Alexandros A. Drosos

Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study.

OBJECTIVE Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.

Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment – a prospective, controlled study

We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushings syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 ± 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients.

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST–RA database

Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US

Remission and rheumatoid arthritis: Data on patients receiving usual care in twenty-four countries

24 000 and 11 “low GDP” countries with GDP per capita less than US

Soluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases

11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r  =  −0.78, 95% CI −0.56 to −0.90, r2  =  61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

Primary Sjögren syndrome in the paediatric age: a multicentre survey.

OBJECTIVE To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Anticardiolipin antibodies in unselected autoimmune rheumatic disease patients

Lymphocytes upon activation release a soluble form of interleukin 2 receptor (IL-2R). Systemic autoimmune disorders are characterized by immune system disregulation associated with cellular activation; therefore we sought to determine the levels of soluble IL-2R molecules in the serum of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjogrens syndrome (1 degree SS). Utilizing an enzyme immunoassay method we found increased serum levels of soluble IL-2R in 65.4% (34/52) of RA, in 34.9% (15/43) of SLE, and in 25.0% (13/52) of 1 degree SS patients, compared to 4.2% (1/24) of healthy individuals. High serum levels of soluble IL-2R correlated with several indices of disease activity in RA and SLE patients, as well as with disease progression to extraglandular involvement and to pseudolymphoma or lymphoma in patients with 1 degree SS. By gel filtration analysis, the soluble IL-2R circulating in the serum of a RA patient corresponded to a high molecular weight molecule (greater than 90 kDa) compared to the 65-kDa soluble IL-2R molecule released by phytohemagglutinin-stimulated normal peripheral lymphocytes.

Systemic Lupus Erythematosus in Greece. Clinical Features, Evolution and Outcome: a Descriptive Analysis of 292 Patients:

Abstract Primary Sjögren syndrome (SS) is very rare in childhood. We collected a series of primary paediatric SS cases from different centres. A data collection form was prepared and sent to rheumatologists who were willing to participate. Data on 40 cases of primary SS with onset before the 16th birthday were collected. Almost all patients (35/40) were females, age at onset varied from 9.3 to 12.4 years (mean 10.7 years). Signs and symptoms at disease onset were mainly recurrent parotid swelling followed by sicca symptoms. Abnormal laboratory tests were found in the majority of cases. Regarding treatment, 22 patients were treated at some time with oral corticosteroids, seven with non-steroidal anti-inflammatory drugs, and five with hydroxychloroquine; two patients needed cyclosporine and one cyclophosphamide. Follow-up varied from 0 to 7.5 years from onset, without major complications in the majority of patients. Conclusion: recurrent parotid swelling is a common feature of primary Sjögren syndrome in childhood and often occurs as a presenting feature. Sicca symptoms may be rarer.

Early Treatment Reduces the Cardiovascular Risk Factors in Newly Diagnosed Rheumatoid Arthritis Patients

Quantitative determination of IgG and IgM antibodies to cardiolipin (anti-CL) was performed with a newly developed sensitive and specific ELISA method. We studied a cohort of 361 unselected patients with various autoimmune rheumatic diseases (ARD), 69 patients with thromboembolic phenomena (TEP) unassociated with ARD, and 267 healthy blood donors (HBD). Anti-CL of at least one immunoglobulin class were found in 42 (11.6%) of the ARD patients, in 3 (4.3%) of the TEP patients (2 with myocardial infarction and 1 with pulmonary emboli), and in 6 (2.3%) of the HBD. In ARD patients anti-CL were more prevalent in patients with systemic lupus erythematosus (SLE) and overlap syndromes. Significant correlations included CNS involvement (particularly seizures) and features of immune hyperreactivity (splenomegaly-lymphadenopathy, ANA, and antibodies to Ro(SSA), U1-nRNP, and double-stranded DNA). No statistical correlation could be demonstrated between the presence of anti-CL and thrombotic events, hematologic disorders, or recurrent abortions in the ARD patients.

Cutting Edge: Coding Single Nucleotide Polymorphisms of Endoplasmic Reticulum Aminopeptidase 1 Can Affect Antigenic Peptide Generation In Vitro by Influencing Basic Enzymatic Properties of the Enzyme

The purpose of this study was the descriptive analysis of patients with systemic lupus erythematosus (SLE) with a particular focus on initial clinical features, evolution and outcome of disease, prevalence of clinical and serological manifestations and identification of clinicoserological associations indicative of renal and CNS involvement. The methodology applied was the following: retrospective analysis of the clinical charts of 292 unselected patients (246 female (84.2%) and 46 male (15.7%)) with SLE examined between 1982 and 1992. Multivariate analysis and hierarchical log linear models were used to examine for clinicoserological associations. Descriptive analysis was based on the prevalence of main clinicoserological features and disease outcome. The outcome was examined on the basis of the number of flares, the presence of chronic renal failure, the presence of central nervous system (CNS) involvement with subsequent disability and deaths. Flares were considered the severe alterations in disease status, requiring additional therapy to be controlled. The disease begins most frequently in the second and third decade of life with cutaneous and joint manifestations, while renal and CNS involvement developed later. The prevalence of serious renal, pulmonary and CNS involvement as well as the prevalence of RF, anti-Sm and anti-nRNP antibodies remain low. Multivariate analysis revealed the associations of renal involvement with leukopenia and serositis, of anti-Sm with leukopenia, of secondary Sjogrens syndrome with RF and of thromboembohc events with anticardiolipin antibodies. Patients with childhood onset SLE have a higher tendency for developing renal involvement than adult onset SLE patients. In addition, anti-Ro(SSA) antibodies were associated with anti-La(SSB) and RF, while anti-Sm antibodies were associated with anti-nRNP and RF. Flares occurred with a frequency of 0.07 per patient per year. Only 63.6% of flares were accompanied by positive anti-dsDNA reactivities. Reported deaths were 0.0047 per patient per year. Hierarchical log linear models indicated that the main variables of the disease were sufficient to describe our disease model and that the arder of the interaction between the variables was insignificant. We conclude that the prevalence of various clinical features associated with SLE is similar, although the prevalence of CNS and pulmonary involvement as well as anti-Sm and anti-nRNP antibodies are less prominent in Greek SLE patients than that reported in the literature. The various clinicaseralogical associations detected do not appear to be of major significance as they are not powerful enough to subgroup the disease.