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.

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

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.

Long-term persistence of anti-ß2 glycoprotein I in treated leprosy patients.

ß2 glycoprotein I (ß2GPI) is a phospholipid binding protein that plays an important role in endothelial stability, blood coagulation, clearance of apoptotic debris and other physiologic processes. Anti-ß2GPI antibodies occur in normal individuals and transiently during the course of infections, but are also associated with thrombotic events in autoimmune disease: the antiphospholipid syndrome (APS). A total of 31 out of 37 treated leprosy patients previously found to present high titers of IgM anti-ß2GPI and/or anticardiolipin antibodies (aCL) remained positive for IgM antiphospholipid antibodies (aPL), and exhibited high titers of anti-ß2GPI. The 37 patients were part of the 77 aPL-positive patients from a previous study that evaluated 158 leprosy patients. The median time elapsed between the first and second sample was 66 months. None of the 37 patients had any thrombotic event and 24 had a reactional state and were still requiring the use of prednisone, thalidomide or both. None of them fulfilled World Health Organization criteria for leprosy recurrence.

The effect of acute physical exercise on cytokine levels in patients with systemic lupus erythematosus.

BACKGROUND: Acute exercise increases IL-6, IL-10 and TNF-α levels in healthy subjects. There is no study evaluating the effect of exercise on cytokines level in systemic lupus erythematosus (SLE) patients. OBJECTIVE: Our aim was to assess IL-10, IL-6 and TNF-α levels at baseline and after acute physical exercise in patients with SLE. METHODS: In total, 27 female SLE patients and 30 healthy controls were evaluated. Serum levels of IL-10, IL-6 and TNF-α at baseline and soon after the ergospirometric test were measured by ELISA test. Student's t-tests and Mann-Whitney test were used for intra- and inter-group comparisons; p values <0.05 were considered significant. RESULTS: Patients with SLE presented worse ergospirometric parameters compared with controls: VO2max (25.78 ± 5.51 vs. 32.74 ± 5.85 ml/kg/min, p < 0.001); maximum heart rate (174.18 ± 12.36 vs. 185.15 ± 2.07 bpm, p = 0.001); maximum ventilation (65.51 ± 15.68 vs. 80.48 ± 18.98 l/min, p = 0.001) and maximum speed (7.70 ± 1.24 vs. 9.40 ± 1.22 km/h, p < 0.001). At baseline, SLE patients presented higher levels of IL-6 (2.38 ± 1.70 vs. 1.71 ± 0.29 pg/ml, p = 0.035) and IL-10 (1.09 ± 1.55 vs. 0.30 ± 0.11 pg/ml, p = 0.037) than controls. Acute exercise in controls increased IL-6 level (1.71 ± 0.29 vs. 2.01 ± 0.27 pg/ml, p = 0.003) without change in IL-10 and TNF-α levels. However, no significant change in cytokine levels was observed in SLE patients after acute exercise. CONCLUSION: This is the first study evaluating the effect of acute exercise on cytokine levels in patients with SLE. In contrast to healthy controls, acute physical exercise did not increase the levels of IL-6 in patients with SLE, and seems to be safe in those patients with inactive or mild active disease.

Short-term effect of leflunomide in patients with Takayasu arteritis: an observational study.

OBJECTIVES: To evaluate the efficacy of leflunomide in controlling disease activity in patients with Takayasu arteritis (TA) refractory or intolerant to conventional treatment. METHODS: We conducted a prospective open-label study of 15 TA patients (mean age 36.2 years) with active disease based on clinical assessment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and magnetic resonance angiography (MRA). Patients received leflunomide 20 mg/day for at least 6 months and were followed up for a mean of 9.1 months. Adverse events attributable to leflunomide were recorded. RESULTS: At baseline, 14 TA patients had active disease despite therapy with corticosteroids and immunosuppressive agents, while one patient had intolerance to current treatment. In the follow-up visit, we found a significant decrease in the frequency of patients with active TA (93% vs. 20%, p = 0.002), in the mean daily dose of prednisone (34.2 vs. 13.9 mg, p < 0.001) and in the median values of ESR (29.0 vs. 27.0 mm/h, p = 0.012) and CRP (10.3 vs. 5.3 mg/L, p = 0.012). Two patients (13.3%) developed new angiographic lesions in the follow-up MRA. Three patients (20%) experienced mild adverse events during the study and none discontinued therapy. CONCLUSIONS: This is the first open-label study to demonstrate improvement in disease activity and acute phase reactants with 20 mg/day of leflunomide in TA patients who were refractory or intolerant to conventional therapy with corticosteroids and immunosuppressive agents. Leflunomide was safe and a steroid-sparing effect was observed. A double-blind controlled study is desirable to confirm this finding.

Oral microbial colonization in patients with systemic lupus erythematous: correlation with treatment and disease activity.

Treating patients with systemic lupus erythematosus (SLE) with steroids and immunosuppressive drugs may interfere in the presence of potentially opportunistic microorganisms in the oral cavity. The aim of this study was to evaluate the presence of Candida spp., Staphylococcus spp., Enterobacteria and Pseudomonas spp. in the oral cavity of SLE patients, compared with healthy controls. A group of 40 patients who had received therapy for at least 60 days was selected (19-53 years). For the control group, 40 healthy individuals matched for age, gender and use of partial prosthesis were selected. Oral rinse samples were collected and plated on specific culture media. After incubation, the number of colony forming units (CFU) was obtained and the isolates were identified at species level. Microbial counts were compared between SLE and control by analysis of variance (ANOVA) and Mann-Whitney (p < 0.05 significant). Microorganism counts in patients with and without immunosuppressive drugs, as well with active and inactive disease (according to SLEDAI score) were also compared. No significant differences in CFU/mL between SLE and control patients were observed (yeasts, p = 0.55; Staphylococci, p = 0.24; Enterobacteria/Pseudomonas spp., p = 0.26). No differences in microbial counts were observed regarding clinical parameters tested. The most frequent species isolated in the SLE group were Candida albicans, Staphylococcus epidermidis and Klebsiella oxytoca. In conclusion, no differences in frequency and microorganism levels were found between SLE patients and healthy individuals.

Anti-ß2-glycoprotein I antibodies are highly prevalent in a large number of Brazilian leprosy patients.

OBJECTIVES: To determine the prevalence of anticardiolipin (aCL) and anti-ß2-glycoprotein I (anti-ß2GPI) antibodies in leprosy patients, during and after specific multidrug therapy (MDT), and to evaluate a possible association between these antibodies and some clinical characteristics of leprosy, including clinical forms, reactional episodes and treatment. METHODS: The study included 158 leprosy patients, 129 gender-and-age matched healthy individuals, and 38 women with primary antiphospholipid syndrome (APS). Clinical and demographic characteristic of leprosy patients were collected, and serum samples, obtained from all participants, were kept frozen at - 20°C. Antibodies were measured either by an in house-developed ELISA (aCL) or by a commercial ELISA (anti-ß2GPI). RESULTS AND CONCLUSIONS: Increased levels of aCL and anti-ß2GPI antibodies were found in leprosy patients and in the APS group, however, in contrast to APS, the predominant isotype in leprosy was IgM. The frequency of aCL and anti-ß2GPI antibodies was significantly higher in leprosy patients than in healthy individuals (15.8% vs. 3.1%; p>0.01; 46.2% vs. 9.4%, p>0.01), respectively. The lepromatous form predominated among aCL positive leprosy patients (p>0.01). There was no difference in aCL and anti-ß2GPI positivity between leprosy patients taking MDT and those completed MDT as cured. Furthermore the duration of discharged period (period between discharge from MDT and the realization of the study) had no effect on anti-ß2GPI positivity, and a slight increase in aCL positivity was observed in patients with longer follow up periods (p=0.04), suggesting that the presence of antiphospholipid antibodies (aPL) was not a transient phenomenon. Although aPL in leprosy were frequent and ß2GPI-dependent as those found in APS, IgM was the predominant isotype, and there was no association with thrombosis or other APS manifestations.

Trends in systemic lupus erythematosus mortality rates in the state of Sao Paulo, Brazil from 1985 to 2004.

OBJECTIVES: To estimate mortality rates and mortality trends from SLE in the state of São Paulo, Brazil. MATERIAL AND METHODS: The official data bank was used to study all deaths occurred from 1985 to 2004 in which SLE was mentioned as the underlying cause of death. Besides the overall mortality rate, the annual gender- and age-specific mortality rates were estimated for each calendar year by age bracket (0-19 years, 20-39 years, 40-59 years and over 60 years) and for the sub-periods 1985-1995 (first) and 1996-2004 (second), by decades. Chi-square test was used to compare the mortality rates between the two periods, as well the mortality rates according to educational level considering years of study. Pearson correlation coefficient test was used to analyse mortality trends. The crude rates were adjusted for age by the direct method, using the standard Brazilian population in 2000. RESULTS: A total of 2,601 deaths (90% female) attributed to SLE were analysed. The mean age at death was significantly higher in the second than in the first sub-period (36.6+/-15.6 years vs. 33.9+/-14.0 years; p<0.001). The overall adjusted mortality rate was 3.8 deaths/million habitants/year for the entire period and 3.4 deaths/million inhabitants/year for the first and 4.0 deaths/million inhabitants/year for the second sub-period (p<0.001). In each calendar year, the mortality rate was significantly lower for the better educated group. Throughout the period, there was a significant increase in mortality rates only among women over 40. CONCLUSIONS: SLE patients living in the state of São Paulo still die at younger ages than those living in developed countries. Our data do not support the theory that there was an improvement in the SLE mortality rate in the last 20 years in the state of Sao Paulo. Socio-economic factors, such as the difficulty to get medical care and adequate treatment, may be the main factors to explain the worst prognosis for our patients.

Atorvastatin therapy reduces interferon-regulated chemokine CXCL9 plasma levels in patients with systemic lupus erythematosus.

A recent study showed transcriptional levels of interferon-inducible chemokines in peripheral blood cells were associated with disease activity and organ damage in systemic lupus erythematosus, and may be useful in monitoring disease activity and prognosis. Our objective was to evaluate the capacity of atorvastatin to reduce plasma levels of interferon-regulated chemokines (CCL2, CCL3 and CXCL9) and to study the correlation between these chemokines and disease activity in patients with systemic lupus erythematosus. Eighty-eight female patients with systemic lupus erythematosus were divided into two groups: 64 receiving 20 mg/day of atorvastatin (intervention group) and 24 without atorvastatin (control group). All patients were followed for 8 weeks. At baseline and after 8 weeks laboratory tests were performed for all patients. Plasma levels of chemokines were measured by ELISA using commercial kits (DuoSet, R&D Systems, Minneapolis, USA). In a univariate analysis we found correlation between CCL2, CCL3 and CXCL9 plasma levels and SLEDAI score. In the intervention group we observed a significant decrease in CXCL9 plasma levels comparing baseline and levels at the end of the study (p = 0.04); however, no differences were observed regarding CCL2 or CCL3 plasma levels in this study. No significant difference was observed in the plasma levels of these chemokines in the control group. We conclude that treatment with atorvastatin was associated with a significant decrease in the plasma levels of CXCL9 in patients with systemic lupus erythematosus. As the plasma levels of CXCL9 correlated with the SLEDAI score, we ask whether reducing levels of this chemokine could help to control systemic lupus erythematosus activity.

Autoantibodies in leprosy patients, with and without joint involvement, in the state of Amazonas / Autoanticorpos em pacientes com hanseníase, com e sem comprometimento articular, no Estado do Amazonas

OBJETIVOS: Determinar a frequência do fator reumatoide (FR-IgM), anticorpos antipeptídeos citrulinados cíclicos (anti-CCP), antinucleares (AAN), anticitoplasma de neutrófilos (ANCA), anticardiolipina (aCL) e anti-β2 glicoproteína I (anti-β2GPI) em pacientes com hanseníase, com e sem comprometimento articular, avaliando a possível associação entre estes autoanticorpos e as manifestações articulares, a forma clínica, a reação hansênica, o tratamento com poliquimioterapia (PQT) e a alta. PACIENTES E MÉTODOS: 158 pacientes com hanseníase foram distribuídos em dois grupos; 73 pacientes com (Grupo I) e 82 sem comprometimento articular (Grupo II). Compuseram o Grupo III 129 indivíduos saudáveis. MÉTODOS: aglutinação com partículas de látex para FR-IgM, imunofluorescência indireta para AAN e ANCA, e, ELISA para anti-CCP, aCL e anti-β2GPI. RESULTADOS: Dentre 158 pacientes com hanseníase, 56 apresentavam a forma virchowiana (VV). A frequência de anticorpos anti-CCP, FR e AAN nos Grupos I e II foi semelhante à do Grupo III. ANCA não foi detectado em nenhum dos grupos. Anticorpos aCL foram mais frequentes nos pacientes com hanseníase (Grupos I e II) que em controles sadios (15,8 por cento vs. 3,1 por cento; P < 0,001), não sendo observada diferença entre Grupos I e II (P = 0,67). Anticorpos anti-β2GPI também foram mais frequentes nos pacientes que nos controles (46,2 por cento vs. 9,4; P < 0,001), sem diferença significativa entre os Grupos I e II. Houve predomínio do isotipo IgM com relação ao IgG tanto para aCL (88 por cento vs. 16 por cento, P = 0,001), quanto para anti-β2GPI (97,3 por cento vs. 12,3 por cento, P < 0,001). Nenhum paciente apresentou manifestações sugestivas de trombose vascular. CONCLUSÃO: A frequência de anticorpos aCL e anti-β2GPI foi significativamente maior nos pacientes com hanseníase que nos controles saudáveis. Entretanto, a positividade dos demais autoanticorpos foi semelhante à dos controles. Não foi observada associação entre autoanticorpos...

OBJECTIVE: Determine the frequency of rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein I antibodies (anti-β2GPI) in leprosy patients, with and without joint involvement, and to evaluate the possible association among those antibodies and articular manifestations, clinical type, reactional episodes, polychemotherapic treatment (PCT), and discharge from PCT. PATIENTS AND METHODS: One hundred and fifty-eight leprosy patients were divided in two groups of 73 patients (Group I) and 82 patients (Group II). Group III was composed of 129 healthy individuals. Methods: Semi-quantitative latex agglutination test for IgM-RF, indirect immunofluorescence for ANA and ANCA, and ELISA for anti-CCP, aCL, and anti-β2GPI. RESULTS: Fifty-six (35.4 percent) of 158 leprosy patients had lepromatous leprosy (LL). The frequency of anti-CCP, RF, and ANA antibodies in Groups I and II was similar to that of Group III. Antineutrophil cytoplasmic antibodies were not detected in any patient. Anticardiolipin antibodies were more frequent in leprosy patients (Groups I and II) than in control group (15.8 percent vs. 3.1 percent; P < 0.001), and differences between Groups I and II (P = 0.67) were not observed. Anti-β2GPI antibodies were also more common in leprosy patients than in control group (46.2 percent vs. 9.4 percent; P < 0.001), without differences between Groups I and II. A predominance of IgM isotype over IgG isotype was observed both for aCL (88 percent vs. 16 percent; P = 0.001) and anti-β2GPI (97.3 percent vs. 12.3 percent; P < 0.001). Patients did not present manifestations suggestive of vascular thrombosis. CONCLUSION: The frequency of aCL and anti-β2GPI antibodies was significantly increased in leprosy patients than in healthy individuals. However, positivity to other autoantibodies...

Vitamin D deficiency in patients with active systemic lupus erythematosus.

UNLABELLED: We investigated the effects of disease activity on bone metabolism in 36 patients with systemic lupus erythematosus (SLE). Changes in bone remodeling were not explained by corticosteroid use. A high prevalence of 25OHD deficiency in SLE patients indicates the need for vitamin D replacement, mainly during high disease activity periods. INTRODUCTION: We investigated the effects of SLE disease activity on bone metabolism, their relation to inflammatory cytokines and vitamin D levels. METHODS: We performed a cross-sectional analysis of 36 SLE patients classified according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in high activity (group I: 12 patients, mean age 29.6 years) or in minimal activity (group II: 24 patients, mean age 30.0 years), and compared them to normal controls (group III: 26 women, 32.8 years). Serum calcium, phosphorus, parathyroid and sex hormones, bone remodeling markers, interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), IL-1, tumor necrosis factor-alpha (TNF), 25-hydroxivitamin D (25OHD), and 1,25-dihydroxyvitamin D3 were measured, plus bone mineral density. RESULTS: All cytokines were significantly higher in SLE groups; IL-6 could differentiate SLE patients from controls. In group I, 25OHD levels were lower (P < 0.05), which was related to the SLEDAI (R = -0.65, P < 0.001). In multiple regression analysis, the 25OHD level was associated with SLEDAI, osteocalcin and bone-specific alkaline phosphatase. The SLEDAI score was positively correlated with all measured cytokines and especially TNF (R = 0.75, P < 0.001). CONCLUSIONS: SLE patients demonstrated changes in bone remodeling strongly related to disease activity. A high prevalence of 25OHD deficiency was observed in SLE patients, indicating the need for vitamin D replacement.

Leprosy-related joint involvement.

We estimate the prevalence and evaluate the clinical characteristics of leprosy related arthritis. One thousand, two hundred fifty-seven leprosy patients were attended at "Alfredo da Matta" outpatient clinic in the state of Amazonas, Brazil from July to October 2004. Among them, 115 patients were identified with articular pain and were referred for evaluation with rheumatologist. Blood samples were collected and radiological evaluation of the involved joints was performed. All patients with arthritis who continued to be followed up were reevaluated. One hundred fifteen leprosy patients (9.1%) were identified with articular involvement. The articular complaints were attributed to a defined rheumatic disease in 36 cases and excluded from further analysis. Twenty-four patients had arthralgia, and 55 (37 males and 18 females) had leprosy-related arthritis. The prevalence of arthritis was similar in both genders, and all patients with leprosy-related arthritis had lepromatous or borderline type. Most of patients had polyarticular and symmetrical arthritis and had completed the multidrug therapy and was under reaction treatment. The mean duration of articular symptoms at the time of study was 1.06 years (ranging from 5 days to 14 years). Ninety-one percent of patients with leprosy-related arthritis presented erythema nodosum leprosum or reversal reactions. Only five patients with arthritis had never presented reactions. Fifty percent of patients became asymptomatic during the mean 24 months of follow-up. Leprosy-related arthritis has a lower prevalence than previously reported. Most cases of leprosy-related arthritis were associated with reactional episodes, and in a large number of cases, the arthritis had a chronic course not responsive to the conventional therapy for reactions.

Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in leprosy patients with articular involvement.

The objective of the present research was to evaluate the usefulness of anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor (IgM RF) test for the differential diagnosis of leprosy with articular involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were measured in the sera of 158 leprosy patients (76 with and 82 without articular involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was performed according to Ridley and Jopling classification criteria and clinical and demographic characteristics of leprosy patients were collected by a standard questionnaire. Leprosy patients with any concomitant rheumatic disease were excluded. Serum samples were obtained from all participants and frozen at -20 degrees C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA, using a commercial second-generation kit, and the latex agglutination test, respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies (2.6 and 1.3%, respectively) in leprosy patients and were not associated with articular involvement. Among healthy individuals both anti-CCP antibodies and IgM RF were each detected in 3.4% of the subjects. In contrast, in the RA group, anti-CCP antibodies were present in 81.2% and IgM RF in 62.3%. In the present study, both anti-CCP antibodies and IgM RF showed good positive predictive value for RA, helping to discriminate between RA and leprosy patients with articular involvement. However, anti-CCP antibodies were more specific for RA diagnosis in the population under study.

Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in leprosy patients with articular involvement

The objective of the present research was to evaluate the usefulness of anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor (IgM RF) test for the differential diagnosis of leprosy with articular involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were measured in the sera of 158 leprosy patients (76 with and 82 without articular involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was performed according to Ridley and Jopling classification criteria and clinical and demographic characteristics of leprosy patients were collected by a standard questionnaire. Leprosy patients with any concomitant rheumatic disease were excluded. Serum samples were obtained from all participants and frozen at _20°C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA, using a commercial second-generation kit, and the latex agglutination test, respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies (2.6 and 1.3 percent, respectively) in leprosy patients and were not associated with articular involvement. Among healthy individuals both anti-CCP antibodies and IgM RF were each detected in 3.4 percent of the subjects. In contrast, in the RA group, anti-CCP antibodies were present in 81.2 percent and IgM RF in 62.3 percent. In the present study, both anti-CCP antibodies and IgM RF showed good positive predictive value for RA, helping to discriminate between RA and leprosy patients with articular involvement. However, anti-CCP antibodies were more specific for RA diagnosis in the population under study.

Impact of hypertension and hyperhomocysteinemia on arterial thrombosis in primary antiphospholipid syndrome.

The aim of this study was to evaluate traditional risk factors for coronary artery disease (CAD), homocysteine, anti-oxidized low-density lipoprotein (anti-oxLDL), anti-lipoprotein lipase (anti-LPL) and endothelin-1 (ET-1) in patients with primary anti-phospholipid syndrome (APS), furthermore verify possible association among these variables and arterial thrombosis. Thirty-eight women with primary APS and 30 age-and-sex-matched controls were evaluated. Patients presented higher-LDL and triglycerides levels and lower-HDL levels than controls. Anti-LPL antibodies were not detected in both groups. The mean number of risk factors was higher in patients than in controls (P = 0.030). Anti-oxLDL antibodies, homocysteine and ET-1 mean levels were similar between groups, but abnormal homocysteine levels were found only among primary APS patients (P = 0.031). Hypertension and the presence of at least one risk factor for CAD were more prevalent in patients with arterial involvement than those without. Homocysteine levels and mean number of risk factors for CAD were significantly higher in patients with arterial thrombosis than controls. In a multivariate analysis hypertension was the only independently associated with arterial thrombosis (OR 14.8, 95% CI = 2.1-100.0, P = 0.006). This study showed that in primary APS patients other risk factors besides anti-phospholipid antibodies contribute for the occurrence of arterial events and the most important factor was hypertension.

Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have recognized reduction in endothelium-dependent vasodilation. Evidence demonstrates that statins are able to improve endothelial function independently on their hypolipemic action. OBJECTIVES: To evaluate the efficacy of atorvastatin in improving vasodilation in SLE patients with and without conventional risk factors for coronary heart disease (CHD). PATIENTS AND METHODS: Sixty-four SLE women, mean age 31 +/- 8 yrs, received atorvastatin 20 mg/day during 8 weeks. Thirty-one patients in this intervention group did not have conventional risk factors for CHD, while 33 others had hypertension, dyslipidaemia and/or obesity. Twenty-four SLE control patients, mean age 34 +/- 7.5 yrs, not receiving atorvastatin were followed during the same time period. High-resolution ultrasound was used to measure brachial artery diameter in resting conditions, during reactive hyperaemia and after sub-lingual glyceryl trinitrate (GTN). Measurements were performed at baseline and at the end of the study (8 weeks). RESULTS: Atorvastatin was associated with a significant increase in flow-mediated dilation (FMD) [3.8 (2.8-7.9%) vs 6.9 (4.2-10.7%), P < 0.001] while GTN-mediated dilation (GTND) was unaffected [20.9 (16.6-26.1%) vs 20.1(16.6-25.4%), P = 0.514]. FMD increase was observed in patients with conventional risk factors [4.1 (3.1-8.7%) vs 6.5 (4-10%), P = 0.046] and also for those without conventional risk factors for CHD [3.6 (2.6-7.3%) vs 7.1 (4.5-10.9%), P = 0.001]. Resting brachial artery diameter also increased significantly in patients receiving atorvastatin (2.79 +/- 0.30 mm vs 2.92 +/- 0.40 mm, P < 0.001). No significant difference in artery diameter and FMD was seen in control patients at the end of the study. When compared to the control patients, atorvastatin treatment was associated with significant increase in resting diameter (+0.13 +/- 0.1 mm vs -0.02 +/- 0.07 mm, P < 0.001) and FMD (+1.9 +/- 3.9% vs -0.3 +/- 1.8%, P = 0.009). CONCLUSION: Our results demonstrate that an 8-week 20 mg/day atorvastatin series improved endothelium-dependent vasodilation in SLE patients independently on the presence of conventional risk factors for atherosclerotic disease.

High prevalence of vertebral deformity in premenopausal systemic lupus erythematosus patients.

In this paper we searched for vertebral deformities in a group of 70 premenopausal systemic lupus erythematosus (SLE) patients (31.8 +/- 8.1 years old) and compared them to a matched control group of 22 healthy women (32.0 +/- 8.9 years old). Patients and controls performed spine X-ray (XR) morphometry and lumbar spine and femoral neck bone mineral density (BMD). Clinical data was obtained by a questionnaire and charts review. Thoracic or lumbar spine fracture was observed in 15 (21.4%) SLE patients, while no deformities were found in the control group (P = 0.018). BMD was not different amongst SLE patients and controls and between SLE patients with or without deformities. Although BMD could not predict what patient have deformity, seven patients (46.6%) with deformity had a lumbar spine or femoral neck Z-score less than - 1 SD [median = -0.59 (-3.72 to +0.88) and -0.20 (-4.05 to + 1.87)] respectively. In addition, we found a negative correlation between number of fracture per patient and lumbar spine and femoral neck BMD (R = 0.58, P = 0.04 and R = 0.84, P = <0.0001 respectively). No significant correlation was found between number of deformities and clinical data. This is the first study to search for vertebral deformities in SLE patients and to demonstrate a high prevalence of deformities in a relative young SLE population. These findings bring up the necessity to look for spine deformities in this group of women regardless the BMD.