Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

First study demonstrating speckle tracking echocardiography has prognostic value in patients with idiopathic inflammatory myopathies.

To measure left ventricular (LV) global longitudinal strain (GLS) using speckle tracking echocardiography in idiopathic inflammatory myopathy (IIM) patients and to determine whether the LV GLS predicts outcomes in those patients. Prospective study consisted of a cross-sectional phase with 61 IIM patients and 32 individuals without IIM and longitudinal phase, in which patients were divided into two subgroups: 26 with reduced LV GLS and 35 with normal LV GLS; patients were followed for a mean of 25 months, and the occurrence of cardiovascular events and criteria for IIM activity were compared. The mean LV GLS (18.5 ± 2.9% vs. 21.6 ± 2.5%; p < 0.001) and right ventricle free wall strain (21.9 ± 6.1% vs. 27.5 ± 4.7%; p < 0.001) were lower in patients than in controls. The mean N-terminal pro B-type natriuretic peptide level was higher in patients than in controls. There were no differences regarding other cardiac involvement. Anti-Jo1 antibody was associated with general electrocardiographic abnormality and LV diastolic dysfunction. The subgroup with reduced GLS progressed with higher mean creatine phosphokinase, myositis disease activity assessment visual analogue scales, the physician's and patient's visual analogue scales, the health assessment questionnaire, and a higher proportion of relapses than the subgroup with normal GLS. There was no difference between the subgroups regarding cardiovascular events. The LV GLS appears to be useful for evaluating patients with IIM. Abnormal values are associated with more frequent relapses and increased disease activity during follow-up.

Pan American League of Associations for Rheumatology Guidelines for the Treatment of Takayasu Arteritis.

OBJECTIVE: To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK). METHODS: A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members. RESULTS: Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible. CONCLUSION: The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries.

Development of an instrument to predict proliferative histological class in lupus nephritis based on clinical and laboratory data.

OBJECTIVES: To compare the correlations of histological class inferences based on clinical manifestations and laboratory tests between rheumatologists and nephrologists, to determine the associations of clinical and laboratory data with histological classes and to develop an instrument that can assist histological class identification in lupus nephritis (LN). METHODS: Retrospective study based on medical records of 80 systemic lupus erythematosus patients (SLICC criteria classification, 2012) who underwent kidney biopsy between 2010 and 2017. Two rheumatologists and two nephrologists received clinical and laboratory data and answered questions regarding which histological class was expected on kidney biopsy. Kappa (K) coefficient was used to assess agreement between evaluators. A decision tree was constructed using the chi-square interaction detector and logistic regression was performed for the development of the proliferative histological class predictor instrument. RESULTS: The mean age and disease duration were 33 ± 10.3 years and 11.5 ± 6.7 years, respectively. The level of agreement between the evaluators and kidney biopsy was poor (global K 0.364 ± 0.029; p < .001). Analyzing clinical and laboratory variables as predictors of proliferative histological class, patients with abnormal urinary sediment and positive anti-dsDNA antibodies presented 13.96 and 4.96 times higher risks of presenting class III or IV, respectively (p < 0.001). Our instrument has a sensitivity of 87.8% and specificity of 80%, using abnormal urinary sediment, anti-dsDNA antibodies, and serum creatinine as variables. CONCLUSIONS: Rheumatologists and nephrologists with experience in treating LN generated evaluations that correlated weakly with kidney biopsy. When kidney biopsy is unavailable or is contraindicated for medical reasons, instruments based on clinical and laboratory predictors may be helpful.

Factors associated with poor outcomes in SLE patients with COVID-19: Data from ReumaCoV-Brazil register.

OBJECTIVES: To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study-"The ReumaCoV Brazil"-designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post-COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04-5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12-96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10-16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97-15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12-0.88], p = 0.02). CONCLUSION: Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.

Incidence and risk factors for moderate/severe COVID-19 in rheumatic diseases patients on hydroxychloroquine: a 24-week prospective cohort.

OBJECTIVES: To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC). METHODS: This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe. RESULTS: A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5; 95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57; 95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8; 95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8; 95%CI 1.1-107.9 and HR=24.8; 95%CI 2.5-249.3, p=0.006, respectively). CONCLUSIONS: Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.

Clinical features, damage accrual, and survival in patients with familial systemic lupus erythematosus: data from a multi-ethnic, multinational Latin American lupus cohort.

OBJECTIVES: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. RESULTS: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08-3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00-2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14-0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30-1.55) or mortality (HR = 1.23; 95% CI 0.26-4.81). CONCLUSION: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.

Jaccoud's arthropathy in SLE: findings from a Latin American multiethnic population.

OBJECTIVE: To compare the clinical, laboratory and outcome features of SLE patients with and without Jaccoud's arthropathy (JA) from the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort. METHODS: 1480 patients with SLE [(34 centres, 9 Latin American countries with a recent diagnosis (≤2 years)] constitute the GLADEL cohort. JA was defined as reducible deformity of the metacarpophalangeal axis, without radiographic erosions at any time. Within this cohort, a nested case-control study was carried out. Control was matched for age, gender and centre in a 1:3 proportion. The variables included were: sociodemographic, clinical and immunological features, disease activity, damage and mortality. Comparisons were performed with Wilcoxon and χ2 tests for continuous and categorical variables, respectively. ORs and 95% CIs and Kaplan-Meier survival curve were estimated. RESULTS: Of 1480 patients, 17 (1.1%) JA patients were identified; 16 (94.1%) of them were women, mean age: 31.0 years (SD 12.0). Five (29.4%) patients presented JA at SLE diagnosis and 12 (70.6%) after. The median follow-up time and all disease features were comparable in both groups except for a higher frequency of pneumonitis in the patients with JA [4 (23.5) vs 1 (2.0); p=0.012; (OR: 15.4; 95% CI 1.6 to 149.6)]. The SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage Index and the Kaplan-Meier survival curve were similar in both groups. CONCLUSION: JA may tend to appear early in the course of SLE; it seems not to have an impact on disease activity, damage accrual or in survival.

(18)F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis.

OBJECTIVE: To evaluate (18)F-fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography-computed tomography (PET-CT) and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu arteritis (TA) and associations with disease activity. METHODS: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of (18)F-FDG in arterial walls was determined by PET-CT scans. TA patients were classified as active disease, inactive disease and possible active disease. RESULTS: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p<0.001). Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p<0.0001). Patients with active disease had higher serum TNFα levels than patients with inactive disease (p=0.049) while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p=0.046). Patients with active disease had higher SUVmax values than those with inactive disease (p=0.042). By receiver operating characteristic (ROC) curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p=0.039). Serum TNF-α levels were higher in patients with SUVmax≥1.3 than <1.3 (p=0.045) and controls (p=0.012). Serum IL-6 levels were higher in patients with SUVmax≥1.3 than in controls (p<0.001). No differences regarding other biomarkers were found between TA patients and controls. CONCLUSIONS: Higher serum IL-6 and TNFα levels as well as higher (18)F-FDG uptake in arterial wall are associated with active TA.

18F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis / Tomografia por emissão de pósitrons com 18F-fluordesoxiglicose e citocinas séricas e metaloproteinases da matriz na avaliação da atividade da doença na arterite de Takayasu

ABSTRACT Objective: To evaluate 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography–computed tomography (PET–CT) and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu arteritis (TA) and associations with disease activity. Methods: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of 18F-FDG in arterial walls was determined by PET–CT scans. TA patients were classified as active disease, inactive disease and possible active disease. Results: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p < 0.001). Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p < 0.0001). Patients with active disease had higher serum TNFα levels than patients with inactive disease (p = 0.049) while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p = 0.046). Patients with active disease had higher SUVmax values than those with inactive disease (p = 0.042). By receiver operating characteristic (ROC) curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p = 0.039). Serum TNF-α levels were higher in patients with SUVmax ≥ 1.3 than <1.3 (p = 0.045) and controls (p = 0.012). Serum IL-6 levels were higher in patients with SUVmax ≥ 1.3 than in controls (p < 0.001). No differences regarding other biomarkers were found between TA patients and controls. Conclusions: Higher serum IL-6 and TNFα levels as well as higher 18F-FDG uptake in arterial wall are associated with active TA.

RESUMO Objetivo: Avaliar a captação de 18F-fluordesoxiglicose (FDG) na tomografia por emissão de pósitrons – tomografia computadorizada (PET-CT) – e os níveis séricos de diferentes citocinas e da metaloproteinases da matriz (MMP) em pacientes com arterite de Takayasu (AT) e associações com a atividade da doença. Métodos: Foram mensurados os níveis séricos do fator de necrose tumoral-α (TNF-α), interleucina (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 e MMP-9 em 36 pacientes com AT e 36 controles. O valor padronizado de captação máximo (SUVmax) de 18F-FDG nas paredes arteriais foi determinado por exames de PET-CT. Os pacientes com AT foram classificados como doença ativa, doença inativa e possível doença ativa. Resultados: Os níveis séricos de IL-6 e MMP-3 foram mais altos em pacientes com AT do que nos controles (p < 0,001). Os níveis séricos de IL-6 foram mais elevados em pacientes com doença ativa e em pacientes com possível doença ativa do que naqueles com doença inativa (p < 0,0001). Os pacientes com doença ativa apresentaram níveis séricos mais elevados de TNF-α do que os pacientes com doença inativa (p = 0,049), enquanto os indivíduos com possível doença ativa apresentaram maiores níveis séricos de IL-18 do que os pacientes com doença inativa (p = 0,046). Aqueles com doença ativa apresentaram maiores valores de SUVmax do que aqueles com doença inativa (p = 0,042). De acordo com a curva ROC, o SUVmax foi capaz de predizer a doença ativa na AT e valores ≥ 1,3 estavam associados à atividade da doença (p = 0,039). Os níveis séricos de TNF-α foram maiores em pacientes com SUVmax ≥ 1,3 do que naqueles com valor < 1,3 (p = 0,045) e controles (p = 0,012). Os níveis séricos de IL-6 foram mais elevados em pacientes com SUVmax ≥ 1,3 do que nos controles (p < 0,001). Não foram encontradas diferenças em relação a outros biomarcadores entre pacientes com AT e controles. Conclusões: Níveis séricos elevados de IL-6 e TNF-α, bem como uma maior captação arterial de 18F-FDG, estão associados à AT ativa.

A Study of Multiple Causes of Death in Rheumatoid Arthritis.

OBJECTIVE: To evaluate rheumatoid arthritis (RA)-related mortality in the state of São Paulo (Brazil). METHODS: Data from all death certificates (DC) from 1996 to 2010 were analyzed using a multiple cause-of-death method. We compared the results from 2 subperiods (1996-2000 and 2006-2010). RESULTS: We found 3955 DC related to RA - 27.6% with RA as the underlying cause of death (UCD) and 72.4% with RA as the nonunderlying cause of death (NUCD). Ninety percent of RA-related deaths occurred at age ≥ 50 years. The mean ages at death were 67.1 ± 13.3 and 67.9 ± 13 years for RA as the UCD and NUCD, respectively. The most frequent NUCD associated with RA were pneumonia, sepsis, renal failure, interstitial lung disease, and heart failure. In the last subperiod, there was an increase in infectious causes. When RA was an NUCD, we observed a decrease in the mean age at death for the last subperiod (p = 0.021). The most common UCD were circulatory and respiratory system diseases. Comparing the mean age at death between RA-related deaths and the general population when deaths occurred at ages beyond 50 years, the linear regression analysis showed a downward curve for RA-related death (p < 0.001 and r = -0.795), while for the general population, as expected, the curve had an upward pattern (p < 0.001 and r = 0.993). CONCLUSION: Unexpectedly, RA-related deaths occurred at earlier ages in the more recent subperiod. Cardiovascular disease remained the most important cause, and infectious diseases are an increasing cause of death associated with RA, raising the question of whether infections were related to the more vigorous immunosuppressive treatment recommended by recent guidelines.

[18F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis]. / Tomografia por emissão de pósitrons com 18F-fluordesoxiglicose e citocinas séricas e metaloproteinases da matriz na avaliação da atividade da doença na arterite de Takayasu.

OBJECTIVE: To evaluate 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT)-and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu's arteritis (TA) and associations with disease activity. METHODS: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of 18F-FDG in arterial walls was determined by PET-CT scans. TA patients were classified as active disease, inactive disease and possible active disease. RESULTS: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p<0.001). Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p<0.0001). Patients with active disease had higher serum TNFα levels than patients with inactive disease (p=0.049) while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p=0.046). Patients with active disease had higher SUVmax values than those with inactive disease (p=0.042). By ROC curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p=0.039). Serum TNF-α levels were higher in patients with SUVmax ≥1.3 than<1.3 (p=0.045) and controls (p=0.012). Serum IL-6 levels were higher in patients with SUVmax ≥1.3 than in controls (p<0.001). No differences regarding other biomarkers were found between TA patients and controls. CONCLUSIONS: Higher serum IL-6 and TNFα levels as well as higher arterial 18F-FDG uptake are associated with active TA.

Perceptions of the population regarding generic drugs in Brazil: a nationwide survey.

BACKGROUND: Generic drugs (GDs) offer a way to reduce health spending without sacrificing quality. Despite this, there are doubts as to their acceptance by the population. This work aims to assess perceptions of GDs among the Brazilian population. METHODS: We conducted a national household survey face-to-face between April and May 2013, with 5000 individuals aged over 15 years. The questions explored socioeconomic and demographic characteristics, the use of GDs, and perceptions about GDs as compared to brand drugs (BDs). The chi-square test was used to examine the associations between the perceptions and the characteristics of the population. RESULTS: Of the 5000 participants, 51.3% were women, 40.2% were white, 48.6% were between 15 and 34 years of age, and 52.3% had income of less than two minimum wages (US$627.78). In terms of the use of GDs, 44.6% of the participants were taking or had taken GDs in the past three months, with the highest figures among the elderly (61.1%) and female (49.2%) populations. Regarding perceptions, 30.4% of the respondents considered GDs less effective than BDs; provided the same price, 59% would prefer BD, and 45.8% agreed that physicians prefer to prescribe GDs. The most negative perceptions about GDs were observed among lower income, elderly and nonwhite populations. CONCLUSION: The findings provide a better understanding of Brazilians' perceptions regarding GDs. This should be considered when formulating healthcare policies aiming at improving access to effective and quality drugs, and reduction of health costs.

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.

IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions.

OBJECTIVE: To analyze cytokine gene expression in keratinocytes from patients with systemic lupus erythematosus (SLE). INTRODUCTION: Keratinocytes represent 95% of epidermal cells and can secrete several cytokines. METHODS: Keratinocytes were obtained by laser microdissection from 21 patients with SLE (10 discoid and 11 acute lesions) at involved and uninvolved sites. All patients were receiving a low/moderate prednisone dose and 18 were receiving chloroquine diphosphate. IL-2, IL-5, TNF-α and IFN-γ gene expression was evaluated by real-time PCR and expressed as the ratio (R) to a pool of skin samples from 12 healthy volunteers. RESULTS: Heterogeneity in cytokine gene expression was found among patients with SLE. Eighteen of 38 valid SLE samples (47%) presented overexpression (R>1) of at least one cytokine. Lesional skin samples tended to show higher cytokine expression than samples from uninvolved skin (p = 0.06). IL-5 and IFN-γ were the most commonly overexpressed cytokines. Samples with cytokine overexpression corresponded to more extensive and severe lesions. Prednisone dose did not differ between samples without cytokine overexpression (15.71±3.45 mg/day) and those with overexpressed cytokines (12.68±5.41 mg/day) (p = 0.216). Samples from all patients not receiving diphosphate chloroquine had at least one overexpressed cytokine. CONCLUSIONS: The heterogeneous keratinocyte cytokine gene expression reflects the complex immunological and inflammatory background in SLE. Patients with severe/extensive skin lesions showed a higher frequency of cytokine gene overexpression. Increased IFN-γ and IL-5 expression suggests that Th1 and Th2 cells are involved in SLE skin inflammation. The possibility that prednisone and antimalarial drugs may have contributed to low cytokine gene expression in some samples cannot be ruled out.

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.

IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions

OBJECTIVE: To analyze cytokine gene expression in keratinocytes from patients with systemic lupus erythematosus (SLE). INTRODUCTION: Keratinocytes represent 95 percent of epidermal cells and can secrete several cytokines. METHODS: Keratinocytes were obtained by laser microdissection from 21 patients with SLE (10 discoid and 11 acute lesions) at involved and uninvolved sites. All patients were receiving a low/moderate prednisone dose and 18 were receiving chloroquine diphosphate. IL-2, IL-5, TNF-α and IFN-γ gene expression was evaluated by real-time PCR and expressed as the ratio (R) to a pool of skin samples from 12 healthy volunteers. RESULTS: Heterogeneity in cytokine gene expression was found among patients with SLE. Eighteen of 38 valid SLE samples (47 percent) presented overexpression (R>1) of at least one cytokine. Lesional skin samples tended to show higher cytokine expression than samples from uninvolved skin (p = 0.06). IL-5 and IFN-γ were the most commonly overexpressed cytokines. Samples with cytokine overexpression corresponded to more extensive and severe lesions. Prednisone dose did not differ between samples without cytokine overexpression (15.71±3.45 mg/day) and those with overexpressed cytokines (12.68±5.41 mg/day) (p = 0.216). Samples from all patients not receiving diphosphate chloroquine had at least one overexpressed cytokine. CONCLUSIONS: The heterogeneous keratinocyte cytokine gene expression reflects the complex immunological and inflammatory background in SLE. Patients with severe/extensive skin lesions showed a higher frequency of cytokine gene overexpression. Increased IFN-γ and IL-5 expression suggests that Th1 and Th2 cells are involved in SLE skin inflammation. The possibility that prednisone and antimalarial drugs may have contributed to low cytokine gene expression in some samples cannot be ruled out.

Trends in dermatomyositis- and polymyositis-related mortality in the state of São Paulo, Brazil, 1985-2007: multiple cause-of-death analysis.

BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) are rare systemic autoimmune rheumatic diseases with high fatality rates. There have been few population-based mortality studies of dermatomyositis and polymyositis in the world, and none have been conducted in Brazil. The objective of the present study was to employ multiple-cause-of-death methodology in the analysis of trends in mortality related to dermatomyositis and polymyositis in the state of São Paulo, Brazil, between 1985 and 2007. METHODS: We analyzed mortality data from the São Paulo State Data Analysis System, selecting all death certificates on which DM or PM was listed as a cause of death. The variables sex, age and underlying, associated or total mentions of causes of death were studied using mortality rates, proportions and historical trends. Statistical analysis were performed by chi-square and H Kruskal-Wallis tests, variance analysis and linear regression. A p value less than 0.05 was regarded as significant. RESULTS: Over a 23-year period, there were 318 DM-related deaths and 316 PM-related deaths. Overall, DM/PM was designated as an underlying cause in 55.2% and as an associated cause in 44.8%; among 634 total deaths females accounted for 71.5%. During the study period, age- and gender-adjusted DM mortality rates did not change significantly, although PM as an underlying cause and total mentions of PM trended lower (p < 0.05). The mean ages at death were 47.76 ± 20.81 years for DM and 54.24 ± 17.94 years for PM (p = 0.0003). For DM/PM, respectively, as underlying causes, the principal associated causes of death were as follows: pneumonia (in 43.8%/33.5%); respiratory failure (in 34.4%/32.3%); interstitial pulmonary diseases and other pulmonary conditions (in 28.9%/17.6%); and septicemia (in 22.8%/15.9%). For DM/PM, respectively, as associated causes, the following were the principal underlying causes of death: respiratory disorders (in 28.3%/26.0%); circulatory disorders (in 17.4%/20.5%); neoplasms (in 16.7%/13.7%); infectious and parasitic diseases (in 11.6%/9.6%); and gastrointestinal disorders (in 8.0%/4.8%). Of the 318 DM-related deaths, 36 involved neoplasms, compared with 20 of the 316 PM-related deaths (p = 0.03). CONCLUSIONS: Our study using multiple cause of deaths found that DM/PM were identified as the underlying cause of death in only 55.2% of the deaths, indicating that both diseases were underestimated in the primary mortality statistics. We observed a predominance of deaths in women and in older individuals, as well as a trend toward stability in the mortality rates. We have confirmed that the risk of death is greater when either disease is accompanied by neoplasm, albeit to lesser degree in individuals with PM. The investigation of the underlying and associated causes of death related to DM/PM broaden the knowledge of the natural history of both diseases and could help integrate mortality data for use in the evaluation of control measures for DM/PM.

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.

[Rheumatic manifestations in leprosy]. / Manifestações reumáticas da hanseníase.

The classical manifestations of leprosy are cutaneous and neurological involvement; however, rheumatic manifestations are relatively common during the course of the disease and can be the initial manifestation. Herein are reviewed the clinical features of leprosy, particularly those that may mimic rheumatic diseases.