Showing papers in "Annals of the Rheumatic Diseases in 2001"

Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care

Abstract: BACKGROUND Osteoarthritis is the single most common cause of disability in older adults, and most patients with the condition will be managed in the community and primary care. AIM To discuss case definition of knee osteoarthritis for primary care and to summarise the burden of the condition in the community and related use of primary health care in the United Kingdom. DESIGN Narrative review. METHOD A literature search identified studies of incidence and prevalence of knee pain, disability, and radiographic osteoarthritis in the general population, and data related to primary care consultations. Findings from UK studies were summarised with reference to European and international studies. RESULTS During a one year period 25% of people over 55 years have a persistent episode of knee pain, of whom about one in six in the UK and the Netherlands consult their general practitioner about it in the same time period. The prevalence of painful disabling knee osteoarthritis in people over 55 years is 10%, of whom one quarter are severely disabled. CONCLUSION Knee osteoarthritis sufficiently severe to consider joint replacement represents a minority of all knee pain and disability suffered by older people. Healthcare provision in primary care needs to focus on this broader group to impact on community levels of pain and disability.

Guidelines for musculoskeletal ultrasound in rheumatology

Abstract: Within the past decade, musculoskeletal ultrasound (US) has become an established imaging technique for the diagnosis and follow up of patients with rheumatic diseases.1-5 This has been made possible through technological improvements, resulting in faster computers and higher frequency transducers. US is most commonly used in the assessment of soft tissue disease or detection of fluid collection and can also be used to visualise other structures, such as cartilage and bone surfaces.6 7 Owing to the better axial and lateral resolution of US, even minute bone surface abnormalities may be depicted. Thus destructive and/or reparative/hypertrophic changes on the bone surface may be seen before they are apparent on plain x rays or even magnetic resonance imaging.8 However, US wave frequencies cannot penetrate into bone, therefore imaging of intra-articular disease is usually not possible. The “real time” capability of US allows dynamic assessment of joint and tendon movements, which can often aid the detection of structural abnormalities. Advantages of US include its non-invasiveness, portability, relative inexpensiveness, lack of ionising radiation, and its ability to be repeated as often as necessary, making it particularly useful for the monitoring of treatment. US can also be used for guidance of aspiration, biopsy, and injection treatment.9 Most musculoskeletal work is performed using “grey scale”, which means images are produced in a black and white format; each white dot in the image represents a reflected sound wave. Sound waves travel in a similar way to light waves and therefore the denser a material is—for example, bone cortex, the more reflective it is and the whiter it appears on the screen. Water is the least reflective body material and therefore appears as black as the sound waves travel straight through it. Newer US techniques, which are currently being evaluated, include colour and power …

The burden of musculoskeletal diseases in the general population of Spain: results from a national survey

Abstract: Objective—The objective of the EPISER study was to estimate the prevalence of rheumatoid arthritis (RA), low back pain, hand and knee osteoarthritis (OA), and fibromyalgia in the adult Spanish population, and to assess the impact of these diseases on function and quality of life, and use of health and social resources Methods—2998 subjects aged 20 years or above were randomly selected by stratified multistage cluster sampling from the censuses of 20 municipalities Trained rheumatologists carried out structured visits at which subjects were asked about rheumatic symptoms and sociodemographic characteristics, completed validated instruments for measuring function (HAQ) and quality of life (SF-12), and underwent a standardised physical examination Cases were defined by previously validated criteria Results—The estimated prevalences with 95% confidence intervals were as follows: RA lifetime cumulative: 05% (03 to 09); low back pain: 148% (122 to 174); symptomatic knee OA: 102% (85 to 119); hand OA: 62% (59 to 65); fibromyalgia: 24% (15 to 32) Most conditions significantly impaired function and quality of life Conclusions—The EPISER study has internal and external validity for application of the results to the adult Spanish population The diseases studied aVect a significant proportion of the population, with various degrees of impact on disability and quality of life resulting in a significant number of physician visits, work disability, and medication use (Ann Rheum Dis 2001;60:1040‐1045)

Static postural sway, proprioception, and maximal voluntary quadriceps contraction in patients with knee osteoarthritis and normal control subjects

Abstract: OBJECTIVES—To investigate whether subjects with knee osteoarthritis (OA) have reduced static postural control, knee proprioceptive acuity, and maximal voluntary contraction (MVC) of the quadriceps compared with normal controls, and to determine possible independent predictors of static postural sway. METHODS—77 subjects with symptomatic and radiographic knee OA (58 women, 19 men; mean age 63.4 years, range 36-82) and 63 controls with asymptomatic and clinically normal knees (45 women, 18 men; mean age 63 years, range 46-85) underwent assessment of static postural sway. 108 subjects (59 patients, 49 controls) also underwent assessment of knee proprioceptive activity and MVC (including calculation of quadriceps activation). In patients with knee OA knee pain, stiffness, and functional disability were assessed using the WOMAC Index. The height (m) and weight (kg) of all subjects was assessed. RESULTS—Compared with controls, patients with knee OA were heavier (mean difference 15.3 kg, p<0.001), had increased postural lateral sway (controls: median 2.3, interquartile (IQ) range 1.8-2.9; patients: median 4.7, IQ range 1.9-4.7, p<0.001), reduced proprioceptive acuity (controls: mean 7.9, 95% CI 6.9 to 8.9; patients: mean 12.0, 95% CI 10.5 to 13.6, p<0.001), weaker quadriceps strength (controls: mean 22.5, 95% CI 19.9 to 24.6; patients: mean 14.7, 95% CI 12.5 to 16.9, p<0.001), and less percentage activation of quadriceps (controls: mean 87.4, 95% CI 80.7 to 94.2; patients: mean 66.0, 95% CI 58.8 to 73.2, p<0.001). The significant predictors of postural sway were knee pain and the ratio of MVC/body weight. CONCLUSIONS—Compared with age and sex matched controls, subjects with symptomatic knee OA have quadriceps weakness, reduced knee proprioception, and increased postural sway. Pain and muscle strength may particularly influence postural sway. The interaction between physiological, structural, and functional abnormalities in knee OA deserves further study.

Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis

Abstract: Methotrexate (MTX) is a folate analogue originally synthesised in the 1940s and designed to inhibit dihydrofolate reductase.1 Reduced folate (tetrahydrofolate) is the proximal single carbon donor in several reactions involved in the de novo synthetic pathways for purine and pyrimidine precursors of DNA and RNA required for cell proliferation. Furthermore, tetrahydrofolate plays a part in a second important biochemical step: the methionine-homocysteine cycle, which is necessary to provide a methyl group for several downstream reactions such as methylation of DNA, RNA proteins, and others. Therefore, MTX has been used extensively for treatment of neoplastic diseases. In 1951 the rationale for the introduction of MTX for the treatment of rheumatoid arthritis (RA) was that it inhibited proliferation of the lymphocytes and other cells responsible for inflammation in the joint.2 No further studies on clinical experience with MTX in RA were published until the early 1980s, when several uncontrolled trials were reported.3-8 Finally, four well designed, blinded, placebo controlled studies published in 1984 and 1985 introduced the use of MTX in the treatment of RA.9-12 The early indications for MTX use in the rheumatic diseases were first reported in a large review in 1984.13 From the considerable experience obtained over the past 15 years, several lines of evidence clearly suggest that MTX does not act simply as a cytotoxic (antiproliferative) agent for the cells responsible for the joint inflammation in RA.14 As a matter of fact, it would be difficult to understand how a drug that diminishes inflammation by preventing proliferation of immune cells might work at effective concentrations for only a very short time and once a week. In addition, the rapid clinical remission and the short term effect on the acute phase reactants, as seen with low dose MTX administration in most patients with …

Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage

Abstract: OBJECTIVE—To analyse the relations between the urinary levels of type II collagen C-telopeptide (CTX-II) and glucosyl-galactosyl pyridinoline (Glc-Gal-PYD)—two newly developed biochemical markers of type II collagen and synovial tissue destruction respectively—disease activity and the severity of joint destruction in patients with knee osteoarthritis (OA). The clinical performance of these two new markers was compared with that of a panel of other established biochemical markers of connective tissue metabolism. METHODS—The following biochemical markers were measured in a group of 67 patients with knee OA (mean age 64 years, median disease duration eight years ) and in 67 healthy controls: for bone, serum osteocalcin, serum and urinary C-telopeptide of type I collagen (CTX-I); for cartilage, urinary CTX-II, serum cartilage oligomeric matrix protein (COMP), and serum human cartilage glycoprotein 39 (YKL-40); for synovium, urinary Glc-Gal-PYD, serum type III collagen N-propeptide (PIIINP), serum hyaluronic acid (HA); and for inflammation, serum C reactive protein. Biochemical markers were correlated with pain and physical function (WOMAC index) and with quantitative radiographic evaluation of the joint space using the posteroanterior view of the knees flexed at 30°. RESULTS—All bone turnover markers were decreased in patients with knee OA compared with controls (−36%, −38%, and −52%, p<0.0001 for serum osteocalcin, serum CTX-I and urinary CTX-I, respectively). Serum COMP (+16%, p=0.0004), urinary CTX-II (+25%, p=0.0009), urinary Glc-Gal-PYD (+18%, p=0.028), serum PIIINP (+33%, p<0.0001), and serum HA (+ 233%, p<0.0001) were increased. By univariate analyses, increased urinary Glc-Gal-PYD (r=0.41, p=0.002) and decreased serum osteocalcin (r=−0.30, p=0.025) were associated with a higher total WOMAC index. Increased urinary CTX-II (r=−0.40, p=0.0002) and Glc-Gal-PYD (r=−0.30, p=0.0046) and serum PIIINP (r=−0.29, p=0.0034) were the only markers which correlated with joint surface area. By multivariate analyses, urinary Glc-Gal-PYD and CTX-II were the most important predictors of the WOMAC index and joint damage, respectively. CONCLUSION—Knee OA appears to be characterised by a systemic decrease of bone turnover and increased cartilage and synovial tissue turnover. CTX-II, Glc-Gal-PYD, and PIIINP may be useful markers of disease severity in patients with knee OA.

Autoantibody profiles in the sera of European patients with myositis

Abstract: Objective—To determine the prevalence of myositis specific autoantibodies (MSAs) and several myositis associated autoantibodies (MAAs) in a large group of patients with myositis. Methods—A total of 417 patients with myositis from 11 European countries (198 patients with polymyositis (PM), 181 with dermatomyositis (DM), and 38 with inclusion body myositis (IBM)) were serologically analysed by immunoblot, enzyme linked immunosorbent assay (ELISA) and/or immunoprecipitation. Results—Autoantibodies were found in 232 sera (56%), including 157 samples (38%) which contained MSAs. The most commonly detected MSA was anti-Jo-1 (18%). Other anti-synthetase, anti-Mi-2, and antiSRP autoantibodies were found in 3%, 14%, and 5% of the sera, respectively. A relatively high number of anti-Mi-2 positive PM sera were found (9% of PM sera). The most commonly detected MAA was anti-Ro52 (25%). Anti-PM/Scl-100, antiPM/Scl-75, anti-Mas, anti-Ro60, anti-La, and anti-U1 snRNP autoantibodies were present in 6%, 3%, 2%, 4%, 5%, and 6% of the sera, respectively. Remarkable associations were noticed between anti-Ro52 and anti-Jo-1 autoantibodies and, in a few sera, also between anti-Jo-1 and anti-SRP or anti-Mi-2 autoantibodies. Conclusions—The incidence of most of the tested autoantibody activities in this large group of European patients is in agreement with similar studies of Japanese and American patients. The relatively high number of PM sera with anti-Mi-2 reactivity may be explained by the use of multiple recombinant fragments spanning the complete antigen. Furthermore, our data show that some sera may contain more than one type of MSA and confirm the strong association of anti-Ro52 with anti-Jo-1 reactivity. (Ann Rheum Dis 2001;60:116‐123)

Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery.

Abstract: OBJECTIVES To determine whether continued methotrexate treatment increases the risk of postoperative infections or of surgical complications in patients with rheumatoid arthritis (RA) within one year of elective orthopaedic surgery. DESIGN A prospective randomised study of postoperative infection or surgical complications occurring within one year of surgery in patients with RA who underwent elective orthopaedic surgery. SUBJECTS 388 patients with RA who were to undergo elective orthopaedic surgery. Patients who were receiving methotrexate were randomly allocated to groups who either continued methotrexate (group A) or who discontinued methotrexate from two weeks before surgery until two weeks after surgery (group B). Their complication rates were compared with complications occurring in 228 patients with RA (group C) who were not receiving methotrexate and who also underwent elective orthopaedic surgery. MAIN OUTCOME MEASURES Signs of postoperative infection were recorded, including rubor, discharge, systemic infection, and frequency of wound dehiscence as well as the incidence of any surgical complication requiring a secondary revision procedure that occurred within one year of surgery. The frequencies of flare up activity of RA at six weeks and six months after surgery were also recorded. A flare of rheumatoid disease was defined as an increase in joint pain in two or more joints notified by the patient as well as by an increase in articular index of at least 25% after surgery. RESULTS Signs of infection or surgical complications occurred in two of 88 procedures in group A (2%), 11 of 72 procedures in group B (15%), and 24 of 228 (10.5%) procedures in group C. The surgical complication or infection frequency in group A was less than that in either group B (p CONCLUSION Continuation of methotrexate treatment does not increase the risk of either infections or of surgical complications occurring in patients with RA within one year of elective orthopaedic surgery. Thus methotrexate treatment should not be stopped in patients whose disease is controlled by the drug before elective orthopaedic surgery.

European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes

Abstract: OBJECTIVE—To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use. METHODS—Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0-10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity ("inactive to moderately active" or "active to very active" disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed. RESULTS—A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Δ-factors—that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Δ-cardiopulmonary (4.0), Δ-skin (3.0), Δ-vascular (2.0), and Δ-articular/muscular (1.0) for patients with dSSc; (b) Δ-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Δ-cardiopulmonary (1.5), Δ-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Δ-cardiopulmonary (2.0), Δ-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Δ-vascular (0.5), arthritis (0.5), TLCO <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for "active to very active" patients. CONCLUSIONS—Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.

Behçet's disease: infectious aetiology, new autoantigens, and HLA-B51

Abstract: Behcet's disease (BD) is a multisystemic disorder with mucocutaneous, ocular, arthritic, vascular, and central nervous system involvements.1 Recent developments in the immunopathogenesis of BD are discussed in this review. Box FB1 summarises the major aspects covered. Figure FB1 Immunopathogenic aspects of Behcet's disease Neutrophils are mature immune cells with a very short life in vitro and have a pivotal role in innate immune responses. As typical BD lesions such as pustular folliculitis, pathergy reactions, and hypopyon have significant neutrophil infiltrations, neutrophil functions and activation status have been extensively investigated.1 2 Conflicting reports of increased, normal, or decreased basal and fMLP stimulated superoxide productions, phagocytosis, chemotaxis, and neutrophil-endothelial adhesion in BD may reflect the status of clinical activity, in vivo neutrophil activation, drug effects, or just methodological problems of investigating neutrophils.3-9 In a recent study, which showed decreased fMLP stimulated superoxide production in BD and patients with sepsis, consecutive restimulations of prestimulated BD neutrophils produced a smaller increase in superoxide production than in healthy controls, implying a state of in vivo neutrophil preactivation.9 An in vivo “primed” state of neutrophils with a dual signalling system for activating neutrophil oxidase has been suggested previously.10 Agents such as fMLP or the cytokines, tumour necrosis factor α (TNFα) and granulocyte monocyte colony stimulating factor, have been shown to increase tyrosine phosphorylation of various intracellular proteins and to prime neutrophils in vivo without full activation, which might also be the case in BD with its proinflammatory cytokines. In HLA-B51 transgenic mice, a presumed model for BD, the only abnormality seen is increased superoxide release …

Responsiveness of the WOMAC osteoarthritis index as compared with the SF-36 in patients with osteoarthritis of the legs undergoing a comprehensive rehabilitation intervention

Abstract: Objective—To compare the responsiveness of the condition-specific Western Ontario and McMaster Universities osteoarthritis (OA) index (WOMAC) and the generic Short Form-36 (SF-36) in patients with OA of the legs undergoing a comprehensive inpatient rehabilitation intervention. Methods—A prospective follow up study of consecutively referred inpatients of a rehabilitation clinic was made. The patients included fulfilled the American College of Rheumatology criteria for knee or hip OA and underwent both passive and, particularly, active physical therapy for three to four weeks. Responsiveness assessment was performed using the standardised response mean (SRM), eVect size, and Guyatt’s responsiveness statistic between admission and discharge (end of rehabilitation) and then again between admission and three months later. For pain and function the SRMs were stratified by sex and OA joint. EVects were tested by the t test and SRMs of diVerent scales were com

Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease.

Abstract: BACKGROUND Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. METHODS Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being RESULTS An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49–255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. CONCLUSION Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin9s lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

Effectiveness of exercise in patients with osteoarthritis of hip or knee: nine months' follow up

Abstract: OBJECTIVE To determine whether the effects of an exercise programme in patients with osteoarthritis of hip or knee are sustained at six and nine months9 follow up. METHODS A randomised, single blind, clinical trial was conducted in a primary care setting. Patients with osteoarthritis of hip or knee (ACR criteria) were selected. Two intervention groups were compared. Both groups received treatment from their general practitioner, including patient education and drug treatment if necessary. The experimental group also received exercise treatment from a physiotherapist in primary care. The treatment period was 12 weeks, with an ensuing 24 week follow up. The main outcome measures were pain, drug use (non-steroidal anti-inflammatory drugs), and observed disability. RESULTS 201 patients were randomly allocated to the exercise or control group, and 183 patients completed the trial. At 24 weeks exercise treatment was associated with a small to moderate effect on pain during the past week (difference in change between the two groups −11.5 (95% CI −19.7 to −3.3). At 36 weeks no differences were found between the groups. CONCLUSIONS Beneficial effects of exercise decline over time and finally disappear.

Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies

Abstract: OBJECTIVES To review the autoimmune and rheumatic manifestations of patients with malignancy. METHODS A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes. RESULTS Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of ( a ) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). ( b ) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. ( c ) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy. CONCLUSION Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.

Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA

Abstract: OBJECTIVES—To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease. METHODS—239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset. RESULTS—An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003). CONCLUSIONS—Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.

Users of oestrogen replacement therapy have more knee cartilage than non-users

Abstract: BACKGROUND Osteoarthritis (OA) is increasingly prevalent in the years after menopause. Epidemiological data suggest that the use of oestrogen replacement therapy (ERT) may protect against knee OA. AIM To test the hypothesis that long term ERT (longer than five years) is associated with increased knee cartilage in postmenopausal women. METHODS The study involved 81 women (42 current users (⩾ five years) of ERT and 39 who had never used it). Articular cartilage volumes were determined by processing images acquired in the sagittal plane using a T1 weighted fat suppressed magnetic resonance sequence on an independent work station. RESULTS After bone size had been accounted for, ERT users had higher tibial cartilage volume than non-users. Total tibial cartilage volume was 7.7% (0.23 ml) greater in the group of ERT users (2.98 (0.47) ml; mean (SD)) than in the untreated group (2.75 (0.50) ml). The difference, after adjustment for the significant explanatory factors (years since menopause, body mass index, age at menopause, and smoking), between the ERT users and non-users increased from 0.23 ml to 0.30 ml (95% confidence interval 0.08 to 0.52, p=0.008). These differences persisted after exclusion of women with OA. CONCLUSIONS After adjustment for multiple confounders, women using long term ERT have more knee cartilage than controls. This may indicate that ERT prevents loss of knee articular cartilage.

Strength training induced adaptations in neuromuscular function of premenopausal women with fibromyalgia: comparison with healthy women

Abstract: Objective—To investigate the eVects of 21 weeks’ progressive strength training on neuromuscular function and subjectively perceived symptoms in premenopausal women with fibromyalgia (FM). Methods—Twenty one women with FM were randomly assigned to experimental (FMT) or control (FMC) groups. Twelve healthy women served as training controls (HT). The FMT and HT groups carried out progressive strength training twice a week for 21 weeks. The major outcome measures were muscle strength and electromyographic (EMG) recordings. Secondary outcome measures were pain, sleep, fatigue, physical function capacity (Stanford Health Assessment Questionnaire), and mood (short version of Beck’s depression index). Results—Female FMT subjects increased their maximal and explosive strength and EMG activity to the same extent as the HT group. Moreover, the progressive strength training showed immediate benefits on subjectively perceived fatigue, depression, and neck pain of training patients with FM. Conclusions—The strength training data indicate comparable trainability of the neuromuscular system of women with FM and healthy women. Progressive strength training can safely be used in the treatment of FM to decrease the impact of the syndrome on the neuromuscular system, perceived symptoms, and functional capacity. These results confirm the opinion that FM syndrome has a central rather than a peripheral or muscular basis. (Ann Rheum Dis 2001;60:21‐26)

Quantitative ultrasonography in rheumatoid arthritis: evaluation of inflammation by Doppler technique

Abstract: OBJECTIVE To evaluate ultrasonographic methods, including the Doppler technique, as measures of synovial inflammation in finger joints of patients with rheumatoid arthritis. METHODS Ultrasonography was performed with a high frequency transducer (13 MHz). Evaluation of the sonographic data was conducted by two independent observers and included measurement of synovial area and thickness (grey tone ultrasound), vascularisation (power/colour Doppler), and indices of the intra- and extrasynovial arterial flow (spectral Doppler). The flow pattern was estimated by the indices of pulsatility (PI) and resistance (RI). RESULTS The sonographic measurements of joint space were reproducible with intraobserver, intraclass correlation coefficients (ICC) 0.82–0.97 (p<0.0001) and interobserver ICC 0.81 (p<0.0001). The mean (SD) fraction of the synovium vascularised in the patients was 0.15 (0.15). The synovial blood flow was characterised by a diastolic flow—that is, the flow persisting during the diastole. The mean (SD) PI was 1.92 (1.18) and RI 0.70 (0.13). The estimated vascular fraction correlated with the erythrocyte sedimentation rate (ESR) ( r s=0.53, p=0.03). The relative Pi (rPi), an estimate of an abnormally low resistance to vascularisation, correlated with both ESR ( r s=−0.557, p<0.05) and Health Assessment Questionnaire score ( r s=−0.584, p<0.05). After an injection of contrast Levovist the vascular fraction increased, while no difference in PI and RI was observed. CONCLUSION Ultrasonography is a reliable tool for estimating the size of the joint space and the synovial activity measured by the degree of vascularisation and pattern of flow. Ultrasonography may be useful in monitoring the synovial inflammation in rheumatoid arthritis.

Employment, work disability, and work days lost in patients with ankylosing spondylitis: a cross sectional study of Dutch patients

Abstract: Objective—To evaluate employment status, work disability, and work days lost in patients with ankylosing spondylitis (AS). Methods—A questionnaire was sent to 709 patients with AS aged 16‐60. The results of 658 of the patients could be analysed. Results—After adjustment for age, labour force participation was decreased by 15.4% in male patients and 5.2% in female patients compared with the general Dutch population. Work disability (all causes) was 15.7% and 16.9% higher than expected in the general population for male and female patients respectively. In particular, the proportion of those with a partial work disability pension was increased. Patients with a paid job lost 5.0% of work days as the result of having AS, accounting for a mean of 10.1 days of sick leave due to AS per patient per year in addition to the national average of 12.3 unspecified days of sick leave. Conclusion—This study on work status in AS provides data adjusted for age and sex, and the diVerences from the reference population were significant. The impact of AS on employment and work disability is considerable. Work status in patients with AS needs more attention as an outcome measure in future research. (Ann Rheum Dis 2001;60:353‐358)

Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus

Abstract: OBJECTIVES To describe infectious complications and analyse their risk factors and prognostic role in adults with systemic lupus erythematosus (SLE). METHODS A monocentric cohort of 87 adults with SLE (1960–1997) was studied to determine the risk factors for infection (disease activity evaluated by SLAM and SLEDAI scores, type of organ(s) involved or any biological abnormality, specific treatments) by comparing patients who had suffered at least one infectious episode (n=35; 40%) with non-infected patients (n=52; 60%). Prognostic indicators were assessed by comparing survivors at 10 years with non-survivors. RESULTS Of the 57 infectious episodes, 47 (82%) were of bacterial origin, 16 (28%) were pneumonia, and 46 (81%) were community acquired. According to univariate analysis, significant risk factors for infection were: severe flares, lupus glomerulonephritis, oral or intravenous corticosteroids, pulse cyclophosphamide, and/or plasmapheresis. No predictors were identified at the time of SLE diagnosis. Multivariate analyses retained intravenous corticosteroids (p CONCLUSION In adults with SLE, infections are common and most often caused by community acquired bacteria. Intravenous corticosteroids and immunosuppressants are independent risk factors for infection, which is the only independent risk factor for death after 10 years of SLE evolution.

Predictors of radiographic joint damage in patients with early rheumatoid arthritis

Abstract: Objective—To determine factors at diagnosis, associated with radiographic damage at diagnosis and after one year, in patients with early rheumatoid arthritis (RA). Methods—New patients with early RA were followed up for one year. Possible prognostic factors were duration of complaints, morning stiVness, disease activity score (DAS28), functional status (Health Assessment Questionnaire (HAQ) score), rheumatoid factor (IgM RF), and C reactive protein (CRP). Outcome was defined as radiographic damage of the hands and feet (Sharp/van der Heijde score).For the statistical analysis,one way analysis of variance and a forward stepwise logistic regression model was used. Results—130 patients with RA (68% female; median age 64 years, range 21‐86) were included. Despite the fact that the median duration of complaints was short (15 weeks, range 2‐106) the radiographic damage at diagnosis was significantly correlated with the duration of complaints (p 34 weeks had significantly more radiographic joint damage at diagnosis than patients with a shorter duration of complaints. Radiographic progression at one year was correlated with high radiographic joint damage, high CRP level, and a positive IgM RF at entry. Conclusions—In early RA, the number of radiographic lesions was correlated with a longer duration of complaints at the first visit. Progression of these lesions was predicted by a high baseline joint damage, high CRP level, and a positive IgM RF. Further reduction of the delay in referral and early treatment may further decrease joint damage in patients with recent onset polyarthritis. (Ann Rheum Dis 2001;60:924‐927) Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes joint damage in an early stage, even within two years after disease onset in the vast majority (70‐93%) of patients.

Epidemiology of vasculitis in Europe

Abstract: We recently compared the annual incidence of primary systemic vasculitis (PSV) in two different regions of Europe (Norwich, UK (latitude 52°N) and Lugo, Spain (latitude 43°N)).1Wegener's granulomatosis (WG) was more common in Norwich (10.6/million) than in Spain (4.9/million), though the overall incidence of PSV was similar. This supports the idea that environmental factors may be important in the aetiopathogenesis of PSV. To extend our observations we have now studied the incidence of PSV in northern Europe (Tromso, Norway (latitude 70°N)). …

Geoepidemiology of systemic vasculitis: comparison of the incidence in two regions of Europe

Abstract: OBJECTIVE—The aetiopathogenesis of the primary systemic vasculitides (PSV) is unknown but includes both environmental and genetic factors. The development of classification criteria/definitions for PSV allows comparison of the epidemiology between different regions. METHODS—The same methods and the American College of Rheumatology (1990) criteria or Chapel Hill definitions were used to compare the epidemiology of Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and polyarteritis nodosa in Norwich (east England population 413 500) and Lugo (northwest Spain population 204 100). Patients with PSV were identified between 1 January 1988 and 31 December 1998. RESULTS—Overall, the incidence of PSV in adults was almost equal in Norwich (18.9/million) and Spain (18.3/million). The incidence of Wegener's granulomatosis in Norwich (10.6/million) was greater than in Spain (4.9/million). There was a marked age-specific increase in incidence in Norwich with a peak age 65-74 years (52.9/million), but a virtually equal age distribution between ages 45 and 74 in Lugo (34.1/million). There was no significant increase with time in either population, or evidence of cyclical changes in incidence. CONCLUSION—These data support the suggestion that environmental factors may be important in the pathogenesis of PSV.

Withdrawal from labour force due to work disability in patients with ankylosing spondylitis

Abstract: OBJECTIVE To investigate withdrawal from the labour force because of inability to work owing to ankylosing spondylitis (AS) and to determine the characteristics of patients with no job because of work disability attributable to AS. METHODS A postal questionnaire was sent to 709 patients with AS aged 16–60 years followed up by a rheumatologist. Kaplan-Meier survival statistics were used to assess the time lapse between diagnosis and withdrawal from work. Standardised incidence ratios were calculated to compare withdrawal from the labour force in patients with AS and the general population. Determinants of withdrawal were assessed by Cox9s proportional hazard regression analysis using variables assumed to be time independent. Cross sectional characteristics of patients without a job owing to disability were further analysed by simple and multiple regression analyses. RESULTS A total of 658 patients returned the questionnaire. Of 529 patients with a paid job before diagnosis of AS, 5% had left the labour force within the first year after the diagnosis, 13% after 5 years, 21% after 10 years, 23% after 15 years, and 31% after 20 years. Age and sex adjusted risk for withdrawal was 3.1 (95% CI 2.5 to 3.7) times higher than in the general population. In patients with AS, determinants of withdrawal from work were older age at diagnosis, manual work, and coping strategies characterised by limiting or adapting activities. Patients with work disability at the time of the study were older, came from a lower social class, and were more likely to have total hip replacement, peripheral arthritis, or comorbidity. Moreover, they reported worse physical function (BAS-FI), experienced lower quality of life, and more often had extraspinal disease than those with a job. CONCLUSION Withdrawal from work is 3.1 times higher in patients with AS than expected in the general population. Within patients, higher age at diagnosis, manual work, and unfavourable coping strategies are important determinants of withdrawal. Patients without a job experience a lower quality of life.

Immunohistological study of entheses in spondyloarthropathies: comparison in rheumatoid arthritis and osteoarthritis

Abstract: OBJECTIVE—To determine which inflammatory cell types are present in entheses from patients with spondyloarthropathy (SpA) compared with patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS—Enthesis specimens were obtained during orthopaedic procedures in eight patients with SpA, four with RA, and three with OA. After decalcification, the lymphocyte subsets (CD3, CD4, CD8, CD20) in the bone marrow component of each enthesis were measured by an immunohistochemical technique. RESULTS—Oedema and an inflammatory infiltrate were present in all the SpA specimens, being clearly predominant in the bone marrow component of the entheses. The density of all cell types in the bone marrow was significantly higher in the SpA group than in the two other groups. The cell type CD3+ showed the greatest difference between the SpA and RA groups, being increased fivefold in the SpA group. Within the SpA group, CD3+ cells were considerably more numerous than CD20+ cells—a difference from the RA group—and the predominant T cells were CD8+. CONCLUSION—Persistent oedema with an inflammatory infiltrate composed predominantly of CD8+ cells was noted in the entheses of patients with SpA, being predominant in the bone marrow. These results suggest that CD8+ cells may have a key role in local inflammation in SpAs.

A longitudinal cohort study of Finnish patients with primary Sjögren's syndrome: clinical, immunological, and epidemiological aspects

Abstract: OBJECTIVE—To evaluate outcome in a cohort of Finnish patients with primary Sjogren's syndrome (pSS). METHODS—Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977-1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994-1997. RESULTS—The mean (SD) erythrocyte sedimentation rate (33 (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p<0.0001) lower than those at baseline. A similar change was observed in a subgroup of patients never treated with glucocorticosteroids or disease modifying antirheumatic drugs. Three non-Hodgkin's lymphomas were diagnosed (standardised incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression model, the patients with pSS with subsequent lymphoma were found to have higher baseline levels of serum β2 microglobulin than the others (odds ratio 1.9; 95% confidence interval 1.1 to 3.4). CONCLUSION—The results suggest that mean concentrations of serum IgG and IgM in patients with pSS decline with time, possibly reflecting diminishing inflammatory activity. As in previous studies, the incidence of non-Hodgkin's lymphomas in this cohort of patients with pSS was significantly higher than in the reference population.

Relation between adverse events associated with allopurinol and renal function in patients with gout

Abstract: BACKGROUND Because serious adverse reactions to allopurinol have been related to a reduce creatinine clearance rate and prolonged half life of oxypurinol, it has been recommended that the dose should be adjusted according to the rate of creatinine clearance However, in some patients with gout the dose is not sufficient to reduce serum levels of uric acid (⩽390 μmol/l) and to halt disease progression OBJECTIVE To determine the prevalence of adverse reactions attributable to allopurinol in patients with primary gout according to dose and creatinine clearance rate METHODS Data on 120 patients with gout receiving allopurinol, in whom the starting dose was adjusted according to creatinine clearance rate and later increased in some patients to control the disease, were retrospectively reviewed Two groups were compared: group A, 52 patients receiving creatinine clearance adjusted maintenance doses of allopurinol and group B, 68 patients receiving non-adjusted higher maintenance doses of allopurinol RESULTS During follow up 57% required higher allopurinol doses than those recommended according to their creatinine clearance rate Only five (4%) of 120 consecutive patients developed allopurinol related adverse reactions: four minor skin reactions and one allopurinol hypersensitivity syndrome (AHS) Three of these (including the case of AHS) occurred in group A and two in group B (p=NS) The duration of allopurinol treatment was the same in both groups (group A: 23 (33) years; group B: 37 (48) years) No patient in group A, but 44% in group B had a creatinine clearance rate of CONCLUSIONS No increase was seen in the prevalence of adverse reactions to allopurinol in patients who received higher allopurinol maintenance doses than those recommended according to creatinine clearance rate

Low T cell production of TNFalpha and IFNgamma in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism.

Abstract: OBJECTIVE—To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon γ (IFNγ), interleukin 4 (IL4), tumour necrosis factor α (TNFα), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls. METHODS—Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and 22 healthy HLA-B27 negative controls) were stimulated with phorbol myristate acetate/ionomycin for six hours, surface stained for CD3 and CD8, intracellularly stained for the cytokines IFNγ, TNFα, IL4, and IL10, and analysed by flow cytometry. TNFα production was related to the genotype of the TNFα promoter at the -308 and -238 polymorphisms. RESULTS—In peripheral blood the percentage of TNFα+ T cells was significantly lower in HLA-B27 positive patients with AS (median 5.1% for CD4+ T cells) than in healthy HLA-B27 negative controls (median 9.5%; p=0.008). Surprisingly, the percentage of TNFα+ T cells was also significantly lower in healthy HLA-B27 positive controls (median 7.48%) than in healthy HLA-B27 negative controls (p=0.034). Furthermore, the percentage of IFNγ+ T cells was lower in patients with AS and in healthy HLA-B27 positive controls than in healthy HLA-B27 negative controls (p=0.005 and p=0.003, respectively). The percentage of IL10+/CD8+ T cells was higher in patients with AS than in both control groups. In HLA-B27 positive subjects, TNF1/2 heterozygosity at -308 (n=6) was associated with a higher percentage of TNFα+ T cells than TNF1/1 homozygosity (n=25; median 9.97% v 5.11% for CD4+ T cells; p=0.017). In contrast, in HLA-B27 negative controls (n=18) there was no such genotype/phenotype correlation (median 9.4% v 10.6%). CONCLUSIONS—The lower T cell production of TNFα and IFNγ shown at the single cell level in HLA-B27 positive patients with AS and healthy HLA-B27 positive controls may contribute to the increased susceptibility of HLA-B27 positive subjects to develop AS. Preliminary genotype-phenotype correlations suggest that in HLA-B27 positive subjects TNF2 at -308 or a linked gene results in higher TNFα production and, therefore, might be a marker for a protective haplotype.

What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using x rays and magnetic resonance imaging over the first two years of disease

Abstract: Objectives—To investigate the progression of erosions at sites within the carpus, in patients with early rheumatoid arthritis (RA), using magnetic resonance imaging (MRI) and plain radiology over a two year period. Methods—Gadolinium enhanced MRI scans of the dominant wrist were performed in 42 patients with RA at baseline (within six months of symptom onset) and one year. Plain wrist radiographs (x rays) and clinical data were obtained at baseline, one year, and two years. Erosions were scored by two musculoskeletal radiologists on MRI and x ray at 15 sites in the wrist. A patient centred analysis was used to evaluate the prognostic value of a baseline MRI scan. A lesion centred analysis was used to track the progression of

Differential roles of Toll-like receptors in the elicitation of proinflammatory responses by macrophages.

Abstract: BACKGROUND—Mammalian Toll-like receptor (TLR) proteins are pattern recognition receptors for a diverse array of bacterial and viral products. Gram negative bacterial lipopolysaccharide (LPS) activates cells through TLR4, whereas the mycobacterial cell wall glycolipids, lipoarabinomannan (LAM) and mannosylated phosphatidylinositol (PIM), activate cells through TLR2. Furthermore, short term culture filtrates of M tuberculosis bacilli contain a TLR2 agonist activity, termed soluble tuberculosis factor (STF), that appears to be PIM. It was recently shown that stimulation of RAW264.7 murine macrophages by LPS, LAM, STF, and PIM rapidly activated NF-κB, AP1, and MAP kinases. RESULTS—This study shows that signalling by TLR2 and TLR4 also activates the protein kinase Akt, a downstream target of phosphatidylinositol-3'-kinase (PI-3-K). This finding suggests that activation of PI-3-K represents an additional signalling pathway induced by engagement of TLR2 and TLR4. Subsequently, the functional responses induced by the different TLR agonists were compared. LPS, the mycobacterial glycolipids, and the OspC lipoprotein (a TLR2 agonist) all induced macrophages to secrete tumour necrosis factor α (TNFα), whereas only LPS could induce nitric oxide (NO) secretion. Human alveolar macrophages also exhibited a distinct pattern of cellular response after stimulation with TLR2 and TLR4 agonists. Specifically, LPS induced TNFα, MIP-1β, and RANTES production in these cells, whereas the TLR2 agonists induced only MIP-1β production. CONCLUSION—Together, these data show that different TLR proteins mediate the activation of distinct cellular responses, despite their shared ability to activate NF-κB, AP1, MAP kinases, and PI-3-K.