[Prevalence of dyslipidemia and elevated cardiovascular risk in patients with rheumatoid arthritis]. / Prevalencia de dislipemia y riesgo cardiovascular elevado en pacientes con artritis reumatoide.

The objectives of this study were to compare the frequency of dyslipidemia (DLP) and the elevated cardiovascular risk between rheumatoid arthritis (RA) patients and a control group, to identify disease-related factors associated with the presence of DLP and to estimate the frequency of RA patients receiving treatment for DLP. This is a cross sectional study that included 409 RA patients and 624 controls. Cardiovascular (CV) risk was determined using the Framingham score, National Cholesterol Education Program (NCEP) and the Systematic Coronary Risk Evaluation (SCORE) adapted versions according to the European League Against Rheumatism (EULAR) guidelines. DLP was defined according to the Adult Treatment Panel III (ATPIII). The frequency of CV risk was similar in RA patients and controls, except when NCEP-EULAR adapted version for RA was applied (7% vs. 2%; p = 0.00002). A 43% of patients and 47% of controls had DLP (p = 0.15). RA patients with DLP tended to have extra-articular manifestations more frequently (36% vs. 24%; p = 0.01) and higher erythrocyte sedimentation rate (ESR) (21 [13-35] vs. 18 [10-30] mm; p = 0.003). RA patients treated for DLP varied between 11% and 32% according to the definition used. Patients with RA showed an elevated CV risk only when the NCEP-EULAR definition was used. Among RA patients, those with higher ESR and the presence of extra-articular manifestations were more likely to show DLP. The vast majority of patients were not receiving treatment for DLP.

Rate and causes of infliximab discontinuation in patients with rheumatoid arthritis in a private clinical practice.

OBJECTIVES: To describe the rate of infliximab discontinuation and the causes of this event in a population of rheumatoid arthritis patients. PATIENTS AND METHODS: Rheumatoid arthritis patients from an out-patient private center treated with infliximab (at least 2 consecutive doses) were retrospectively studied. The infliximab discontinuation rate was examined by the Kaplan-Meier survival method. Variables associated with infliximab discontinuation were analyzed by univariable and multivariable Cox proportional hazards regression analyses. RESULTS: Seventy-seven patients treated with infliximab between August 2000 and December 2006 were identified; of them, 33 (43%) discontinued this drug. The cumulative discontinuation rate was of 23%, 35%, and 43% at 12, 24, and 36 months, respectively. Causes of discontinuation were drug-related adverse reactions (41%), financial constraints (15%), lack of efficacy (12%), and others (32%). Variables independently associated with infliximab discontinuation were the number of tender joints on an average during infliximab treatment [hazard ratio (HR) = 1.17, 95% confidence interval (CI) 1.05-1.31; P = 0.005] and the occurrence of any adverse reaction attributed to infliximab (HR = 2.86, 95% CI 1.37-7.19; P = 0.026), whereas having full pharmacy coverage for infliximab (HR = 0.32, 95% CI 0.13-0.79, P = 0.014) was protective. CONCLUSION: Forty-three percent of patients discontinued infliximab at 3 years; most of them because of adverse reactions and financial constraints. Rheumatologists should be aware that those patients with more active disease were also at higher risk of discontinuing infliximab.

Lack of correlation between satisfaction and knowledge in clinical trials participants: a pilot study.

OBJECTIVES: To address participants' knowledge of informed consent and to explore whether knowledge level is related to clinical trial satisfaction. METHODS: One hundred and fourteen patients enrolled in three ongoing randomized controlled trials of osteoarthritis and rheumatoid arthritis were asked to complete a mailed form. The survey was related to aspects of the informed consent process: quality of information given during the informed consent process, participants' self perception of knowledge, objective evaluation of participants' knowledge and participants' overall trial satisfaction. These four aspects were categorized as high, intermediate or low. Correlation between participants' knowledge and satisfaction was measured using the Spearman's Rho test and variables associated with knowledge by standard univariable analyses. A p value< or =0.05 was considered significant. RESULTS: One hundred and five participants answered the questionnaire. The quality of information given during the informed consent process was rated as being high by 81% participants, intermediate by 15.2% and low by 3.8%. Fifty-one percent of the participants believed they had a good level of knowledge, but, objective evaluation qualified as high in only 14.3% of them. Overall trial satisfaction was high in 95% of the participants. No significant correlation was found between knowledge and satisfaction (r=0.16; p=0.086). Age was negatively associated with a higher level of knowledge (48 vs. 58 years old, p=0.008). CONCLUSIONS: We found a lack of correlation between satisfaction and knowledge in clinical trials participants. During a randomized controlled trial the investigator should consider encouraging activities to improve not only participants' satisfaction, but also their level of knowledge.

Factors associated with patients' loss to follow-up after finishing randomized clinical trial participation.

OBJECTIVES: To study patient's follow-up after finishing participation in randomized clinical trials (RCTs), and to identify factors associated with loss to follow-up (FU). PATIENTS AND METHODS: Medical charts of 212 rheumatoid arthritis (RA) and osteoarthritis (OA) patients from a rheumatological out-patient center were analyzed. Loss to FU was considered when patients did not return to their regular appointments within the first year after finishing their participation in an RCT assessing anti-cyclooxygenase-2 non-steroidal anti-inflammatory drugs (anti-COX-2 NSAIDs). Mann-Whitney U-test, chi2 test and Wilcoxon test were performed as appropriate. Logistic regression was performed to identify factors which might be related to loss to FU. A survey was conducted to obtain lost to FU patients' opinions. p values less than 0.05 were considered significant. RESULTS: The mean frequency of patients' visits in the year before enrollment in an RCT was 3.73 SD 2.06, and during the year after participation was 2.6 SD 1.96 (p<0.0001). Fifty patients (23.6%) did not return to their usual rheumatologic visit. On multivariate analysis, the number of daily tablets of study medication (odds ratio (OR)=2.64, 95% confidence interval (CI) 1.1 to 6.3) and the frequency of clinical visits (OR=0.56, 95% CI 0.37 to 0.85) were associated with loss to FU (p<0.008). Lost to FU patients' opinions did not support these findings. CONCLUSIONS: After participating in a RCT assessing anti-COX-2 NSAIDs, many patients return with less frequency, or do not return at all to their regular rheumatologic visit. Although a high number of tablets of the investigational drug and a low frequency of protocol visits may be contributors to patient loss to FU, investigators should consider that personal situations not related to the RCTs may also influence patients' return to consultation in the private setting.

[Use of infliximab in patients of a rheumatologic center]. / Uso de infliximab en pacientes de un centro reumatológico.

The objective of this study was to obtain post-marketing information about the use of infliximab in an ambulatory setting. We studied--retrospectively and prospectively--the case records of patients with rheumatoid arthritis (n=37), psoriatic arthritis (n=5), mixed connective tissue disease (n=1), and ankylosing spondylitis (n=2) who received infliximab (3 mg/kg) from August 2000 to January 2003. Descriptive values were given as percentage, mean or median, and standard deviation or interquartile range. Wilcoxon test was used for paired analysis of pre/post doses of corticosteroids, non-steroidal anti-inflammatory drugs, and methotrexate therapy. A p value < or = 0.05 was considered significant. Forty-five patients were included. A total of 207 infusions were administered. In 4 patients the treatment was permanently discontinued due to severe back pain during the infusion (2 cases) and serious anaphylactic reactions (2 cases). Other adverse reactions occurring during infusions were mild and successfully managed with standard treatment. A case of staphylococcal septic arthritis resolved with standard antibiotic treatment. No patient had evidence of active tuberculosis. One patient with rheumatoid arthritis and chronic renal insufficiency, received treatment with infliximab 1.9 mg/kg, every 30 days, with no changes in renal function. Due to improvement of symptoms, 14/39 (35.9%) patients could decrease the doses of corticosteroids, 15/43 (34.8%) decreased the doses of antiinflammatory drugs and 12/34 (35.3%) decreased methotrexate dosage. Although some questions remain to be elucidated, this case series shows the drug safety profile, the possibility to reduce concomitant drug doses, as well as individual approaches for situations where there are not yet guidelines available, so that rheumatologists have to make decisions based on clinical needs.

[Severe polyarthritis and tenosynovitis due to Streptococcus agalactiae in a patient with functional hyposplenia]. / Poliartritis y tenosinovitis grave por Streptococcus agalactiae en un paciente con hipoesplenia funcional.

Cases of arthritis caused by Streptococcus agalactiae are infrequent and in our knowledge there are no case reports of tenosynovitis caused by S. agalactiae. A 46-year-old woman presented with fever, polyarthralgia, myalgia, diarrhea and vomiting. She had a history of papillary thyroid carcinoma and functional hyposplenia. She was febrile, with arthritis in hands, wrists, elbows, right shoulder and left ankle joints, and presented tenosynovitis in both feet and left hand. Blood and right olecranon bursa sample cultures were positive for S. agalactiae. An ultrasound scan made at the musculus tibialis anterior of left foot revealed signs of tenosynovitis. She was treated with intravenous cefazolin for 20 days and oral cefuroxime for 12 days. The joint involvement completely subsided in 60 days. Streptococcus agalactiae can cause, infrequently, a polyarthritis and tenosynovitis syndrome similar to disseminated gonococcal infection.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): LXI. Value of C-reactive protein as a marker of disease activity and damage.

OBJECTIVE: To determine whether C-reactive protein (CRP) measured by a high sensitivity (hs) assay is a surrogate marker of disease activity and damage in systemic lupus erythematosus (SLE). METHODS: Five hundred eighty-eight patients with SLE participating in a multiethnic cohort (Hispanic, African American, and Caucasian) were studied. Disease activity was measured with the Systemic Lupus Activity Measure-Revised (SLAM-R) and damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). hs-CRP was measured by immunometric assay. Disease activity and hs-CRP were measured at enrollment and damage accrual at last visit. The association of hs-CRP with the SLAM-R and SDI was examined by univariable (Pearson's correlation) and multivariable (linear regression) analyses. The association of hs-CRP and each individual domain of the SLAM-R and SDI was examined by Spearman's correlation. RESULTS: hs-CRP was associated with the SLAM-R in the univariable (r = 0.35, p < 0.001) and multivariable (t = 7.11, coefficient beta = 0.27, p < 0.001) analyses. It also correlated with the constitutional, eye, pulmonary, gastrointestinal, neuromotor, and laboratory domains of the SLAM-R. hs-CRP was associated with the SDI (r = 0.12, p = 0.004) in the univariable analysis but not in the multivariable analysis. When the individual domains of the SDI were analyzed, hs-CRP correlated with the renal, pulmonary, cardiovascular, musculoskeletal, and diabetes domains. CONCLUSIONS: hs-CRP was associated with disease activity but not with overall damage accrual; however, it correlated with specific domains of the damage index. hs-CRP may be useful to monitor the course of the disease and predict its intermediate outcome, but longitudinal studies with serial hs-CRP measurements are necessary to define its clinical value.

Prevalencia de dislipemia y riesgo cardiovascular elevado en pacientes con artritis reumatoide / Prevalence of dyslipidemia and elevated cardiovascular risk in patients with rheumatoid arthritis

Los objetivos del estudio fueron comparar la frecuencia de riesgo cardiovascular (CV) elevado y dislipemia (DLP) en pacientes con artritis reumatoide (AR) y en controles, identificar variables de la enfermedad asociadas a DLP y estimar el porcentaje de pacientes con AR medicados para DLP. Estudio de corte transversal que incluyó 409 pacientes con AR y 624 controles. El riesgo CV se determinó con las clasificaciones NCEP y SCORE modificados por European League Against Rheumatism (EULAR). Para DLP se utilizó la definición de Adult Treatment Panel III (ATP III). La frecuencia de riesgo CV elevado fue similar en pacientes con AR y controles excepto cuando fue definida por NCEP-EULAR (7% vs. 2%; p = 0.00002). La DLP fue encontrada en el 43% de los pacientes con AR y en el 47% de los controles (p = 0.15). Los pacientes con AR y DLP tuvieron más manifestaciones extra-articulares (36% vs. 24%; p = 0.01) y mayor velocidad de sedimentación globular (VSG) (21 (13-35) vs. 18 (10-30) mm; p = 0.003). El tratamiento recibido para DLP varió según la definición utilizada (11% a 32%). Se encontró mayor riesgo CV en los pacientes con AR solo cuando se definió por NCEP- EULAR. Los pacientes con AR y DLP tuvieron mayor VSG y manifestaciones extra-articulares. La mayoría de los pacientes con AR y DLP no estaban recibiendo tratamiento hipolipemiante.

The objectives of this study were to compare the frequency of dyslipidemia (DLP) and the elevated cardiovascular risk between rheumatoid arthritis (RA) patients and a control group, to identify disease-related factors associated with the presence of DLP and to estimate the frequency of RA patients receiving treatment for DLP. This is a cross sectional study that included 409 RA patients and 624 controls. Cardiovascular (CV) risk was determined using the Framingham score, National Cholesterol Education Program (NCEP) and the Systematic Coronary Risk Evaluation (SCORE) adapted versions according to the European League Against Rheumatism (EULAR) guidelines. DLP was defined according to the Adult Treatment Panel III (ATPIII). The frequency of CV risk was similar in RA patients and controls, except when NCEP-EULAR adapted version for RA was applied (7% vs. 2%; p = 0.00002). A 43% of patients and 47% of controls had DLP (p = 0.15). RA patients with DLP tended to have extra-articular manifestations more frequently (36% vs. 24%; p = 0.01) and higher erythrocyte sedimentation rate (ESR) (21 [13-35] vs. 18 [10-30] mm; p = 0.003). RA patients treated for DLP varied between 11% and 32% according to the definition used. Patients with RA showed an elevated CV risk only when the NCEP-EULAR definition was used. Among RA patients, those with higher ESR and the presence of extra-articular manifestations were more likely to show DLP. The vast majority of patients were not receiving treatment for DLP.

The impact of increased body mass index on systemic lupus erythematosus: data from LUMINA, a multiethnic cohort (LUMINA XLVI) [corrected].

OBJECTIVE: The aim of this study was to examine the impact of an increased body mass index (BMI) on disease activity, damage accrual, fatigue, self-reported health-related quality of life (HRQOL), and fibromyalgia in patients with lupus using longitudinal data from LUMINA, a large multiethnic cohort. METHODS: SLE patients (>/=4 ACR revised criteria), /=30 kg/m). An increased BMI was associated with older age, less social support, higher degree of helplessness, depression, more abnormal illness-related behaviors, poorer self-reported HRQOL, fatigue, and fibromyalgia, but not with disease activity or damage accrual by univariable analyses. In multivariable analyses, BMI was independently associated with fibromyalgia but not with disease activity, fatigue, or self-reported HRQOL. CONCLUSIONS: An increased BMI is independently associated with presence of fibromyalgia but not with disease activity, damage accrual, fatigue or self-reported quality of life in patients with SLE. Optimizing weight merits investigation to see if it can significantly impact this pervasive SLE-associated manifestation.

African-American and Hispanic ethnicities, renal involvement and obesity predispose to hypertension in systemic lupus erythematosus: results from LUMINA, a multiethnic cohort (LUMINAXLV).

OBJECTIVE: To examine the predictors of the occurrence of hypertension in a large multiethnic US cohort. PATIENTS AND METHODS: There were 614 patients with systemic lupus erythematoses (SLE; > or = 4 American College of Rheumatology revised criteria) with < or = 5 years of disease duration at entry into the cohort (T0) and of Hispanic (Texan or Puerto Rican), African-American or Caucasian ethnicity. T0 variables were compared between patients who did and did not develop hypertension (blood pressure > or = 140/90 mm Hg on at least two occasions and/or the use of antihypertensive drugs) after T0. Significant and clinically relevant variables were then examined by a stepwise logistic regression model. RESULTS: A total of 379 patients without hypertension at T0 were included (patients who developed hypertension prior to SLE diagnosis (n = 126) or before T0 (n = 109) were excluded). Predictors of hypertension were African-American and Texan-Hispanic ethnicities, renal involvement and a higher body mass index. CONCLUSIONS: Traditional cardiovascular risk factors, disease-related factors and ethnicity play a role in the occurrence of hypertension in patients with SLE. Controlling renal involvement and optimising body weight may prevent the occurrence of hypertension.

Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L).

OBJECTIVE: In patients with systemic lupus erythematosus (SLE), hydroxychloroquine prevents disease flares and damage accrual and facilitates the response to mycophenolate mofetil in those with renal involvement. A study was undertaken to determine whether hydroxychloroquine also exerts a protective effect on survival. METHODS: Patients with SLE from the multiethnic LUMINA (LUpus in MInorities: NAture vs nurture) cohort were studied. A case-control study was performed within the context of this cohort in which deceased patients (cases) were matched for disease duration (within 6 months) with alive patients (controls) in a proportion of 3:1. Survival was the outcome of interest. Propensity scores were derived by logistic regression to adjust for confounding by indication as patients with SLE with milder disease manifestations are more likely to be prescribed hydroxychloroquine. A conditional logistic regression model was used to estimate the risk of death and hydroxychloroquine use with and without the propensity score as the adjustment variable. RESULTS: There were 608 patients, of whom 61 had died (cases). Hydroxychloroquine had a protective effect on survival (OR 0.128 (95% CI 0.054 to 0.301 for hydroxychloroquine alone and OR 0.319 (95% CI 0.118 to 0.864) after adding the propensity score). As expected, the propensity score itself was also protective. CONCLUSIONS: Hydroxychloroquine, which overall is well tolerated by patients with SLE, has a protective effect on survival which is evident even after taking into consideration the factors associated with treatment decisions. This information is of importance to all clinicians involved in the care of patients with SLE.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA L II): relationship between vascular events and the use of hormone replacement therapy in postmenopausal women.

OBJECTIVES: To examine the influence of hormone replacement therapy (HRT) in the occurrence of vascular arterial and venous thrombotic events in postmenopausal women with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: SLE women aged > or =16 years, disease duration < or =5 years from LUMINA, a multiethnic, longitudinal outcome study, were included. Menopause was defined at disease onset as the presence of amenorrhea >6 months and/or oophorectomy, and/or increased follicle stimulating hormone values, and/or HRT use regardless of the presence or absence of climacteric symptoms (hot flashes). Patients were divided into HRT ever users and nonusers. Patients with positive antiphospholipid antibodies (n = 9) or vascular arterial events (n = 1) occurring before HRT use were excluded. The occurrence of vascular arterial and venous thrombotic events was compared between HRT users and HRT nonusers and its role examined by logistic regression after adjusting for "confounding by indication" using propensity score or logistic regression analyses. RESULTS: Seventy-two postmenopausal women, 32 (44%) HRT users and 40 (56%) HRT nonusers, were studied. HRT use was associated with fewer vascular arterial but not venous thrombotic events (P = 0.021) in the univariable analyses. However, after adjusting for the propensity score, HRT use was no longer significant (P = 0.064). Comparable results were obtained by logistic regression. CONCLUSIONS: HRT use was not associated with the occurrence of vascular arterial events in the LUMINA patients. HRT use in women with SLE should be individualized, but our data suggest its use may be safe if antiphospholipid antibodies are not present or vascular arterial events have not previously occurred.

Systemic lupus erythematosus in a multiethnic US cohort. XXXIII. Clinical [corrected] features, course, and outcome in patients with late-onset disease.

OBJECTIVE: To examine the clinical differences and the type and extent of organ damage in late- versus early-onset systemic lupus erythematosus (SLE). METHODS: A nested case-control study was performed in the context of LUMINA (LUpus in MInorities, NAture versus nurture), a large, longitudinal, multiethnic cohort. Patients who developed SLE at or after the age of 50 years were considered cases. Two controls (patients who developed SLE at age < or = 49 years) per case, matched for sex and disease duration, were randomly chosen. Selected baseline socioeconomic/demographic, behavioral, and psychological features, self-reported quality of life, and cumulative clinical data (clinical manifestations, laboratory data, disease activity, damage, and mortality) were compared between cases and controls. Multivariable analyses with late-onset lupus, damage accrual, and mortality as dependent variables were then performed. RESULTS: Two hundred seventeen patients were studied. Of them, 73 were cases. Cases were more likely to have neurologic involvement, arterial thrombotic events, osteoporosis, and hypertriglyceridemia, while renal involvement and anti-Sm antibodies were less frequent. Disease activity at baseline was lower among cases. Cases also exhibited more cardiovascular and ocular damage. Late-onset lupus was an independent predictor of damage accrual (t-test = 2.23, P = 0.028), any damage at last visit (odds ratio [OR] 23.32, 95% confidence interval [95% CI] 3.98-141.56) (P < 0.001), and mortality (OR 10.74, 95% CI 3.07-37.56) (P < 0.001). CONCLUSION: Patients with late-onset lupus exhibit distinct clinical features. Although disease activity tends to be lower in these patients, they tend to accrue more damage and experience higher mortality than patients with early-onset lupus. These findings probably reflect the contribution exerted by other comorbid conditions in the overall impact of lupus in these patients.

Classification of the vasculitides: are they clinically useful?

Several classification systems for the vasculitides have been developed over the second half of the past century. These classifications systems have been modified according to the advances made in the differentiation of these syndromes, particularly their histopathologic features (the vessel size involved) and their clinical features. Although these classifications have been widely used in the clinical setting for the diagnosis of these disorders, they were developed for research purposes. Given the common clinical and, sometimes, histopathologic features of the different vasculitides, a classification system that facilitates a diagnosis and the formulation of a therapeutic plan is still needed. The development and utilization of novel serum markers and new imaging modalities coupled with advances in the understanding of these disorders, may allow the development of a classification system for the vasculitides that will be of greater value in the clinical setting.

Soft tissue metastases presenting as greater trochanteric pain syndrome.

Greater trochanteric pain syndrome includes a complex differential diagnosis. We report the case of a 71-year-old woman who consulted us because of pain in the lateral aspect of the hip. A diagnosis of greater trochanter bursitis was suggested, and she was treated with local injections of a mixture of corticosteroids plus anesthetic, but the condition did not improve. A pelvic MRI showed a high intensity signal in the gluteus medius and minimus and a subsequent biopsy revealed a metastasis of an adenocarcinoma of unknown origin. Although pain on the lateral aspect of the hip is often attributed to trochanteric bursitis, other diagnoses, including this rare finding of malignant disease, should be considered in the differential diagnosis of the greater trochanteric pain syndrome.

Poliartritis y tenosinovitis grave por Streptococcus agalactiae en un paciente con hipoesplenia funcional / Severe polyarthritis and tenosynovitis due to Streptococcus agalactiae in a patient with functional hyposplenia

Cases of arthritis caused by Streptococcus agalactiae are infrequent and in our knowledge there are no case reports of tenosynovitis caused by S. agalactiae. A 46-year-old woman presented with fever, polyarthralgia, myalgia, diarrhea and vomiting. She had a history of papillary thyroid carcinoma and functional hyposplenia. She was febrile, with arthritis in hands, wrists, elbows, right shoulder and left ankle joints, and presented tenosynovitis in both feet and left hand. Blood and right olecranon bursa sample cultures were positive for S. agalactiae. An ultrasound scan made at the musculus tibialis anterior of left foot revealed signs of tenosynovitis. She was treated with intravenous cefazolin for 20 days and oral cefuroxime for 12 days. The joint involvement completely subsided in 60 days. Streptococcus agalactiae can cause, infrequently, a polyarthritis and tenosynovitis syndrome similar to disseminated gonococcal infection