Search

Objective To determine whether LJP 394 delays or prevents renal flare in patients with systemic lupus erythematosus (SLE) and a history of renal disease. Methods In a 76-week, double-blind, placebo-controlled study, 230 SLE patients were randomized to receive 16 weekly doses of 100 mg of LJP 394 or placebo, followed by alternating 8-week drug holidays and 12 weekly doses of 50 mg of LJP 394 or placebo. An assay measuring the affinity of the serum IgG fraction for the DNA epitope of LJP 394 identified a high-affinity population of patients (189 of 213 patients; 89% taking LJP 394 and 90% taking placebo). Analyses were performed on both the intent-to-treat population and the high-affinity population. Results Anti–double-stranded DNA antibodies decreased and C3 levels tended to increase during treatment with LJP 394. In the intent-to-treat population, the time to renal flare was not significantly different between treatment groups, but patients taking LJP 394 had a longer time to institution of high-dose corticosteroids and/or cyclophosphamide (HDCC) and required 41% fewer treatments with HDCC. In the high-affinity population, the LJP 394 group experienced a longer time to renal flare, 67% fewer renal flares, longer time to institution of HDCC, and 62% fewer HDCC treatments compared with the placebo group. In patients with serum creatinine levels ≥1.5 mg/dl at study entry, those taking LJP 394 had 50% fewer renal flares; no renal flares were observed in the high-affinity group taking LJP 394. Serious adverse events were observed in 25 of the 114 LJP 394–treated patients (21.9%) and 34 of the 116 placebo-treated patients (29.3%). Conclusion Treatment with LJP 394 in patients with high-affinity antibodies to its DNA epitope prolonged the time to renal flare, decreased the number of renal flares, and required fewer HDCC treatments compared with placebo. The study drug appeared to be well tolerated.

Objective: To investigate the role of HLA-B and HLA-DR genes as contributors to genetic susceptibility and clinical expression of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 172 patients with SpA (undifferentiated SpA 83, ankylosing spondylitis (AS) 64, and reactive arthritis 25) and 99 healthy controls. The HLA-B and HLA-DR alleles were detected by the polymerase chain reaction with sequence-specific primers technique. Patient assessment included demographic data, diagnostic categories, and disease patterns. Statistical methods included the Mantel-Haenzel χ2 test, Fisher's exact test, and Woolf method for odds ratio (OR). Differences of continuous variables between HLA allele groups were calculated by Student's t test. Results: Increased frequencies of HLA-B27 (pCh10-3, OR=28.7), HLA-DR1 (pC=0.045, OR=2.77), and HLA-B15 (p=0.034, pC=NS, OR=2.04) alleles in the whole group were found. HLA-B27 strength of association (OR) was 41.4 in AS; 20.9 in undifferentiated SpA; 27.2 in reactive arthritis. HLA-DR1 and HLA-B15 were increased in undifferentiated SpA (pC=0.045, OR=2.98 and p=0.004, pC=NS, OR=2.75). By analysing 58 HLA-B27 negative patients it was found that HLA-B15 and HLA-DR1 associations with SpA were independent of HLA-B27; increased frequencies of HLA-B15 were found in the whole SpA group and in patients with undifferentiated SpA (pC=0.03, OR=3.09 and pCh0.01, OR=3.77) and of HLA-DR1 in the latter (p=0.04, pC=NS, OR=3.15). HLA-B27 positive patients were younger than HLA-B27 negative patients at onset (p=0.03), but HLA-DR1 positive patients were older than HLA-DR1 negative patients (p=0.03). Bath indices for disease activity and functioning were higher in HLA-B27 positive patients (p=0.006 and p=0.004 v HLA-B27 negative patients). In contrast, neither HLA-DR1 nor HLA-B15 influenced these indices. Conclusion: Apart from HLA-B27, there is a significant association of HLA-DR1 and HLA-B15 with SpA in Mexicans which is independent of B27. HLA-B27 is associated with younger age at onset and increased disease severity and HLA-DR1 with older age at onset. The strength of HLA-B15, HLA-B27, and HLA-DR1 associations varied in different forms of SpA.

Objectives To determine the agreement of scores on the original visual analog scale (VAS) or Likert scale of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Dougados Functional Index (DFI) with scores on a numerical rating scale (NRS). To assess the reproducibility and responsiveness of the instruments with the original scale and NRS. Methods Five hundred thirty-six patients with ankylosing spondylitis from the Netherlands, Mexico, and Switzerland completed a questionnaire in which all questions from the BASDAI, BASFI, and DFI were presented twice in random order with an 11-point NRS and either a 10-cm VAS (BASDAI and BASFI) or a 5-point Likert scale (DFI). Agreement of scores using Bland-Altman plots and intraclass correlation coefficients (ICCs), reproducibility using ICCs, and responsiveness were assessed. Results Large variability between the scores on the original scales and the NRS was found in individual questions of all 3 questionnaires, although total scores showed ICCs of at least 0.88. Reproducibility of all answer modalities showed low ICCs in individual questions, but moderate to good ICCs in total scores (Dutch group 0.62–0.89; Mexican group 0.53–0.72). Moderate to large effects (0.48–1.04) were found in responsiveness scores in the 3 questionnaires. No major differences in reproducibility and responsiveness between the answer modalities were found. Conclusion Although large variability between the scores on the original answer scales and the NRS was observed, the BASDAI, BASFI, and DFI can be administered with an NRS, which does not show important differences compared with the original scales.

Objective: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, χ2, Fisher's exact test, and Woolf's method for odds ratio (OR). Results: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC

Background This study was undertaken in order to identify the prevalence and factors associated with depression in a group of patients with type 2 diabetes mellitus. Methods Our design consisted of a cross-sectional study at the Department of Neurology and Psychiatry of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City. Study units included 189 patients with type 2 diabetes mellitus (DM). Beck Depression Inventory scale was used to measure the presence of depression, while the independent variables evaluated to explain depression were sociodemographic (gender, marital status, religion, education, occupation, socioeconomic status) and characteristics of the disease were disease duration, comorbidity, compliance, and glycemic control. Results Prevalence of depression was 39% (74 patients). The following risk factors were identified by univariate analysis: being widowed (OR 3.54, confidence interval [CI] 1.56–8.11, p = 0.0007); female (OR 2.95, CI 1.50–5.82, p = 0.006); housewife (OR 2.08, CI 1.10–3.94, p = 0.01); poor compliance (OR 2.14, CI 1.12–4.10, p = 0.01), and presence of comorbidity (OR 5.60, CI 1.51–24.5, p = 0.002). On the other hand, the most constant associations were presence of blood glucose at the last appointment ≥200 (OR 3.23, CI 1.59–6.60, p = 0.0003) and ≥250 (OR 2.15, CI 0.93–5.03, p = 0.05), as the average of the last five blood glucoses ≥200 (OR 3.67, CI 1.76–7.73, p = 0.0001), ≥250 (OR 4.07, CI 1.61–10.49, p = 0.0007) and ≥300 (OR 2.12, CI 1.48–3.02, p = 0.003). Discriminant function analysis of the variables, previously studied in univariate analysis, was carried out for the presence of depression. A stepwise model included the following variables: average of the last five blood glucoses; 2) widowed or divorced, and 3) female. Conclusions Frequency of depression in patients with type 2 DM was high (39%). High level of blood glucose stands out as a variable associated with presence of depression. Other associations were presence of comorbidity, being a female, and being widowed or divorced.

Rheumatoid arthritis (RA) is a systemic inflammatory chronic disease of unknown origin that mainly affects adult women and tends to be more prevalent in the oldest group of people [1]. Fascinating facts have been seen during its history and many hypotheses have been raised on when it appeared, how it affects human beings and some interesting epidemiological findings and trends [2]. It is universally distributed and there is no ethnic group who have been described without it. Nevertheless, there is prominent information related to an unequal distribution of this potentially disabling disease around the world.

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Multilevel studies have gained importance for highlighting social inequalities in health. These associations have been reported previously in diseases such as arthritis and chronic pain. We conducted a cross-sectional study using multilevel analysis to identify individual and contextual factors associated with the variation of prevalence of osteoarthritis (OA) in the Mexican population. The sample included 17,566 individuals of which 10,666 (60.7 %) were women. The relationship between individual and contextual factors and OA were analyzed with a multilevel strategy. From the total population, 1,681 individuals had OA. Multilevel analysis showed that individual variables such as female gender (odds ratio (OR) = 1.3, 95 % confidence interval (CI) 1.1, 1.4), age range 55–65 years (OR = 1.6, 95 % CI 1.3, 2.0), musculoskeletal pain in the last 7 days (OR = 2.6, 95 % CI 2.3, 3.0), and use of pain treatments (OR = 1.4, 95 % CI 1.2, 1.7) were associated with OA. At the regional level, the Social Gap Index (SGIx) was associated with the diagnosis of OA (coefficient 0.5, 95 % CI 0.2–1.1). The SGIx contextual variable was positively associated with the regional prevalence of OA and the variation in prevalence of OA in different regions. The larger the social gap, the greater the variation in OA prevalence. These factors were independently associated with the prevalence of OA: female gender, pain intensity, physical limitation, and the use of pain treatments were individual variables associated with OA. The association between OA prevalence and regional variations with SGIx reflects inequities in health provisions that should be considered in health programs.

Objective To show evidence of the cross-cultural equivalence between the original English version of a 5-item scale for measuring helplessness and a translated Spanish version. Methods English and Spanish versions of the 5 items that constitute the helplessness factor of the Rheumatology Attitudes Index were tested in 3 separate groups of patients: 1) 20 bilingual rheumatology patients; 2) 100 consecutive English- and 50 consecutive Spanish-speaking monolingual rheumatology patients; and 3) 192 English- and 44 Spanish-speaking patients with rheumatoid arthritis who were consecutively enrolled in a cohort to study disease outcomes. English–Spanish concordance among bilingual subjects was measured using intraclass correlation coefficients (ICC). Internal consistency was measured by Cronbach's coefficient alpha. Associations between the helplessness scale and variables measured simultaneously in English- and Spanish-speaking patients were measured by correlation analysis. Results Agreement between the English and Spanish versions of the helplessness scale among bilingual subjects was excellent (ICC = 0.87), and internal consistency among monolingual subjects was acceptable (coefficient alpha = 0.73 in English and 0.87 in Spanish). The correlation between helplessness and most other measured variables was of similar size and direction in English as in Spanish (10-point pain scale r = −0.53 and −0.52; modified Health Assessment Questionnaire physical disability r = −0.45 and −0.43; self-assessed joint count r = 0.36 and 0.36; Medical Outcomes Study Short Form 36 [SF-36] physical function r = 0.37 and 0.39; SF-36 mental health r = 0.27 and 0.35; Center for Epidemiological Studies Depression scale r = −0.37 and −0.33, respectively). Conclusion The evidence shown supports the cross-cultural equivalence between the original 5-item helplessness scale developed in English and our translated Spanish version.

Evaluation of: Davis JM III, Roger VL, Crowson CS, Maradit Kremers H, Therneau TM, Gabriel SE: The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population. Arthritis Rheum. 58, 2603–2611 (2008). A community-based cohort study was undertaken in Olmsted County, Minnesota, USA, from 1979 to 2000 to compare the clinical presentation, management and outcome of incident heart failure in patients with rheumatoid arthritis (RA) compared with non-RA patients. This paper by Davis et al. studied 103 patients with RA and 852 non-RA patients who were compared with age- and sex-adjusted rates and multivariable logistic regresion models to evaluate clinical features and mortality. Patients with RA were more often female and had less frequency of obesity, hypertension and ischemic heart disease. Patients with RA had fewer typical symptoms of heart failure and were less likely to have undergone echocardiography. Patients with RA were more likely to have p...

Evaluation of: Tseng CE, Buyon JP, Kim M et al. The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 54, 3623-3632 (2006). Systemic lupus erythematosus is an autoimmune disease of unknown origin. Flares and remissions are commonly seen in clinical settings. These clinical flares can have several degrees of severity, some of which require intensive immunosuppressive treatment and/or hospitalization. Clinicians treating these patients have looked at different strategies for prevention, early detection and prompt treatment of a lupus flare. Clinical information and laboratory findings have been proposed to reach these goals and preventive steroid adjustment has even been used in some cases without convincing results. This paper presents results from a controlled, multicenter, double-blind clinical trial evaluating the effectiveness of short-term corticosteroid treatment for preventing severe flares in which elevations of C3a by 50% were accompanied by a 25% increase in the anti-double-stranded DNA titer in patients with inactive or stable/active systemic lupus erythematosus. Results suggest that this strategy can prevent severe lupus flares.

Objectives To review background, pharmacological properties, mechanisms of action, and published clinical experience using omega-3 fatty acids in rheumatoid arthritis. Materials and methods English language publications were identified through a computerized search (using MEDLINE) between 1979 and 1995 using the terms "omega-3 fatty acids" and "fish oil". In addition, manual search and cross references were used to obtain published articles on the subject. Papers showing evidence of pharmacological properties and mechanisms of action were analyzed. For therapeutic efficacy, only randomized clinical trials are presented in this article. All papers were reviewed by a board certified rheumatologist with training in research methodology and critical appraisal skills. He was aware of study objectives. Results Main results are summarized in the text and presented in tables. Mean change from baseline is presented only for patients treated with omega-3 fatty acids. Omega-3 fatty acids are superior with respect to placebo in improving some outcome measures, and decrease the long-term requirements for nonsteroidal antiinflammatory drugs. Some of these effects are statistically significant, but their clinical significance remain to be established. Conclusions Treatment with omega-3 fatty acids has been associated with improvement in some outcome measures in rheumatoid arthritis. Studies are needed to determine if they might represent an alternative to nonsteroidal antiinflammatory drugs in certain circumstances.

Recent reports have associated NCF2, encoding a core component of the multi-protein NADPH oxidase (NADPHO), with systemic lupus erythematosus (SLE) susceptibility in individuals of European ancestry. To identify ethnicity-specific and -robust variants within NCF2, we assessed 145 SNPs in and around the NCF2 gene in 5325 cases and 21 866 controls of European-American (EA), African-American (AA), Hispanic (HS) and Korean (KR) ancestry. Subsequent imputation, conditional, haplotype and bioinformatic analyses identified seven potentially functional SLE-predisposing variants. Association with non-synonymous rs17849502, previously reported in EA, was detected in EA, HS and AA (P(EA) = 1.01 × 10(-54), PHS = 3.68 × 10(-10), P(AA) = 0.03); synonymous rs17849501 was similarly significant. These SNPs were monomorphic in KR. Novel associations were detected with coding variants at rs35937854 in AA (PAA = 1.49 × 10(-9)), and rs13306575 in HS and KR (P(HS) = 7.04 × 10(-7), P(KR) = 3.30 × 10(-3)). In KR, a 3-SNP haplotype was significantly associated (P = 4.20 × 10(-7)), implying that SLE predisposing variants were tagged. Significant SNP-SNP interaction (P = 0.02) was detected between rs13306575 and rs17849502 in HS, and a dramatically increased risk (OR = 6.55) with a risk allele at each locus. Molecular modeling predicts that these non-synonymous mutations could disrupt NADPHO complex assembly. The risk allele of rs17849501, located in a conserved transcriptional regulatory region, increased reporter gene activity, suggesting in vivo enhancer function. Our results not only establish allelic heterogeneity within NCF2 associated with SLE, but also emphasize the utility of multi-ethnic cohorts to identify predisposing variants explaining additional phenotypic variance ('missing heritability') of complex diseases like SLE.

Introduction Chronic diseases have a great impact on the morbidity and mortality and on the health-related quality of life (HRQoL) of patients around the world. The impact of rheumatic diseases has not been fully recognized. We conducted a comparative study to evaluate the HRQoL in different chronic diseases. Objectives The aim of the present study was to assess the HRQoL and identify specific areas affected in patients with rheumatoid arthritis (RA), osteoarthritis (OA), diabetes mellitus, and end-stage renal disease, in geriatric subjects and in a control group. Patients and methods We conducted a cross-sectional study, in a General Hospital in Morelia, Mexico. All patients met the classification criteria for RA, OA, diabetes mellitus, and end-stage renal disease; the geriatric subjects group was aged ≥65 years and the control group ≥30 years. Demographic characteristics were recorded, different instruments were applied: SF-36, visual analog scale for pain, patient's and physician's global assessments, Beck Depression Inventory and specific instruments (DAS-28, HAQ-Di, WOMAC, Diabetes Quality of Life [DQOL] and Kidney Disease Questionnaire of Life [KDQOL]). Biochemical measures: erythrocyte sedimentation rate, blood count, glucose, HbA 1 C, serum creatinine and urea. Results We evaluated 290 subjects (control group: 100; geriatric subjects: 30 and the rest of groups: 160). Differences were detected in baseline characteristics ( P P =.007). The worst HRQoL was observed in the end-stage renal disease group (SD: 48.06±18.84 x /SD). General health was the principal affected area in RA. Pain was higher in rheumatic diseases: OA (5.2±2.4) and RA (5.1±3). HAQ was higher in OA compared to RA (1.12±.76 vs .82±.82, respectively; P =.001). Forty-five percent of all subjects had depression. Conclusions The HRQoL in RA patients is poor and comparable to that of other chronic diseases (end-stage renal disease and diabetes mellitus). Rheumatic diseases should be considered as high impact diseases and therefore should receive more attention.

Objectives The objective of this paper is to assess the predictors of time-to-lupus renal disease in Latin American patients. Methods Systemic lupus erythematosus (SLE) patients ( n = 1480) from Grupo Latino Americano De Estudio de Lupus (GLADEL’s) longitudinal inception cohort were studied. Endpoint was ACR renal criterion development after SLE diagnosis (prevalent cases excluded). Renal disease predictors were examined by univariable and multivariable Cox proportional hazards regression analyses. Antimalarials were considered time dependent in alternative analyses. Results Of the entire cohort, 265 patients (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%) developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both; 233 patients (87.9%) were women; mean (± SD) age at diagnosis was 28.0 (11.9) years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians ( p = 0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19–2.17), hypertension (HR 3.99, 95% CI 3.02–5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01–1.06) were associated with a shorter time-to-renal disease occurrence; antimalarial use (HR 0.57, 95% CI 0.43–0.77), older age at onset (HR 0.90, 95% CI 0.85–0.95, for every five years) and photosensitivity (HR 0.74, 95% CI 0.56–0.98) were associated with a longer time. Alternative model results were consistent with the antimalarial protective effect (HR 0.70, 95% CI 0.50–0.99). Conclusions Our data strongly support the fact that Mestizo patients are at increased risk of developing renal disease early while antimalarials seem to delay the appearance of this SLE manifestation. These data have important implications for the treatment of these patients regardless of their geographic location.

Clinical and laboratory features were analyzed in 107 Latin American male patients with systemic lupus erythematosus (SLE) who were compared with a group of 1,209 Latin American female patients with SLE to determine the presence of gender-associated differences. Males had an increased prevalence of renal disease, vascular thrombosis, and the presence of anti-dsDNA antibodies, as well as the use of moderate to high doses of corticosteroids, compared with female SLE patients. Although there was no difference in mortality from all causes, SLE-related mortality was higher in the male group. All these findings are consistent with a more severe disease in Latin American males than in female patients from the same region.

To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry.Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software.A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA-DQB1- DQA2 (P = 7.6 × 10(-10) ), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10(-6) ), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10(-7) ). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10(-6) ). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti-cyclic citrullinated peptide antibodies.Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.

BACKGROUND Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, little is known about the way rheumatologists in Latin America treat their patients in clinical practice, outside the scope of clinical trials. OBJECTIVE The objective of this study was to describe treatment patterns at disease onset in early RA with data from a large, multicenter, multinational inception cohort of Latin American patients. METHODS Consecutive patients with early RA (

Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting the synovium of joints, tendons, and some extra-articular sites. RA prevalence in Latin America ranges from 0.4 to 1.6%. Early treatment of RA translates into a substantial reduction in the cost to society. In light of this, early disease clinics are being established in some countries. Barriers to RA management, such as delay in referral to rheumatologists and limited access to therapy, have been identified. Evidence-based treatment guidelines have been adapted by countries according to their own situations. The need for keeping accurate records of biologics prescribed has been addressed by biologic registries, thereby contributing toward a better understanding of rheumatic diseases and their treatment. Current biologics include the tumor necrosis factor (TNF)-α inhibitors (etanercept, infliximab, and adalimumab), B-cell depletion agent (rituximab), interleukin-6 receptor blocker (tocilizumab), and T-cell co-stimulatory blocker (abatacept). Future therapies include kinase inhibitors (tofacitinib and fostamatinib), alternative TNF-α inhibitors (golimumab and certolizumab), and biosimilars.

Treating rheumatoid arthritis (RA) with a goal or «Treat to target» strategy is a therapeutic proposal taken from cardiovascular and endocrine literature. It proposes that the therapeutic target in RA should be a state of remission, or an alternative goal could be a low disease activity. Rheumatologists should measure and register disease activity in every clinical visit and if the goal has not been reached, therapeutic adjustments should be made. Current evidence from clinical trials and a meta-analysis supports the notion that this strategy has important clinical benefits in patients with early RA when compared with routine care. It is also described that using protocolized treatment offers greater benefits. Recent data from Dutch cohorts is presented showing its successful implementation. A discussion is offered on the need of more studies in established RA.

Objective To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline. Methods Clinical evaluation, ethnicity, socioeconomic status (SES), 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire (HAQ) disability index (DI), and erosions were recorded in 1,093 patients with early RA (

Secondary osteoporosis is a frequently underestimated bone disorder. It is a secondary cause of bone loss that affects more than half of men and premenopausal and perimenopausal women, and about one-fitfth of postmenopausal women. We herein report an uncommon case of multiple fractures due to secondary osteoporosis caused by Cushing's disease. In this case the appearance of fractures in a 41 years old woman was the sign of alarm that ultimately lead us to the diagnosis.

Objective. To estimate the prevalence of musculoskeletal (MSK) disorders and to describe predicting variables associated with rheumatic diseases in 5 regions of Mexico. Methods. This was a cross-sectional, community-based study performed in 5 regions in Mexico. The methodology followed the guidelines proposed by the Community Oriented Program for the Control of the Rheumatic Diseases (COPCORD). A standardized methodology was used at all sites, with trained personnel following a common protocol of interviewing adult subjects in their household. A “positive case” was defined as an individual with nontraumatic MSK pain of > 1 on a visual analog pain scale (0 to 10) during the last 7 days. All positive cases were referred to internists or rheumatologists for further clinical evaluation, diagnosis, and proper treatment. Results. The study included 19,213 individuals; 11,602 (68.8%) were female, and their mean age was 42.8 (SD 17.9) years. The prevalence of MSK pain was 25.5%, but significant variations (7.1% to 43.5%) across geographical regions occurred. The prevalence of osteoarthritis was 10.5%, back pain 5.8%, rheumatic regional pain syndromes 3.8%, rheumatoid arthritis 1.6%, fibromyalgia 0.7%, and gout 0.3%. The prevalence of MSK manifestations was associated with older age and female gender. Conclusion. The prevalence of MSK pain in our study was 25.5%. Geographic variations in the prevalence of MSK pain and specific diagnoses suggested a role for geographic factors in the prevalence of rheumatic diseases.

To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE).Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression.A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele.Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.

Background In Latin America, the medical attention directed to systemic autoimmune diseases competes with a budget designed to fight poverty, lack of education, etc. In this context, the access to treatments recommended internationally are expensive and limited; therefore, research of methods that make these treatments cheaper is of paramount importance. Objective Our objective was to describe the 24-month clinical outcome of patients with active systemic lupus erythematosus (SLE) who received low doses of rituximab (RTX), followed by hydroxychloroquine (HCQ), prednisone and low doses of mycophenolate mofetil (MMF). Methods Forty-six patients with active SLE received 500 mg of RTX (together with 500 mg of methylprednisolone as a premedication) administered on two occasions 2 weeks apart, followed by HCQ (200–400 mg/day), prednisone and MMF (500–1000 mg/day) during a 24-month follow-up period. Clinical outcome was assessed using the MEX-SLE Disease Activity Index (MEX-SLEDAI) and serial serologic measurements. Remission was defined as MEX-SLEDAI scores 0–1, mild disease activity 2–5, moderate disease activity 6–9, severe 10–13, and very severe 14 or more. Results Disease activity decreased over time with treatment. At baseline, 19 (41.3%) patients had very severe, 16 (34.8%) severe, and 9 (19.6%) moderate disease activity. Improvement on disease activity was detected at 3 months, since 9 (19.6%) patients reached disease remission after this period of time and remission increased to 16 (34.8%) patients at 6 months, 19 (41.3%) at 1 year, and 23 (50%) at 2 years of follow-up ( p Conclusion The administration of low doses of RTX followed by HCQ, prednisone and low doses of MMF is an effective therapy in Latin American patients with active SLE.

Rheumatoid arthritis (RA) is a systemic autoimmune disease which is characterized by chronic inflammation of the joints. Patients experience chronic pain and suffering, and increasing disability; without treatment, life expectancy is reduced. It is imperative to identify patients early so that control of inflammation can prevent joint destruction and disability. Although great advances have been made in the developed nations, early diagnosis remains a great challenge for developing countries during the Bone and Joint Decade (2000-2010) and beyond. Developing countries face important and competitive social, economic, health- and poverty-related issues, and this frequently results in chronic diseases such as RA being forgotten in health priorities when urgent health needs are considered in an environment with poor education and scarce resources. Epidemiological studies in developing countries show a lower but still important prevalence in different regions when compared to that in Caucasians. It seems that the severity of RA varies among different ethnic groups, and probably starts at a younger age in developing countries. Practising rheumatologists in these regions need to take into account several important problems that include suboptimal undergraduate education, inadequate diagnosis, late referrals, lack of human and technical resources, poor access to rheumatologists, and some deficiencies in drug availability. Infections are very important in RA, and special care is needed in developing countries as some endemic infections include tuberculosis, human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. These infections should be carefully taken into account when medications are prescribed and monitored. This chapter presents published information covering the main challenges faced in these environments, and suggests strategies to overcome these important problems in RA management.

Background Previous trans-ethnic meta-analysis including samples from European and Asian individuals support the hypothesis that the genetic component of rheumatoid arthritis is shared. However, our knowledge about populations such as the native population of Americans, also called Amerindians or Native Americans, is poor. Few genetic studies have been conducted in Amerindian populations. Objectives We conducted a meta-analysis of Latin American, with Amerindian-European (primarily South European) admixed individuals and Spanish, in order to find new risk loci for RA susceptibility shared and specific for each one of them. Methods A total of 5,533 subjects were genotyped with the immunochip custom array and included in the final data set. The OR of the meta-analysis of both populations was performed using the inverse variance method under fixed-effects model. The imputation process of the MHC region was performed with a dense reference panel using the Beagle software. Results We confirm the association in this population at genome-wide significant level of the HLA and PTPN22 . The MCH analysis showed that four amino acids in positions 11, 13, 70 and 86 of the HLA-DRβ1 explain all the association in our combined analysis. Interestingly, we observed differential associations in each cohort separately. In the Spanish cohort, only amino acids 13 and 86 of HLA-DRβ1 were necessary to explain all the association in the MHC region, while for the Latin American population, amino acids at positions 13 and 70 were the important ones. Outside of the HLA region, the most interesting signals observed were on 2p25.3, 3q25.33 and 7p12.2 where the MYTL1 , IL12A and IKZF1 genes are located, respectively. Conclusions Our results show that the comparative use of two populations provides clues on the diversity and the history of the genetic susceptibility behind a complex disease such as RA. References Kim, K. et al. Ann. Rheum. Dis. (2014). doi:10.1136/annrheumdis-2013-204749 Jia, X. et al. PloS One 8, e64683 (2013). Raychaudhuri, S. et al. Nat. Genet. 44, 291–296 (2012). Acknowledgements This work was supported by the followuing grants: Instituto de Salud Carlos III (ISCIII) from Spanish Health Ministry RETICS Program RD12/0009 and PI12/02558, the C2A Andalusian recruitment program from Junta de Andalucia (Spain), the European IMI BTCure Program and the Swedish Research Council. MT is supported by the Instituto de Salud Carlos III (Spanish Health Ministry), through the Sara Borrell subprogram [CD13/00316]. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation leading to both cartilage destruction and bone erosions. Early identification of patients with RA, and in particular those with erosive course of the disease would allow a timely therapeutic strategy for cartilage and bone protection. Objectives To investigate the degree of agreement between local expert rheumatologists and central trained readers in the detection of erosions (presence/absence) on plain radiographs of hands and feet. Methods Patients with early RA ( Results From 1069 patients in the GLADAR cohort, there were 516 RA patients with hands and feet radiographs available for standardized radiographic scoring system. According to local and central reading 137 patients (26.6%) and 276 patients (53.5%) displayed erosions, respectively. Agreement between local and central reading was poor (kappa =0.171). From a total of 525 patients with hands radiographs available for standardized scoring, according to local reading 153 (29.1%) fulfilled the radiographic changes criteria RA 1987, whereas central reading showed that 227 (43.2%) presented hand erosions. Again, agreement was poor (kappa =0.120). Conclusions In patients with early RA trained readers and local rheumatologists agreed poorly on the recognition of erosions. This is relevant as therapeutic decisions may change in the presence of erosions and indicate the necessity of more/better training for radiologists/rheumatologists in evaluating articular damage in RA in LA. References Early Rheumatoid Arthritis in Latin America: Low Socioeconomic Status Related to High Disease Activity at Baseline. Arthritis Care & Research 2012; 64: 1135-1143 Treatment of Early Rheumatoid Arthritis in a Multinational Inception Cohort of Latin American Patients. The GLADAR Experience. J Clin Rheumatol 2012; 18: 327-335 Acknowledgements To Dr. Daniel E. Furst, Geffen School of Medicine, University of California Los Angeles Disclosure of Interest L. Massardo Grant/research support from: Abbott, B. PonsEstel Grant/research support from: Abbott, C. Pineda Grant/research support from: Abbott, E. Soriano Grant/research support from: Abbott, M. Cardiel Grant/research support from: Abbott, C. Galarza Grant/research support from: Abbott, R. Levy Grant/research support from: Abbott, M. Sacnum Grant/research support from: Abbott, C. V. Caballero Grant/research support from: Abbott, E. Acevedo Grant/research support from: Abbott, W. Bianchi Grant/research support from: Abbott, H. Gonzalez Grant/research support from: Abbott, R. Montufar Grant/research support from: Abbott, R. Pinto Grant/research support from: Abbott, L. A. Ramirez Grant/research support from: Abbott, C. Zerbini Grant/research support from: Abbott

Introduction Laboratory tests have an important role in rheumatology for evaluation, diagnosis, and follow up in several diseases. Specialized tests such as antinuclear antibodies (ANA), anti single, or double stranded DNA antibodies (anti-DNA), and anticardiolipin antibodies (ACL) are frequently used and its diagnostic performance is well known in tertiary care centers. Our setting is a secondary care center that implemented these tests 2 years ago. After 1 year of implementation, we decided to evaluate the frequency of use, who orders these tests, and their diagnostic properties for the diagnosis of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APLS). Patienst and method All patients with clinical charts and a request for these tests were evaluated from September 1, 2005 to June 30, 2006. These evaluations were done prospectively by a single, trained evaluator following a standardized format looking at pretest clinical information such as pretest diagnosis, physician's level of training, service, and posttest results as well as therapeutic changes after results. Statistical analysis: descriptive statistics and 2 by 2 tables to estimate diagnostic performance of most common indications. Results Two hundred and eighty-six requests were reviewed and only 157 were evaluated. Rheumatology and Internal Medicine services sent 63 and 31 requests for these tests respectively. Diagnostic properties of ANA for SLE were sensitivity (sen) 70%, specificity (spec): 92%, positive predictive value (PPV): 81%, negative predictive value (NPP): 86%, positive likelihood ratio (PLR): 8.73, and negative likelihood ratio (NLR): 0.33. Anti-double stranded DNA, Sen: 78%, spec: 50%, PPV: 80%, NPP: 46%, PLR: 1.56, NLR: 0.44; ACACL y Sen: 78%, spec: 92%, PPV: 78%, NPV 92%, PLR: 10, NLR 0,24. Conclusions These specialized tests are not frequently used in our setting. Their diagnostic properties are not as accurate as those published in medical literature. Guidelines are needed in our hospital to improve their diagnostic performance.

Background Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that involves synovial joints, resulting in severe dysfunction or burden for individual patients, families and society. Latin American Rheumatology Associations have acknowledged its relevance and recognized multiple limitations for its diagnosis and treatment in Latin America and the Caribbean. This document underscores issues regarding the impact and relevance of this disease in these countries. Objectives To develop a consensus document that may unify and guide the pharmacological management of RA in Latin America and the Caribbean. Methods An Executive Committee appointed by the Epidemiology, Rheumatoid Arthritis and Radiology Committees of Pan-American League of Association for Rheumatology (PANLAR), held a meeting at Lisbon in May 2003. The goal was to establish a task force for the development of a Latin American consensus on the management of RA. Efforts focused on the problems encountered in the region regarding the availability of appropriate treatment for RA and the development of treatment guidelines for clinical practice. A secondary objective was the diffusion of the consensus conclusions and recommendations in participating countries. Results Six major issues were identified for discussion by six working groups. All Latin American Rheumatology Associations registered in PANLAR were invited to participate in the consensus. PANLAR members were well-represented in each group. Coordinators identified essential literature to be reviewed, analysed, and electronically discussed before the consensus meeting. Conclusions The consensus' results and recommendations of this effort to delineate RA management in Latin America are contained in this article, which has been reviewed by participant societies and authors during 2004/2005 and endorsed by PANLAR.

To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) gene as susceptibility marker for spondyloarthritis (SpA), two polymorphisms (-238 and -308 positions) were analyzed in 229 patients with SpA (113 with ankylosing spondylitis [AS], 92 with undifferentiated SpA [U-SpA], 24 with reactive arthritis), and 169 ethnically matched healthy control subjects. The HLA-B alleles were detected by PCR-SSP technique and the TNF-alpha polymorphism by PCR-RFLP. In comparison with healthy control subjects, the frequencies of TNF-238 in SpA were similar. In contrast, the analysis of -308 polymorphism showed increased frequencies of the T2(A) allele in the whole SpA group (p0.05, pC = NS, OR = 1.83) as well as the T2(A) allele (pC0.05, OR = 2.4) and T1T2(AG) genotype (p0.05, pC = NS, OR = 2.25) in U-SpA patients. Comparison of B27-negative patients and healthy control subjects yielded similar results. There was no significant correlation between TNF genotypes and clinical data. The present study demonstrates that TNF-alpha -308 polymorphism appears to be associated with the genetic susceptibility U-SpA. The association seems independent of the susceptibility conferred by the HLA-B27 in this group of patients.

Objective To assess the costs of standard care in patients with active rheumatoid arthritis (RA) seen in a tertiary care center in Mexico City in the context of a clinical trial. To analyze the relationship between costs and utility units obtained by the patients in this scenario. Patients and methods This economic evaluation was performed during a clinical trial with a 48-week followup in a tertiary care center in Mexico City. The trial compared the efficacy of omega-3 fatty acids versus placebo in patients with active RA who also received standard rheumatology care. The costs of medical consultations, complementary tests and drugs were assessed. Other direct costs were also measured. Hypothetical scenarios with fewer medical consultations and complementary tests than those in the clinical trial were also analyzed. Utilities were assessed by the Health Utility Index. A cost-utility ratio was calculated using the baseline utilities score as comparator. A descriptive statistical analysis was performed. Results Ninety RA patients (83 women [92%], age [X ± SD] 43.2 ± 14.2 years with disease duration of 3.3 ± 4.6 years) were included. Data from 88 patients were analyzed. The total direct costs were 152,704.11 US$ 2005 divided into medical attention (78,386.43 US$ 2005, 51.33%), drugs (39,339.5 US$ 2005, 25.76%) and other direct costs (34,978.18 US$ 2005. 22.91%). In scenarios with fewer medical consultations and complementary tests than those in the clinical trial, the total direct costs ranged from 39,507.4 to 103,880.6 US$ 2005. Patients improved by a mean of 0.18 utility units on a 0-1 scale equivalent to 0.18 quality adjusted lifeyears (QALYs). The cost-utility ratios ranged from 2,494.1 to 9,640.38 US$ 2005 per QALY in the scenarios analyzed. Conclusions The direct costs of the standard care of RA in the scenarios analyzed are substantial in the social and economic context of Mexico. The cost per gained QALY is high.

Objective To examine the relationship between changes in anti–double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials. Methods Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used. Results Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26–68%, nominal P = 0.0007) and a 53% reduction (95% CI 33–69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively). Conclusion Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.

To determine whether there is familial aggregation of systemic lupus erythematosus (SLE) and/or other autoimmune diseases in SLE patients and to identify clinical differences between patients with and those without familial autoimmunity.We interviewed members of the Grupo Latinoamericano de Estudio del Lupus Eritematoso (GLADEL) inception cohort of 1,214 SLE patients to ascertain whether they had relatives with SLE and/or other autoimmune diseases. Identified relatives were studied. Familial aggregation was tested using reported highest and intermediate population prevalence data for SLE, rheumatoid arthritis (RA), or all autoimmune diseases, and studies were performed to identify the genetic model applicable for SLE.We identified 116 first-, second-, or third-degree relatives with SLE, 79 with RA, 23 with autoimmune thyroiditis, 3 with scleroderma, 1 with polymyositis, and 16 with other autoimmune diseases, related to 166 of the 1,177 SLE patients in the GLADEL cohort who agreed to participate. Forty-two SLE patients had 2 or more relatives with an autoimmune disease. We found a lambda(sibling) of 5.8 and 29.0 for SLE and of 3.2-5.3 for RA, when comparing with their reported high or intermediate population prevalence, respectively. We also found familial aggregation for autoimmune disease in general (lambda(sibling) = 1.5) and determined that for SLE, a polygenic additive genetic model, rather than a multiplicative one, is applicable.In SLE there is familial aggregation of SLE, RA, and autoimmune disease in general. A polygenic additive model applies for SLE. American Indian-white Mestizo SLE patients and those with higher socioeconomic level were more likely to have familial autoimmunity.

The aim of this study was to determine the frequency and potential relevance of the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha) in the severity of rheumatoid arthritis (RA) in Mexicans. HLA-DR and polymorphisms at positions -238 and -308 of TNF-alpha gene were determined in 137 Mexican RA patients (44 with severe and 93 with non-severe RA) as well as in 169 healthy controls (99 were typed for HLA-DR). We observed an increased frequency of HLA-DR4 in severe RA compared to healthy controls (pC=0.02, OR=2.33). TNF polymorphism analysis showed a significant increased frequency of TNF -238 GG genotype in the whole group of RA patients when compared to healthy controls (pC=0.007, OR=4.71). When the analyses were carried out separately in severe and non-severe RA patients, the increased frequency of -238 GG genotype only was observed in patients with non-severe forms of the disease. Analysis of -308 polymorphism showed increased frequency of -308 T2 (A) allele in severe RA when compared to non-severe disease (pC=0.011, OR=3.29) and to healthy controls (pC=0.002, OR=3.97). The data demonstrate that -308 T2 (A) allele is associated with susceptibility to develop severe RA in Mexicans. This association could be independent from HLA-DR alleles and might be used as a prognostic marker for severe RA.

To evaluate the role of LMP (low molecular weight protein) genes as susceptibility markers for spondyloarthritis (SpA), LMP gene polymorphisms were analyzed in 223 Mexican patients with SpA (81 undifferentiated SpA [U-SpA], 117 with ankylosing spondylitis [AS], 25 with reactive arthritis) and in 139 ethnically matched healthy individuals. LMP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The LMP2 and LMP7 allele frequencies were similar in patients and healthy controls. Genotype analysis revealed an increased frequency of LMP2 R/R genotype in the whole group of SpA (pC = 0.003, OR = 2.06, 95%CI = 1.3-3.25) and in the clinical subgroups of AS (pC = 0.039, OR = 1.88, 95%CI = 1.1-3.22) and U-SpA (pC = 0.003, OR = 2.56, 95%CI = 1.37-4.8) compared with healthy controls. Analysis in the LMP7 did not reveal significant differences in patients and healthy controls. The HLA-B27-negative AS subgroup also showed an increased frequency of LMP2 R/R genotype (pC = 0.027, OR = 4.81, 95%CI = 1.21-22.13). The LMP2-R/R AS patients were younger than LMP2-H/R and H/H patients at onset of the disease (16.0 +/- 6.8 years for R/R, 22.0 +/- 11.2 years for H/R and 28.6 +/- 10.9 years for H/H) (p0.05). The data suggest that, besides HLA-B27, LMP2 genotypes are also involved in the genetic susceptibility to develop AS in Mexicans. Furthermore, the age at onset of this disease might also be influenced by genotypes of this gene.

Antimalarials are very useful drugs in the treatment of various rheumatic diseases. One of their main side effects is ocular toxicity, specifically retinopathy. Our objective was to identify risk factors associated with chloroquine retinopathy. A single, trained evaluator reviewed patient records with rheumatic diseases. They were taking chloroquine and identified by the ophthalmology department as having retinopathy during their routine eye evaluation. These cases were classified according to clinical evaluation, visual fields and fluorangiographic study. Up to four controls were selected for each case, matched by age, gender, diagnosis and similar time on chloroquine. In all, 34 variables were studied, among these: weight, age, disease duration, keratopathy, total cumulative dose (TCD), mean daily dose (MDD), lean body weight adjusted daily dose (LBWDD) and laboratory tests. Descriptive and inferential statistics comparing cases and controls in all patients and subgroup analysis were carried out. Significance was set at the 0.05 level. Odds ratio and 95% confidence intervals were calculated. Sixteen cases of chloroquine retinopathy were identified, eight patients with rheumatoid arthritis (RA), seven with systemic lupus erythematosus (SLE) and one with dermatomyositis. All were female. Mean age was 47.3 +/- 12.2 years; weight 59.5 +/- 10.7 kg; disease duration 12.8 +/- 6.0 years; time on chloroquine 54.1 +/- 27.8 (min-max: 30-197) months. There was a significant difference in the following variables in all patients: MDD 212.3 +/- 52.6 versus 170 +/- 51.3, p = 0.009; and LBWDD 5 +/- 1 versus 4.2 +/- 1.5, p = 0.03, for cases and controls, respectively. In subgroup analysis the MDD remained significantly different (235.5 +/- 45.8 versus 169.7 +/- 46.1, p = 0.004) only in RA, whereas LBWDD was different both in SLE and RA. Keratopathy increased the risk for retinopathy: OR, 95% CI: 5, 1.4-17.6, p = 0.01. In conclusion, in accordance with previous studies, the MDD, LBWDD and keratopathy were risk factors associated with chloroquine retinopathy. Periodic ophthalmologic evaluations are mandatory.

Clinical and laboratory manifestations and outcome of systemic lupus erythematosus (SLE) may vary in different populations. A prospective multinational inception cohort should prove useful in identifying the influence of ethnicity on the clinical characteristics of SLE. We therefore analyzed clinical, laboratory, and prognostic variables in Latin American SLE patients with disease of recent onset who were entered into a prospective cohort, and compared these variables in the cohort's 3 major ethnic groups. Thirty-four centers from 9 Latin American countries participated by randomly incorporating SLE patients within 2 years of diagnosis into a standardized database. Participating centers were selected for their expertise in diagnosing and managing SLE. We were then able to evaluate prospectively socioeconomic variables, ethnicity, type of medical care, clinical and laboratory features, disease activity, damage, and mortality at each site. A coordinating center controlled the quality of the information submitted. Of the 1,214 SLE patients included in the cohort, 537 were mestizos, 507 were white, and 152 were African-Latin American (ALA). (There were also small numbers of pure Amerindian and oriental individuals.) Significant differences were found between them in socioeconomic characteristics, type of care, and level of education favoring whites. Mestizos and ALA were younger at onset. Delay to diagnosis and disease duration was shorter in ALA. Fever was more frequent in whites; discoid lesions in ALA; renal disease and lymphopenia in mestizos and ALA. Although we found differences in background variables between ethnic groups from different countries, mestizos from 2 distant countries (Argentina and Mexico) were clinically akin and showed similar differences to whites. Mortality was associated with lower education, poor medical coverage, and shorter follow-up. In an exploratory model nonwhite ethnicity was associated with renal disease and lymphopenia, damage, and cumulative American College of Rheumatology criteria. These differences in clinical, prognostic, socioeconomic, educational, and access to medical care features in Latin American lupus patients of 3 major ethnic groups from 9 different countries may have an impact on the patients' disease. "Hispanics," as they have come to be generically termed on the basis of language, actually constitute a markedly heterogeneous group of subjects.

In a 76-week, randomized controlled trial, patients received 100 mg LJP 394 or placebo weekly for 16 weeks followed by three 12-week treatment cycles of 50 mg LJP 394 or placebo weekly each separated by eight-week periods when no therapy was administered. Health-related quality of life (HRQOL) was assessed using SF-36 at baseline, 16 weeks and every 12 weeks thereafter. Analyses populations included intent to treat (ITT) (n = 179) and patients with high-affinity anti-dsDNA antibody binding (HA): 157/179; 85% active, 90% placebo. In the ITT population, there were improvements in role emotional (RE) (+7.3 versus -8.2), social functioning (SF) (+4.3 versus +0.7), and role physical (RP) (+11.3 versus +6.0) domains in the active treatment group when compared with placebo, with similar changes observed in the HA population. In 37 patients with data pre- and post-renal flares, those receiving LJP 394 reported stabilization or improvement in all but one domain compared with deterioration in all domains with placebo. Changes in RE domain scores following a flare differed by 22.7 points between the two treatment groups, favouring LJP 394 treatment. Patients receiving LJP 394 reported stable or improved HRQOL with active treatment following renal flares compared with deterioration in placebo. Differences between treatment groups in RE and SF domains are clinically important and were replicated irrespective of the protocol population analysed.

To determine whether LJP 394 delays or prevents renal flare in patients with systemic lupus erythematosus (SLE) and a history of renal disease.In a 76-week, double-blind, placebo-controlled study, 230 SLE patients were randomized to receive 16 weekly doses of 100 mg of LJP 394 or placebo, followed by alternating 8-week drug holidays and 12 weekly doses of 50 mg of LJP 394 or placebo. An assay measuring the affinity of the serum IgG fraction for the DNA epitope of LJP 394 identified a high-affinity population of patients (189 of 213 patients; 89% taking LJP 394 and 90% taking placebo). Analyses were performed on both the intent-to-treat population and the high-affinity population.Anti-double-stranded DNA antibodies decreased and C3 levels tended to increase during treatment with LJP 394. In the intent-to-treat population, the time to renal flare was not significantly different between treatment groups, but patients taking LJP 394 had a longer time to institution of high-dose corticosteroids and/or cyclophosphamide (HDCC) and required 41% fewer treatments with HDCC. In the high-affinity population, the LJP 394 group experienced a longer time to renal flare, 67% fewer renal flares, longer time to institution of HDCC, and 62% fewer HDCC treatments compared with the placebo group. In patients with serum creatinine levels/=1.5 mg/dl at study entry, those taking LJP 394 had 50% fewer renal flares; no renal flares were observed in the high-affinity group taking LJP 394. Serious adverse events were observed in 25 of the 114 LJP 394-treated patients (21.9%) and 34 of the 116 placebo-treated patients (29.3%).Treatment with LJP 394 in patients with high-affinity antibodies to its DNA epitope prolonged the time to renal flare, decreased the number of renal flares, and required fewer HDCC treatments compared with placebo. The study drug appeared to be well tolerated.

Secondary osteoporosis is a frequently underestimated bone disorder. It is a secondary cause of bone loss that affects more than half of men and premenopausal and perimenopausal women, and about one-fifth of postmenopausal women. We herein report an uncommon case of multiple fractures due to secondary osteoporosis caused by Cushing's disease. In this case the appearance of fractures in a 41 years old woman was the sign of alarm that ultimately led us to the diagnosis.

a b s t r a c t Secondary osteoporosis is a frequently underestimated bone disorder. It is a secondary cause of bone loss that affects more than half of men and premenopausal and perimenopausal women, and about one-fitfth of postmenopausal women. We herein report an uncommon case of multiple fractures due to secondary osteoporosis caused by Cushing's disease. In this case the appearance of fractures in a 41 years old woman was the sign of alarm that ultimately lead us to the diagnosis.

To determine the agreement of scores on the original visual analog scale (VAS) or Likert scale of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Dougados Functional Index (DFI) with scores on a numerical rating scale (NRS). To assess the reproducibility and responsiveness of the instruments with the original scale and NRS.Five hundred thirty-six patients with ankylosing spondylitis from the Netherlands, Mexico, and Switzerland completed a questionnaire in which all questions from the BASDAI, BASFI, and DFI were presented twice in random order with an 11-point NRS and either a 10-cm VAS (BASDAI and BASFI) or a 5-point Likert scale (DFI). Agreement of scores using Bland-Altman plots and intraclass correlation coefficients (ICCs), reproducibility using ICCs, and responsiveness were assessed.Large variability between the scores on the original scales and the NRS was found in individual questions of all 3 questionnaires, although total scores showed ICCs of at least 0.88. Reproducibility of all answer modalities showed low ICCs in individual questions, but moderate to good ICCs in total scores (Dutch group 0.62-0.89; Mexican group 0.53-0.72). Moderate to large effects (0.48-1.04) were found in responsiveness scores in the 3 questionnaires. No major differences in reproducibility and responsiveness between the answer modalities were found.Although large variability between the scores on the original answer scales and the NRS was observed, the BASDAI, BASFI, and DFI can be administered with an NRS, which does not show important differences compared with the original scales.

Objective: To develop and test an index to evaluate the radiographic changes that occur in the tarsus and adjacent areas of the foot in patients with spondyloarthropathies (SpA). Methods: The spondyloarthropathy tarsal radiographic index (SpA-TRI) was developed in three consecutive steps: (a) detection of descriptors after reviewing 70 radiographic files; (b) descriptor gradation and subsequent modifications performed by a consensus committee, and (c) interobserver variability assessed by three blinded and independent observers on 272 radiographs: anteroposterior 118, lateral 90, oblique 64 from 121 patients with SpA, and intraobserver variability on 75 radiographs from 25 patients with SpA. Statistical analysis included percentage of agreement and κ test. SpA-TRI score ranges from 0 to 4 (0=normal; 1=osteopenia or suspicious findings; 2=definite joint space narrowing, bony erosion(s), periosteal whiskering, or enthesophyte(s) in the plantar fascia or Achilleal tendon attachments; 3=para-articular enthesophyte(s); 4=bony ankylosis (joint space fusion or complete bridging)). Results: Complete agreement for every evaluation was >40%, and discordance >1 grade was

Lasenfermedades reumaticas constituyenunacausa importante demorbilidad en la poblacion general. Sonmas de doscientos padecimientos que producen grados variables de dolor, discapacidad y deformidad. En general, estas enfermedades no aumentan la mortalidad a corto plazo y por ello no se toman en cuenta en las prioridades de salud y educacion. Sin embargo, se reconoce cada vez mas su influencia en el deterioro de la calidad de vida1. Latinoamerica presenta desde hace varios anos una transicion epidemiologica. No se han superado los problemas de salud, de educacion ni las necesidades sociales vinculadas a la pobreza y se debe enfrentar al mismo tiempo al reto de las patologias del desarrollo. Entre estas ultimas se incluyen las enfermedades cronico-degenerativas y de ellas son especialmente relevantes los padecimientos reumaticos. Este fenomeno impone desafios importantes en los sistemas de salud y frecuentemente los escasos recursos se emplean para resolver necesidades urgentes y se posterga la atencion de problemas emergentes. A ningun reumatologo le resultan ajenas las cifras contundentes que reflejan el impacto global de las enfermedades musculoesqueleticas. Se calcula que aproximadamente el 10% de la poblacion general padece alguna enfermedad reumatica. Estas enfermedades ocupan uno de los primeros diez motivos de invalidez total en paises como Estados Unidos, Canada y Mexico. En el Instituto Mexicano del Seguro Social, la tasa de invalidez se ha calculado en 1,38 por cada 1.000 derechohabientes. Existen problemas metodologicos para medir el impacto global de las enfermedades reumaticas. Se cuenta solamente con informacion fragmentada sobre otros aspectos igualmente importantes, tales como la repercusion en la calidad de vida (el dolor, el sufrimiento, la deformidadprogresiva y la incapacidadpara llevar a cabo actividades de la vida diaria). Tambien es importante medir otras variables como el aislamiento social, la perdida de oportunidades para el trabajo, la promocion laboral o la educacion, la dependencia economica y los cambios indeseables en proyectos de vida. No deben olvidarse tampoco las consecuencias para la familia y los cuidadores. Por lo anterior, se debe enfatizar que el estudio de las

Rheumatic diseases constitute a group of more than 200 clinical conditions affecting the musculoskeletal system and in most cases a number of other organs and systems. As a group, rheumatic diseases are highly prevalent in most populations of the world and their consequences span from joint pain and swelling to severe musculoskeletal and multisystemic diseases, leading to poor function, impaired health, and reduced survival. Epidemiologic studies describing the frequency, distribution, and determinants of diseases in human population are the initial strategies for disease control1. Despite the fact that the rheumatic diseases impose an important burden of illness in developed countries, little is known about the prevalence and impact of this group of diseases in developing countries. Not surprisingly, the rheumatic diseases are frequently unrecognized by health authorities and are not usually included in healthcare programs2. Consequently, …