Prevalence, risk factors, and impact of knee pain suggesting osteoarthritis in Spain.

OBJECTIVE: To estimate the point prevalence of knee pain suggesting osteoarthritis (OA) in the adult Spanish population. Secondary objectives were to examine the distribution of associated factors, as well as to assess the impact of knee pain on quality of life and function in the general population. METHODS: A population survey was conducted in year 2000 for which 2,192 subjects over 20 years of age were selected by stratified polystage cluster sampling from the censuses of 20 towns. Trained rheumatologists administered structured interviews that permitted them to rule out the presence of rheumatic symptoms, and which included validated instruments to measure function and quality of life. We used the definition of clinical symptomatic knee OA of the American College of Rheumatology. RESULTS: The estimated prevalence of knee pain suggesting OA in the general adult population is 10.2% (95% confidence interval: 7.9-12.5). Elderly women with fewer studies and from the lower social class, as well as those subjects involved in physically demanding jobs are more frequently affected. Obesity is also an important determinant for knee pain suggesting OA. Knee pain is associated to a significant decrease in functional ability and quality of life, even after adjustment for age, sex, and comorbidity. CONCLUSION: The prevalence of knee pain suggesting OA in the general Spanish population is higher than expected, mainly related to a high rate of knee pain in women over 55. The proportion of very old persons and of those obese are important factors to take into account when comparing the rate of knee OA between populations.

Assessment of inflammatory activity in rheumatoid arthritis: a comparative study of clinical evaluation with grey scale and power Doppler ultrasonography.

OBJECTIVE: To compare the clinical assessment of overall inflammatory activity in patients with rheumatoid arthritis (RA) with grey scale and power Doppler (PD) ultrasonography (US). METHODS: Ninety four consecutive patients with RA were included. Demographic and clinical data, C reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were recorded for each patient. The presence of tenderness, swelling, and a subjective swelling score from 1 to 3 were independently assessed by two rheumatologists, who reached a consensus in 60 joints examined in each patient. All patients underwent a US examination by a third blinded rheumatologist, using PD. US joint effusion, synovitis, and PD signal were graded from 1 to 3 in the 60 joints. Joint count and joint index for effusion, synovitis, and PD signal were recorded. A 28 joint count for clinical and US variables was calculated. Interobserver reliability of the US examination was evaluated by a fourth blinded rheumatologist. RESULTS: US showed significantly more joints with effusion (mean 15.2) and synovitis (mean 14.6) than clinical examination (mean 11.5, p<0.05). A significant correlation was found between joint count and joint index for swelling, US effusion, synovitis, and PD signal. The 28 joint count for effusion, synovitis, and PD signal correlated highly with the corresponding 60 joint counts. US findings correlated better with CRP and ESR than clinical measures. Interobserver reliability was better for US findings than for clinical assessment. CONCLUSION: US is a sensitive method for assessing joint inflammatory activity in RA, complementary to clinical evaluation.

Ultrasonographic assessment of inflammatory activity in rheumatoid arthritis: comparison of extended versus reduced joint evaluation.

OBJECTIVE: To investigate the validity of reduced joint counts for ultrasonographic (US) assessment of joint inflammatory activity in patients with rheumatoid arthritis (RA). METHODS: Ninety-four patients with RA were included. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were recorded for each patient. The presence of tenderness, swelling and a subjective swelling score from 0 to 3 were assessed by two rheumatologists who reached consensus in 60 joints examined in each patient. All patients underwent an US examination by a third blinded rheumatologist, using power Doppler (PD). US joint effusion, synovitis and PD signal were graded from 0 to 3 in the 60 joints. A 60-joint count and index for effusion, synovitis and PD signal were recorded. A 6-, 10-, 16-, 18-, and two 12-joint counts and indices for US parameters that included the most frequently US involved joints were calculated for each patient. RESULTS: A 12-joint assessment for effusion, synovitis and PD signal, including bilateral wrist, second and third MCP, second and third PIP of hands and knee joints highly correlated with corresponding 60-joint US counts and indices. This reduced-joint US evaluation showed a similar correlation with clinical and laboratory parameters of disease activity to corresponding 60-joint assessment. CONCLUSION: We propose that a 12-joint evaluation may be a useful tool for US assessment of overall joint inflammatory activity in RA.

Increased serum levels of interleukin-15 in rheumatoid arthritis with long- term disease.

OBJECTIVE: To study the serum levels of IL-15 in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), seronegative spondyloarthropathies (SSd) and healthy donors. METHODS: The IL-15 serum levels were measured by ELISA in sera from 50 RA patients, 30 patients with SLE, 30 patients with SSd and 30 healthy donors. In RA patients, several clinical and demographic parameters were also obtained at the time of sample collection. IL-15 levels were compared in different RA subpopulations (positive or negative rheumatoid factor [RF], long term or recent onset disease, high or low disease activity). In addition, the possible association with other demographic and clinical parameters (gender, age, disease duration, etc) was also analysed. RESULTS: RA patients had significantly higher serum levels of IL-15 (102.4 +/- 150 pg/ml; p = 0.0001) than SLE patients (9.8 +/- 15.3 pg/ml), SSd patients (7.9 +/- 14.6 pg/ml) and healthy donors' (5.2 +/- 11.6 pg/ml). RA patients with a disease evolution less than 2 years showed lower IL-15 levels (33.7 +/- 62.2 pg/ml) than those with long-term disease (152.4 +/- 64.6 pg/ml; p = 0.004). In addition, a significant correlation between IL15 in serum and the number of disease-modifying antirheumatic drugs (DMARDs) prescribed was detected in RA patients (r = 0.42; p = 0.002). No association between IL-15 levels and age, gender, RF or disease activity was observed in this group. CONCLUSION: IL-15 is elevated in RA patients, specially in those with long term disease, compared to other rheumatic disorders. This finding supports that IL-15 is involved in the perpetuation of RA synovitis.

Impacto del consumo de AINE en la población general española. Resultados del estudio EPISER / Effect of non-steroidal antiinflammatory agents in the general population in Spain. Results of the EPISER study

Objetivo: Estimar la frecuencia del uso significativo de los antiinflamatorios no esteroides (AINE) en la población adulta en España, así como de episodios adversos gastrointestinales (GI) y su repercusión sociosanitaria. Diseño: Encuesta poblacional. Sujetos: Se seleccionaron 2.988 sujetos mediante muestreo polietápico estratificado, a partir del padrón de 20 municipios. Intervención: Diversos reumatólogos específicamente entrenados administraron una entrevista estructurada en la que, entre otras preguntas, se interrogaba sobre el consumo de analgésicos y AINE, al menos durante un mes del año precedente (consumo significativo) para el alivio de síntomas musculosqueléticos. A todos los que habían tomado AINE se les preguntó si habían padecido episodios adversos GI y si su aparición había afectado a su actividad laboral o había obligado al uso de recursos asistenciales. Resultados: La tasa de captación fue del 73 por ciento (205 errores censales confirmados, 390 no localizados y 213 rechazos).La prevalencia acumulada en un año del consumo de AINE, durante al menos un mes, se estima en un 20,6 por ciento (IC del 95 por ciento, 15,8-25,4). La frecuencia de episodios adversos GI entre los consumidores de AINE se estima en el 23,7 por ciento (IC del 95 por ciento, 12,0-35,5), siendo causa de consultas médicas en un 72,5 por ciento de las veces. En 3 episodios adversos GI fue necesaria la hospitalización y en 10 tuvo lugar una pérdida de días de trabajo. Conclusión: El consumo significativo de AINE para el alivio de síntomas musculosqueléticos en la población general española es elevado. Existe una alta frecuencia de efectos adversos GI por AINE que ocasionan importantes consecuencias sanitarias y económicas. Impacto del consumo de AINE en la población general española. Resultados del estudio EPISER (AU)

The prevalence of rheumatoid arthritis in the general population of Spain.

OBJECTIVE: To estimate the prevalence of rheumatoid arthritis (RA) in the adult Spanish population and to assess its distribution by basic sociodemographic characteristics. METHODS: Two thousand nine hundred and ninety-eight adults were selected randomly from the censuses of 20 municipalities. Trained rheumatologists administered a structured interview that included a screening questionnaire for RA. Subjects with a positive screening result were examined according to a standardized protocol. Cases were defined by the 1987 American College of Rheumatology (ACR) criteria adapted to epidemiological surveys. RESULTS: One hundred and eighty-six persons (8.5%) had a positive screening result for RA and 11 of these fulfilled the ACR criteria for RA. The estimated prevalence was 0.5% (95% confidence interval 0.25-0.85). The ratios of women to men and of urban to rural were both 4:1. Function and health perception of the cases were significantly impaired, even after controlling for age and sex. CONCLUSION: The prevalence of RA in Spain is comparable to that in other Mediterranean countries. RA may be less frequent in rural settings, a finding that merits further research. A significant proportion of RA cases in the community remain undiagnosed despite impaired functional status.

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

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: 0.5% (0.3 to 0.9); low back pain: 14.8% (12.2 to 17.4); symptomatic knee OA: 10.2% (8.5 to 11.9); hand OA: 6.2% (5.9 to 6.5); fibromyalgia: 2.4% (1.5 to 3.2). 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 affect 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.

Cyclosporin A inhibits CD69 expression induced on synovial fluid and peripheral blood lymphocytes by interleukin 15.

OBJECTIVE: To study the modulation of CD69 expression on peripheral blood (PB) and synovial fluid (SF) lymphocytes by interleukin 15 (IL-15) and several other cytokines and chemokines widely detected in the rheumatoid microenvironment. The effect of cyclosporin A (CSA) or methotrexate (MTX) in the cytokine mediated regulation of CD69 was analyzed. METHODS: CD69 expression on lymphocytes was assessed by flow cytometry after incubation with different cytokines, chemokines, phorbol myristate acetate, or calcium ionophore in the presence or absence of CSA, MTX, or both. The effect of IL-15 and SF supernatants in maintaining CD69 expression on SF lymphocytes was also assessed. IL-15 levels in SF supernatants were measured by ELISA. RESULTS: IL-15 induced the greatest upregulation of CD69 expression on PB lymphocytes in a time and dose dependent manner. IL-15 was able to maintain a high CD69 expression on SF lymphocytes. SF supernatants from rheumatoid arthritis (RA), which contain significant amounts of IL-15, also reversed the CD69 downregulation of SF lymphocytes in culture. CSA, but not MTX, inhibited the CD69 upregulation mediated by IL-15 both in PB and SF lymphocytes. CONCLUSION: IL-15 appears to be responsible, at least in part, for the high CD69 expression on lymphocytes from the rheumatoid microenvironment. Consistent with the virtual absence of lymphocyte derived cytokines in RA synovium, the prevention of IL-15 mediated CD69 upregulation on lymphocytes may explain the effect of CSA in the treatment of RA.

Primary solitary Echinococcosis in cervical spine. Postsurgical successful outcome after long-term albendazole treatment.

STUDY DESIGN: A case report of a young man with isolated cervical hydatidosis treated postoperatively with sustained cyclical albendazole therapy for 9 years of follow-up. OBJECTIVES: To communicate the efficacy and safety of prolonged albendazole treatment in the postoperative management of spinal hydatid disease, and recommend therapeutic regimes for preventing its recurrence. SUMMARY AND BACKGROUND DATA: Bone involvement in hydatid disease is uncommon and the cervical region of the spine is rarely affected. Surgical excision remains the treatment of choice but high rates of postoperative recurrence have highlighted the importance of adjuvant anthelmintic therapy. The selection of the drug(s) and the duration of the medical treatment is still controversial. METHODS: The patient described herein presented with isolated bone lesions, in an unusual cervical location, and without coincidental visceral involvement. Therefore, diagnosis was delayed and surgical debridement was carried out without any preoperative anthelmintic therapy. To prevent late recurrences, therapy with intermittent courses of albendazole has been maintained for nine years and is still ongoing. Response and toxicity related to therapy has been closely monitored by clinical, biochemical and radiological follow up. RESULTS: After surgery the patient has remained asymptomatic without sequelae or evidence of relapses. No clinically relevant side effects has been observed. CONCLUSION: Prolonged albendazole treatment appears to be safe and effective in the prevention of late recurrences after spine hydatidosis surgery. Long-term chemotherapeutic schedules should be considered after surgical excision of spine or bone lesions.

Aceclofenac, a new nonsteroidal antiinflammatory drug, decreases the expression and function of some adhesion molecules on human neutrophils.

OBJECTIVE: To study the effect of aceclofenac, a new nonsteroidal antiinflammatory drug (NSAID), on the expression and function of adhesion molecules in human neutrophils. METHODS: We used flow cytometry analysis to determine peripheral blood neutrophil expression of L-selectin, CD11a, CD11b, CD31, CD43, CD44, and intercellular adhesion molecule 2 (ICAM-3) surface adhesion molecules after treatment with aceclofenac, diclofenac, or dexamethasone. Granular enzyme activity was quantitated in extracellular medium of neutrophils treated with different NSAID: In vitro adhesion assays were developed to examine the effects of aceclofenac on both neutrophil adhesion to tumor necrosis factor alpha stimulated human umbilical vein endothelial cells under nonstatic conditions, and homotypic neutrophil aggregation induced by anti-ICAM-3 and anti-CD18 monoclonal antibodies (Mab). RESULTS: Aceclofenac induced a dramatic decrease of L-selectin expression, whereas a moderate and slight decrement of CD43 and ICAM-3 expression was also observed. In contrast, the expression of other adhesion molecules by neutrophils was unaffected (CD11a, CD31, CD44) or slightly increased (CD11b). Cell adhesion assays, performed under nonstatic conditions, revealed that aceclofenac significantly diminished the L-selectin dependent neutrophil adhesion to endothelial cells. Neutrophil aggregation induced with anti-CD43 Mab was also significantly inhibited by aceclofenac. CONCLUSION: Aceclofenac had a faster and more potent effect than the other NSAID studied, mainly on the expression of cell adhesion molecules. This new NSAID efficiently interferes with neutrophil adhesion to endothelium and this effect may represent an additional relevant mechanism in its antiinflammatory activity.

Nontropical pyomyositis in adults.

Pyomyositis (PMS) is a primary infection of striated muscle. Recent scanty reports suggest that non-tropical PMS may differ from classical tropical PMS. To address this question, 12 cases of nontropical PMS seen at two hospitals between 1976 and 1992 were reviewed and an English-literature search of similar cases was conducted. Both the series and reported cases are pooled together and herein reported. The age distribution of the 97 patients showed 30-50 and 60-70-year peaks, with a 3:1 (male-female) ratio. Fever, high erythrocyte sedimentation rate, and muscle stiffness or inflammation were present in more than 75% of patients. Muscles of the thigh (54%), back (13%), buttock (11%), arm (9%), or chest wall (4%) were involved. Staphylococci (61%), gram-negative bacilli (16%), streptococci (12%), and fungi (2%) were isolated from muscle specimens. Human immunodeficiency virus infection, diabetes mellitus, hemopoietic disorders, and other conditions with defective neutrophil function were present in 64 patients (66%). Drainage of pus and antibiotic therapy were the standard treatments. The mortality rate reached 10%. Analysis of patients classified by the comorbid condition showed differences in age, causative microorganisms, clinical features, and death rate. It is concluded that several clinical presentations of nontropical PMS are at variance with that of tropical PMS.

Expression of L-selectin, CD43, and CD44 in synovial fluid neutrophils from patients with inflammatory joint diseases. Evidence for a soluble form of L-selectin in synovial fluid.

OBJECTIVE: To study the expression of L-selectin, CD43, and CD44 on peripheral blood (PB) and synovial fluid (SF) neutrophils from patients with inflammatory joint diseases, and to investigate the presence of soluble L-selectin in both SF and plasma from patients with acute and chronic arthritis. METHODS: PB and SF neutrophils were isolated from 13 patients with rheumatoid arthritis (RA) and 17 patients with various inflammatory joint diseases other than RA. Expression of L-selectin, CD43, CD44, CD11a, and CD11b was determined in both unstimulated and in vitro-activated cells by immunofluorescence flow cytometry. Soluble L-selectin levels were estimated in SF and plasma by a semiquantitative radioimmunoassay. RESULTS: Neutrophils from SF showed diminished expression of L-selectin compared with PB neutrophils; CD43 expression and CD44 expression were decreased in SF neutrophils from most patients. In contrast, SF neutrophils exhibited significantly increased expression of CD11b, to an extent similar to that seen with in vitro-activated PB neutrophils. Soluble L-selectin was detected at similar levels in SF and PB. CONCLUSION: The phenotypic profile of SF neutrophils (low levels of L-selectin, CD43, and CD44, and high levels of CD11b) from most patients with RA or other inflammatory joint conditions resembles that observed in in vitro-activated neutrophils. Our results suggest that SF neutrophils are activated to a similar degree in inflammatory joint diseases with different pathogenic mechanisms.

The role of adhesion molecules in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by infiltration of mononuclear cells, mainly T lymphocytes, into the synovial membrane (SM). The interaction of peripheral blood T cells with the different components of the rheumatoid synovium is mediated by cell surface proteins such as selectins, integrins, members of the immunoglobulin superfamily and homing receptors. T lymphocytes infiltrating the rheumatoid SM show an activated phenotype and display an increased avidity of their adhesion receptors that results in an enhanced interaction of these cells with both extracellular matrix proteins (ECM) and cellular ligands (VCAM-1, ICAMs). The interaction of T cell integrins with their ligands, besides an additional antigenic stimulus, could trigger a mitogenic response on these cells, a phenomenon that can contribute to increased cellularity observed into the rheumatoid SM. Moreover, cell attachment to ECM through integrins induces the secretion of several proteases that can contribute to the tissue damage observed in RA. The increased knowledge about the role of adhesion receptors in the pathogenesis of RA and other inflammatory diseases will allow the introduction of a new therapeutic approach by: the use of specific blocking reagents designed to interfere with the function of adhesion molecules.

VLA family in rheumatoid arthritis: evidence for in vivo regulated adhesion of synovial fluid T cells to fibronectin through VLA-5 integrin.

Adhesion of T cells to extracellular matrix (ECM) proteins through VLA integrin receptors is crucial for lymphocyte trafficking, tissue localization and inflammatory function. We have investigated the expression of different VLA integrins (VLA-1-5) on peripheral blood (PB) and synovial fluid (SF) T lymphocytes from patients with rheumatoid arthritis (RA). Their expression on different cell types from synovial membrane (SM) is also reported. The role of VLA-4 fibronectin (FN) receptors in the interaction of activated SF T cells from RA patients with a 38-kD fragment of FN has been previously demonstrated. Here we have focused functional studies on VLA-5 as an alternative FN receptor for RA T cells. A significant higher proportion of SF T cells were able to bind to an 80-kD fragment of FN, containing the Arg-Gly-Asp (RGD) cell binding site, compared with PB T cells. This attachment was almost completely inhibited by anti-VLA-5 MoAbs as well as by RGD peptides. This enhanced capability by SF T cells appears to be independent of the level of the surface expression of the receptor and correlates better with their activation state as determined by the expression of the activation molecule AIM (CD69). The evidence for the expression of VLA heterodimers on both SF and SM cells from RA patients suggests the possible implication of ECM proteins in mediating and perpetuating inflammation in vivo.

Increased binding of synovial T lymphocytes from rheumatoid arthritis to endothelial-leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1).

The infiltration of the synovial membrane (SM) by mononuclear cells, mostly T cells, is a typical histopathological feature associated with rheumatoid arthritis (RA). The entry of T lymphocytes into the SM is believed to be mediated by a number of molecules in the endothelium that are induced in response to a series of inflammatory mediators. In this study, we have investigated the adhesion of synovial T cells from RA patients to two endothelial ligands: endothelial-leukocyte adhesion molecule-1 (ELAM-1), the only selectin known to function as a vascular addressin for T cells, and vascular cell adhesion molecule-1 (VCAM-1), the cellular ligand of VLA-4. Our results clearly demonstrate that synovial T cells isolated from both SM and synovial fluid (SF), bearing an activated and memory phenotype, displayed an enhanced capacity to interact with these two endothelial molecules as compared with T cells from peripheral blood (PB) either of the same RA patients or healthy donors. A further enhancement of VLA-4-mediated T cell binding to VCAM-1 and fibronectin could be observed when already in vivo-activated synovial T cells were stimulated in vitro with phorbol esters, suggesting the existence of several cellular affinity levels for both very late activation-4 (VLA-4) ligands. Moreover, both PB and synovial T cells from RA patients exhibited strong proliferative responses when they were cultured with either fibronectin or VCAM-1 in combination with submitogenic doses of anti-CD3 mAb. This increased endothelial binding ability of synovial T lymphocytes together with their proliferation in response to the interaction with VCAM-1 and fibronectin may represent important mechanisms in the regulation of T cell penetration and persistence in the chronically inflamed SM of RA.

Activation markers on peripheral blood T cells from patients with active or inactive systemic lupus erythematosus. Correlation with proliferative responses and production of IL-2.

Using various monoclonal antibodies to T cell activation molecules it has been shown that purified T cells from patients with active systemic lupus erythematosus overexpress the 4F2, IL-2R (CD25), HLA-DR and T10 antigens. T cells from patients with inactive disease had increased expression of VLA-1 and HLA-DR. Increased T10 expression on T cells from patients with active disease correlated inversely with the production of IL-2, whereas expression of CD25 was slightly increased after 3-day culture with either PHA or anti-CD3. These results provide further evidence of the in vivo activation of T cells in SLE and suggest that such activation comes slowly to a halt upon disease remission.

Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis.

The VLA-4 (CD49d/CD29) integrin is a cell surface receptor involved in the interaction of lymphoid cells with both extracellular matrix (ECM) and endothelial cells. We have investigated the expression and function of VLA-4 fibronectin (FN) receptors on T cells localized in the inflammed synovium of patients with rheumatoid arthritis (RA). A high proportion of T cells in both synovial membrane (SM) and synovial fluid (SF) expressed the activation antigens AIM (CD69) and gp95/85 (Ea2) as well as an increased number of VLA-4 alpha and beta 1 adhesion molecules, as compared with peripheral blood (PB) T cells from the same patients. Furthermore, the majority of these activated SF T cells were able to adhere to a 38-kD FN proteolytic fragment containing the connecting segment-1 (CS-1) specifically through VLA-4 receptors, whereas a significantly lower proportion of PB T cells displayed this capacity. Therefore, our results show that activated T cells selectively localize at sites of tissue injury in RA disease and provide evidence for the in vivo regulation of the expression and function of the VLA-4 integrin. This regulatory mechanism may enable T cells either to facilitate migration or to persist at sites of inflammation.