Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort.

AIM: The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. RESULTS: Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20-37) years and 47.8 (17.9-68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48-0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69-10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35-16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10-2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01-1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11-1.34; p < 0.0001) were predictive factors of serious infections. CONCLUSIONS: Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.

Factors Associated with Health-Related Quality of Life in Mexican Lupus Patients Using the LupusQol.

INTRODUCTION: Health-related quality of life (HRQOL) is affected by numerous clinical variables, including disease activity, damage, fibromyalgia, depression and anxiety. However, these associations have not yet been described in Mexican patients with systemic lupus erythematosus (SLE). OBJECTIVE: To evaluate the relationship between disease activity, damage, depression and fibromyalgia and HRQOL measured by the LupusQoL-instrument in Mexican patients with SLE. METHODS: A cross-sectional study was conducted in women fulfilling the 1997 ACR classification criteria for SLE. HRQOL was evaluated using a disease-specific instrument for SLE, the LupusQoL (validated for the Spanish-speaking population). Patients were evaluated clinically to determine the degree of disease activity and damage using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and Systemic Lupus International Collaborating Clinics-Damage Index (SLICC), respectively. Fibromyalgia and depression were assessed using the ACR criteria and the CES-D scale, respectively. The relationship between HRQOL and these variables was measured using Spearman's rank correlation coefficient and linear regression analysis. RESULTS: A total of 138 women with SLE, age 40.3±11 years, disease duration 8.8±6.4 years, with disease activity in 51.4%, depression in 50%, damage in 43% and fibromyalgia in 19.6% were included. Poorer HRQOL correlated with depression (r = -0.61; p< 0.005), fibromyalgia (r = -0.42; p< 0.005), disease activity (r = -0.37; p < 0.005) and damage (r = -0.31; p < 0.005). In the multivariate linear regression analysis, damage (ß = -3.756, p<0.005), fibromyalgia (ß = -0.920, p<0.005), depression (ß = -0.911, p<0.005) and disease activity (ß = -0.911, p<0.005) were associated with poor HRQOL. CONCLUSION: SLE disease activity, damage, fibromyalgia and depression were associated with poor HRQOL in our sample of Mexican SLE patients.

Early discoid lupus erythematosus protects against renal disease in patients with systemic lupus erythematosus: longitudinal data from a large Latin American cohort.

OBJECTIVES: The objective of this study was to examine whether early discoid lupus erythematosus (DLE) would be a protective factor for further lupus nephritis in patients with systemic lupus erythematosus (SLE). METHODS: We studied SLE patients from GLADEL, an inception longitudinal cohort from nine Latin American countries. The main predictor was DLE onset, which was defined as physician-documented DLE at SLE diagnosis. The outcome was time from the diagnosis of SLE to new lupus nephritis. Univariate and multivariate survival analyses were conducted to examine the association of DLE onset with time to lupus nephritis. RESULTS: Among 845 GLADEL patients, 204 (24.1%) developed lupus nephritis after SLE diagnosis. Of them, 10 (4.9%) had DLE onset, compared to 83 (12.9%) in the group of 641 patients that remained free of lupus nephritis (hazard ratio 0.39; P = 0.0033). The cumulative proportion of lupus nephritis at 1 and 5 years since SLE diagnosis was 6% and 14%, respectively, in the DLE onset group, compared to 14% and 29% in those without DLE (P = 0.0023). DLE onset was independently associated with a lower risk of lupus nephritis, after controlling for sociodemographic factors and disease severity at diagnosis (hazard ratio 0.38; 95% confidence interval 0.20-0.71). CONCLUSIONS: Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.

Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: Phase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05). RESULTS: We identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15-161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)). CONCLUSIONS: Within the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.

Burden of illness of rheumatoid arthritis in Latin America: a regional perspective.

Rheumatoid arthritis (RA) is one of the most important rheumatic diseases. Its prevalence varies among ethnic groups. Genetic and environmental factors influence its incidence and prevalence. This chronic disease will increase its frequency in the future due to population aging. The personal impact of this disease on many relevant areas of an individual requires special efforts to prevent and treat it properly. Adequate advice on several recently described risk factors such as tobacco and alcohol exposure, infections, obesity, and physical exercise should be part of every medical consultation. This knowledge should be incorporated to improve health care prevention programs. Patients and clinicians must work together through better communication skills to finally improve outcomes. Including RA in priority health care lists will need special effort from rheumatology societies and better communication with policy makers.

Lupus in Latin-American patients: lessons from the GLADEL cohort.

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 G: rupo L: atino A: mericano D: e E: studio del L: upus (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.

Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: data from a Latin American cohort.

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.

Health related quality of life in Mexican women with systemic lupus erythematosus: a descriptive study using SF-36 and LupusQoL(C).

The LupusQoL© questionnaire is a disease-specific health related quality of life (HRQOL) instrument for adults with systemic lupus erythematosus (SLE). The Short Form-36 (SF-36) is a generic instrument that captures the physical, psychological, and social impact. We conducted a descriptive study of women aged ≥ 18 years attending our Lupus Clinic. HRQOL was assessed by applying the LupusQoL© and SF-36. Lupus activity was measured using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and chronic damage using the Systemic Lupus Collaborative Clinics Damage Index (SDI). Data were analyzed using descriptive statistics, the chi-square test and Pearson's product moment correlation coefficient. A total of 127 patients were included with a mean age of 40.5 ± 12.6 years. The mean disease duration was 8.2 ± 5.6 years, the mean disease activity score was 2.4 ± 3.0, and the mean SDI score 0.77 ± 1.06. The mean SF-36 score was 58.1 ± 21.1 and the mean LupusQoL© score was 69 ± 22.7. The correlation between global scores of the SF-36 and LupusQoL© was rho = 0.73 (p < 0.001). The correlation between lupus disease activity and the SF-36 and the LupusQoL© was -0.26 (p = 0.003) and -0.25 (p = 0.004), respectively. The correlation between the SDI and the SF-36 and the LupusQoL© was -0.28 (p = 0.001) and -0.38 (p < 0.0001), respectively. In conclusions: both LupusQoL© and SF-36 were useful instruments in assessing HRQOL in Mexican lupus female patients. The usefulness of the LupusQoL© should be evaluated in lupus patients with moderate to severe disease activity.

Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children.

To evaluate disease characteristics of childhood onset SLE in Latin America and to compare this information with an adult population in the same cohort of GLADEL. A protocol was designed as a multicenter, multinational, inception cohort of lupus patients to evaluate demographic, clinical, laboratory and serological variables, as well as classification criteria, disease activity, organ damage and mortality. Descriptive statistics, chi square, Fisher's exact test, Student's t test and multiple logistic regression were used to compare childhood and adult onset SLE. 230 patients were <18 years and 884 were adult SLE patients. Malar rash, fever, oral ulcers, thrombocytopenia and hemolytic anemia and some neurologic manifestations were more prevalent in children (p<0.05). On the other hand, myalgias, Sjögren's syndrome and cranial nerve involvement were more frequently seen in adults (p<0.05). Afro-Latin-American children had a higher prevalence of fever, thrombocytopenia and hemolytic anemia. White and mestizo children had a higher prevalence of malar rash. Mestizo children had a higher prevalence of cerebrovascular disease and cranial nerve involvement. Children met SLE ACR criteria earlier with higher mean values than adults (p: 0.001). They also had higher disease activity scores (p: 0.01), whereas adults had greater disease damage (p: 0.02). In Latin America, childhood onset SLE seems to be a more severe disease than adults. Some differences can be detected among ethnic groups.

Low grade radiographic sacroiliitis as prognostic factor in patients with undifferentiated spondyloarthritis fulfilling diagnostic criteria for ankylosing spondylitis throughout follow up.

OBJECTIVE: To determine the rate and factors associated with ankylosing spondylitis in a cohort of patients with undifferentiated spondyloarthritides (SpA). METHODS: 62 consecutive patients with undifferentiated SpA seen between 1998 and 1999 underwent clinical and imaging evaluations throughout follow up. The main outcome measure was a diagnosis of ankylosing spondylitis. RESULTS: 50 patients with peripheral arthritis (n = 35) and inflammatory back pain (n = 24) (26 male; mean (SD) age at onset, 20.4 (8.8) years; disease duration 5.4 (5.7) years) were followed up for 3-5 years. At baseline, >90% of patients had axial and peripheral disease, while 38% had radiographic sacroiliitis below the cut off level for a diagnosis of ankylosing spondylitis (BASDAI 3.9, BASFI 2.9). At the most recent evaluation, 21 patients (42%) had ankylosing spondylitis. Two factors were associated with a diagnosis of ankylosing spondylitis in multivariate analysis: radiographic sacroiliitis grade <2 bilateral, or grade <3 unilateral (odds ratio (OR) = 11.18 (95% confidence interval, 2.59 to 48.16), p = 0.001), particularly grade 1 bilateral (OR = 12.58 (1.33 to 119.09), p = 0.027), and previous uveitis (OR = 19.25 (1.72 to 214.39), p = 0.001). Acute phase reactant levels, juvenile onset, and HLA-B27 showed a trend to linkage with ankylosing spondylitis (NS). CONCLUSIONS: Low grade radiographic sacroiliitis is a prognostic factor for ankylosing spondylitis in patients originally classified as having undifferentiated SpA. Low grade radiographic sacroiliitis should be regarded as indicative of early ankylosing spondylitis in patients with undifferentiated SpA.

Prevalence and factors associated with headache in patients with systemic lupus erythematosus.

Headache is common in systemic lupus erythematosus with reported prevalence as high as 70%. The aims of this study were: to estimate the prevalence and types of headache in a sample of patients with systemic lupus erythematosus comparing it with rheumatoid arthritis, to determine clinical and serological associations. Eighty-one systemic lupus erythematosus and 29 rheumatoid arthritis consecutive patients seen in our outpatient clinic were interviewed. Headache was evaluated using the diagnostic criteria proposed by the International Headache Society. Additional evaluations were carried out in the 81 systemic lupus erythematosus patients including depression, disease activity, lupus damage, function disability, quality of life, and severity degree using a validated scales. We analysed the following autoantibodies: anti-double stranded DNA, anti-nucleosomes, anti-histones, anti-ribosomal P, anti-cardiolipin antibodies, anti-beta2-glycoprotein-I (GPI), and antinuclear antibodies. Forty-one per cent of systemic lupus erythematosus and 17% of rheumatoid arthritis patients suffered from headache (P = 0.02). No significant difference for any primary headache type between the two groups was found. Frequency of headache types in systemic lupus erythematosus patients was: migraine 24%, tensional-type headache 11%, and mixed headache 5%. In systemic lupus erythematosus patients the risk factors associated with headaches were Raynaud's phenomenon (OR 3.6; 95% CI 1.3-9.5; P = 0.009) and beta2GPI antibody positivity (OR 4.5; 95% CI 1.2-16.2; p = 0.016). We conclude that headache is more common in systemic lupus erythematosus than in rheumatoid arthritis patients and was independently associated with Raynaud's phenomenon and beta2GP-I antibodies.

HLA-DRB1 alleles encoding the "shared epitope" are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the beta-chain are protective in Mexican Mestizos.

The risk to develop rheumatoid arthritis (RA) has been associated with the presence of HLA-DRB1 alleles encoding the "shared epitope" (SE). Additionally, HLA-DRB1 alleles encoding an aspartic acid at position 70 (D70+ ) have been associated with protection against the development of RA. In this study we tested the association between either SE or D70+ and rheumatoid arthritis in Mexican Mestizos. We included 84 unrelated Mexican Mestizos patients with RA and 99 unrelated healthy controls. The HLA-typing was performed by PCR-SSO and PCR-SSP. We used the chi-squared test to detect differences in proportions of individuals carrying at least one SE or D70+ between patients and controls. We found that the proportion of individuals carrying at least one HLA-DRB1 allele encoding the SE was significantly increased in RA cases as compared to controls (p(c) = 0.0004, OR = 4.1, 95% CI = 2.2-7.7). The most frequently occurring allele was HLA-DRB1*0404 (0.161 vs 0.045). Moreover, we observed a significantly increased proportion of HLA-DRB1 SE+ cases with RF titers above the median (p = 0.005). Conversely, the proportion of individuals carrying at least one HLA-DRB1 allele encoding the D70+ was significantly decreased (p(c) = 0.004, OR = 0.4, 95% CI 0.2-0.7) among RA patients compared with controls. In conclusion, the SE is associated with RA in Mexican Mestizos as well as with the highest titers of RF.

Factors associated with chloroquine-induced retinopathy in rheumatic diseases.

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.

Prevalence and factors associated with fibromyalgia in Mexican patients with systemic lupus erythematosus.

In total, 189 consecutive women diagnosed with SLE were evaluated using the ACR 1990 criteria for fibromyalgia. Patients were classified into three subgroups. The fibromyalgia group (FM) included patients experiencing pain on palpation in at least 11 of the 18 tender points examined, as well as having a history of widespread pain for at least three months. Patients who were noted to have pain in fewer than four quadrants with less than 11 of 18 tender points were considered to have regional pain (RP). All patients who did not meet criteria for either FM or RP were classified as having no pain (NP). Measurement of SLE disease activity, sleep complaints, depression, fatigue severity and health status were performed. Only 18 of the SLE patients (9.5%) (95% CI 5.3-14%) fulfilled the ACR criteria for the classification of FM. Of the patients, 106 (56.1%) fulfilled criteria for RP and had a number of tender points of 5.4 +/- 3.4, and the rest of the patients (34.4%) had no tenderness at specific tender point sites. Age, body mass index, educational level and disease duration were comparable between the groups. FM and RP groups had different patterns of symptoms prevalence, with dysmenorrhea being more distinctive for FM. Sleep disturbances were more severe in the FM than in the RP group. Daytime complaints such as sleepiness, fatigue and depression were similar for RP and FM groups, but patients with FM reported more disability. Fibromyalgia is not common in Mexican patients with SLE and has a different pattern of symptoms in RP and NP patients. These data add evidence that ethnicity can play an important role in FM manifestations.

Improvement in health-related quality of life in systemic lupus erythematosus patients enrolled in a randomized clinical trial comparing LJP 394 treatment with placebo.

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.

Translation, cross-cultural adaptation, and validation of the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Dougados Functional Index (DFI) in a Spanish speaking population with spondyloarthropathies.

OBJECTIVES: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI) are the most commonly used instruments to measure disease activity and functioning in ankylosing spondylitis (AS). The aim of this study was to translate, adapt and validate these instruments into the Spanish language. METHODS: The BASDAI, BASFI, and DFI questionnaires were translated into Spanish by three independent bilingual physicians who were familiar with the medical aspects of AS and by one professional translator. Two rheumatologists familiar with instrument validation, and who were aware of the purpose of the study, examined semantic, idiomatic and conceptual issues and produced by consensus unified versions of each instrument. English back-translations from the Spanish were done by a professional translator unaware of the original version. Both English versions were compared, and where needed, modifications to the Spanish versions were made. The Spanish versions were administered to 61 ambulatory patients with AS and to 80 patients with undifferentiated spondyloarthropathy for validation purposes. Reliability and responsiveness were measured in 28 patients participating in a physiotherapy program. RESULTS: Reliability showed an acceptable 24-hour test-retest intraclass correlation coefficient (ICC)--BASFI ICC: 0.68, 95% CI: 0.29-0.85; BASDAI ICC: 0.74, 95% CI: 0.52-0.88 and DFI ICC: 0.87, 95% CI: 0.73-0.94. The construct validity of the instruments was evaluated, and BASDAI was correlated with disease activity measured by the total enthesis count (rs: 0.34); general well being in the last week (rs: 0.7); spinal pain (rs: 0.53) and duration of morning stiffness (rs: 0.64). BASFI correlated with Schöber's test (rs: -0.4); occipital-wall distance (rs: 0.38) and thoracic expansion (rs: -0.3). DFI correlated with Schöber's test (rs: -0.36); occipital-wall distance (rs: 0.29) and chest expansion (rs: -0.3). The correlation among DFI and BASFI was rs: 0.83. All instruments showed clinical responsiveness in the physiotherapy program (baseline and end of program; mean +/- SD): BASDAI: 6.25 +/- 1.97 and 3.07 +/- 2.04 (p = 0.0001); BASFI: 5.68 +/- 2.29 and 2.88 +/- 1.77 (p = 0.0001); DFI: 16 +/- 7.6 and 8.0 +/- 5.5 (p = 0.001) with effect sizes and standardized effect sizes > 1. CONCLUSIONS: The Mexican Spanish versions of the BASDAI, BASFI, and DFI showed adequate reliability, validity and responsiveness to clinical change. These instruments can be used in the clinical evaluation of Spanish-speaking patients with AS.

Biological relevance of the polymorphism in the CCR5 gene in refractory and non-refractory rheumatoid arthritis in Mexicans.

OBJECTIVE: The aim of this study was to analyze the frequencies of the CCR5 delta 32 deletion and HLA class II alleles in Mexican Amerindian populations and its relevance in the development and severity of RA. METHODS: We studied 212 Mexican Mestizo subjects (40 patients with refractory RA, 102 patients with non-refractory RA and 70 healthy individuals). At the same time, to evaluate the ethnicity of the CCR5 delta 32 deletion we also studied 192 individuals from three Mexican Amerindian populations (70 Mayo (Capomo) individuals, 61 Teenek individuals, and 61 Mazatecan Indians). The delta 32 deletion in the CCR5 structural gene and HLA-DRB1 were determined by a PCR-SSP and a PCR-SSO procedure, respectively. RESULTS: In the non-refractory RA group the CCR5 delta 32 gene frequency was 0.019 and the following genotype frequencies were observed: CCR5/CCR5 = 98.0%, CCR5/CCR5 delta 32 = 1.9% and CCR5 delta 32/CCR5 delta = 1.0%. In the refractory RA group the CCR5 delta 32 gene frequency was 0.025 and the genotype distribution was similar to that in the non-refractory RA group. The deletion was not detected in the Mexican Mestizo healthy group, or among the Teenek and Mayo Amerindians, all being individuals homozygous for the wild type allele. In the Mazatecan group the deletion frequency was 1.6% (g.f. = 0.016). We observed a significant increase in the frequency of the DRB1*07 allele in severe RA patients in relation to the non-severe RA group (p = 0.02, OR = 5.65, 95% CI = 0.95-43.05). CONCLUSION: Our results suggest that the CCR5 delta 32 deletion is not common in Mexican Amerindian populations and this study does not support an important role of CCR5 delta 32 in the pathogenesis of RA or a severe form of the disease in Mexicans.

Community based study to estimate prevalence, burden of illness and help seeking behavior in rheumatic diseases in Mexico City. A COPCORD study.

OBJECTIVE: To estimate the prevalence, burden of illness and help seeking behavior of musculoskeletal complaints and provide point prevalence estimates of osteoarthritis, low back pain, fibromyalgia, rheumatoid arthritis and gout among adult population in a suburban community in Mexico city. METHODS: Home survey of adults in a balanced and stratified sample validated against physical exam. Three trained interviewers applied a validated COPCORD core questionnaire. Subjects with pain (in the last seven days or ever) > or = 4 (0-10) and no trauma; or with current or past disability were evaluated preferably the same day by a trained clinician in a structured interview. A diagnosis using ACR criteria when available, recommendation or referral was provided as required. Analysis was based on descriptive statistics of participant characteristics, pain site and distribution, patterns of help seeking behavior. Point prevalence with 95% confidence intervals of most common diseases and associated disability rate. RESULTS: 1169 men and 1331 women were included. Pain in the last 7 days not associated with trauma was reported in 419 (17%) participants. The most common sites of involvement were knee (12.3%); low back (6.3%); ankles (6%) and shoulders (5.3%). The mean/SD pain score was 4.8/2.5. Thirteen percent of the total sample had some treatment. The general practitioner treated 72% of those; 75% perceived good efficacy with medications. Point prevalence estimates and 95% CI were: disability: 1.4% (0.0-1.9); osteoarthritis: 2.3% (1.7-2.9); fibromyalgia: 1.4 (1.0-2.0); low back pain: 6.3% (5.4-7.3); rheumatoid arthritis: 0.3% (0.1-0.6) and gout 0.4% (0.1-0.7). CONCLUSION: Pain in the last 7 days due to musculoskeletal disorders is 17% in this community. Medications were commonly prescribed. Point prevalence estimates of most common diagnoses was similar to other community surveys using COPCORD methodology but very different help seeking behavior.

Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients.

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 chi(2) 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.