophil iNOS may be membrane associated, thus differing from the cytosolic location in other cell types. Since NOS activity was not demonstrated in isolated cells, the notion that neutrophil iNOS is regulated primarily at the transcriptional level must be questioned. NO production from iNOS requires the presence of its substrate, L-arginine. To test the hypothesis that neutrophil arginase prevents neutrophil NO-production, we investigated whether arginase inhibition affects neutrophil NO-dependent oxidative function. Initial data revealed a difference in the effect of arginase inhibition comparing neutrophil stimulus with a soluble formylated tri-peptide (fMLF) and integrin-mediated stimulation with particle-bound collagen type-1. This led to the hypothesis that integrin-ligation on neutrophils induces extracellular liberation of arginase, which was confirmed both by measuring arginase and its enzyme activity. The findings in this thesis may be important not only regarding the role of neutrophils in chronic joint inflammation, but also as a link in the accelerated atherosclerosis observed in chronic inflammatory disorders, e.g. RA.

The objective was to study the expression of inducible nitric oxide synthase (NOS II) in and NO production by human blood neutrophils and in in vivo exudated neutrophils. Cellular expression of NOS II was evaluated by flow cytometry in whole blood, in isolated blood neutrophils, and in neutrophils obtained by exudation in vivo into skin chambers. Neutrophil NOS II was also demonstrated by Western blotting. Uptake of ³H-labelled L-arginine was studied in vitro and NOS activity measured in a whole cell assay by the conversion of ³H-arginine to ³H-citrulline. In contrast to unseparated blood cells, NOS II was demonstrable both in isolated blood neutrophils and exudated cells. The failure to detect NOS II by flow cytometry in whole blood cells thus proved to be due to the quenching effect of hemoglobin. Western blotting revealed a 130 kD band corresponding to NOS II in isolated blood neutrophils, but detection was dependent on diisopropylfluorophosphate for proteinase inhibition. L-arginine was taken up by neutrophils, but enzymatic activity could not be demonstrated. We conclude that human neutrophils constitutively express NOS II, but that its demonstration by FITC-labelling is inhibited by hemoglobin-mediated quenching in whole blood samples.

The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure L-arginine and L-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess' reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0.001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. L-arginine was elevated in SF compared to serum (257 ± 78 versus 176 ± 65 µmol/l, P = 0.008), whereas a slight increase in L-citrulline (33 ± 11 versus 26 ± 9 µmol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19.2 ± 20.7 versus 8,6 ± 6.5 µmol/l,P = 0.054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis.

Objective: To compare total and intracellular oxidative activation of blood and synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA) and other arthritides with blood donor neutrophils.

Methods: Peripheral blood and SF samples were obtained from 26 gonarthritis patients (13 RA, 13 non-RA) attending the rheumatology unit for therapeutic joint aspiration. Isolated neutrophils were stimulated by a formylated tripeptide (fMLF) or by microbeads coated with collagen-I. Formation of superoxide-anion-derived reactive oxygen species (ROS) was studied by luminol-enhanced chemiluminescence. Paired samples of blood and SF neutrophils from patients with active arthritis were compared with blood neutrophils from patients in remission and from 47 healthy blood donors.

Results: SF neutrophils from patients with RA, but not from non-RA patients, showed high baseline intracellular ROS production. Blood neutrophils from arthritis patients in remission existed in a primed state as revealed by more rapid oxidative response after collagen-bead challenge and a more pronounced response after fMLF stimulation compared to healthy blood donors. Blood neutrophils from RA patients with ongoing gonarthritis, however, did not differ from healthy blood donors concerning oxidative activation, whereas blood neutrophils from non-RA patients with gonarthritis showed a significantly lower peak ROS production.

Conclusions: A novel finding with pathogenetic implications in our study is that SF neutrophils from patients with RA, but not other arthritides, are activated and produce ROS intracellularly. This implies that synovial neutrophils in RA are engaged in the processing of endocytosed material.

Background: Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication. Methodology and Principal Findings: 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population. Conclusion: We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population.

Fibromyalgia is currently classified as chronic widespread pain with widespread allodynia to pressure pain. There are few data describing pain characteristics, quality of life, consequences for daily living, and psychosocial status in patients who meet the classification criteria for fibromyalgia proposed by the American College of Rheumatology compared with patients with chronic widespread pain but not widespread allodynia. This study used a randomly selected sample from the general population. A postal questionnaire and a pain mannequin were sent to 9952 people. The response rate was 76.7%. The pain drawings showed that 345 people had widespread pain, that is, they noted pain in all four extremities and axially. Clinical examination, which included a manual tender point examination, was performed in 125 subjects. These people answered commonly used questionnaires on pain, quality of life, coping strategies, depression, and anxiety. Compared with chronic widespread pain without widespread allodynia, fibromyalgia was associated with more severe symptoms/consequences for daily life and higher pain severity. Similar coping strategies were found. Chronic widespread pain without widespread allodynia to pressure pain was found in 4.5% in the population and fibromyalgia in 2.5%. © 2007 European Federation of Chapters of the International Association for the Study of Pain.

The aim of this study was to identify the social and organizational requirements for a decision support system (DSS) to be implemented in a clinical rheumatology setting, utilizing data-mining techniques. Field observations and focus group interviews were used for data collection. The decision-making was found to be situated, patient-focused, and long-term in nature. At the same time, the main part of peer-to-peer communication was informal. Patient records were involved in almost every decision. The conclusion is that the main challenges, when introducing a DSS at a rheumatology unit, are adapting the system to informal communication structures and integrating it with patient records. Considering incentive structures, understanding workflow and incorporating awareness are relevant issues when addressing these issues in future studies.

Identification of prognostic subgroups is of key clinical interest at the early stages of chronic disease. The aim of this study is to examine whether representation of physicians' expert knowledge in a simple heuristic model can improve data mining methods in prognostic assessments of patients with rheumatoid arthritis (RA). Five rheumatology consultants' experiences of clinical data patterns among RA patients, as distinguished from healthy reference populations, were formally represented in a simple heuristic model. The model was used in K-mean-clustering to determine prognostic subgroups. Cross-sectional validation using physician's global assessment scores indicated that the simple heuristic model performed better than crude data made in identification of prognostic subgroups of RA patients. A simple heuristic model of experts' knowledge was found useful for semi-automatic data mining in the chronic disease setting. Further studies using categorical baseline data and prospective outcome variables are warranted and will be examined in the Swedish TIRA-program.

Introduction: There is a need for tools that are easy to use in clinical practice supporting decision making upon treatment in early rheumatoid arthritis (RA). Aim: The aim was to identify components of prognosticators in early RA and to identify individual patients with a poor prognosis as early as possible.

Methods: Two cohorts from the Swedish TIRA project including 320+408 patients with recent onset RA were included in the study. Disease activity was measured by C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the 28-joint count disease activity score (DAS-28), and by the physicians’ global assessment of disease activity (PGA). Disability was assessed as activity limitation by the Swedish version of the Health Assessment Questionnaire (HAQ) and impairment was reported by pain on a visual analogue scale of 0–100 mm. Serological markers were rheumatoid factor (RF) and anti-CCP. RF was measured at the time for diagnosis, and anti-CCP at the time of diagnosis or at one or some of the follow-ups. If at least one anti-CCP test was positive, the patient was judged to be anti-CCP-positive. Assuming different clinical practice in the different cohorts, two different treatment strategies were assumed based on clinical practice in real-world settings. Principal Component Analysis and Multiple Linear Regression Analysis were used to identify prognosticators. Prediction rules were identified by data-driven approach, controlling for different treatment strategies.

Results: Progression of disease and disability measures and inflammation measures the first three months after inclusion predicted a considerable part of DAS-28 at the 1-year follow-up. Serological markers had a larger explanatory power for men than for women. Anti-CCP was a significant predictor for men, but not for women. Two versions of rules, one for women and one for men, predicting good or poor prognosis at one year after inclusion were produced by using measures of disability (Health Assessment Questionnaire), DAS-28, relative change in DAS-28 during first three months, sex, and test of anti-CCP. The rules demanded high prognostic specificity but the prognostic sensitivity was moderate.

Conclusion: A considerable part of DAS-28 at one year after inclusion could be explained by the first 3 months’ progression of disease, disability and inflammation. Anti-CCP was predictive for men but not for women, and needs further investigation. A decision tree predicting poor prognosis among individual early RA-patients showed high specificity and moderate sensitivity on a validationcohort. The medical informatics approach used, controlling for different treatment strategies, yields promising results and further studies will control for more specific differences in treatment strategies, e.g. different DMARDs initiated.

Objective. C-reactive protein (CRP) is synthesized by hepatocytes in response to interleukin-6 (IL-6) during inflammation. Despite raised IL-6 levels and extensive systemic inflammation, serum CRP levels remain low during most viral infections and disease flares of systemic lupus erythematosus (SLE). Because both viral infections and SLE are characterized by high levels of interferon-alpha (IFN alpha), the aim of this study was to determine whether this cytokine can inhibit the induction of CRP. Methods. The interference of all 12 IFN alpha subtypes with CRP promoter activity induced by IL-6 and IL-1 beta was studied in a CRP promoter- and luciferase reporter-transfected human hepatoma cell line, Hep-G2. CRIP secretion by primary human hepatocytes was analyzed by enzyme-linked immunosorbent assay. Results. CRP promoter activity was inhibited by all single IFN alpha subtypes, as well as by 2 different mixtures of biologically relevant IFN alpha subtypes. The most prominent effect was seen using a leukocyte-produced mixture of IFN alpha (56% inhibition at 1,000 IU/ml). The inhibitory effect of IFN alpha was confirmed in primary human hepatocytes. CRP promoter inhibition was dose dependent and mediated via the type I IFN receptor. Transferrin production and Hep-G2 proliferation/viability were not affected by IFN alpha. Conclusion. The current study demonstrates that IFN alpha is an inhibitor of CRP promoter activity and CRP secretion. This finding concords with previous observations of up-regulated IFN alpha and a muted CRP response during SLE disease flares. Given the fundamental role of both IFN alpha and CRP in the immune response, our results are of importance for understanding the pathogenesis of SLE and may also contribute to understanding the differences in the CRP response between viral and bacterial infections.

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In the 1960s and 1970s, intestinal bypass surgery was performed to treat patients with extreme obesity. However, this is now done with great restriction due to the risk of complications, for instance, polyarthritis. An association between severe achalasia and arthritis has also been described, but very few articles on this topic are cited in PubMed, and most of the published case reports are old. In this article, we present a retrospective case series of three patients with severe achalasia and arthritis from the departments of rheumatology and surgery at a university hospital. The complaints from the esophagus as well as arthritis were resolved after esophagectomy and esophageal reconstruction. We conclude that severe achalasia can be associated with arthritis, and both can be cured by esophageal reconstruction. Thus, we want to remind of this rare, but probably largely unrecognized, association between achalasia and joint disease.

OBJECTIVES: 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. DESIGN: Survival analyses were performed by Kaplan-Meier survival curves, SMR and proportional hazards regression models. SETTING: The nephrology and rheumatology clinics at Linköping University Hospital, Sweden. SUBJECTS: 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. RESULTS: 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 micromol L(-1) (16% dialysis-dependent) vs. 192 micromol 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. CONCLUSION: 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.

Objective. The use of rituximab in vasculitis has increased interest in B cell biology. A subpopulalion of B cells expressing CD25 shows antigen-presenting properties and may have regulatory functions. We assessed subpopulations of B cell maturation (Bm) and markers related to activity and antigen presentation, and related the findings to disease activity. Methods. Multiparameter flow cytometry was used to assess numbers and proportions of circulating lymphocytes from 34 patients with vasculitis (16 remission, 18 active) and 20 controls. Results. Active vasculitis samples showed decreased proportions of Bm1 (7.8% vs 11%; p = 0.041), Bm2 (0.2% vs 0.7%; p = 0.002), and Bm3/Bm4 (0.1% vs 0.3%; p = 0.006), compared with controls; Bm2 cells were the most frequently occurring B cells but they were not significantly different in active vasculitis (74% vs 62%; p = 0.083). In patients with remission the proportion of CD25+ B cells was increased compared to controls (48% vs 29%, respectively; p = 0.006) and also compared to active vasculitis (23%; p = 0.006). The proportion of CD86+ B cells was also increased (31%) compared to active vasculitis (8%; p = 0.001), and to controls (6%; p = 0.0003). In multivariate analysis. Bm2 cells and CD25+27- B cells were independently influencing the patient group. Conclusion. In active vasculitis, a lower proportion of Bm I cells may indicate activated B cells. Patients in remission had higher proportions of CD25+ (a-chain of interleukin 2 receptor) and CD86+ (costimulatory molecule) B cells. We suggest that these B cells may have a regulatory role, or alternatively may result from previous treatment.

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Objective. T helper cells lacking CD28 (CD4+CD28-) have been implicated in the pathogenesis of granulomatosis with polyangiitis (Wegener; GPA) and microscopic polyangiitis (MPA). Expansions of CD4+CD28- and CD8+CD28- T cells have also been associated with latent cytomegalovirus (CMV) infection. We assessed these T cells with and without coexpression of CD56 and CD57 in relation to vasculitis as well as CMV status. less thanbrgreater than less thanbrgreater thanMethods. Blood from 16 patients in remission (12 GPA, 4 MPA), 18 patients with active vasculitis (12 GPA, 6 MPA), and 20 healthy controls was examined by flow cytometry for expression of CD4, CD8, CD56, CD57, and CD28 on T cells. The influence of age, CMV status, presence of disease, and disease activity on T cell subpopulations was tested with multiple regression analyses. less thanbrgreater than less thanbrgreater thanResults. In active vasculitis, the total numbers and proportion of lymphocytes were decreased. Total numbers of CD4+, CD8+, CD4+CD28-, CD8+CD28-, CD4+CD57+, and CD8+CD57+ T subpopulations were decreased to the same extent, implying unchanged proportions. Multivariate analyses showed no associations between vasculitis and CD28- or CD57+ T subpopulations, whereas immunoglobulin G antibodies to CMV were associated with expanded proportions of CD28 and CD57+ T cells, in both the CD4+ and the CD8+ compartments. less thanbrgreater than less thanbrgreater thanConclusion. CD28- and CD57+ T cells were associated with latent CMV infection and not with a diagnosis of GPA or MPA. Vasculitis assessment should include CMV status.

Major clinical symptoms in fibromyalgia (FM) are muscle pain, stiffness and fatigue. Studies have shown reduced voluntary strength and exercise capacity, lower endurance and more muscular pain even at low workload. An impaired muscle energy metabolism has therefore been proposed as a result of the disease. An earlier study using magnetic resonance spectroscopy (MRS) showed that at maximal dynamic and static contractions the concentration of inorganic phosphate was lower in FM [1]. A decrease in ATP, ADP and PCr and an increase in AMP and creatine was found in FM biopsies [2]. The purpose of this study was to non-invasively analyze the quantitative content of  phosphagens in the resting muscle in FM in comparison to healthy controls using 31P MRS of the quadriceps muscle.

Objective Antinuclear antibody (ANA) analysis by immunofluorescence (IF) microscopy remains a diagnostic hallmark of systemic lupus erythematosus (SLE). The clinical relevance of ANA fine-specificities in SLE has been addressed repeatedly, whereas studies on IF-ANA staining patterns in relation to disease manifestations are very scarce. This study was performed to elucidate whether different staining patterns associate with distinct SLE phenotypes.

Design Observational cohort study.

Setting One university hospital rheumatology unit in Sweden.

Participants The study population consisted of 222 cases (89% women; 93% Caucasians), where of 178 met ≥4/11 of the 1982 American College of Rheumatology (ACR-82) criteria. The remaining 20% had an SLE diagnosis based on positive IF-ANA (HEp-2 cells) and ≥2 typical organ manifestations at the time of diagnosis (Fries’ criteria).

Outcome measures The IF-ANA staining patterns homogenous (H-ANA), speckled (S-ANA), combined homogenous and speckled (HS-ANA), centromeric (C-ANA), nucleolar (N-ANA)±other patterns and other nuclear patterns (oANA) were related to disease manifestations and laboratory measures. Antigen-specificities were also considered regarding double-stranded DNA (Crithidia luciliae) and the following extractable nuclear antigens: Ro/SSA, La/SSB, Smith antigen (Sm), small nuclear RNP (snRNP), Scl-70 and Jo-1 (immunodiffusion and/or line-blot technique).

Results 54% of the patients with SLE displayed H-ANA, 22% S-ANA, 11% HS-ANA, 9% N-ANA, 1% C-ANA, 2% oANA and 1% were never IF-ANA positive. Staining patterns among patients meeting Fries’ criteria alone did not differ from those fulfilling ACR-82. H-ANA was significantly associated with the 10th criterion according to ACR-82 (‘immunological disorder’). S-ANA was inversely associated with arthritis, ‘immunological disorder’ and signs of organ damage.

Conclusions H-ANA is the dominant IF-ANA pattern among Swedish patients with SLE, and was found to associate with ‘immunological disorder’ according to ACR-82. The second most common pattern, S-ANA, associated negatively with arthritis and organ damage.

Background. This population study based on a representative sample from a Swedish county investigates the prevalence, duration, and determinants of widespread pain (WSP) in the population using two constructs and estimates how WSP affects work status. In addition, this study investigates the prevalence of widespread pain and its relationship to pain intensity, gender, age, income, work status, citizenship, civil status, urban residence, and health care seeking. Methods. A cross-sectional survey using a postal questionnaire was sent to a representative sample (n = 9952) of the target population (284,073 people, 18-74 years) in a county (Östergötland) in the southern Sweden. The questionnaire was mailed and followed by two postal reminders when necessary. Results. The participation rate was 76.7% (n = 7637), the non-participants were on the average younger, earned less money, and male. Women had higher prevalences of pain in 10 different predetermined anatomical regions. WSP was generally chronic (90-94%) and depending on definition of WSP the prevalence varied between 4.8-7.4% in the population. Women had significantly higher prevalence of WSP than men and the age effect appeared to be stronger in women than in men. WSP was a significant negative factor - together with age 50-64 years, low annual income, and non-Nordic citizen - for work status in the community and in the group with chronic pain. Chronic pain but not the spreading of pain was related to health care seeking in the population. Conclusion. This study confirms earlier studies that report high prevalences of widespread pain in the population and especially among females and with increasing age. Widespread pain is associated with prominent effects on work status. © 2008 Gerdle et al, licensee BioMed Central Ltd.

BACKGROUND AND METHODS:

Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P magnetic resonance spectroscopy (31P-MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (Controls; n = 14) using (31) P-MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity.

RESULTS:

Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28-29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in Controls [FMS: 9.0 ± 0.5% vs. Controls: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities.

CONCLUSIONS:

Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.

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The genetic background of primary Sjogrens syndrome (pSS) is partly shared with systemic lupus erythematosus (SLE). Immunoglobulin G Fc receptors are important for clearance of immune complexes. Fcg receptor variants and gene deletion have been found to confer SLE risk. In this study, four Fc gamma receptor single-nucleotide polymorphisms (SNPs) and one copy number variation (CNV) were studied. Swedish and Norwegian pSS patients (N = 527) and controls (N = 528) were genotyped for the Fc gamma receptor gene variant FCGR2A H131R (rs1801274) by the Illumina GoldenGate assay. FCGR3A F158V (rs396991) was analysed in 488 patients and 485 controls, FCGR3B rs447536 was analysed in 471 patients and 467 controls, and FCGR3B rs448740 was analysed in 478 cases and 455 controls, using TaqMan SNP genotyping assays. FCGR3B CNV was analysed in 124 patients and 139 controls using a TaqMan copy number assay. None of the SNPs showed any association with pSS. Also, no FCGR3B CNV association was detected. The lack of association of pSS with Fc gamma receptor gene variants indicates that defective immune complex clearance may not be as important in pSS pathogenesis as in SLE, and may point to important differences between SLE and pSS.

Rheumatoid arthritis (RA) is a major cause of progressive joint damage and disability, and is associated with decline in quality of life, reduced ability to work and increased health care utilisation. The economic consequences of the disease are substantial for the individuals and their families and for the society as a whole. This thesis describes a 5-year follow up of 320 patients with early RA, enrolled between January 1996 and April 1998 in the Swedish multi-centre inception cohort TIRA (early interventions in rheumatoid arthritis). Health status, function and costs were investigated. Predictors of high costs were calculated, and an algorithm was constructed to predict future need for TNFinhibitor treatment in patients not responding to traditional disease-modifying antirheumatic drugs (DMARDs). Clinical and laboratory data, measures of functional capacity and self-reported assessments were collected regularly. In addition, patients completed biannual/annual questionnaires concerning all health care utilisation and days lost from work due to the disease. Within 3 months, improvements were seen regarding all variables assessing disease activity and functional ability, but 15% of the patients had sustained high or moderate disease activity throughout the study period. The scores of ‘health assessment questionnaire’ (HAQ) were similar for men and women at baseline, but had a less favourable course in women, who also had DMARDs more frequently prescribed.

Ambulatory care accounted for 76% of the direct costs during the first year. Women had more ambulatory care visits and higher usage of complementary medicine compared to men. Men ≥65 years had low costs compared to younger men and compared to women of all ages. In multiple logistic regression tests, HAQ, high levels of IgM-class rheumatoid factor (RF), and poor hand function increased the odds of incurring high direct costs. Poor hand function and pain increased the odds of incurring high indirect costs.

Indirect costs exceeded direct costs all three years. The average direct costs were €3,704 (US$ 3,297) year 1 and €2,652 (US$ 2,360) year 3. All costs decreased over the years, except those for medication and surgery. The indirect costs were €8,871 (US$ 7,895) year 1 and remained essentially unchanged, similarly for both sexes. More than 50% were on sick leave or early retirement at inclusion. Sick leave decreased but was offset by increase in early retirement. 14 patients (5%) were prescribed TNF-inhibitors at the 3- year follow up, thus increasing drug costs substantially. However, they incurred higher costs even before prescription of anti-TNF therapy.

At the 5-year follow-up (2001-2003), 31 patients (12%) were prescribed TNFinhibitors. Baseline values of erythrocyte sedimentation rate, C-reactive protein, anti-CCP antibodies and morning stiffness were significantly higher in this group. These patients were also to a larger extent RF-positive and carriers of the ‘shared epitope’ (SE). Anti-TNF treated patients were significantly younger and more often women. For men, a predictive model was constructed using baseline data including SE+ and IgA-RF >100 U/L and anti-CCP >240 U/L yielding a specificity of 98% and a sensitivity of 71%. For women, disease activity score (DAS28) at the 3-month follow-up proved to be a better predictor, and the final model comprised SE+ and 3-month DAS28>5.2, giving a specificity of 95% and a sensitivity of 59%.

OBJECTIVE: To compare women and men regarding course of disease activity and disability over 8 years from diagnosis of recent onset rheumatoid arthritis (RA). PATIENTS AND METHODS: 149 patients were followed for 8 years from RA diagnosis (1996-98) regarding 28-joint count disease activity score (DAS28), pain (visual analogue scale, VAS), grip force, Grip Ability Test (GAT), Signals of Functional Impairment (SOFI hand, upper/lower extremity), walking speed, activity limitation (Health Assessment Questionnaire, HAQ) and prescribed disease-modifying anti-rheumatic drugs (DMARDs). RESULTS: Disease activity pattern over time was similar in women and men, showing improvement during the first year and thereafter a stable situation during 6 years. However, at the 7- and 8-year follow-ups deterioration was seen with a less favourable course in women. HAQ did not differ between sexes at diagnosis, but at all follow-ups women had significantly higher scores than men. Women also had lower grip force and lower walking speed, but higher upper extremity mobility. DMARD prescription was similar for both sexes. Over eight years, disease duration, sex, biologics, grip force, SOFI-hand and pain intensity together explained 43% of the variation in DAS, while grip force, SOFI-lower, GAT and pain intensity could together explain 55% of variations in HAQ. CONCLUSIONS: Disease activity was fairly well managed, but disability gradually deteriorated. Despite similar medication, women had more disability than men. The discrepancy between disease activity and disability indicates unmet needs for multi-professional interventions to prevent progressing disability and patients at risk for disability need to be identified early in the process. © 2012 by the American College of Rheumatology.

Objective. To calculate direct and indirect costs in early rheumatoid arthritis (RA) and to characterize patients generating high and low costs respectively.

Methods. Two hundred and ninety-seven patients with recent-onset (≤12 months) RA were recruited. Clinical/laboratory data and 'health assessment questionnaire' (HAQ) were registered at inclusion and after 3, 6 and 12 months. After 6 and 12 months, the patients completed a questionnaire concerning health-care utilization and days lost from work. A cut-off point for direct costs was set at 34 000 Swedish kronor (3675) defining one-third of the patients as a high-cost group and two-thirds as low-cost group. Indirect costs were calculated for patients aged <65 yr.

Results. Two hundred and eleven patients completed the HAQ on both occasions. Indirect costs exceeded direct costs by a factor of 2.3. Sixty three per cent experienced work disability during the first year and were identified as the 'high-indirect-cost group'. Indirect costs accounted for >70% of total costs. Direct costs included ambulatory health care (76%), hospitalization (12%) and medication (9%). Men aged ≥65 yr had low costs compared with younger men and women of all ages. In multiple logistic regression tests, HAQ, high levels of IgM rheumatoid factor (IgM RF) and poor hand function increased the odds of entering the high-direct-cost group, and poor hand function and pain increased the odds of entering the high-indirect-cost group.

Conclusions. Substantial costs were incurred during the first year after diagnosis of early RA, mainly due to work disability. Indirect costs were two to three times higher than direct costs. High levels of IgM RF, high HAQ score, poor hand function and pain increased the odds of entering high-cost groups.

Methods. Three-hundred and twenty patients with early (1 year) RA were assessed at regular intervals. Clinical and laboratory data were collected and patients reported health-care utilization and number of days lost from work. At 3-month follow-up, patients were divided into two groups according to disease activity, using DAS-28 with a cut-off level at 3.2. Direct and indirect costs and EuroQol-5D over the following 4 years were compared between the groups. Multivariate regression models were used to control for possible covariates. Results. Three months after diagnosis, a DAS-28 level of epsilon 3.2 was associated with high direct and indirect costs over the following 4 years. Patients with DAS-28 epsilon 3.2 at 3-month follow-up had more visits to physician, physiotherapist, occupational therapist and nurse, higher drug costs, more days in hospital and more extensive surgery compared with patients with 3-month DAS-28 less than 3.2. Number of days lost from work due to sick leave and permanent work disability was also higher in this group. The effect of disease activity on health-related quality of life was highly significant. In regression models, DAS-28 at 3-month follow-up was significantly associated with costs over the following years. Conclusions. Three months after diagnosis, DAS-28 is an important prognostic marker regarding health-care utilization and costs. Achieving remission or low disease activity 3 months after diagnosis is likely to decrease morbidity, increase quality of life and save costs for the patient and for society over the following years.

Objective. To calculate direct and indirect costs and to studydisease activity and functional ability over 3 yr in early rheumatoidarthritis (RA).

Methods. Three hundred and three patients with early (≤1 yr)RA were recruited during a period of 27 months (1996–1998).Data were recorded during 3 yr to assess disease activity, functionalability, medication, health-care utilization and days lost fromwork.

Results. Within 3 months, improvements were seen regarding allrecorded variables assessing disease activity and functionalability, but 15% had sustained high or moderate disease activitythroughout the study period. Indirect costs exceeded directcosts in all 3 yr. The average direct costs were € 3704 (US$3297) in year 1 and € 2652 (US$ 2360) in year 3. All costs decreased,except those for medication and surgery. Compared with men,women had more ambulatory care visits and used more complementarymedicine. The indirect costs were € 8871 (US$ 7895) in year 1and remained essentially unchanged; this was similar for bothsexes. Almost 50% were on sick leave or early retirement atinclusion. Sick leave decreased but was offset by an increasein early retirement. The 14 patients who eventually receivedTNF inhibitors incurred higher costs even before prescriptionof anti-TNF therapy.

Conclusion. Disease activity and functional ability improvedwithin 3 months after diagnosis of early RA. Direct costs decreased,except for medication and surgery. Indirect costs remained unchanged.Fifteen per cent of the patients had high or moderate diseaseactivity in all 3 yr, indicating a need for more aggressiveearly anti-rheumatic therapy.

Objective: To describe the course of recent onset rheumatoidarthritis (RA) and to compare consequences of the disease inmen and women.

Methods: 284 patients with recent onset RA were followed upprospectively for two years from the time of diagnosis. Measuresof disease activity (for example, 28 joint disease activityscore (DAS28), C reactive protein, morning stiffness, physician’sglobal assessment) and function outcome (for example, rangeof movement, hand function, walking time) were determined. Thepatients’ self reported assessment of functional capacity(Health Assessment Questionnaire (HAQ)) and grading of wellbeingand pain (visual analogue scale) were registered. Changes overtime and differences between men and women were evaluated.

Results: Improvements were seen for all variables within thefirst three months. Disease activity then remained unchanged.Function variables followed the same pattern during the firstyear, but then tended to worsen. HAQ scores were similar atbaseline, but significantly worse in women than in men at theone and two year follow ups.

Conclusions: Disease activity was well managed and had improvedsubstantially after two years, whereas function seemed slowlyto deteriorate. Although disease variables were similar formen and women, functional ability (HAQ) had a less favourablecourse in women.