Blanca Elena Rios Gomes Bica

Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis : a randomised trial

BACKGROUND Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis. METHODS We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedmans test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960. FINDINGS Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35.5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0.0228). Median time to clinical remission was 41.9 months in patients assigned prednisone plus methotrexate but was not observable in the other two treatment groups (2.45 fold [95% CI 1.2-5.0] increase with prednisone plus methotrexate; p=0.012). Median time to treatment failure was 16.7 months in patients allocated prednisone, 53.3 months in those assigned prednisone plus ciclosporin, but was not observable in patients randomised to prednisone plus methotrexate (1.95 fold [95% CI 1.20-3.15] increase with prednisone; p=0.009). Median time to prednisone discontinuation was 35.8 months with prednisone alone compared with 29.4-29.7 months in the combination groups (p=0.002). A significantly greater proportion of patients assigned prednisone plus ciclosporin had adverse events, affecting the skin and subcutaneous tissues, gastrointestinal system, and general disorders. Infections and infestations were significantly increased in patients assigned prednisone plus ciclosporin and prednisone plus methotrexate. No patients died during the study. INTERPRETATION Combined treatment with prednisone and either ciclosporin or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate. FUNDING Italian Agency of Drug Evaluation, Istituto Giannina Gaslini (Genoa, Italy), Myositis Association (USA).

Consenso de imunização para crianças e adolescentes com doenças reumatológicas

Criancas e adolescentes com doencas reumatologicas apresentam maior prevalencia de doencas infecciosas quando comparados com a populacao em geral, em decorrencia de atividade da doenca, possivel deficiencia imunologica secundaria a propria doenca, ou uso de terapia imunossupressora. A vacinacao e uma medida eficaz para a reducao da morbidade e mortalidade nesses pacientes. O objetivo deste artigo foi realizar um consenso de eficacia e seguranca das vacinas em criancas e adolescentes com doencas reumatologicas infantis baseadas em niveis de evidencia cientifica. Imunizacao passiva para os pacientes e orientacoes para as pessoas que convivem com doentes imunodeprimidos tambem foram incluidas. Os 32 pediatras reumatologistas membros do Departamento de Reumatologia da Sociedade de Pediatria de Sao Paulo (SPSP) e/ou da Comissao de Reumatologia Pediatrica da Sociedade Brasileira de Reumatologia elaboraram o consenso, sendo que alguns desses profissionais estao envolvidos em pesquisas e publicacoes cientificas nesta area. A pesquisa dos termos eficacia e/ou seguranca das diferentes vacinas em criancas e adolescentes com doencas reumatologicas foi realizada nas bases de Medline e Scielo, de 1966 ate marco de 2009, incluindo revisoes, estudos controlados e relatos de casos. O grau de recomendacao e o nivel cientifico de evidencias dos estudos foram classificados em quatro niveis para cada vacina. De um modo geral, as vacinas inativadas e de componentes sao seguras nos pacientes com doencas reumatologicas, mesmo em uso de terapias imunossupressoras. Entretanto, vacinas com agentes vivos atenuados sao, em geral, contraindicadas para os pacientes imunossuprimidos.Incidence of infectious diseases is higher in children and adolescents with rheumatic diseases than in the general population due to disease activity, possible immune deficiency secondary to the disease itself, or the use of immunosuppressive drugs. Vaccination is effective in reducing morbidity and mortality in those patients. The objective of this study was to establish an evidence-based consensus on the efficacy and safety of vaccination in children and adolescents with rheumatic diseases. Passive immunization of patients and guidelines for people who live with immunosuppressed patients were also included. The 32 pediatric rheumatologists of the Rheumatology Department of the Pediatrics Society of Sao Paulo, (SPSP, from the Portuguese), Sao Paulo, SP, Brazil, and/or the Commission on Pediatrics Rheumatology of the Brazilian Society of Rheumatology are responsible for this consensus; some of those professionals are involved on research and scientific publications in this field. The words efficacy and/or safety of different vaccines in children and adolescents with rheumatologic diseases were searched in Medline and Scielo data bases from 1966 to March 2009, including reviews, controlled studies, and case reports. The degree of recommendation and the scientific evidence of the studies were classified in four levels for each vaccine. As a rule, inactive and protein components vaccines are safe for patients with rheumatologic diseases, even in the presence of immunosuppressive therapy. However, live attenuated vaccines are, in general, contraindicated for immunosuppressed patients.

Avaliação da função endotelial em pacientes com esclerose sistêmica limitada por meio do eco Doppler da artéria braquial

OBJECTIVES The aim of this study was to compare the brachial artery endothelium-dependent and endothelium-independent dilating responses in patients with limited systemic sclerosis (LSSc) with those of healthy subjects of the same gender, age and color. METHODS Twenty adult, non-obese, non-smoker, non-diabetic, non-dyslipidemic, and non-hypertensive women, who fulfilled the American College of Rheumatology criteria for the diagnosis of SSc, were submitted to right brachial artery Doppler ultrasound. The vasodilating responses were analyzed as follows: the endothelium-dependent dilating response, after a 5-minute ischemia in the right arm; and the endothelium-independent dilating response, after administering 300 mcg of nitroglycerin (NTG) sublingually. The results were compared with the response obtained in healthy subjects. RESULTS Brachial artery longitudinal diameter was significantly low at baseline 1: 3.57 ± 0.52 mm and 3.93 ± 0.39 mm for the LSSc group and the control group, respectively, P = 0.005. The vascular reactivity after the ischemia/reactive hyperemia and the NTG showed no significant difference between the groups (8.60 ± 5.45 mm vs. 9.26 ± 5.91 mm and 25.01 ± 12.55 mm vs. 19.59 ± 7.94 mm for the LSSc and control groups, respectively). Also, no statistically significant difference was found between red blood cell velocity (RBCV) after reactive hyperemia and NTG (110.2 ± 43.86 cm/s vs. 102.0 ± 25.89 cm/s and 63.80 ± 17.69 cm/s vs. 65.4 ± 12.90 cm/s in the LSSc and control groups, respectively). CONCLUSION Although the LSSc group showed lower brachial artery diameter, the endothelium-dependent and the endothelium-independent dilating responses were preserved in both groups.

Brazilian multicenter study of 71 patients with juvenile-onset Takayasu's arteritis: clinical and angiographic features

OBJECTIVE To describe the clinical and angiographic characteristics of Takayasus arteritis in Brazilian children and adolescents. METHODS A retrospective data collection was performed in 71 children and adolescents followed in 10 Brazilian reference centers in Pediatric Rheumatology. The evaluation was carried out in three different time points: from onset of symptoms to diagnosis, from the 6th to 12th month of diagnosis, and in the last visit. RESULTS Of 71 selected patients, 51 (71.8%) were girls. The mean age of onset of symptoms and of time to diagnosis was 9.2 (±4.2) years and 1.2 (±1.4) years, respectively. At the end of the study, 20 patients were in a state of disease activity, 39 in remission and 5 had evolved to death. The most common symptoms in baseline assessment, second evaluation, and final evaluation were, respectively: constitutional, musculoskeletal, and neurological symptoms. A decrease in peripheral pulses was the most frequent cardiovascular signal, and an increase in erythrocyte sedimentation rate was the most frequent laboratory finding in all three evaluation periods. The tuberculin test was positive in 41% of those tested. Stenosis was the most frequent angiographic lesion, abdominal artery was the most affected segment, and angiographic type IV the most frequent. Most (90%) participants were treated with glucocorticoids, 85.9% required another immunosuppressive drug, and 29.6% underwent angioplasty. CONCLUSION This is the largest study on juvenile-onset Takayasu arteritis, and a high number of patients under the age of 10 years, with predominance of constitutional symptoms early in the disease, was observed.

Avaliação colonoscópica em pacientes com espondilite anquilosante

INTRODUCTION Patients with ankylosing spondylitis can have intestinal inflammatory lesions, thus the use of colonoscopy for such patients should be defined. OBJECTIVES To assess the gross intestinal colonoscopic changes and microscopic histopathologic findings of patients with ankylosing spondylitis; to correlate the colonoscopic and histopathologic findings; and to study the relationship of the histopathologic findings with extra-articular manifestations of the disease, HLA-B27, BASFI and BASDAI. METHODS This is a cross-sectional study of 22 patients with ankylosing spondylitis. The patients underwent clinical assessment, BASDAI and BASFI application, blood collection for HLA-B27 measurement, and colonoscopy with biopsy of four intestinal segments (terminal ileum, right and sigmoid colons, and rectum). RESULTS Abnormal colonoscopic results were obtained in 13 (59.1%) patients, the major abnormality being intestinal polyps. The groups of normal and abnormal colonoscopic results (n=9 and n=13, respectively) were homogeneous regarding age, BASFI, BASDAI, and categorical variables, and the P-value showed no significant difference between groups. The histopathological findings revealed abnormal biopsies in 81%, 90.9%, 90.9% and 86.4% for terminal ileum, right colon, sigmoid colon, and rectum, respectively. The histopathologic results showed no statistically significant association with the extra-articular manifestations, BASFI, BASDAI and HLA-B27 positivity. CONCLUSIONS The histological analysis of the four intestinal segments evidenced inflammatory lesions in patients with normal and abnormal colonoscopic results, independently of bowel symptomatology and therapy used in the treatment of the basal disease.

Associação entre artrite idiopática juvenil e osteogenesis imperfecta: relato de caso

The authors report a rare association case of juvenile idiopathic arthritis (JIA) and osteogenesis imperfecta (OI) in a 53 years-old female patient, present a literature review and discuss the radiological aspects of the temporo-mandibular joint involvement. To our knowledge, this is the first case report of JIA an OI association.

Efeitos adversos durante a infusão de infliximabe em crianças e adolescentes: estudo multicêntrico

OBJECTIVE: To evaluate the frequency and the severity of the adverse reactions during the infusion of infliximab. METHODS: We performed a retrospective chart review of 58 patients, followed up at 5 paediatric rheumatology centers. All patients presented refractory disease or were intolerant to one or more disease modifying drugs and received one or more infliximab infusions. The data analysis was descriptive, considering the frequency and the kind of adverse reactions as well as the number of the infusions, the infliximab dose and the indication. RESULTS: The mean age at the onset of infliximab was 12 years and 9 months and the mean of the disease duration was 7 years and 7 months. The main indication of the drug was juvenile idiopathic arthritis (43). Twenty five out of 58 patients (43.1%) presented adverse reactions during the infusion and 17 (29,3%) had to withdraw the treatment. The reactions were: dyspnea (ten), nausea and vomiting (eight), rash (seven), anaphylaxis (six), flush (five), angioedema (four), chest pain (four) besides urticaria, hypertension, among others. The anaphylaxis was more frequent between the fourth and the sixth infusion. CONCLUSION: The frequency and the severity of adverse reactions to infliximab must be considered not only in relation to its indication, but mainly for the choice of the center to the drug infusion where emergency treatment may be performed.

Tocilizumab is a promising treatment option for therapy resistant juvenile localized scleroderma patients

Introduction Juvenile localized scleroderma (jlSc) usually responds well to treatment with methotrexate or mycophenolate. In case of nonresponse or partial response, tocilizumab (TOC) appears to be a promising option. Methods Participants of the Pediatric Rheumatology Email Board were asked to report patients with jlSc treated with TOC. Results Six centers responded and reported 11 patients. The mean age at disease onset was 5.5 years. Disease duration at time of the initiation of TOC was 4.5 years. A total of 5 patients had linear subtype, 2 Parry Romberg syndrome, and 1 morphea en coup de sabre. Three had a generalized subtype, 2 a mixed subtype, and 1 a limited subtype/morphea. Before starting TOC, 10 of 11 patients received methotrexate, 7/11 combination methotrexate and mycophenolate, 1 abatacept, and 1 antitumor necrosis factor therapy. The indications for starting TOC were: (i) an increase in the score of the Localized Scleroderma Activity Index (mLoSSI) in 9 patients; and (ii) evidence of increased extra-cutaneous activity in 2 patients. The mean duration of TOC therapy was 14.75 months. Three of 11 patients received TOC as monotherapy, and 8/11 as combination therapy. Therapy success was reflected by a decreased mLoSSI in 9/11 patients, no new lesion occurrence, and – with Parry Romberg syndrome subtype – no increase in facial atrophy. In 8/8 patients, both the physicians’ and patients’ global assessment of disease activity decreased. In 3/3 patients, the number of active joints decreased. The mean modified Rodnan skin score decreased from 8.7 to 5.6. Conclusions In this small cohort of patients, TOC seems to be a promising rescue medication.

Staphylococcal superantigen-specific IgE antibodies: degree of sensitization and association with severity of asthma

ABSTRACT Objective: To determine the presence of staphylococcal superantigen-specific IgE antibodies and degree of IgE-mediated sensitization, as well as whether or not those are associated with the severity of asthma in adult patients. Methods: This was a cross-sectional study involving outpatients with asthma under treatment at a tertiary care university hospital in the city of Rio de Janeiro, Brazil. Consecutive patients were divided into two groups according to the severity of asthma based on the Global Initiative for Asthma criteria: mild asthma (MA), comprising patients with mild intermittent or persistent asthma; and moderate or severe asthma (MSA). We determined the serum levels of staphylococcal toxin-specific IgE antibodies, comparing the results and performing a statistical analysis. Results: The study included 142 patients: 72 in the MA group (median age = 46 years; 59 females) and 70 in the MSA group (median age = 56 years; 60 females). In the sample as a whole, 62 patients (43.7%) presented positive results for staphylococcal toxin-specific IgE antibodies: staphylococcal enterotoxin A (SEA), in 29 (20.4%); SEB, in 35 (24.6%); SEC, in 33 (23.2%); and toxic shock syndrome toxin (TSST), in 45 (31.7%). The mean serum levels of IgE antibodies to SEA, SEB, SEC, and TSST were 0.96 U/L, 1.09 U/L, 1.21 U/L, and 1.18 U/L, respectively. There were no statistically significant differences between the two groups in terms of the qualitative or quantitative results. Conclusions: Serum IgE antibodies to SEA, SEB, SEC, and TSST were detected in 43.7% of the patients in our sample. However, neither the qualitative nor quantitative results showed a statistically significant association with the clinical severity of asthma.

[Lipoma arborescens of the knee in a patient with ankylosing spondylitis: case report and literature review].

Lipoma arborescens (LA) is defined as a villous lipomatous proliferation of the synovial membrane with diffuse substitution of the synovial tissue by mature fat cells. The injury is very rare, involving the knee joint (suprapatellar region) and is associated with degenerative joint disease. We describe the case of a male patient, suffering from ankylosing spondylitis with monoarthritis of the right knee and swelling in suprapatellar region important. The diagnosis of lipoma arborescens was confirmed from the MRI of the right knee.