Emilia Inoue Sato

Pattern on the antinuclear antibody–HEp‐2 test is a critical parameter for discriminating antinuclear antibody–positive healthy individuals and patients with autoimmune rheumatic diseases

OBJECTIVE To identify features of antinuclear antibody (ANA)-HEp-2 test results that discriminate ANA-positive healthy individuals and patients with autoimmune rheumatic diseases (ARDs). METHODS We sequentially retrieved data on 918 healthy individuals and 153 patients with ARDs after clinical assessment. ANA-positive healthy individuals for whom data were available were reevaluated after 3.6-5.0 years. An ANA-HEp-2 test result was considered positive when a clear ANA pattern was observed at 1:80 dilution in 2 distinct commercial HEp-2 slides by 2 blinded independent observers. RESULTS ANAs were present in 118 healthy individuals (12.9%) and 138 patients with ARDs (90.2%). The ANA titer was higher in patients with ARDs than in healthy individuals (P<0.001). The ANA pattern profile was distinct in the 2 groups. Nuclear homogeneous, nuclear coarse speckled, and nuclear centromeric patterns appeared exclusively in patients with ARDs. The nuclear dense fine speckled pattern occurred only in healthy individuals. The most frequent ANA pattern in both groups was the nuclear fine speckled pattern, which occurred at lower titer in healthy individuals than in patients with ARDs (P<0.001). Anti-extractable nuclear antigen was present in 1 healthy individual (anti-SSA/Ro) and in 52 patients with ARDs (37.7%). None of the 40 reevaluated healthy individuals developed ARDs, and 29 (72.5%) remained ANA positive. All healthy individuals who became ANA negative had an ANA titer of 1:80 at baseline. CONCLUSION Our findings suggest that the titer, and especially the pattern, on the ANA-HEp-2 test strongly enhances our ability to discriminate ANA-positive healthy individuals and patients with ARDs.

Antimalarial treatment may have a time‐dependent effect on lupus survival: Data from a multinational Latin American inception cohort

OBJECTIVE To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. METHODS Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). RESULTS Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). CONCLUSION Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.

Controlled trial with chloroquine diphosphate in systemic lupus erythematosus

Introduction: Antimalarials have been recognized as effective drugs for the treatment of articular and cutaneous manifestations of systemic lupus erythematosus (SLE), but its potential in the management of systemic features of the disease has not yet been thoroughly evaluated. Objectives: This study intended to evaluate the efficacy of chloroquine diphosphate (CDP) in preventing flares and in reducing the maintenance corticosteroid dose in patients with SLE without life-threatening manifestations. Materials and methods: Twenty-four SLE patients with no life-threatening manifestation were enrolled in a 12-month double blind placebo-controlled trial with CDP (250 mg/day). Patients were subjected each month to clinical examination by a rheumatologist and to SLE-relevant laboratory tests. At each visit, prednisone dose could be adjusted according to the clinical status. Ophthalmologic examination was performed every six months. Outcome measures included SLEDAI score and the required prednisone dose. SLE flare was defined as an increase in SLEDAI score of at least three points. Prednisone dose reduction was defined as a minimum 50% dose decrease with no concomitant disease flare. Results: Twenty-three patients completed the study. One patient in the placebo (PL) group dropped out due to severe dyspepsia. No major side-effect was observed in the remaining patients. PL and CDP groups showed no significant difference at the beginning of the study with regard to sex, age, ethnic classification, disease duration, SLEDAI and prednisone dose. Along the trial the prednisone dose became progressively lower in CDP group as compared to PL group and the difference reached statistical significance at 4, 6 and 12 months. SLEDAI score was higher in PL group in all evaluations, being the difference statistically significant at 4 months. Flare-up episodes were registered in two patients in CDP group and in ten patients in PL group. The estimated reactivation risk was 4.6 times greater in PL group as compared to CDP group. Conclusions: CDP at a 250 mg/day dose was able to prevent disease exacerbation, reduce the required prednisone dose, and help inducing a better control of patients with non life- threatening SLE. These data suggest that antimalarials might have a broader indication in the treatment of SLE other than solely the management of skin and articular manifesta tions.

Estimating the incidence of systemic lupus erythematosus in a tropical region (Natal, Brazil)

The objective of the study was to evaluate the incidence of Systemic Lupus Erythematosus (SLE) in a tropical urban community (Natal city, Brazil). Only patients living in Natal, a city in the northeastern area of Brazil, older than 15 years, and who fulfilled at least four of the American College of Rheumatology criteria between 1 January 2000 and 31 December 2000, were included. Four sources were used to identify new cases of SLE: (1) the University Hospital; (2) ‘health units’ and hospitals of the public health network; (3) specialists at private hospitals and outpatient clinics; and (4) three laboratories performing antinuclear antibody (ANA) determination. Census data from 2000 for Brazilian population was used to calculate incidence rate. The standardized mortality ratio (SMR) method and 95% confidence intervals (95% CI) were calculated. Forty-three patients were diagnosed as new SLE cases in 2000. The calculated incidence was 8.7/100 000/year (95% CI 6.3–11.7). Thirty-eight patients were female 14.1/100000/year (95% CI 10.0–19.3) and five were male 2.2/100 000/year (95% CI 0.7–5.2). The mean age of new SLE cases was 31.8 years old. (95% CI 27.8–35.8). The mean age for females was 31.4 and for males was 35.0 years old. The median of disease duration (time between onset of the first ACR criterion for SLE and diagnosis) was 10 months (1–72 months). This study demonstrated a high incidence of SLE in Natal, apparently higher than reported in other places. The mean age at diagnosis seems lower than referred by other studies. The observed differences may be due to ethnic and/or environmental factors.

Scleroderma-like nailfold capillaroscopic abnormalities are associated with anti-U1-RNP antibodies and Raynaud's phenomenon in SLE patients.

This study aimed to evaluate the association between nailfold capillary abnormalities and the presence of Raynauds phenomenon (RP), anti-U1-RNP, and anti-cardiolipin (aCL) antibodies in SLE patients. One-hundred SLE patients were studied. Widefield nailfold capillaroscopy was considered abnormal according to five criteria. Intercapillary distance, capillary width and capillary length were registered by videomorphometry in two fingers in 100 patients and in four fingers in 40 of these patients. Both the presence of alterated capillaroscopy and the presence of scleroderma-pattern (SD-pattern), characterized by the presence of avascular areas and enlarged or giant loops, were associated with the isolated presence of RP (P < 0.001) or anti-U1-RNP antibodies (P < 0.01), as well as with the simultaneous presence of RP and anti-U1RNP antibodies (P < 0.001). There was a negative association between the presence of aCL antibodies and SD-pattern (P < 0.05). Higher figures for the videomorphometric parameters capillary width, intercapillary distance and capillary length (measured on four fingers) were observed in patients with RP. Patients presenting both RP and anti-U1-RNP antibodies showed higher figures for intercapillary distance and capillary width. This study demonstrated significant association between nailfold capillaroscopic abnormalities and either RP or anti-U1-RNP antibodies in SLE patients. The association of RP, anti-U1-RNP antibodies, and ‘scleroderma-like’ findings on nailfold capillaroscopy (SD-pattern) in patients with SLE may suggest a new SLE subset with subclinical features of systemic sclerosis.

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.

Myocardial perfusion scintigraphy and coronary disease risk factors in systemic lupus erythematosus.

Objective: To evaluate the prevalence of myocardial perfusion abnormalities and the possible association between myocardial perfusion defects and traditional coronary artery disease (CAD) risk factors as well as systemic lupus erythematosus (SLE) related risk factors. Patients and methods: Female patients with SLE, disease duration >5 years, age 18–55 years, who had used steroids for at least one year were enrolled. Traditional CAD risk factors evaluated were arterial hypertension, diabetes mellitus, dyslipidaemia, postmenopausal status, smoking, obesity, and premature family CAD profile. Myocardial perfusion scintigraphy was evaluated by single photon emission computed tomography with technetium 99m-sestamibi at rest and after dipyridamole induced stress. Results: Eight two female patients with SLE without angina pectoris with mean (SD) age 37 (10) years, disease duration 127 (57) months, SLE Disease Activity Index (SLEDAI) score 6 (5), and SLICC/ACR-DI score 2 (2) were evaluated. Myocardial perfusion abnormalities were found in 23 patients (28%). The mean (SD) number of CAD risk factors was 2.2 (1.6). There was a significant positive correlation between age and number of CAD risk factors. Lower high density lipoprotein (HDL) cholesterol level showed a significant association with abnormal scintigraphy. Logistic regression analysis showed that lower HDL cholesterol level and diabetes mellitus were associated with myocardial perfusion abnormalities. Current vasculitis was also associated with abnormal scintigraphy. Conclusions: Lower HDL cholesterol level and diabetes mellitus have a significant influence on abnormal myocardial perfusion results found in asymptomatic patients with SLE. Current vasculitis was associated with abnormal myocardial scintigraphy. These data suggest that abnormal myocardial scintigraphy may be related to subclinical atherosclerosis.

Mortality Profile Related to Systemic Lupus Erythematosus: A Multiple Cause-of-death Analysis

Objective. To analyze the mortality profile related to systemic lupus erythematosus (SLE) in the state of São Paulo, Brazil. Methods. For the 1985–2007 period, we analyzed all death certificates (n = 4815) on which SLE was listed as an underlying (n = 3133) or non-underlying (n = 1682) cause of death. We evaluated sex, age, and the causes of death, comparing the first and last 5 years of the period, as well as determining the observed/expected death ratio (O/E ratio). Results. For SLE as an underlying cause, the mean age at death was 35.77 years (SD 15.12) and the main non-underlying causes of death were renal failure, circulatory system diseases, pneumonia, and septicemia. Over the period, the proportional mention of infectious causes and circulatory system diseases increased, whereas renal diseases decreased. For SLE as a non-underlying cause of death, the most common underlying causes of death were circulatory, respiratory, genitourinary, and digestive system diseases, and certain infections. The overall death O/E ratio was > 1 for renal failure, tuberculosis, septicemia, pneumonia, and digestive system diseases, as well as for circulatory system diseases at < 50 years of age, particularly acute myocardial infarct. Conclusion. Unlike in developed countries, renal failure and infectious diseases are still the most frequent causes of death. The increase in SLE deaths associated with infection, especially pneumonia and septicemia, is worrisome. The judicious use of immunosuppressive therapy together with vigorous treatment of cardiovascular comorbidities is crucial to the successful management of SLE and to improving survival of patients with SLE.

Takayasu arteritis: Treament 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.

Consenso de lúpus eritematoso sistêmico

DESCRICAO DO METODO DE COLETA DE EVIDENCIAS Dez reumatologistas que trabalham em servicos que atendem grande numero de pacientes com lupus eritematoso sistemico, alguns dos quais tem pesquisa e publicacoes cientificas nesta area, foram convidados a participar do grupo de trabalho. Todos se reuniram para discutir o tratamento das diferentes manifestacoes da doenca, subdivididos em grupos de trabalho, cada qual ficando responsavel por buscar a melhor evidencia para o tratamento de um ou mais comprometimentos da doenca. A ultima edicao de Dubois’s Lupus Erythematosus, editado por Wallace D e Hahn B, em 2007 (Lippincott Williams & Wilkins), foi utilizada como base da discussao. Trabalhos publicados nos ultimos cinco anos foram pesquisados no MedLine. Em virtude da frequencia e da heterogeneidade de manifestacoes da doenca, a maioria dos trabalhos terapeuticos nao contempla grande casuistica, nem sao randomicos e controlados. Como as manifestacoes e a gravidade da doenca variam em diferentes grupos populacionais, devem ser avaliados com cuidado os estudos realizados em grupos populacionais distintos.