Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis

Background: Genetic and epigenetic factors interacting with the environment over time are the main causes of complex diseases such as autoimmune diseases (ADs). Among the environmental factors are organic solvents (OSs), which are chemical compounds used routinely in commercial industries. Since controversy exists over whether ADs are caused by OSs, a systematic review and meta-analysis were performed to assess the association between OSs and ADs. Methods and Findings: The systematic search was done in the PubMed, SCOPUS, SciELO and LILACS databases up to February 2012. Any type of study that used accepted classification criteria for ADs and had information about exposure to OSs was selected. Out of a total of 103 articles retrieved, 33 were finally included in the meta-analysis. The final odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by the random effect model. A sensitivity analysis confirmed results were not sensitive to restrictions on the data included. Publication bias was trivial. Exposure to OSs was associated to systemic sclerosis, primary systemic vasculitis and multiple sclerosis individually and also to all the ADs evaluated and taken together as a single trait (OR: 1.54; 95% CI: 1.25-1.92; p-value, 0.001). Conclusion: Exposure to OSs is a risk factor for developing ADs. As a corollary, individuals with non-modifiable risk factors (i.e., familial autoimmunity or carrying genetic factors) should avoid any exposure to OSs in order to avoid increasing their risk of ADs.

Grupos sanguíneos e lúpus eritematoso crônico discoide

FUNDAMENTOS: Lesão discoide é a manifestação cutânea mais comum do lúpus eritematoso, e formas cutâneas crônicas apresentam características imunológicas próprias, direcionadas ao polo Th1. Diversas doenças possuem associação com grupos sanguíneos, o que não foi ainda estudado no lúpus discoide. OBJETIVO: Investigar a associação entre tipos sanguíneos (ABO e Rh) e lúpus eritematoso discoide. MÉTODOS: Estudo prospectivo tipo transversal envolvendo tipagem sanguínea ABO e Rh, inquérito de dados clínicos e dosagem de FAN e C4 de portadores de lúpus discoide sem critérios de doença sistêmica, atendidos em hospital universitário. RESULTADOS: Foram incluídos no estudo 69 pacientes, sendo 71,0% do sexo feminino (p 1:160, em 31,9%; e níveis baixos de C4, em 8,7%. Não houve diferença significativa entre as frequências dos grupos sanguíneos dos pacientes e da população local; entretanto, o grupo A foi associado às formas disseminadas da doença (OR 4,1 e p < 0,05). CONCLUSÕES: Grupos sanguíneos de pacientes com lúpus discoide apresentam frequência semelhante à da população; porém, formas clínicas disseminadas foram mais prevalentes entre portadores do grupo A.

Corpo, feminino e subjetivação: uma análise a partir de sujeitos portadores de Lúpus Eritematoso Sistêmico

Esta dissertação se propôs investigar, a partir do método psicanalítico, o modo de subjetivação de sujeitos portadores de Lúpus Eritematoso Sistêmico (LES). Partindo do caráter psicossomático” da doença e de sua predominância no sexo feminino, indagamos se é possível existir uma relação entre o modo de subjetivação do feminino e o desenvolvimento da doença. Para verificar esta relação, tomamos como referência o atendimento de duas pacientes acometidas de LES, atendidas no contexto da pesquisa. Aliado a isso, a fim de embasar teoricamente os atendimentos, debruçamo-nos nas obras de Freud, Lacan e seguidores que se detiveram no estudo das manifestações sintomáticas do corpo, bem como na temática envolvendo o modo de subjetivação do feminino e seus desdobramentos. Ao considerar que a concepção de corpo para a psicanálise vai além do determinismo biológico, foi possível verificar que o sujeito, na tentativa de alcançar sua satisfação, recorre ao corpo como objeto de obtenção de prazer psíquico e sexual, destituindo as leis da fisiologia e da anatomia. O fenômeno psicossomático e a histeria de conversão vêm evidenciar isso, na medida em que, ao mesmo tempo em que desafiam o saber médico, também demandam de nós, psicólogos e psicanalistas, uma explicação para tais manifestações corporais, sem causa orgânica determinada. Nessa perspectiva, ao nos colocar teoricamente frente a essas manifestações, pudemos identificar a diferença entre os fenômenos psicossomáticos e a conversão histérica, a qual, por se enlaçar ao registro simbólico, torna-se passível de decifração e interpretação. Os fenômenos psicossomáticos, por outro lado, caracterizam-se por ser da ordem do impossível de se representar, por esta razão, aproximam-se das manifestações decorrentes do modo feminino de subjetivação, que está para fora da linguagem do inconsciente e, portanto, das associações simbólicas.

Associação entre doenças imunológicas e suas manifestações clínicas semelhantes

Trata-se de um caso de uma paciente de 30 anos do sexo feminino, com prótese biológica valvar mitral em razão de estenose mitral sintomática e antecedentes de infarto agudo do miocárdio, episódios de convulsões tônico-clônicas generalizadas, alucinações visuais, eventos tromboembólicos cerebrais, apresentando no momento coreia e cardite aguda. Foram diagnosticados na paciente febre reumática em atividade, lúpus eritematoso sistêmico e síndrome do anticorpo antifosfolipídeo. A combinação de três diagnósticos incomuns em um mesmo paciente torna esse caso único, modificando o tratamento e seu prognóstico.

Trombose coronariana como primeira complicação da aíndrome antifosfolípide

A síndrome do anticorpo antifosfolípide (SAF) é uma trombofilia autoimune, caracterizada pela presença de anticorpos plasmáticos contra fosfolípides, associada a episódios recorrentes de trombose venosa e/ou arterial e morbidade gestacional (especialmente abortamento de repetição). Reportamos o caso de uma paciente feminina, jovem, com diagnóstico de lúpus eritematoso sistêmico (LES), associado à presença de anticorpos antifosfolípide de longa data, com apresentação de infarto agudo do miocárdio (IAM) por trombose proximal da artéria descendente anterior como primeira complicação clínica da SAF.

Manifestação rara de edema agudo de pulmão associado à miocardite lúpica aguda

O lupus eritematoso sistêmico (LES) é a mais comum das doenças auto-imunes sistêmicas, ocorrendo com maior freqüência no sexo feminino, usualmente na faixa etária entre 16 e 55 anos1,2. Embora os rins classicamente sejam os órgãos mais acometidos no LES, o coração e a circulação cardiopulmonar também podem ser afetados de forma significativa3. Nesse contexto, a ocorrência de edema agudo de pulmão associado à miocardite lúpica é rara e de tratamento imunossupressor específico ainda incerto.

Utilização de agentes biológicos no tratamento do lúpus eritematoso cutâneo

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells

Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.

LDLR and PCSK9 Are Associated with the Presence of Antiphospholipid Antibodies and the Development of Thrombosis in aPLA Carriers

Introduction The identification of the genetic risk factors that could discriminate non-thrombotic from thrombotic antiphospholipid antibodies (aPLA) carriers will improve prognosis of these patients. Several human studies have shown the presence of aPLAs associated with atherosclerotic plaque, which is a known risk factor for thrombosis. Hence, in order to determine the implication of atherosclerosis in the risk of developing thrombosis in aPLA positive patients, we performed a genetic association study with 3 candidate genes, APOH, LDLR and PCSK9. Material & Methods For genetic association study we analyzed 190 aPLA carriers -100 with non-thrombotic events and 90 with thrombotic events-and 557 healthy controls. Analyses were performed by chi(2) test and were corrected by false discovery rate. To evaluate the functional implication of the newly established susceptibility loci, we performed expression analyses in 86 aPLA carrier individuals (43 with thrombotic manifestations and 43 without it) and in 45 healthy controls. Results Our results revealed significant associations after correction in SNPs located in LDLR gene with aPLA carriers and thrombotic aPLA carriers, when compared with healthy controls. The most significant association in LDLR gene was found between SNP rs129083082 and aPLA carriers in recessive model (adjusted P-value = 2.55 x 10(-3); OR = 2.18; 95% CI = 1.49-3.21). Furthermore, our work detected significant allelic association after correction between thrombotic aPLA carriers and healthy controls in SNP rs562556 located in PCSK9 gene (adjusted P-value = 1.03 x 10(-2); OR = 1.60; 95% CI = 1.24-2.06). Expression level study showed significantly decreased expression level of LDLR gene in aPLA carriers (P-value < 0.0001; 95% CI 0.16-2.10; SE 0.38-1.27) in comparison to the control group. Discussion Our work has identified LDLR gene as a new susceptibility gene associated with the development of thrombosis in aPLA carriers, describing for the first time the deregulation of LDLR expression in individuals with aPLAs. Besides, thrombotic aPLA carriers also showed significant association with PCSK9 gene, a regulator of LDLR plasma levels. These results highlight the importance of atherosclerotic processes in the development of thrombosis in patients with aPLA.

Gravidez e Anticorpos Antifosfolípidos em Doentes com Lúpus Eritematoso Sistémico. Uma Avaliação do Prognóstico

Introdução e Objectivo: A presença de anticorpos antifosfolípidos (AAF) está associada a perdas embrionárias e fetais e a outras complicações obstétricas como pré-eclâmpsia, restrição de crescimento intra-uterino e parto pré-termo. Os doentes com lúpus eritematoso sistémico (LES) com frequência possuem AAF e síndroma antifosfolípidica (SAAF) secundária. O objectivo deste estudo é avaliar comparativamente o prognóstico da gravidez em mulheres com LES na presença e na ausência de AAF. Material e Métodos:Avaliação retrospectiva de 136 gestações em mulheres com diagnóstico prévio de LES cujo seguimento foi realizado na nossa instituição entre 1993 e 2007. As grávidas com e sem AAF foram consideradas separadamente. Dados relativos a idade materna, história obstétrica passada, actividade do LES no início da gravidez, existência de nefropatia, evolução da gravidez actual, idade gestacional no parto, tipo de parto, peso do recém-nascido e a existência de complicações hipertensivas na gravidez foram analisados. Resultados: 28% (38) das grávidas com LES apresentavam AAF. Deste grupo, 28,9% tinham história de perdas fetais do segundo e/ou terceiro trimestre, em oposição a 6,12% nas doentes sem AAF(p<0,05). A avaliação da actual gravidez demonstrou uma taxa de insucesso na gravidez significativamente mais elevada na população com AAF(8,1% versus 2,1%, p<0,05). Não se verificaram diferenças significativas no peso médio do recém-nascido e na taxa de restrição intra-uterina em função da presença de AAF. A idade gestacional media no parto foi de 36,9 semanas em ambos os grupos com uma taxa idêntica de parto pré-termo. O parto ocorreu por cesariana em 47% das doentes com AAF e em 44,1% das doentes sem AAF. Conclusões:Os antecedentes obstétricos de perda fetal do 2º e 3º trimestre e a probabilidade de aborto espontâneo são mais frequentes em grávidas com LES e AAF. Nos restantes parâmetros analisados não se verificaram diferenças significativas em função da presença de AAF.

Características clínicas y sociodemográficas de pacientes colombianos con Síndrome de Sjögren solo y asociado a otras enfermedades autoinmunes

Introducción: Dado que una de las principales comorbilidades asociadas al síndrome de Sjögren es la presencia de otra enfermedad autoinmune, el objetivo de este estudio fue investigar la frecuencia de poliautoinmunidad en pacientes con síndrome de Sjögren y evaluar sus factores asociados. Métodos: Este fue un estudio de corte transversal en el que 410 pacientes con síndrome de Sjögren (por criterios del Consenso Americano-Europeo, incluyendo biopsia positiva) fueron sistemáticamente incluidos e investigados para la presencia de otra enfermedad autoinmune. Los datos recogidos fueron evaluados mediante análisis de regresión logística y el índice de Rogers y Tanimoto para evaluar factores asociados y agrupamiento. Resultados: Hubo 134 (32.6%) de pacientes con síndrome de Sjögren y otra enfermedad autoinmune. La enfermedad tiroidea autoinmune, artritis reumatoide, lupus eritematosos sistémico y enfermedad inflamatoria intestinal fueron observados en un 21.5%, 8.3%, 7.6% y 0.7% respectivamente. Hubo 35 (8.5%) pacientes con síndrome autoinmune múltiple. El hábito de fumar, historia previa de abortos, positividad de los anticuerpos antinucleares (ANAS) y una mayor duración de la enfermedad fueron los factores de riesgo más fuertes para el desarrollo de poliautoinmunidad. Discusión: Este estudio da a conocer la alta prevalencia de poliautoinmunidad en una población bien definida de pacientes con síndrome de Sjögren, los factores asociados para el desarrollo de esta complicación y su patrón de agrupamiento. Estos resultados pueden servir para definir enfoques plausibles para estudiar los mecanismos comunes de las enfermedades autoinmunes.

The Autoimmune Tautology: An In Silico Approach

There is genetic evidence of similarities and differences among autoimmune diseases (AIDs) that warrants looking at a general panorama of what has been published. Thus, our aim was to determine the main shared genes and to what extent they contribute to building clusters of AIDs. We combined a text-mining approach to build clusters of genetic concept profiles (GCPs) from the literature in MedLine with knowledge of protein-protein interactions to confirm if genes in GCP encode proteins that truly interact. We found three clusters in which the genes with the highest contribution encoded proteins that showed strong and specific interactions. After projecting the AIDs on a plane, two clusters could be discerned: Sjögren’s syndrome—systemic lupus erythematosus, and autoimmune thyroid disease—type1 diabetes—rheumatoid arthritis. Our results support the common origin of AIDs and the role of genes involved in apoptosis such as CTLA4, FASLG, and IL10.

Targeting medication non-adherence behavior in selected autoimmune diseases: a systematic approach to digital health program development

Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were discovered. Over one third of articles identified the following risk factors as common contributors to medication non-adherence (percent of studies reporting): patients not understanding treatment (44%), side effects (41%), age (37%), dose regimen (33%), and perceived medication ineffectiveness (33%). An unanticipated finding that emerged was the need for risk stratification tools (81%) with patient-centric approaches (67%). Conclusions This study systematically identifies and categorizes medication non-adherence risk factors in select autoimmune diseases. Findings indicate that patients understanding of their disease and the role of medication are paramount. An unexpected finding was that the majority of research articles called for the creation of tailored, patient-centric interventions that dispel personal misconceptions about disease, pharmacotherapy, and how the body responds to treatment. To our knowledge, these interventions do not yet exist in digital format. Rather than adopting a systems level approach, digital health programs should focus on cohorts with heterogeneous needs, and develop tailored interventions based on individual non-adherence patterns.

A doença como ponto de mutação :os processos de significação em mulheres portadores de lúpus eritematoso sistêmico

Systemic lupus erythematous (SLE) is a chronic and auto-immune disease that can affect several systems of one´s body, including the nervous system, causing several clinical evidences, which can put in risk the person´s life. Although the illness could manifest itself at any age or sex, studies indicate higher incidence among women. Its etiology points to the combination of genetic, hormonal and environmental factors. Due to the disease´s complexity, it is evident that it affects all the person´s life as a whole and not only its organic dimension. It is believed that the signification attributed to all the process of sickening influences its treatment, as well as the person´s capacity to cope with the difficulties and implicit profits involved in the process.In this study, eight women who were affected by SLE were interviewed, with the aim of examining carefully the processes of signification as well as the generation of meanings which permeate these women´s sickening processes. The analysis of their speeches evidences distinct forms of giving meaning to the process, regardless of the time of the diagnosis. The fact that the disease is incurable was shocking to all the participants, and it demanded changes in their lives, in order to detain a relative control of their condition. The majority of the participants were able to deal with these modifications, since strategies have been created to face the difficulties and thus to preserve their social life, without damaging their health. However, some of the participants did not obtain strenght to cope with the disease, eventually developing a depressive state. It is observed that not only SLE has innumerable ways of manifestation, but the experience of the illness is very subjective and dynamic. There are also several ways of expressing this experience, according to the implications in the social, cultural and economic context where the participants are inserted. This ratifies the necessity of a interdisciplinary approach to embrace SLE complexity. (310 words, 1.610 characters)

Vulvar carcinoma in young patients and its relationship with genital warts

We report the occurrence of aggressive vulvar carcinoma associated with condyloma acuminata in three patients: under 33 years old. Discussion of the role of the human papilloma virus (HPV) in the development of vulvar cancer is also presented. Three patients with condyloma associated with aggressive vulvar squamous cell carcinoma, in situ (1 case) and invasive (2 cases), documented by biopsy and/or vulvectomy are presented. In situ hybridization (ISH) was used to characterize the subtypes of HPV. One patient with erythematous systemic lupus developed in situ carcinoma after 5 years. The other two cases also developed aggressive multicentric, invasive squamous cell carcinoma after 10 years of diagnosis of condyloma. In all cases HPV cytological abnormalities were seen throughout the pathological examination. HPV 16 and 18 were present in cells of invasive squamous cell carcinoma in cases 2 and 3. HPV 6 and 11 were detected only in the condyloma area in case 2. HPV 30 was seen only in the condyloma area in case 3. This report emphasizes the need for biopsies of all unusually persistent or treatment-resistant condylomas, particularly in young and/or immunoisuppressed patients.