TP53 and p21 (CDKN1A) polymorphisms and the risk of systemic lupus erythematosus.

BACKGROUND: The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C-rs1042522; p53 PIN3-rs17878362; p21 31 C > A-rs1801270; p21 70 C > T-rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population. METHODS: Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis. RESULTS: Protective effect was observed for the genotype combinations p53 PIN3 A1/A1-p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively). CONCLUSIONS: Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients.

Anal cancer in systemic lupus erythematosus patients is a neglected condition / Câncer anal em pacientes com lúpus eritematoso sistêmico é uma condição negligenciada

Patients with systemic lupus erythematosus have a higher incidence of neoplasms associated with human papillomavirus infections, such as those that affect the vulva, the vagina, and the cervix; however, little is known about the frequency of anal cancer among these patients. Although there are recommendations for screening for this cancer in immunosuppressed individuals, it is possible that this procedure is not strictly followed. We describe the case of a 47-year-old woman with systemic lupus erythematosus who was treated with immunosuppressants and developed advanced anal squamous cell carcinoma after adequate treatment and healing of a high-grade cervical squamous intraepithelial lesion. Five years after the completion of the anal cancer treatment, the patient presented with cystic hepatic lesions that were histopathologically confirmed to be metastatic squamous cell carcinoma. This report aimed to highlight the need for anal cancer screening in patients with lupus, particularly if there was a history of cervical cytopathological alterations. (AU)

Resumo Pacientes com lúpus eritematoso sistêmico apresentam maior incidência de neoplasias associadas a infecções por HPV, como aquelas que acometem a vulva, a vagina e o colo do útero, mas pouco se sabe sobre a frequência de câncer anal entre essas pacientes. Embora existam recomendações para o rastreamento desse câncer em indivíduos imunossuprimidos, é possível que esse procedimento não esteja sendo rigorosamente seguido. Descrevemos uma mulher de 47 anos com lúpus eritematoso sistêmico, tratada com imunossupressores, que desenvolveu um carcinoma escamocelular anal avançado após tratamento adequado e cicatrização de lesão intraepitelial escamosa cervical de alto grau. Cinco anos após o término do tratamento do câncer anal, a paciente apresentou lesões císticas hepáticas cujo resultado citopatológico confirmou ser carcinoma escamocelular metastático. O presente relato teve como objetivo chamar atenção para a necessidade do rastreamento do câncer anal em pacientes com lúpus, principalmente se houver história prévia de alterações citopatológicas cervicais. (AU)

TP53 and p21 (CDKN1A) polymorphisms and the risk of systemic lupus erythematosus

Abstract Background The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C—rs1042522; p53 PIN3—rs17878362; p21 31 C > A—rs1801270; p21 70 C > T—rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population. Methods Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis. Results Protective effect was observed for the genotype combinations p53 PIN3 A1/A1 -p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively). Conclusions Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients. Highlights The polymorphisms TP53 rs1042522 (G > C) and TP53 rs17878362 (16 bp Del/Ins) were associated with SLE risk in whites. In whites, the combined genotype TP53 rs1042522 GC- TP53 rs17878362 A1A2 and the haplotype TP53 rs1042522 C-rs17878362 A2 represented higher SLE risk. Combination of TP53 rs17878362 (16 bp Del/Ins) and p21 rs1801270 (C > A) protected against SLE in non-white women. TP53 and p21 (CDKN1A) polymorphisms may be SLE susceptibility markers for specific groups.

Risk factors associated with infections in pregnant women with systemic lupus erythematosus

SUMMARY OBJECTIVE: The aim of this study was to analyze the occurrence and risk factors associated with infections during pregnancy in patients with systemic lupus erythematosus. METHODS: This is a retrospective cohort study using the data of pregnant women who were followed up between 2011 and 2018 at a university hospital. RESULTS: The data of 221 pregnant women with systemic lupus erythematosus were analyzed. The incidence of infections was 22.6% (50/221), with the urinary tract being the most frequent site of infection (32/221, 14.5%) followed by the respiratory tract (15/221, 6.8%). The bivariate analysis showed that active disease, hematological systemic lupus erythematosus, reduced complement, and use of prednisone ≥5 and ≥10 mg increased the chance of infection during early pregnancy (p=0.05, p=0.04, p=0.003, p=0.008, and p=0.02, respectively), while disease activity and anti-DNA positivity increased it at the end of pregnancy (p=0.03 and p=0.04, respectively). Prednisone at a dose ≥5 mg increased the chance of infection in the beginning (p=0.01) and at the end of pregnancy (p=0.008). Multivariate analysis showed that increasing the dose of prednisone from 5 to 10 mg tripled the chance of developing infections in pregnant women with lupus (p=0.02). CONCLUSION: The study showed an increased chance of infections in pregnant women with systemic lupus erythematosus and it was associated with the use of prednisone.

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil

Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

Correction to: Mortality burden associated with all-cause pneumonia among adults with autoimmune inflammatory rheumatic diseases, human immunodeficiency virus infection, and malignancies: a population-based comparative study for informed decision-making in public health policies.

The Table 2 in the original version of the above article was incorrectly presented. The data where misaligned during publication process.].

Evaluation of toxic retinopathy caused by antimalarial medications with spectral domain optical coherence tomography / Avaliação da frequência de retinopatia por antimaláricos com o exame tomografia de coerência óptica de domínio espectral

ABSTRACT Purpose: To investigate the frequency of toxic retinopathy in patients with lupus erythematosus and rheumatoid arthritis with long-term use of chloroquine diphosphate or hydroxychloroquine through spectral domain optical coherence tomography and the outcomes of ophthalmological exams (visual acuity - Snellen's table, color vision test - Ishihara's table, fundoscopy, and retinography - red-free). Methods: A cross-sectional study was carried out involving the ophthalmologic evaluation of patients using regular chloroquine diphosphate or hydroxychloroquine for a period of 1 year or longer. The patients completed a questionnaire on their opinions and treatment regularity. The same patients underwent ophthalmologic examination and spectral domain optical coherence tomography. Results: The prevalence of toxic retinopathy caused by antimalarials was 4.15% (9 of 217 patients), 7.4% (4 of 54 patients) following chloroquine diphosphate usage, and 0.82% (1 of 121 patients) following hydroxychloroquine usage. Only patients with advanced stage maculopathy presented abnormalities during the ophthalmologic exam: the color vision test was altered in 11.1%, and visual acuity and fundoscopy were altered in 33.3%. Identification of early toxic retinopathy, detected in six patients, was possible using spectral domain optical coherence tomography. The mean duration of antimalarial drug usage among patients with toxic retinopathy was 10.4 years. Only 31% of the patients reported some symptoms during treatment, and although 24% were afraid to use the medication, they did so as prescribed. Conclusion: Use of spectral domain optical coherence tomography was essential for the diagnosis of early-stage antimalarial toxic retinopathy in patients with the following characteristics: asymptomatic, antimalarial use 7 days a week for a period of more than 5 years, and normal clinical ophthalmologic examination.

RESUMO Objetivo: Investigar a frequência da retinopatia tóxica em pacientes com lúpus eritematoso e artrite reumatóide com uso crônico de difosfato de cloroquina ou hidroxicloroquina, através de tomografia de coerência óptica de domínio espectral e os resultados dos exames oftalmológicos (acuidade visual - tabela de Snellen, teste de visão de cor - tabela de Ishihara, fundoscopia e retinografia - red free). Métodos: Foi realizado um estudo transversal envolvendo a avaliação oftalmológica de pacientes em uso regular de difosfato de cloroquina ou hidroxicloroquina por um período de um ano ou mais. Os pacientes responderam a um questionário sobre a sua opinião e regularidade do tratamento. Os mesmos pacientes realizaram exame oftalmológico clínico e tomografia de coerência óptica de domínio espectral. Resultados: A prevalência de retinopatia tóxica por antimaláricos foi de 4,15% (9 dos 217 pacientes), 7,4% (4 de 54 pacientes) após uso de difosfato de cloroquina e 0,82% (1 de 121 pacientes) após uso de hidroxicloroquina. Apenas os pacientes com maculopatia em fase avançada apresentaram alterações durante os exames clínicos: teste de visão de cores alterado em 11,1%, e a acuidade visual e fundoscopia foram alteradas em 33,3%. A identificação de retinopatia tóxica precoce, detectada em seis pacientes, foi possível por meio da tomografia de coerência óptica de domínio espectral. A duração média do tempo de uso de drogas antimaláricas entre os pacientes com retinopatia tóxica foi de 10,4 anos. Apenas 31% dos pacientes relataram algum sintoma durante o tratamento e apesar de 24% terem medo de usar a medicação, eles o fizeram conforme prescrito. Conclusão: O uso da tomografia de coerência óptica de domínio espectral foi essencial para o diagnóstico de retinopatia tóxica antimalárica em estágio inicial em pacientes com as seguintes características: uso assintomático, antimalárico 7 dias por semana por um período maior que cinco anos e exame oftalmológico clínico normal.

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases

Abstract Background: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Main body of the abstract: Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. Conclusion: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV.

Pp65 antigenemia and cytomegalovirus diagnosis in patients with lupus nephritis: report of a series / Antigenemia pp65 e diagnóstico de citomegalovírus em pacientes com nefrite lúpica: série de casos

ABSTRACT Introduction: In contrast to organ transplantation, few studies correlate the monitoring of pp65 antigenemia with a diagnosis of cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE). Objective: To highlight the importance of CMV outside transplantation, we monitored pp65 antigenemia in a series of SLE patients. Methods: From March 2015 to March 2016, SLE patients presenting kidney involvement, fever, and an unclear infection at hospital admission were monitored through pp65 antigenemia. The pp65 antigenemia assay, revealed by immunofluorescence, was correlated with clinical and laboratory findings. Results: We included 19 patients with a suspected unclear infection. A positivity for pp65 antigenemia was found in seven patients (36.8%). The mean age was 33.5 ± 11.2 years, 16 (84%) were females, and 16 (84%) were black. Lymphopenia, anemia, and higher scores of SLEDAI were significantly more common in pp65-positive patients. Five patients received antiviral therapy with ganciclovir. Although receiving specific CMV treatment, one patient died because of suspected CMV disease. Conclusions: Pp65 antigenemia might be relevant in SLE patients, and studies with a greater number of patients are needed in order to establish sensitivity and specificity of pp65 antigenemia in different clinical contexts of SLE patients.

RESUMO Introdução: Diferentemente do transplante de órgãos, poucos estudos correlacionam o monitoramento da antigenemia pp65 com o diagnóstico de citomegalovírus (CMV) em pacientes com lúpus eritematoso sistêmico (LES). Objetivo: De modo a destacar a importância do CMV para além do transplante, monitorizamos a antigenemia pp65 em uma série de pacientes com LES. Métodos: De março de 2015 a março de 2016, pacientes com LES que apresentaram acometimento renal, febre e infecção indeterminada na internação foram monitorados através da antigenemia pp65. O ensaio de antigenemia, revelada por imunofluorescência, foi correlacionado com achado clínicos e laboratoriais. Resultados: Foram incluídos 19 pacientes com suspeita de infecção indeterminada. Positividade para antigenemia pp65 foi encontrada em sete pacientes (36,8%). A idade média foi de 33,5 ± 11,2 anos; 16 (84%) eram do sexo feminino e 16 (84%) eram negros. Linfopenia, anemia e escore de SLEDAI mais elevado foram significativamente mais comuns em pacientes pp65 positivos. Cinco pacientes receberam terapia antiviral com ganciclovir. Apesar de receber tratamento específico para CMV, um paciente com suspeita de doença por CMV veio a óbito. Conclusões: Antigenemia pp65 pode ser relevante em pacientes com LES, e estudos com maior número de pacientes são necessários para estabelecer a sensibilidade e a especificidade da antigenemia pp65 em diferentes contextos clínicos envolvendo pacientes com LES.

Polymorphisms in NAT2 (N-acetyltransferase 2) gene in patients with systemic lupus erythematosus / Polimorfismos no gene NAT2 (N-acetiltransferase 2) em pacientes com lúpus eritematoso sistêmico

ABSTRACT Objective: To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes. Methods: Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, from DNA extracted from peripheral blood samples obtained from patients with SLE (n = 91) and controls (n = 97). Results and conclusions: The 857GA genotype was more prevalent among nonwhite SLE patients (OR = 4.01, 95% CI = 1.18-13.59). The 481T allele showed a positive association with hematological disorders that involve autoimmune mechanisms, specifically autoimmune hemolytic anemia or autoimmune thrombocytopenia (OR = 1.97; 95% CI = 1.01-3.81).

RESUMO Objetivo: Investigar potenciais associações de quatro substituições do gene NAT2 (N-acetiltransferase 2) e do fenótipo acetilador de NAT2 com o lúpus eritematoso sistêmico (LES) e os fenótipos clínicos. Métodos: A análise molecular das substituições 481C > T, 590G > A, 857G > A e 191G > A do gene NAT2 foi feita com a técnica de PCR-RFLP, usando DNA extraído de amostras de sangue periférico obtidas de pacientes com LES (n = 91) e controles (n = 97). Resultados e conclusões: O genótipo 857GA foi mais prevalente entre pacientes com LES não brancas (OR = 4,01, IC 95% = 1,18-13,59). O alelo 481 T apresentou associação positiva com as alterações hematológicas que envolvem mecanismos autoimunes, especificamente anemia hemolítica autoimune ou trombocitopenia autoimune (OR = 1,97; IC 95% = 1,01-3,81).

Roles of CDKN1A gene polymorphisms (rs1801270 and rs1059234) in the development of cervical neoplasia.

The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38-0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39-0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32-0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions.

Consenso da Sociedade Brasileira de Reumatologia para o diagnóstico, manejo e tratamento da nefrite lúpica / Consensus of the Brazilian Society of Rheumatology for the diagnosis, management and treatment of lupus nephritis

Objetivo Elaborar recomendações para o diagnóstico, manejo e tratamento da nefrite lúpica no Brasil. Método Revisão extensa da literatura com seleção dos artigos com base na força de evidência científica e opinião dos membros da Comissão de Lúpus Eritematoso Sistêmico da Sociedade Brasileira de Reumatologia. Resultados e conclusões 1) A biópsia renal deve ser feita sempre que possível e houver indicação e quando não for possível, o tratamento deve ser orientado com base na inferência da clase histológica. 2) Devem ser implementados medidas e cuidados idealmente antes do início do tratamento, com ênfase na atenção ao risco de infecção. 3) Devem-se compartilhar riscos e benefícios do tratamento com pacientes e familiares. 4) O uso da hidroxicloroquina (preferencialmente) ou difosfato de cloroquina é recomendado para todos os pacientes (exceto contraindicação) durante as fases de indução e manutenção. 5) A avaliação da eficácia do tratamento deve ser feita com critérios objetivos de resposta (remissão completa/remissão parcial/refratariedade). 6) Os IECA e/ou BRA são recomendados como antiproteinúricos para todos os pacientes (exceto contraindicação). 7) A identificação de sinais clínicos e/ou laboratoriais sugestivos de GN laboratoriais sugestivos de glomerulonefrite proliferativa ou membranosa deve indicar início imediato de terapia específica incluindo corticosteroides e agente imunossupressor, mesmo que não seja possível comprovação histológica. 8) O tempo de uso dos imunossupressores deve ser no mínimo de 36 meses, mas eles podem ser mantidos por períodos mais longos. A sua suspensão só deve ser feita quando o paciente atingir e mantiver remissão completa sustentada. 9) Deve-se considerar nefrite lúpica refratária quando a remissão completa ou parcial não for alcançada após 12 meses de tratamento adequado, quando uma nova biópsia renal deve ser considerada para auxiliar na identificação da causa da refratariedade e decisão terapêutica. .

Objective To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. Method Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. Results and conclusions (1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. (2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. (3) Risks and benefits of treatment should be shared with the patient and his/her family. (4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. (5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). (6) Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers are recommended as antiproteinuric agents for all patients (unless contraindicated). (7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including corticosteroids and an immunosuppressive agent, even though histological confirmation is not possible. (8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient could achieve and maintain a sustained and complete remission. (9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when ...

[Consensus of the Brazilian Society of Rheumatology for the diagnosis, management and treatment of lupus nephritis]. / Consenso da Sociedade Brasileira de Reumatologia para o diagnóstico, manejo e tratamento da nefrite lúpica.

OBJECTIVE: To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. METHOD: Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS: 1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. 2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. 3) Risks and benefits of treatment should be shared with the patient and his/her family. 4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. 5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). 6) ACE inhibitors and/or ARBs are recommended as antiproteinuric agents for all patients (unless contraindicated). 7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including steroids and an immunosuppressive agent, even though histological confirmation is not possible. 8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient achieve and maintain a sustained and complete remission. 9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision.

Effects of MDM2 promoter polymorphisms on the development of cervical neoplasia in a Southeastern Brazilian population.

We investigated the importance of two adjacent functional polymorphisms in the Murine Double Minute 2 (MDM2) gene, SNP285 G > C and SNP309 T > G, for the development of cervical lesions in a Southeastern Brazilian population (293 cases and 184 controls). MDM2 genotyping was performed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) and/or DNA sequencing. MDM2 SNP309 has potential as a biomarker of cervical neoplasia in non-smokers, patients with family history of cancer, or those who had late sexual debut (>16 years). Besides, this polymorphism may help identify women at risk of developing severe cervical lesion at a young age (<30 years).

Association of CDKN2A polymorphisms with the severity of cervical neoplasia in a Brazilian population.

Variants of p16(INK4a) and p14(ARF), encoded by the CDKN2A locus, may respond differently to the presence of human papillomavirus (HPV). We investigated the potential association of two CDKN2A polymorphisms, 500C > G (rs11515) and 540C > T (rs3088440), with cervical neoplasia in patients with cervical lesions and healthy controls (n = 492). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-strand conformation polymorphism (SSCP) and/or DNA sequencing techniques were employed for genotyping. The 500G allele was found higher, whereas the 540T/T genotype was less frequent in patients with more severe lesions. The CDKN2A variants may have the potential to be markers for the management of patients with cervical neoplasia.

Diffuse systemic sclerosis with bullous lesions without systemic manifestations / Esclerose sistemica difusa bolhosa sem acometimentos sistemicos

Here, we describe an atypical case of systemic sclerosis in its diffuse cutaneous form with acute and rapid progression of the cutaneous condition, without any systemic manifestations and the infrequent formation of bullae, showing the importance of diagnosis and early treatment in such cases. This case also shows that special measures should be taken for bullous cutaneous lesions and ulcerations resulting from serious sclerosis, which are entry points and increase morbidity and risk of death. Other prognostic factors include age, ESR and renal and pulmonary involvement. Capillaroscopies can be useful predictors of greater severity of systemic scleroderma, revealing a greater link with systemic, rather than cutaneous, involvement.

Descrevemos um caso atípico de esclerose sistêmica em sua forma cutânea difusa com instalação aguda e rápida progressão do quadro cutâneo sem qualquer acometimento sistêmico e a infrequente formação de bolhas, demostrando a importância do diagnóstico e tratamento precoce frente a casos semelhantes e mostrando, com a experiência deste caso, que cuidados especiais devem ser tomados com as lesões cutâneas bolhosas e as ulcerações decorrentes da grave esclerose que são portas de entrada e aumentam a morbidade e risco de morte. Outros fatores prognósticos descritos são idade, VHS e envolvimento pulmonar e renal. A capilaroscopia pode ser preditor de maior gravidade da esclerodermia sistêmica, guardando maior relação com o envolvimento sistêmico do que cutâneo.

Achados bucais no lúpus eritematoso sistêmico / Oral findings of systemic lupus erythematosus

O lúpus eritematoso sistêmico (LES) é uma doença auto-imune, de etiologia desconhecida, influenciada por fatores ambientais e genéticos, que afeta principalmente mulheres nas segunda e terceira décadas de vida. A prevalência das lesões bucais nos pacientes com LES varia entre 6,5% e 21%, acometendo principalmente língua, mucosa jugal, lábios e palato. Caracterizam-se como úlceras crônicas ou eritema, de dimensões variadas, com períodos de exacerbação e remissão e aspectos histopatológicos diversos. O objetivo deste trabalho é apresentar uma atualização sobre o LES e seus achados bucais.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology, influenced by environmentaland genetic factors, that affects mainly women in their second and third decades of life. The prevalence of oral lesions in the SLE patients is variable, ranging from6,.5% to 21%, affecting mainly tongue, buccal mucosa, lips and palate. They are characterized as chronic ulcers or erythema, of variable sizes, with periods of exacerbation and remission and variable histopathologic aspects. The aim of this study is to present an updating about SLE and its oral findings.

Achados bucais e laboratoriais em pacientes com lúpus eritematoso sistêmico / Oral and laboratorial findings in patients with systemic lupus erythematosus

INTRODUÇÃO: O lúpus eritematoso sistêmico (LES) é uma doença inflamatória crônica caracterizada por manifestações clínicas variadas. Os poucos trabalhos existentes na literatura relatam uma prevalência entre 6,5 por cento e 21 por cento de acometimento bucal. OBJETIVO: Investigar os achados bucais e laboratoriais em pacientes com LES. MATERIAL E MÉTODO: Foram analisados 155 pacientes com diagnóstico de LES, segundo critérios do American College of Rheumatology (ACR). O índice de dentes cariados, perdidos e obturados (CPO-D) foi registrado e avaliou-se a necessidade de tratamento periodontal por meio do índice periodontal comunitário (IPC). Foram realizados esfregaços e biópsias das lesões e bordas laterais de língua para exames citopatológicos. Exames laboratoriais foram correlacionados com os achados bucais destes pacientes. RESULTADOS: Dos 155 pacientes, 94,1 por cento eram mulheres. Altos níveis de anticorpos circulantes (FAN-Hep2) foram observados em todos os pacientes, sendo 41,9 por cento positivos para a pesquisa de anticorpos anti-DNA de fita dupla. O índice CPO-D médio correspondeu a 18,5 e de acordo com o IPC, 18 por cento apresentaram bolsas periodontais de 4-5 mm e 5,9 por cento de 6 mm ou mais. Foram biopsiadas oito lesões bucais, mas somente três casos foram considerados compatíveis com a indicação clínica de LES. Os principais sítios acometidos foram dorso de língua, mucosa jugal e lábios. A prevalência de candidíase correspondeu a 20,1 por cento e a de leucoplasia pilosa oral a 3,7 por cento. CONCLUSÃO: Pacientes com LES apresentam condição periodontal precária e baixa prevalência de lesões bucais e, além disso, a citopatologia mostrou-se importante no diagnóstico de infecções relacionadas com imunossupressão, como candidíase e leucoplasia pilosa oral.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, which is characterized by several clinical manifestations. A few studies in the literature state estimated prevalence of 6.5 percent to 21 percent in oral manifestations. OBJECTIVE: To investigate the oral and laboratorial findings in patients with SLE. MATERIAL AND METHOD: One hundred fifty-five patients diagnosed with SLE were analyzed in accordance with the American College of Rheumatology (ACR) criteria. The index of decayed, missed and filled teeth (DMFT) was registered and the necessity of periodontal treatment was evaluated by the Community Periodontal Index (CPI). Furthermore, biopsies and smears of the lateral borders of the tongue were performed for cytopathological exams. Laboratory exams were correlated with patients' oral findings. RESULTS: Ninety-four comma one percent of 155 patients were women. High levels of circulating autoantibodies (ANA-Hep2) were observed in all patients and 41.9 percent of them were positive for anti-double stranded DNA. Mean DMFT index was 18.5. According to CPI, 18 percent showed periodontal pockets of 4-5 mm and 5.9 percent pockets of 6mm or more. Eight oral lesions were biopsied, but only three cases were considered compatible with clinical indication of SLE. The main affected sites were dorsum of the tongue, buccal mucosa and lips. The prevalence of candidiasis and oral hairy leucoplakia corresponded to 20.1 percent and 3.7 percent, respectively. CONCLUSION: These data suggest that patients with SLE present low prevalence of oral lesions and poor periodontal conditions. Moreover, the cytopathology showed infections associated with immunosuppression such as candidiasis and oral hairy leucoplakia.