ABSTRACT
BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.
Subject(s)
Raynaud Disease , Rheumatology , Scleroderma, Systemic , Scleroderma, Systemic/complications , Scleroderma, Systemic/drug therapy , Humans , Brazil , Rheumatology/standards , Raynaud Disease/drug therapy , Societies, Medical , Lung Diseases, Interstitial/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Rituximab/therapeutic use , Randomized Controlled Trials as Topic , Skin Ulcer/etiology , Antirheumatic Agents/therapeutic useABSTRACT
ABSTRACT Objective: To evaluate autoinflammatory diseases (AID) according to age at diagnosis and sex, and response to therapy in a large population. Methods: This is a cross-sectional observational study of a Latin American registry using a designed web system for data storage, collected between 2015 and 2018. Any altered findings during follow-up were recorded. The forms were translated into Portuguese and Spanish, including demographic, clinical, laboratory, genetic and treatment characteristics. Results: We included 152 patients, 51.3% male and 75% Caucasian. The median age at disease onset was 2.1 years (0-15.6 years) and median age at diagnosis 6.9 years (0-21.9 years); 111 (73%) were children (0-9 years old), and 41 (27%) were adolescents and young adults (AYA) (10-21 years old). Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) occurred in 46/152 (30%), chronic non-bacterial osteomyelitis (CNO) in 32/152 (21%), and familial Mediterranean fever (FMF) in 24/152 (15.7%). PFAPA was significantly higher in young children than in AYA (38.7% vs. 7.3%, p<0.001), while CNO were lower (13.5% vs. 41.5%, p<0.001). The frequency of females was significantly higher in CNO (28.4% vs. 14.1%, p=0.031) and lower in FMF (8.1% vs. 23.1%, p=0.011). The most used drugs were glucocorticoids, non-steroidal anti-inflammatory drugs (NSAID), and colchicine. Glucocorticoids and colchicine treatment were used in all AID with good to moderate response. However, cryopyrin-associated periodic syndromes (CAPS) seemed unresponsive to glucocorticoids. NSAIDs and methotrexate were the main medications used to treat CNO. Conclusions: Differences among AID patients were observed in the LA population regarding sex and age at disease diagnosis.
RESUMO Objetivo: Avaliar as doenças autoinflamatórias (DAI) de acordo com sexo e idade no momento do diagnóstico e a resposta terapêutica em uma grande população. Métodos: Este é um estudo observacional transversal de um registro latino-americano que usou um sistema de dados coletados entre 2015 e 2018. Quaisquer achados alterados ao longo do acompanhamento foram registrados. Os formulários foram traduzidos para os idiomas português e espanhol, incluindo características demográficas, clínicas, laboratoriais, genéticas e de tratamento. Resultados: Incluímos 152 pacientes, sendo 51,3% do sexo masculino e 75% da raça branca. A média de idade de início da doença foi de 2,1 anos (0-15,6 anos) e a média de idade de diagnóstico 6,9 anos (0-21,9 anos); 111 (73%) eram crianças (0-9 anos) e 41 (27%) adolescentes/adultos jovens (10-21 anos). A síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA) ocorreu em 46/152 (30%), osteomielite não bacteriana crônica (CNO) em 32/152 (21%) e febre familiar do Mediterrâneo (FMF) em 24/152 (15,7%). A PFAPA foi significativamente maior em crianças pequenas (38,7 vs. 7,3%, p<0,001), e a CNO, em adolescentes/adultos jovens (13,5 vs. 41,5%, p<0,001). A frequência do sexo feminino foi significativamente maior na CNO (28,4 vs. 14,1%, p=0,031) e menor na FMF (8,1 vs. 23,1%, p=0,011). Os medicamentos mais utilizados foram glicocorticoides, anti-inflamatórios não esteroidais (AINE) e colchicina. O tratamento com glicocorticoides e colchicina foi usado em todas as DAI com resposta boa a moderada. No entanto, as síndromes periódicas associadas à criopirina (CAPS) pareciam não responder aos glicocorticoides. AINE e metotrexato foram os principais medicamentos utilizados no tratamento da CNO. Conclusões: Diferenças de pacientes com DAI foram observadas na população latino-americana em pacientes agrupados por sexo e idade ao diagnóstico da doença.
ABSTRACT
Abstract Background Cognitive dysfunction (CD) is a widespread manifestation in adult systemic lupus erythematosus (SLE) patients, but this subject is rarely examined in patients with childhood-onset SLE (cSLE). This study aimed to assess the frequency of CD, its associations with lupus clinical manifestations and its impact on the health-related quality of life (HRQL) in young adult cSLE patients. Methods We evaluated 39 cSLE patients older than 18 years. They underwent a rheumatologic evaluation and extensive neuropsychological assessment, encompassing all cognitive domains described by the American College of Rheumatology. HRQL was assessed with the WHOOQOL-BREEF, General Activities of Daily Living Scale (GADL) and Systemic Lupus Erythematosus-specific quality-of-life instrument (SLEQOL). The activity of SLE was evaluated with the modified sle disease activity index (sledai-2k). Results Impairment in at least one cognitive domain was found in 35 (87.2%) patients. The most compromised domains were attention (64.1%), memory (46.2%), and executive functions (38.5%). Patients with cognitive impairment were older, had more accumulated damage and had worse socioeconomic status. Regarding the association between cognitive dysfunction and HRQL, memory impairment was correlated with worse environmental perception and a worse relationship with the treatment. Conclusion In this study, the frequency of CD in cSLE patients was as high as that in the adult SLE population. CD can significantly impact the response of cSLE patients to treatment, justifying preventive measures in the care of this population.
ABSTRACT
Objective: This study aims to describe the development and online distribution of a patient education booklet about systemic scleroderma focused on occupational therapy orientations. Methods: The research-action methodology was applied and divided into the following five steps: analysis of patients' requests, preparation of the content, choice of illustrations and graphic design, developers' approval of the education booklet, and online distribution. Results: The education booklet entitled "Occupational Therapy Guidelines for People with Systemic Sclerosis" was developed, and its online distribution reached nearly 5000 people. Conclusion: Educational materials serve as adjuncts to the treatment of chronic diseases, as systemic scleroderma. The online distribution of these materials expands its reach among these patients.
Objetivo: Este estudo visou descrever o desenvolvimento e distribuição online de uma cartilha educativa para pacientes com esclerodermia sistêmica com foco em orientações da terapia ocupacional. Métodos: A metodologia de pesquisa-ação foi aplicada e dividida em cinco etapas: análise das solicitações dos pacientes, elaboração do conteúdo, escolha das ilustrações e do projeto gráfico, aprovação dos autores da cartilha educativa e distribuição online. Resultados: Foi desenvolvida a cartilha educativa intitulada "Orientações da Terapia Ocupacional para Pessoas com Esclerose Sistêmica" e sua distribuição online atingiu quase 5.000 pessoas. Conclusão: Os materiais educativos constituem recurso útil no tratamento de doenças crônicas, como a esclerodermia sistêmica. A distribuição online desses materiais expande seu alcance entre os pacientes.
ABSTRACT
OBJECTIVE: The aim of this study was to access the prevalence of 19 neuropsychiatric syndromes in childhood-onset systemic lupus erythematosus (cSLE), as defined by the American College of Rheumatology (ACR) in 1999, by performing a systematic review and meta-analysis of relevant publications. METHODS: A literature search from April 1999 to March 2018 identified studies investigating neuropsychiatric syndromes in cSLE patients, applying 1999 ACR Case Definitions, with a sample of at least 20 patients. Case reports, small case series, reviews, articles that did not use 1999 ACR case definitions, and those with adult SLE patients were excluded. The methodological quality of the studies was determined through the Loney quality assessment. Prevalence estimates with a 95% confidence interval were combined using random-effect (DerSimonian-Laird) models. RESULTS: A total of 143 articles were identified and 9 were included. In a population of 1463 cSLE patients, 351 (29.9%) presented 869 neuropsychiatric cSLE events (2.48 events/patient). The results for each syndrome were headache (52.2%), seizure disorders (48.6%), cognitive dysfunction (32.9%), mood disorder (28.3%), psychosis (22.7%), cerebrovascular disease (19.5%), acute confusional state (15.7%), movement disorder (9.4%), anxiety disorder (7.2%), aseptic meningitis (5.1%), mononeuropathy single/multiplex (4.9%), myelopathy (4.2%), demyelinating syndrome (3.2%), cranial neuropathy (2.7%), polyneuropathy (2.6%), Guillain-Barré syndrome (2.5%), autonomic disorder (1.9%), plexopathy (1.3%), and myasthenia gravis (1.3%). CONCLUSIONS: Neuropsychiatric syndromes are prevalent among cSLE patients. The most prevalent were headaches, seizures, cognitive dysfunction, mood disorders, and psychosis. Determining the prevalence of each neuropsychiatric syndrome in cSLE may improve clinical awareness of these potentially fatal and disabling conditions.
Subject(s)
Lupus Erythematosus, Systemic , Lupus Vasculitis, Central Nervous System , Adult , Headache , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , Lupus Vasculitis, Central Nervous System/diagnosis , Lupus Vasculitis, Central Nervous System/epidemiology , Seizures , SyndromeABSTRACT
OBJECTIVE: To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS: 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. RECOMMENDATIONS: 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints. 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene. 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment. 4. The therapy of choice is colchicine; this drug has proven its effectiveness in preventing acute inflammatory episodes and progression toward amyloidosis in adults. 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.
Subject(s)
Amyloidosis, Familial/prevention & control , Colchicine/therapeutic use , Familial Mediterranean Fever/diagnosis , Familial Mediterranean Fever/therapy , Practice Guidelines as Topic , Pyrin/genetics , Amyloidosis, Familial/genetics , Evidence-Based Medicine , Familial Mediterranean Fever/genetics , Humans , Phenotype , SyndromeABSTRACT
OBJECTIVE: To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS: 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. RECOMMENDATIONS: 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1ß inhibitors prevents progression of bone lesions.
Subject(s)
Cryopyrin-Associated Periodic Syndromes/diagnosis , Cryopyrin-Associated Periodic Syndromes/therapy , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Practice Guidelines as Topic , Age of Onset , Cryopyrin-Associated Periodic Syndromes/genetics , Evidence-Based Medicine , Fever , Humans , Inflammation/genetics , Inflammation/immunology , Interleukin-1beta , Mutation , Prognosis , Severity of Illness Index , UrticariaABSTRACT
OBJECTIVE: To establish guidelines based on scientific evidence for the management of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. RESULTS: 806 articles were retrieved and evaluated by title and abstract; from these, 32 articles were selected to support the recommendations. RECOMMENDATIONS: 1. PFAPA is a diagnosis of exclusion established on clinical grounds, and one must suspect of this problem in children with recurrent and periodic febrile episodes of unknown origin, or with recurrent tonsillitis interspersed with asymptomatic periods, especially in children in good general condition and with preservation of weight and height development. 2. Laboratory findings are nonspecific. Additional tests do not reveal pathognomonic changes. 3. The evidence supporting an indication for surgical treatment (tonsillectomy with or without adenoidectomy), is based on two non-blinded randomized clinical trials with small numbers of patients. 4. The use of prednisone at the onset of fever in patients with PFAPA proved to be an effective strategy. There is still need for more qualified evidence to support its use in patients with PFAPA. 5. Despite promising results obtained in studies with IL-1ß inhibitors, such studies are limited to a few case reports.
Subject(s)
Fever/therapy , Lymphadenitis/therapy , Pharyngitis/therapy , Practice Guidelines as Topic , Stomatitis, Aphthous/therapy , Adenoidectomy , Fever/diagnosis , Fever/surgery , Humans , Lymphadenitis/diagnosis , Lymphadenitis/surgery , Pharyngitis/diagnosis , Pharyngitis/surgery , Stomatitis, Aphthous/diagnosis , Stomatitis, Aphthous/surgery , Syndrome , TonsillectomyABSTRACT
Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo da febre familiar do Mediterrâneo (FFM). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de 5 questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultados: Foram recuperados, e avaliados pelo título e resumo, 10.341 trabalhos e selecionados 46 artigos para sustentar as recomendações. Recomendações: 1. O diagnóstico da FFM é baseado nas manifestações clínicas, caracterizadas por episódios febris recorrentes associados a dor abdominal, torácica ou artrite de grandes articulações; 2. A FFM é uma doença genética que apresenta traço autossômico recessivo ocasionada por mutação no gene MEFV; 3. Exames laboratoriais são inespecíficos e demonstram níveis séricos elevados de proteínas inflamatórias na fase aguda da doença, mas também, com frequência, níveis elevados mesmo entre os ataques. Níveis séricos de SAA podem ser especialmente úteis no monitoramento da eficácia do tratamento; 4. A colchicina é a terapia de escolha e demonstrou eficácia na prevenção dos episódios inflamatórios agudos e progressão para amiloidose em adultos; 5. Com base na informação disponível, o uso de medicamentos biológicos parece ser opção para pacientes com FFM que não respondem ou que são intolerantes à terapia com colchicina.
Abstract Objective: To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. Description of the evidence collection method: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. Recommendations: 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints; 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene; 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment; 4. The therapy of choice is colchicine; this drug has proven effectiveness in preventing acute inflammatory episodes and progression towards amyloidosis in adults; 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.
Subject(s)
Humans , Familial Mediterranean Fever/diagnosis , Familial Mediterranean Fever/therapy , Colchicine/therapeutic use , Practice Guidelines as Topic , Amyloidosis, Familial/prevention & control , Pyrin/genetics , Familial Mediterranean Fever/genetics , Phenotype , Syndrome , Evidence-Based Medicine , Amyloidosis, Familial/geneticsABSTRACT
Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo das síndromes periódicas associadas à criopirina (criopirinopatias – Caps). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de quatro questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultado: Foram recuperados, e avaliados pelo título e resumo, 1.215 artigos e selecionados 42 trabalhos para sustentar as recomendações. Recomendações: 1. O diagnóstico de Caps é baseado na anamnese e nas manifestações clínicas e posteriormente confirmado por estudo genético. Pode se manifestar sob três fenótipos: FCAS (forma leve), MWS (forma intermediária) e Cinca (forma grave). Avaliações neurológica, oftalmológica, otorrinolaringológica e radiológica podem ser de grande valia na distinção entre as síndromes; 2. O diagnóstico genético com análise do gene NLRP3 deve ser conduzido nos casos suspeitos de Caps, isto é, indivíduos que apresentam, antes dos 20 anos, episódios recorrentes de inflamação expressa por urticária e febre moderada; 3. As alterações laboratoriais incluem leucocitose e elevação nos níveis séricos de proteínas inflamatórias; 4. Terapias alvo dirigidas contra a interleucina 1 levam a rápida remissão dos sintomas na maioria dos pacientes. Contudo, existem limitações importantes em relação à segurança em longo prazo. Nenhuma das três medicações anti-IL1β evita progressão das lesões ósseas.
Abstract Objective: To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. Description of the evidence collection method: The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. Recommendations: 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions.
Subject(s)
Humans , Practice Guidelines as Topic , Cryopyrin-Associated Periodic Syndromes/diagnosis , Cryopyrin-Associated Periodic Syndromes/therapy , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Prognosis , Urticaria , Severity of Illness Index , Age of Onset , Evidence-Based Medicine , Interleukin-1beta , Cryopyrin-Associated Periodic Syndromes/genetics , Fever , Inflammation/genetics , Inflammation/immunology , MutationABSTRACT
Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo da síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA). Descrição do método de coleta de evidência: A Diretriz foi elaborada a partir de cinco questões clínicas que foram estruturadas por meio do Pico (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultados: Foram recuperados e avaliados pelo título e resumo 806 trabalhos e selecionados 32 artigos, para sustentar as recomendações. Recomendações: 1. O diagnóstico da PFAPA é clínico e de exclusão, deve a suspeita ser considerada em crianças que apresentam episódios febris de origem indeterminada recorrentes e periódicos ou amidalites de repetição, intercalados com períodos assintomáticos, sobretudo em crianças em bom estado geral e com desenvolvimento pondero-estatural mantido; 2. Os achados laboratoriais são inespecíficos. Não existem alterações patognomônicas nos exames complementares; 3. A evidência que sustenta a indicação do tratamento cirúrgico (tonsilectomia com ou sem adenoidectomia) é baseada em dois ensaios clínicos randomizados não cegos que incluíram pequeno número de pacientes; 4. O uso de prednisona no início do quadro febril em pacientes com PFAPA mostrou ser eficaz. Melhores evidências ainda são necessárias para apoiar seu uso na PFAPA; 5. Apesar de os resultados obtidos de estudos com inibidores de IL-1ß serem promissores, esses são limitados a poucos relatos de casos.
Abstract Objective: To establish guidelines based on scientific evidence for the management of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Description of the evidence collection method: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 806 articles were retrieved and evaluated by title and abstract; from these, 32 articles were selected to support the recommendations. Recommendations: 1. PFAPA is a diagnosis of exclusion established on clinical grounds, and one must suspect of this problem in children with recurrent and periodic febrile episodes of unknown origin, or with recurrent tonsillitis interspersed with asymptomatic periods, especially in children in good general condition and with preservation of weight and height development. 2. Laboratory findings are nonspecific. Additional tests do not reveal pathognomonic changes. 3. The evidence supporting an indication for surgical treatment (tonsillectomy with or without adenoidectomy), is based on two non-blinded randomized clinical trials with small numbers of patients. 4. The use of prednisone at the onset of fever in patients with PFAPA proved to be an effective strategy. There is still need for more qualified evidence to support its use in patients with PFAPA. 5. Despite promising results obtained in studies with IL-1β inhibitors, such studies are limited to a few case reports.
Subject(s)
Humans , Stomatitis, Aphthous/therapy , Pharyngitis/therapy , Practice Guidelines as Topic , Fever/therapy , Lymphadenitis/therapy , Stomatitis, Aphthous/surgery , Stomatitis, Aphthous/diagnosis , Syndrome , Tonsillectomy , Adenoidectomy , Pharyngitis/surgery , Pharyngitis/diagnosis , Fever/surgery , Fever/diagnosis , Lymphadenitis/surgery , Lymphadenitis/diagnosisABSTRACT
A síndrome de ativação macrofágica (SAM) é uma doença rara e potencialmente fatal, normalmente associada às doenças reumáticas crônicas, em especial a artrite idiopática juvenil. É incluída no grupo das formas secundárias de síndrome hemofagocítica, cujas outras causas podem ser as doenças linfoproliferativas e infecções. As manifestações clínicas e laboratoriais mais importantes são a febre não remitente, esplenomegalia, hemorragias, disfunção hepática, citopenias, hipoalbuminemia, hipertrigliceridemia e hiperferritinemia. O tratamento deve ser iniciado rapidamente, e a maioria dos casos responde bem aos corticosteroides e à ciclosporina (CSA). O vírus Epstein-Barr (EBV) é descrito como possível gatilho para muitos casos de SAM, especialmente naqueles em tratamento com bloqueadores do fator de necrose tumoral (TNF). Nos casos refratários ao tratamento convencional, etoposide (VP16) deve ser administrado, em associação com corticosteroides e CSA. Nosso objetivo foi descrever um caso raro de síndrome hematofagocítica provavelmente secundária à infecção pelo vírus Epstein-Barr (EBV), em paciente com artrite idiopática juvenil sistêmica, confirmada pelas manifestações clínicas e laboratoriais típicas, mielograma e sorologia positiva contra o EBV, que atingiu remissão completa após inclusão no protocolo de tratamento HLH-04.
Machrophage activation syndrome (MAS) is a rare and potentially fatal disease, commonly associated with chronic rheumatic diseases, mainly juvenile idiopathic arthritis. It is included in the group of secondary forms of haemophagocytic syndrome, and other causes are lymphoproliferative diseases and infections. Its most important clinical and laboratorial manifestations are non-remitting fever, splenomegaly, bleeding, impairment of liver function, cytopenias, hypoalbuminemia, hypertriglyceridemia, hypofibrinogenemia and hyperferritinemia. The treatment needs to be started quickly, and the majority of cases have a good response with corticosteroids and cyclosporine. The Epstein–Barr virus is described as a possible trigger for many cases of MAS, especially in these patients in treatment with tumor necrosis factor (TNF) blockers. In these refractory cases, etoposide (VP16) should be administered, associated with corticosteroids and cyclosporine. Our objective is to describe a rare case of MAS probably due to EBV infection in a subject with systemiconset juvenile idiopathic arthritis, which achieved complete remission of the disease after therapy guided by 2004-HLH protocol.
Subject(s)
Humans , Female , Child , Arthritis, Juvenile/complications , Macrophage Activation Syndrome/etiologyABSTRACT
Machrophage activation syndrome (MAS) is a rare and potentially fatal disease, commonly associated with chronic rheumatic diseases, mainly juvenile idiopathic arthritis. It is included in the group of secondary forms of haemophagocytic syndrome, and other causes are lymphoproliferative diseases and infections. Its most important clinical and laboratorial manifestations are non-remitting fever, splenomegaly, bleeding, impairment of liver function, cytopenias, hypoalbuminemia, hypertriglyceridemia, hypofibrinogenemia and hyperferritinemia. The treatment needs to be started quickly, and the majority of cases have a good response with corticosteroids and cyclosporine. The Epstein-Barr virus is described as a possible trigger for many cases of MAS, especially in these patients in treatment with tumor necrosis factor (TNF) blockers. In these refractory cases, etoposide (VP16) should be administered, associated with corticosteroids and cyclosporine. Our objective is to describe a rare case of MAS probably due to EBV infection in a subject with systemic-onset juvenile idiopathic arthritis, which achieved complete remission of the disease after therapy guided by 2004-HLH protocol.
Subject(s)
Arthritis, Juvenile/complications , Macrophage Activation Syndrome/etiology , Child , Female , HumansABSTRACT
2'5'OAS are template-independent RNA polymerases with antiviral activity and important to homeostasis maintenance. Here we have developed quantitative PCR (qPCR) reactions for the detection of each individual 2'5'OAS human gene and used them to evaluate these gene levels in systemic sclerosis patients cells. The method was efficient for quantification of 2'5'OAS genes on human cells after interferon (IFN) treatment, and revealed that primary cells from patients with systemic sclerosis have increased basal levels of OASL and OAS2 genes. When treated, patients cells are able to induce all four 2'5'OAS genes. Our hypothesis is that abnormally circulating type I IFNs on the disease could be establishing a desensitized state on patients cells, making them refractory to subsequent IFN doses, and that OASL and OAS2 genes upregulation may be due to an IFN-independent stimulus. Further characterizing the biological activities of these genes, their induction pathways and their regulatory functions can lead to better understanding of systemic sclerosis molecular mechanisms and of their biological activities.
Subject(s)
2',5'-Oligoadenylate Synthetase/genetics , Leukocytes, Mononuclear/immunology , Polymerase Chain Reaction/methods , Scleroderma, Systemic/genetics , 2',5'-Oligoadenylate Synthetase/immunology , Adult , Aged , Cell Line, Tumor , Female , Gene Expression , Humans , Interferon-alpha/pharmacology , Interferon-beta/pharmacology , Isoenzymes/genetics , Isoenzymes/immunology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Organ Specificity , Primary Cell Culture , Scleroderma, Systemic/immunology , Scleroderma, Systemic/pathology , Up-RegulationABSTRACT
Hemorragia alveolar é afecção clínica grave e com alta taxa de mortalidade. Pode ocorrer em indivíduos com lúpus eritematoso sistêmico e a instituição de imunossupressão precoce é medida salvadora. Como é de diagnóstico difícil, sua condução clínica é um desafio. No presente artigo relata-se a experiência recente com dois pacientes e as recomendações de terapêutica, segundo revisão de literatura médica.
Alveolar hemorrhage is a severe clinical disease with high rate of mortality. It can affect individuals with systemic lupus erythematosus, and early immunosuppression is a life-saving measure. However, the difficulty of diagnosis is a challenge for clinical handling of the disease. This paper reports on a recent experience with two patients, and provides treatment recommendations drawing on a review of the literature.
Subject(s)
Humans , Male , Adolescent , Pulmonary Alveoli/pathology , Hemorrhage/diagnosis , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Biopsy , Nasal Lavage Fluid , Radiography, ThoracicABSTRACT
Objective. Systemic sclerosis (SSc) is a complex autoimmune disease in which interferons (IFNs) may play an essential role. We hypothesized that type I and III IFNs may be found in increased levels in patients and be responsible for SSc autoimmune status. Methods. Type I and III IFN and ISG basal expression profiles were measured by qPCR using RNA from PBMCs of patients and controls . Results. Type I IFNs are increased in SSc patients, while no induction of type III IFNs was detected. This induction cannot be related to IRF7, since no upregulation of this gene was seen on patients. Of the ISGs tested, 2'5'OAS levels were increased in patients, while 6-16 and MxA levels were not. Conclusions. While there is no indication of type III IFN induction, increased levels of type I IFNs may lead to abnormal regulation of ISGs that can be responsible for immune system alterations described for SSc.
ABSTRACT
O termo artrite idiopática juvenil (AIJ) descreve um grupo clinicamente heterogêneo de artrites com mais de seis semanas de duração, de causa desconhecida e início até os 16 anos de idade. Objetivo: descrever o perfil clínico de um grupo de pacientes com diagnóstico de AIJ. Métodos: os prontuários de 72 indivíduos foram revistos com o objetivo de classificá-los conforme critérios propostos pelo ILAR. Os dados obtidos foram comparados com a literatura. Resultados: eram 37 crianças (51,4%) do sexo masculino e 35 do sexo feminino, com mediana de idade de 164,5 meses; 23 (31,9%) estavam classificados como sistêmicos, 25 (34,7%) como oligoarticulares, três (4,2%) poliarticulares fator reumatoide positivo, 13 (18,1%) poliarticulares fator reumatoide negativo, três (4,2%) com artrite psoriásica, quatro (5,6%) com artrite associada à entesite e um (1,4%) com doença indiferenciada. O fator reumatoide foi positivo em 10 (13,9%) e o FAN em 14 (19,4%). Uveíte crônica foi encontrada em quatro (5,6%) crianças, todas do sexo feminino (p=0,05), com doença iniciada antes dos quatro anos de idade (p=0,03) e com FAN positivo (p < 0,001). Conclusão: sabe-se que há diferenças na prevalência e na distribuição dos subtipos de AIJ dependendo da origem da população. Os dados analisados neste estudo, o primeiro do gênero em nosso país, indicaram importantes diferenças entre os diversos grupos geográficos/étnicos acometidos pela AIJ, sugerindo a influência de fatores genéticos, associados ou não a fatores ambientais, que deverão ser estudados e confirmados posteriormente, na expressão da AIJ.
The term Juvenile Idiopathic Arthritis (JIA) describes an arthritis clinically heterogeneous group of over six week?s duration, unknown causes and beginning up to 16 years old. Objective: to describe the clinic profile of a patients? group with JIA diagnosis. Methods: the records of 72 individuals were reviewed with the aim of classifying them according to the ILAR proposed criteria. The collected data were compared with the literature. Results: there was 37 male children (51,4%) and 35 female, with the mean age of 164,5 months; 23 (31,9%) were classified as systemic, 25 (34,7%) as oligoarticular, three (4,2%) as polyarticular positive rheumatoid factor, 13 (18,1%) polyarticular negative rheumatoid factor, three (4,2%) psoriatic arthritis, four (5,6%) with arthritis associated to enthesitis and one (1,4%) with indifferenced disease. The rheumatoid factor was positive in 10 (13,9%) and the FAN in 14 (19,4%). Chronic uveitis was found in four (5,6%) children, all female (p=0,05), with the disease started before four years old (p=0,03) and with positive FAN (p < 0,001). Conclusion: it is known that there are differences in the prevalence and distribution of the JIA subtypes depending on the population origins. The data analyzed in this study, the first of the kind in our country, indicate relevant differences between the several geographic / ethnical groups affected by the JIA, suggesting the influence of docugenetic factors, whether associated or not to environmental factors, which must be further studied and confirmed.
Subject(s)
Humans , Male , Female , Adolescent , Arthritis, Juvenile/epidemiology , Brazil , UveitisABSTRACT
O pioderma gangrenoso (PG) faz parte do espectro das dermatoses neutrofílicas, processos que têm em comum um padrão histológico similar, formado por infiltrado de leucócitos polimorfonucleares, de caráter não infeccioso e não neoplásico e sem vasculite primária. Caracteriza-se por úlceras dolorosas, com bordas imprecisas, de variados tamanhos e profundidade, localizadas principalmente nos membros inferiores, mas outras partes da pele, mucosas e outros órgãos podem estar envolvidos. A doença tem grande morbidade e seu curso pode ser crônico ou recidivante. A patogênese não é bem conhecida. Em 50 a 70 por cento dos pacientes, está associado a uma doença de base, como doença inflamatória intestinal, doenças reumáticas, hematológicas ou malignidades; pode apresentar-se de forma isolada. São analisados dois pacientes com o diagnóstico de pioderma gangrenoso e artrite associada, para ressaltar a importância do conhecimento dessa dermatose pelo reumatologista, já que o acometimento articular ocorre em cerca de 37 por cento dos pacientes que apresentam essa síndrome neutrofílica.
Pyoderma gangrenosum (PG) is a necrotizing neutrophilic dermatosis, a condition with polymorphonuclear infiltrates, which is non-infective, non neoplastic and has no primary vasculitis. It may be idiopathic or associated with a systemic disorder. It is characterized by painful ulcers with undermined edge, of variable depth and size. The legs are most commonly affected but other parts of the skin and mucous membranes may also be involved. The course can be mild or malignant, chronic or relapsing, and has a remarkable morbidity. The pathogenesis is unknown. In 50 to 70 percent of the patients, PG is associated with underlying systemic diseases such as inflammatory bowel disease, myeloproliferative disorders, hematological or malignancies; it can appear in isolated form. This is a report of two patients with PG and arthritis which intends to show the importance, for rheumatologists, of considering this dermatosis, since articular complaints are present in 37 percent of the PG patients.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Arthritis , Neutrophils , Pyoderma Gangrenosum , Skin Ulcer , VasculitisABSTRACT
A pancreatite aguda é uma manifestação incomum do lúpus eritematoso sistêmico (LES) e a freqüência desta associação não é conhecida. Contudo, a pancreatite aguda é um diagnóstico diferencial importante da dor abdominal em pacientes com LES. Os pacientes, normalmente, apresentam dor de intensidade variável, algumas vezes simulando abdome agudo. Vários fatores têm sido implicados na patogênese desta condição, tais como fenômeno autoimunes, vasculite, anticorpos antifosfolípides e drogas. O papel dos corticosteróides como um fator etiológico é ainda controverso. Além disso, em alguns relatos a manutenção do corticosteróide foi fundamental na recuperação dos pacientes. Relatamos duas pacientes com lúpus eritematoso sistêmico que apresentaram pancreatite aguda. Em nenhum dos casos havia evidências de quaisquer fatores predisponentes conhecidos para a pancreatite aguda, portanto esta condição foi considerada uma manifestação de atividade lúpica. Uma das pacientes faleceu por síndrome da resposta inflamatória sistêmica secundária à pancreatite. No outro caso, utilizou-se corticóide em doses de estresse durante o tratamento, com boa evolução
Subject(s)
Humans , Female , Adolescent , Adrenal Cortex Hormones , Lupus Erythematosus, Systemic , PancreatitisABSTRACT
Relata-se um caso de acometimento inflamatório da articulação cricoaritenóide em um paciente com diagnóstico de artrite reumatóide juvenil (ARJ), em vigência de atividade sistêmica exuberante, com consequente obstrução significante das vias aéreas superiores. Ressalta-se que, apesar da terapêutica imunossupressora sistêmica, foi fundamental o uso de corticoterapia inalatória para a melhora do paciente