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.

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.

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.

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.

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.

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.

Clinical implications of autoantibodies in HIV infection.

OBJECTIVE: To study the frequency and specificity of autoantibodies in HIV-infected subjects and their association with rheumatic manifestations, immunodeficiency, and prognosis. DESIGN: Prospective study of sequentially selected HIV-infected patients. Indirect immunofluorescence reading was performed by two independent observers blinded for the patient diagnosis. Enzyme-linked immunosorbent assay (ELISA) was performed using coded serum samples. SETTING: The study was performed at the Infectious Disease and Rheumatology Divisions of a tertiary care university hospital. PATIENTS: One hundred sequentially selected HIV-infected patients formed group A. Controls included 80 non-HIV-infected high-risk individuals (group B), 20 herpesvirus-infected patients (group C), and 30 healthy blood donors (group D). MAIN OUTCOME MEASURES: Patients were followed for 2 years and evaluated for the presence of immunodeficiency, rheumatic manifestations, circulating autoantibodies and total CD4+ cell count. Indirect immunofluorescence was used to investigate antinuclear antibodies, antibodies to native DNA, smooth muscle, parietal cell, glomeruli, thyroid, and neutrophil cytoplasm. Agglutination was used to detect antibodies to erythrocytes and rheumatoid factor. ELISA was used to determine antibodies to cardiolipin and denatured DNA. CD4+ lymphocytes were counted by flow cytometry. Immunoglobulin (Ig) G, IgM and IgA serum levels were determined by radial immunodiffusion. RESULTS: HIV-infected patients presented higher overall frequency of autoantibodies than the other groups. No difference was observed between immunodeficient and asymptomatic HIV-infected patients. The most frequent specificities were antibodies to cardiolipin and to denatured DNA. Ig serum levels did not correlate with the occurrence of autoantibodies. The presence of autoantibodies was associated with lower CD4+ cell counts and with higher mortality within 2 years. Rheumatic manifestations were observed in 35 HIV-infected patients and were not associated with the occurrence of autoantibodies or the presence of immunodeficiency. CONCLUSIONS: HIV infection is associated with an increased incidence of autoantibodies. Although not related to the occurrence of rheumatic manifestations, the presence of autoantibodies was significantly associated with lower CD4+ lymphocyte counts and increased mortality, which implies prognostic significance to this phenomenon in the context of HIV infection.

PIP: A study was conducted at the Infectious Disease and Rheumatology Divisions of a tertiary care university hospital in Sao Paulo to assess the frequency and specificity of autoantibodies in HIV-infected subjects and their association with rheumatic manifestations, immunodeficiency, and prognosis. 100 sequentially selected HIV-infected patients formed group A, 80 non-HIV-infected high-risk subjects served as controls in group B, 20 herpesvirus-infected patients formed group C, and 30 healthy blood donors formed group D. The patients were followed for 2 years and evaluated for the presence of immunodeficiency, rheumatic manifestations, circulating autoantibodies, and total CD4+ cell counts. HIV-infected patients presented with a higher overall frequency of autoantibodies than did the other groups. No difference was observed between immunodeficient and asymptomatic HIV-infected patients. The most frequent specificities were antibodies to cardiolipin and to denatured DNA, while Ig serum levels did not correlate with the occurrence of autoantibodies. The presence of autoantibodies was associated with lower CD4+ cell counts and with higher mortality within 2 years. Rheumatic manifestations were observed in 35 HIV-infected patients and were not associated with the occurrence of autoantibodies or the presence of immunodeficiency.

Treatment of the cutaneous lesions of systemic lupus erythematosus with thalidomide.

Twenty three patients with SLE and cutaneous lesions not responsive to chloroquine, photoprotectors and corticosteroid in doses < 0.5 mg/kg/day were treated with thalidomide 300 mg/day. Three patients presented side effects and had to discontinue treatment. Eighteen of the remaining 20 patients (90%) had complete remission of the cutaneous lesions and 2 had partial improvement. Another important parameter of improvement was a reduction in the average prednisone dose required from 40.5 mg/day to 17.4 mg/day. The most frequent side effects were drowsiness in 52% of cases and abdominal distention in 22%. These symptoms were reversed by dose reductions in all but one patient. Thalidomide was shown to be efficient in the treatment of cutaneous lesions unresponsive to more usual treatments.

Systemic lupus erythematosus: a family study of 25 probands.

We studied 120 first-degree relatives (FDRs) of 25 systemic lupus erythematosus (SLE) probands and 59 non-genetically associated individuals who were in close contact with the SLE patients. A significantly greater frequency of antinuclear antibody (ANA) positivity was found among the FDRs than in the control group (p less than 0.01). No significant difference was found in ANA positive between the female and male FDRs. Articular complaints or Raynaud's phenomenon were observed in 15% of the FDRs and in only 2% of the controls (p less than 0.05). Female FDRs had a greater number of rheumatic complaints than male FDRs (p less than 0.05) and a significant association was found between rheumatic complaints and ANA positivity (p less than 0.001) among the total FDRs.

Takayasu arteritis. Treatment and prognosis in a university center in Brazil.

The aim of this study was to evaluate the treatment and evolution of TA patients in a University Center in Brazil. This is a retrospective and descriptive study, that included all patients with TAs who attended the out-patient clinic at the Universidade Federal de Sao Palo, between 1993 and 1998. Twenty-four patients were women and 22 where white. The median age at the time of diagnosis was 27 yo. Full arteriography was performed in 28 patients and carotid duplex ultrasound plus computed tomography of aorta was done in two patients. Type I was found in 4, type II-a and type II in one case each, the type IV in 4 cases and the type V in 20 patients. Regarding the treatment only three patients with quiescent disease did not receive any medications. Twenty-seven patients (90%) received prednisone and only ten of these patients achieved disease control. Forth-eight percent of patients who received prednisone showed some side effects. Twelve patients received methotrexate associated to prednisone and 58% of them had a good response. Two patients who did not control disease activity with prednisone plus methotrexate received cyclophosphamide without good results. Some surgical procedure was performed in ten TA patients. Three patients died during the follow-up. This study showed that the majority of TA patients attended at a University Center needed association of prednisone and methotrexate to control disease activity, 30% needed some surgical procedures and that may be a cause of death in a young patient.

Demographic, clinical, and angiographic data of patients with Takayasu arteritis in Brazil.

We collected clinical, demographic, and angiographic data of Takayasu arteritis (TA) patients followed at Rheumatology Division of three Public University Centers (UNIFESP, USP, and UNICAMP) located in São Paulo State, Brazil. Clinical and demographic data were obtained from 73 patients (61 female; 50 white) The mean age at time of diagnosis was 27 y.o. and the mean follow-up time was 5 years. The following clinical features were observed along the evolution of these patients: absent or reduced pulses in upper limbs (85%), arterial bruit (64.5%), claudication of upper members (57%), headache (45%), hypertension (35.5%), dizziness (29%), cardiac bruit (29%), weight loss (27.5%), arthralgia or arthritis (26%), fever (24.5%) and claudication of lower limbs (20.5%). According to new angiographic classification of Takayasu arteritis performed in 28 patients followed at UNTFESP, with routine full aortography, 21% were classified as type I, 4% as type IIa, 4% as type III, 14% as type IV and 57% as type V. No patients had type IIb. Patients with Takayasu arteritis in São Paulo State Brazil showed female predominance and arterial involvement pattern similar to the one observed in Japan, with more than 20% classified as type I with exclusive involvement of the branches from the aortic arch.

A study of the gram-negative bacterial flora in patients with ankylosing spondylitis.

1. Twenty-eight patients with active definite primary ankylosing spondylitis and fifty-four healthy control subjects were studied. 2. The HLA-B27 antigen was found in 75% of patients and 3.7% of controls. 3. Fecal samples from these subjects were cultured for gram-negative enteric bacteria on two occasions within one month. Positive cultures for Klebsiella sp were found in 32.1% of patients and in 22.2% of healthy controls, but this difference was not statistically significant. All other microorganisms detected were qualitatively and quantitatively similar in both groups. 4. Significantly increased mean values of serum IgA levels were found in the patient group when compared with the control group (P less than 0.01). The mean serum IgG and IgM levels did not differ statistically between the two groups. There was no correlation between any laboratory or clinical parameter and presence of Klebsiella sp carriage in ankylosing spondylitis patients. 5. These data are consistent with the view that a long time elapses between exposure to a trigger factor and clinical manifestations of the disease.

Vena cava thrombosis associated with nephrotic syndrome in the puerperal gestational cycle.

CONTEXT: The puerperal gestational cycle is accompanied by a state of physiological hypercoagulability. Thromboembolic phenomena may occur at this time. OBJECTIVE: To report on a clinic case involving a patient that presented a family history of thromboembolism and developed deep vein thrombosis in a lower limb and vena cava thrombosis during the puerperal gestational cycle, displaying nephrotic syndrome as the main complication. DESIGN: Case report.

[Study of bone density in systemic scleroderma]. / Estudo da densidade óssea na esclerodermia sistêmica.

BACKGROUND: Osteopenia in systemic sclerosis (scleroderma) patients was reported in X-ray studies of hands and by proximal and distal forearm bone mass measurement. It has been suggested that bone loss in these patients might be due to chronic ischemia, immobilization and early menopause. Nevertheless, it is not established if these patients present generalized osteopenia. To shed light into this point we studied bone mineral density in the spine, proximal femur and total body in patients with systemic sclerosis. PATIENTS AND METHOD: Twenty-five Caucasian women were evaluated. Mean age of patients was 48 +/- 12 years and mean time of disease was 7 +/- 7 years; 13 were postmenopausal (8 +/- 8 years). Bone mass was measured in the spine, proximal femur and total body by using a dual-photon absorptiometry with X rays source (Lunar-Model DPX). RESULTS: Bone mass in different sites was not statistically different from the age-matched control healthy women. Mean bone mass of patients with limited form was not different from patients with diffuse form of systemic sclerosis. Patients with calcinosis had lower bone mass at proximal femur than those without this alteration. CONCLUSIONS: Patients with systemic sclerosis do not present bone loss and this disease in not a risk factor for generalized osteoporosis.

Long-term thalidomide use in refractory cutaneous lesions of systemic lupus erythematosus.

OBJECTIVE: To evaluate the efficacy of long-term thalidomide treatment in cutaneous lesions of systemic lupus erythematosus (SLE), not responsive to conventional therapy. PATIENTS AND METHODS: Were selected 18 SLE patients (ACR criteria) with active cutaneous lesions not responsive to chloroquine, photoprotectors and low doses prednisone and who presented good response to thalidomide but relapsed after withdrawal of the drug. All female patients had no risk of pregnancy. Thalidomide was reintroduced and maintained at low dose (25-100 mg/day) for a minimum of 6 months. RESULTS: Eighteen patients (16 females) with mean age of 34.2 yo (16-57 y.o.) received thalidomide for 6-21 months (mean 8.5 m). The mean dose of prednisone at beginning of study was 38.3 mg/d and at the end was 9.7 mg/d (p < 0.05). Complete remission of cutaneous lesions was observed in thirteen patients (72%) and partial remission in five (28%). Side effects observed were: drowsiness in eight patients, intestinal constipation in 5, transient oliguria in 1, paresthesia of hand with normal electromyography in another one. All side effects disappeared with reduction of thalidomide dose and no patient needed to stop treatment owing to side effect. CONCLUSION: Thalidomide is a good alternative therapy to SLE patients with refractory cutaneous lesions and without any risk of pregnancy.

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.