Ana Júlia Pantoja de Moraes

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.

Reproductive health in male systemic lupus erythematosus

OBJECTIVE: To assess reproductive health in male systemic lupus erythematosus (SLE) patients and compare them with controls. METHODS: Twenty-five male SLE patients were evaluated for demographic data, urologic evaluation (including pubertal parameters, sexual/erectile function), testicular Doppler ultrasound, hormone profile, semen analysis, clinical features and treatment. The control group included 25 healthy men. RESULTS: The current median age was similar in SLE patients compared with controls (26 versus 27 years, P = 0.756). The frequencies of sexual/erectile disfunction were significantly higher (20% versus 0%, P = 0.0001) and the number of spontaneous pregnancies were lower in SLE patients than in controls (20% versus 60%, P = 0.0086). A trend to low contraceptive use was observed in SLE patients compared with controls (48% versus 76%, P = 0.079). Moreover, the frequencies of gonadal dysfunction parameters, such as testicular atrophies measured by ultrasound (36% versus 8%, P = 0.037), elevated FSH and/or LH levels (36% versus 0%, P = 0.002), and sperm abnormalities (48% versus 0%, P = 0.0001), were statistically higher in SLE patients versus controls. SLE patients with sexual/erectile disfunction had no sexual activity in the last month versus 95% of SLE patients without dysfunction (P = 0.0001). On the other hand, no differences were evidenced in SLE patients with or without sexual/erectile disfunction according to demographic data, disease activity, cumulative damage and treatment. CONCLUSION: This is the first study to identify sexual/erectile and gonadal disfunction in male SLE patients. A multidisciplinary approach is essential in order to offer preventive measures for these patients.

ERICA: sexual initiation and contraception in Brazilian adolescents

ABSTRACT OBJECTIVE To estimate the prevalence of sexual initiation and contraceptive use at the last sexual intercourse of Brazilian adolescents, according to sociodemographic features. METHODS The data were obtained from the Study of Cardiovascular Risks in Adolescents (ERICA), a national school-based cross-sectional study. We included 74,589 adolescents from 32 geographic strata (27 capitals and five sets of municipalities with more than 100,000 inhabitants of each of the five macro-regions of the Country). Information on sexual initiation and contraceptive use at the last sexual intercourse (male condom and oral contraceptive pill) has been used. We have estimated prevalence and confidence intervals (95%CI) considering sample weights according to sex, age, type of school, residence status, macro-region and capitals. RESULTS We observed that 28.1% (95%CI 27.0-29.2) of the adolescents had already initiated sexual life, with higher prevalence among those aged 17 years (56.4%, 95%CI 53.9-58.9), males (33.5%, 95%CI 31.8-35.2), studying at public schools (29.9%, 95%CI 28.5-31.4), and from the Northern region (33.9%, 95%CI 32.3-35.4), mainly from Macapa, Manaus, and Rio Branco. Among those who had started their sexual life, 82.3% (95%CI 81.1-83.4) reported the use of contraceptive methods at the last intercourse, and the prevalence of use was higher among adolescents aged 17 years (85.3%, 95%CI 82.7-87.6), females (85.2%, 95%CI 83.8-86.5) and those living in the Southern region (85.9%, 95%CI 82.9-88.5). Male condom was used by 68.8% (95%CI 66.9-70.7), with no difference by type of school or macro-regions; the contraceptive pill was used by 13.4% (CI95% 12.2-14.6), and more frequently used among women (24.7%, 95%CI 22.5-27,0) and 17-year-old adolescents (20.8%, 95%CI 18.2-23.6) from urban settings(13.7%, 95%CI 12.5-14.9) and from the Southern region (22.6%, 95%CI 19.0-26.8), and less often in the Northern region. CONCLUSIONS ERICA’s data analysis on sexuality and contraception shows heterogeneities in the prevalence of sexual initiation and use of contraceptive methods among Brazilian adolescents, depending on their age, where they live, and the type of school they study at. Younger adolescents and those living in the Northern region seem to be more vulnerable to the consequences of unprotected sexual intercourses.

Guidelines for the management and treatment of periodic fever syndromes familial Mediterranean fever

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.

Aspectos da saúde reprodutiva em homens com miopatia inflamatória idiopática: um estudo multicêntrico

OBJECTIVE: To evaluate reproductive health of males with idiopathic inflammatory myopathies (IIM), and comparing them with a control group. METHODS: Demographic data, urologic evaluation (including pubertal parameters and sexual/erectile function), testicular ultrasound, hormone profile, semen analysis, clinical features, and treatment of 25 IIM patients were evaluated. The control group was composed of 25 healthy males. RESULTS: Median age of IIM patients was similar to that of the control group (24 versus 27 years, P = 0.566). The frequency of sexual activity, number of partners with spontaneous pregnancies after the onset of the disease, and use of condom were significantly lower in IIM patients than in the control group (60% versus 96%, P = 0.004; 16% versus 60%, P = 0.0031; 40% versus 76%, P = 0.021, respectively). Moreover, the frequency of testicular atrophy (28% versus 4%, P = 0.049), elevated levels of FSH and/or LH (25% versus 0%, P = 0.05), and sperm abnormalities (40% versus 0%, P = 0.0006) were statistically higher in IIM patients than in the control group. Median age of onset of IIM and current age were significantly higher in IIM patients with sexual/erectile dysfunction than in patients without this dysfunction (41 versus 12.5 years, P = 0.014; 46 versus 21 years, P = 0.027, respectively). On the other hand, differences in the age of spermarche, parameters of gonadal function, disease activity, muscle enzymes, and treatment were not observed between IIM patients with or without sexual/erectile dysfunction. CONCLUSION: This is the first study to identify changes in reproductive health and gonadal dysfunction in male IIM patients. Rheumatologists should discuss sexual problems with their patients, counseling them on contraceptive methods.

Avaliação dos óbitos e necropsias em pacientes internados em um serviço de reumatologia pediátrica por um período de dez anos

OBJETIVO: correlacionar os dados clinicos do obito com achados de necropsia em pacientes internados em uma unidade de reumatologia pediatrica. METODOS: o estudo e uma coorte historica. Em dez anos, no periodo compreendido entre janeiro de 1994 e dezembro de 2003, ocorreram 57.159 internacoes com 1.907 (3%) obitos no Instituto da Crianca. Destas internacoes, 548 (1%) apresentaram doencas reumaticas ou pediatricas e foram acompanhadas pela Unidade de Reumatologia Pediatrica, incluindo 348 pacientes. Os obitos e as necropsias foram analisados e a classificacao de Goldman foi utilizada para detectar discordância entre o diagnostico clinico do obito e a necropsia. RESULTADOS: no periodo do estudo, 34 (10%) pacientes evoluiram para obito. As principais doencas associadas ao obito foram: lupus eritematoso sistemico juvenil (LESJ) em 18 pacientes (53%) e artrite idiopatica juvenil (AIJ) em sete casos (21%). Necropsias foram realizadas em 21 pacientes (64% dos obitos). Nos 18 casos de LESJ, a atividade da doenca esteve presente em 16 casos, sendo associada a septicemia em 15 deles. Discordância entre o diagnostico clinico e necropsia foi evidenciada em seis casos com LESJ: tres com infeccoes fungicas, um com tuberculose, um com nefrite proliferativa difusa e outro com aterosclerose. Sete pacientes com AIJ evoluiram para obito: septicemia em quatro e sindrome de ativacao macrofagica em tres. Em um caso de AIJ foi diagnosticado, exclusivamente na necropsia: linfoma de Hodgkin, aterosclerose e infarto anterior do miocardio. CONCLUSOES: a frequencia de obitos foi 10% e necropsia evidenciou doenca infecciosa, aterosclerose ou neoplasia nao diagnosticadas previamente. A necropsia e importante para determinar eventos nao esclarecidos ou duvidosos no obito e deve ser sempre solicitada.

Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study

Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2–17) vs. 12 (1.9–17.7) vs. 12.5 (3–18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4–12) vs. 6 (4–13) vs. 6 (4–12), P < 0.0001) and SLEDAI-2 K (18 (6–57) vs. 16 (2–63) vs. 13 (1–49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.

Guidelines for the management and treatment of periodic fever syndromes: periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome

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.

Guidelines for the management and treatment of periodic fever syndromes: Cryopyrin-associated periodic syndromes (cryopyrinopathies - CAPS).

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.