Mielopatia no lúpus eritematoso sistêmico: achados clínicos, laboratoriais, radiológicos e evolutivos em uma coorte de 1.193 pacientes

ResumoObjetivoDescrever características clínicas, laboratoriais, radiológicas e evolutivas de mielopatia no lúpus eritematoso sistêmico (LES).Pacientes e métodosFoi feita análise retrospectiva de uma coorte de 1.193 pacientes com LES (critérios ACR) para identificar os pacientes com mielopatia (ACR neuropsiquiátrico). A atividade de doença foi analisada pelo Índice de Atividade do LES (Sledai) na data do evento e a capacidade funcional pela Escala Expandida do Estado de Incapacidade (EDSS) na última consulta.ResultadosForam identificados 14 (1,2%) pacientes com mielopatia. Todas eram mulheres com média de 30 anos (DP±11,5 anos). A mielopatia ocorreu no diagnóstico do LES em quatro (28%) e em nove (64%) havia outro tipo de manifestação neuropsiquiátrica associada. Recorrência do quadro neurológico foi observado em uma (7%) paciente. Atividade de doença foi observada em dois (14%) pacientes. O líquido cefalorraquidiano apresentava pleocitose em sete (53%) pacientes anticorpos antifosfolípides eram positivos em cinco (45%). A ressonância magnética (RM) demonstrou hipersinal em T2 com predomínio do comprometimento longitudinal em seis (86%) pacientes. A maioria foi tratada com corticosteroides e ciclofosfamida endovenosos. Nenhuma paciente teve completa recuperação e quatro (36%) tinham escores altos da EDSS. Óbito foi observado em três (21%) durante episódio de mielopatia, por septicemia durante ou após terapia imunossupressora.ConclusõesA mielopatia ocorreu em 14 (1,2%) dos pacientes da nossa coorte e pode ser a primeira manifestação da doença e ocorrer independentemente de atividade sistêmica da doença. Embora rara, é de grande morbimortalidade, pode ser recorrente e a RM é fundamental para o diagnóstico.AbstractObjectiveTo describe clinical, laboratory, radiological and progression characteristics of myelopathy in systemic lupus erythematosus (SLE).Patients and methodsA retrospective analysis was performed on a cohort of 1193 patients with SLE (ACR criteria) in order to identify patients with myelopathy (neuropsychiatric ACR). Disease activity was assessed by the SLE activity index (Sledai) on the date of the event and functional capacity was assessed by the Expanded Disability Status Scale (EDSS) at the last visit.ResultsWe identified 14 (1.2%) patients with myelopathy. All were women with a mean age of 30±11.5 years. Myelopathy occurred at the diagnosis of SLE in four (28%) patients; and nine (64%) patients had another type of neuropsychiatric manifestation associated. Neurological recurrence was observed in one (7%) patient. Disease activity was observed in 2 (14%) patients. Cerebrospinal fluid presented pleocytosis on 7 (53%) patients; antiphospholipid antibodies were positive in 5 (45%). Magnetic resonance imaging (MRI) showed T2 hyperintensity with a predominance of longitudinal involvement in 6 (86%) patients. Most were treated with intravenous corticosteroids and cyclophosphamide. No patient had full recovery and four (36%) had high EDSS scores. Three (21%) patients died from sepsis early in the course of their myelopathy, during or after immunosuppressive therapy.ConclusionsMyelopathy occurred in 14 (1.2%) of the patients in our cohort and this may be the first manifestation of the disease occurring independently of systemic disease activity. Although rare, myelopathy shows great morbidity and mortality, can be recurrent and MRI is critical for diagnosis

Cumulative organ damage evaluation using the SLICC/ACR-DI in brazilian patients with systemic lupus erythematosus

OBJECTIVE: to evaluate the frequency and the different types of organ damage in relation to disease duration in Brazilian patients with SLE followed in a tertiary reference center through the application of the SLICC/ACR-DI. METHODS: sixty SLE patients were enrolled in this study, and relevant data were obtained through medical history, physical and laboratory examinations reviewing the hospital records. The frequency and different types of organ damage were determined using the SLICC/ACR-DI. Statistics were performed through qui-square and t-tests. Multivariate regression was used to correlate damage with disease duration. RESULTS: forty-one patients (68.3%) presented some cumulative organ damage. Non-caucasoid patients and patients with longer disease duration had a slight tendency to have more damage (p = 0.058). Skin (35.0%), neuropsychiatric (18.3%), ocular (15.0%), peripheral vascularization (16.6%) and cardiovascular (10.0%) systems were more frequently affected. Patients with more than 60 months of disease had a slight tendency to present greater ocular, neuropsychiatric, renal, skin and musculoskeletal damage than patients with shorter disease duration. Patients with more than 120 months of disease had greater pulmonary, cardiovascular and peripheral vascular damage. CONCLUSIONS: in this study, 68.3% of permanent damage was observed. Skin, neuropsychiatric, ocular, peripheral vascularization and cardiovascular systems were more frequently affected. Renal and gonadal involvement was not as frequent as previously described. Non-caucasoid patients had a tendency to present higher scores, but more studies are necessary to determinate if ethnic or economic factors are involved.OBJETIVO: avaliar a freqüência e os tipos de danos permanentes com relação ao tempo da doença em pacientes brasileiros com lúpus eritematoso sistêmico (LES) de um hospital universitário, através da aplicação do índice de dano do Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR/DI). MÉTODOS: foram incluídos 60 pacientes neste estudo. Os dados utilizados, extraídos dos prontuários dos pacientes, foram obtidos através de anamnese, exame físico e exames complementares. A freqüência e os tipos de danos permanentes foram avaliados através do SLICC/ACR/DI. A estatística foi realizada através do teste quiquadrado e teste t. Regressão multivariada foi utilizada para correlacionar o dano com o tempo de doença. RESULTADOS: entre os 60 pacientes, 41 (68,3%) apresentaram algum tipo de dano. Houve tendência, entre os pacientes não caucasóides e com maior tempo de doença, a apresentarem mais danos (p=0,058). Os sistemas mais acometidos foram: pele (35,0%); neuropsiquiátrica (18,3%); ocular (15,0%); vascularização periférica (16,6%); e cardiovascular (10,0%). Com o aumento do tempo de doença (superior a 60 meses), houve maior tendência a danos oculares, neuropsiquiátricos, renais, musculoesquelético e da pele. Com evolução superior a 120 meses houve aumento dos danos pulmonares, cardiovasculares e aqueles relacionados com a vascularização periférica. CONCLUSÕES: observou-se 68,3% de dano permanente, havendo maior freqüência de danos relacionados com acometimentos neuropsiquiátricos, oculares, da vascularização periférica e da pele. Não se observou importante acometimento renal e gonadal, ao contrário do descrito anteriormente. Pacientes não caucasóides apresentaram tendência a maiores escores de dano. No entanto, outros estudos são necessários para se comprovar o envolvimento de fatores étnicos e/ou fatores sócioeconômicos nesse processo de dano irreversível.10911

Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50), 64 firstdegree relatives (mean age 39.95±5.66), and 57 healthy (mean age 19.30±4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their firstdegree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares

Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

INTRODUCTION: Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations. OBJECTIVE: To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis. METHODS: In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis. RESULTS: Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82). In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9). CONCLUSION: Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking and shared epitope alleles were correlated with anti-cyclic citrullinated peptide-antibody-positive rheumatoid arthritis. Of the risk factors, only anticyclic citrullinated peptides antibodies were independently associated with rheumatoid arthritis susceptibility

Serum Interleukin-17 levels are associated with nephritis in childhood-onset systemic Lupus Erythematosus

To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus705313317CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP300447/2009-4; 471343/2011-0; 302205/2012-8; 473328/2013-52008/02917-0; 2010/13636-2; 2012/21071-

Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus

Coexistence of hypothyroidism and polymyositis

Patients with hypothyroidism frequently present with musculoskeletal complaints and elevated serum levels of muscle enzymes, like creatine kinase (CK). With adequate hormonal treatment, the maintenance of high values of CK and muscle symptoms are uncommon. This work reports a 47-year-old woman with hypothyroidism, proximal muscle weakness and increased CK, who didn't improved with levothyroxine treatment. The diagnosis of polymyositis was based on electromyography and muscle biopsy. After treatment with prednisone plus methotrexate and increase of the levothyroxine dose, there were a clinical improvement and a normalization of CK values.Pacientes com hipotiroidismo freqüentemente apresentam sintomas músculo-esqueléticos e aumento de enzimas musculares, como a creatinaquinase (CK). Com o tratamento hormonal adequado é incomum ocorrer grandes aumentos de CK e manutenção de queixas musculares. Este trabalho relata o caso de uma paciente com hipotiroidismo, queixa de fraqueza muscular proximal e aumento de CK, sem melhora clínica com uso de levotiroxina. O diagnóstico de polimiosite foi confirmado por eletroneuromiografia e biópsia muscular. Após tratamento com prednisona e metotrexato, além de adequação da dose de levotiroxina, houve melhora clínica significativa e normalização da CK.33033

Consensus of systemic lupus erythematosus

Universidade de São Paulo Faculdade de MedicinaHospital Heliópolis de São Paulo Serviços de Clínicas MédicasUniversidade Federal do Rio Grande do Sul Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de Goiás Faculdade de MedicinaUniversidade Federal de Santa Catarina Hospital UniversitárioUniversidade Federal de Minas Gerais Faculdade de MedicinaSanta Casa de Belo Horizonte Clínica ReumatológicaUniversidade Estadual de Campinas Faculdade de Ciências MédicasUSP da Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP)UNIFESP, EPMUNIFESPSciEL

Subsidios para o diagnostico sorologico do envolvimento neuropsiquiatrico no lupus eritematoso sistemico : determinação dos anticorpos anticardiolipina, antigangliosideos e antigalactocerebrosideos

Orientador: Adil Mulib SamaraTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: As manifestações neuropsiquiátricas (MNP) do lupus eritematoso sistêmico(LES),importantes por sua frequência e gravidade,são de difícil caracterização laboratorial,não existindo elementos seguros que possam confirmar a sua presença. Com o intuito de encontrar um marcador sorológico para estas manifestações estudou-se uma população de 66 pacientes lúpicos classificados em três grupos: grupo A com MNP definidas, grupo B com MNP prováveis e grupo C sem MNP. Os soros destes pacientes foram analisados através de um ensaio imunoenzimático (ELISA) à procura de anticorpos antifosfolípides (anticardiolipina) e antiglicoesfingolípides (antigangliosídeos e antigalactocerebrosídeos). Os resultados reveleram que tanto os pacientes do grupo A como do grupo B tiveram aumento significativo dos anticorpos IgM antigangliosídeos e antigalactocerebrosídeos em oposição ao grupo C onde eles não ocorreram de modo significativo. Os anticorpos da classe IgG antigangliosídeos e antigalactocerebrosídeos não foram significativos nos três grupos. Nessa casuística os anticorpos anticardiolipina IgG e IgM não foram suficientes para caracterizar o envolvimento neuropsiquiátrico. Quando observados em relação à atividade dessas manifestações, se recentes ou não, sete pacientes do grupo A mostraram desaparecimento dos antigangliosídeos IgM e em alguns ocorreram posterior aparecimento de anticorpo da classe IgG. A análise dos anticorpos antigangliosídeos e anti-galactocerebrosídeos IgM por este método mostraram ter importante valor preditivo das MNP no LES, ressaltando-se que a negatividade do teste diminui sensivelmente a chance do paciente ter tal sintomatologia.Abstract: Neuropsychiatric manifestations (NPM) of Systemic Lupus Erythematosus (SLE) are common, therefore, their laboratorial characterization remains difficult. In an attempt to find a serologic marker for those manifestations, sera from 66 patients with SLE were classificated and studied into three groups: A - with defined NPMi B - with probable NPM and C - without NPM. They were analysed by Enzyrne-linked immunoabsorbent assay (ELISA) for measuring IgG and IgM anticardiolipin, antigangliosides and antigalactocerebrosides antibodies. A strong correlation was found between IgM antigangliosides and antigalactocerebrosides antibodies and neuropsychiatry involvement. That correlation was not found with IgG class antibodies. In this study, anticardiolipin IgG and IgM antibodies were not sufficient for monitoring patients with SLE and NPM. The IgM antigangliosides and antigalactocerebrosides antibodies disapeared in seven patients in group A with clinical inactive disease. In two of those, IgG class antibodies occured late. The analysis of antigangliosides and antigalactocerebrosides IgM antibodies in the ELISA assay showed a important role as predictive for NPM in SLE. The negative test decreases the chance of the NPM.DoutoradoDoutor em Medicin