Teresa Cristina Martins Vicente Robazzi

Withdrawal from glucocorticosteroid therapy: clinical practice recommendations

OBJECTIVE To present an up-to-date and practical review of how to safely withdraw glucocorticosteroid therapy. SOURCES A review of the published literature identified by searching the MEDLINE and LILACS databases (1997-2007), selecting the most representative articles on the subject. SUMMARY OF THE FINDINGS Three clinical situations may occur during glucocorticoid withdrawal: adrenal insufficiency secondary to negative feedback on the hypothalamic-pituitary adrenal (HPA) axis, steroid withdrawal syndrome and relapse of the disease for which the glucocorticoids were prescribed. Although there is no consensus on how to best discontinue prolonged glucocorticosteroid therapy, there is agreement that this withdrawal should be gradual. This article updates pediatricians on how to recognize these problems and provides recommendations on how to safely suspend glucocorticosteroid therapy. A brief review of the pharmacology of glucocorticoids is also presented. CONCLUSIONS There is no good predictive test for predicting the risk of adrenal insufficiency in patients who have been on corticosteroid therapy chronically. There is a need for prospective studies to assess the true incidence of this problem and to propose rational strategies for preventing it. The current recommendation is that patients who have been on chronic and/or high dose glucocorticoids should be administered glucocorticoids during stress situations unless the integrity of the HPA axis has been established by dynamic tests.OBJECTIVE: To compare the prevalence rates of breastfeeding and the principal causes of consultations at the infant and neonatal clinic of a basic healthcare center in the city of Rio de Janeiro, before and after its being accredited by the Breastfeeding Friendly Primary Care Initiative. METHODS: Information was analyzed from 121 and 200 children followed-up at the healthcare center before and after certification, respectively. Type of feeding was classified as exclusive breastfeeding, predominant breastfeeding or breastfeeding, and the 10th International Classification of Diseases was used to classify the complaints causing consultations. RESULTS: A statistically significant increase was observed in the prevalence of exclusive breastfeeding, both among those less than 4 months old (68 vs. 88%; p < 0.0001) and among children aged from 4 to 6 months (41 vs. 82%; p < 0.0001). Furthermore, an impressive increase was observed in the prevalence of breastfeeding in children more than 6 months old, especially those aged 9 to 12 months (24 vs. 82%; p < 0.0001). After certification, there was also a reduction in the number of consultations motivated by some type of disease among infants more than 4 months old. CONCLUSION: Implementation of the Breastfeeding Friendly Primary Care Initiative proved to be an important strategy for increasing the rate of breastfeeding and reducing consultations due to disease among infants less than one year old cared for at this health center.OBJETIVO: Apresentar uma revisao atualizada e pratica sobre como efetuar de forma segura a retirada da corticoterapia. FONTES DOS DADOS: Revisao da literatura utilizando os bancos de dados MEDLINE e LILACS (1997-2007), selecionando os artigos mais atuais e representativos do tema. SINTESE DOS DADOS: Tres situacoes clinicas podem ocorrer durante a retirada da corticoterapia prolongada: insuficiencia adrenal secundaria a supressao do eixo hipotalamo-hipofise-adrenal, sindrome de retirada ou deprivacao dos corticoides e reativacao da doenca de base. Embora nao exista consenso sobre o melhor esquema para descontinuar a terapia prolongada com corticoides, existe concordância quanto ao fato desta retirada ser gradual. Este artigo atualiza o pediatra quanto ao reconhecimento desses problemas e fornece orientacoes para a suspensao do tratamento prolongado com corticoide. Uma breve revisao da farmacologia dos corticoides tambem e descrita. CONCLUSAO: Nao existe teste com bom valor preditivo para antecipar o risco de insuficiencia adrenal nos pacientes que receberam terapia cronica com corticoide. Sao necessarios estudos prospectivos para avaliar a real incidencia desse problema e assim propor estrategias racionais para sua prevencao. No momento, a menos que a integridade do eixo hipotalamo-hipofise-adrenal esteja estabelecida por testes dinâmicos, recomenda-se a administracao de corticoide em situacoes de estresse nos pacientes que fizeram uso de corticoterapia cronica e/ou em doses elevadas.

Osteoarticular manifestations as initial presentation of acute leukemias in children and adolescents in Bahia, Brazil.

Objective This study was to determine the prevalence and characteristics of the osteoarticular manifestations on initial clinical presentation of acute leukemias (ALs) on childhood in the state of Bahia, Brazil. Materials and Methods This retrospective study assessed the medical records of 406 patients with AL from January 1995 to December 2004. Results Acute lymphocytic leukemia (ALL) was diagnosed in 313 (77.1%) patients and acute myeloid leukemia (AML), in 93 (22.9%) patients, including 241 males (59.4%) and 165 females (40.6%). Age ranged from 9 months to 15 years (average: 6.18 y). The most common presenting features were fever (18.5%), musculoskeletal diffuse tenderness (15.0%), pallor (11.4%), and leg tenderness (5.7%). Prior referral to our center, the most frequent initial diagnosis was anemia (15.8%), leukemia (15.0%), amygdalitis (3.7%), and rheumatic fever (2.7%). Osteoarticular manifestations were found on 54.7% of the patients with AL, with a higher frequency among patients between 1 and 9 years of age (58.7%, P=0.0007). The presence of joint tenderness (16.2% in ALL×5.4% in AML), arthritis (26.6% in ALL×9.7 in AML), bone tenderness (26.1% in ALL×16.1% in AML), limb tenderness (49.5% in ALL×25.8% in AML), and antalgic gait (32.8% in ALL×9.7% in AML) had higher prevalence on ALL. The large joints, chiefly the knees (10.6%), ankles (9.4%), elbows (4.4%), and shoulders (3.6%) were more often affected. Conclusions AL should be considered on the differential diagnosis of osteoarticular symptoms of unknown etiology in children.

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.

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.

Manifestações articulares atípicas em pacientes com febre reumática

OBJECTIVES To describe the clinical characteristics and the occurrence of atypical arthritis in children diagnosed with rheumatic fever (RF) and followed in tertiary care clinics in Salvador, Bahia, Brazil. METHODOLOGY A descriptive study of a case series, of the initial clinical presentation, and of recurrence in 41 children diagnosed with RF. RESULTS Of the patients studied (n=41), 61% were male, mean age of 9.2 years, and mean age at diagnosis between 5 and 16 years. Arthritis was present in 75.6% of patients; carditis in 75.6%; chorea in 31.7%; erythema marginatum in 14.6%; and subcutaneous nodules in 4.9%. An atypical pattern was observed in 22 of 31 cases of arthritis (70.9%): involvement of small joints and/or axial skeleton in 12 cases (38.7%); >3 weeks of duration in 9 (29%); inadequate response to NSAIDs in 2 (6.5%); oligoarthritis (≤4 joints) in 22/31 (71%), with monoarthritis in 6/31 (1 in the foot, 1 in the ankle, and 4 in the knee). Fever was present in 78% of the cases, and 82.9% of patients were regularly on secondary prophylaxis. CONCLUSION Atypical arthritis was present in most patients presenting with joint involvement, being a confounding factor against a proper diagnosis and of therapeutic delay.

Biological therapy and development of neoplastic disease in patients with juvenile rheumatic disease: a systematic review

Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.

Coexistência de lúpus eritematoso sistêmico e doença falciforme: relato de caso e revisão da literatura

OBJECTIVE To report a case of coexisting systemic lupus erythematosus (SLE) and sickle cell disease (SCD) with a review of the literature on the topic. METHODOLOGY Report of case and research of the association between SLE and SCD in literature through scientific articles in health sciences databases, such as LILACS, MEDLINE/Pubmed and Scielo, until May 2012. Descriptors used: 1. Sickle cell anemia; 2. Sickle cell disease; 3. Systemic lupus erythematosus; 4. Hemoglobinopathies. RESULTS The authors describe an association between SLE and SS hemoglobinopathy in an eight-year-old female patient displaying articular, hematologic and neuropsychiatric manifestations during clinical evolution. Forty-five cases of association between SLE and SCD are described in literature, mostly adult (62.2%), women (78%) and with the SS phenotype in 78% of the cases, and different clinical manifestations. Compared with our patient, articular, hematologic and neuropsychiatric manifestations were present in 76%, 36% and 27% of the cases, respectively. CONCLUSION SLE and SCD are chronic diseases that have several clinical and laboratory findings in common, meaning difficult diagnosis and difficulty in finding the correct treatment. Although the association between these diseases is not common, it is described in literature, so it is imperative that physicians who treat such diseases be alert to this possibility.

Takayasu arteritis in childhood: misdiagnoses at disease onset and associated diseases

Juvenile-Takayasu arteritis (j-TA) is a difficult diagnosis and some patients develop uncommon manifestations and associated diseases that may contribute to the delayed diagnosis. Our aim was to identify the misdiagnoses, the associated diseases and the atypical manifestations observed in a j-TA Brazilian multicentre study. 71 children and adolescents who met the classification criteria for j-TA were included. The misdiagnoses, the associated diseases and the atypical manifestations were evaluated. 19 (26.8%) patients had misdiagnoses. The most common of them was aortic coarctation in six (8.4%) patients, followed by rheumatic fever in five (7.0%) and one patient presented with both former diagnoses. Limb pain (two patients), spondyloarthropathy, juvenile idiopathic arthritis (JIA), spinal arteriovenous malformation, polyarteritis nodosa (PAN) and fever of unknown origin (FUO) were other misdiagnoses. Patients who had misdiagnoses previously to j-TA diagnosis presented a trend to have a longer diagnosis delay. 11 (15.5%) patients had 14 TA-associated diseases, such as pulmonary tuberculosis (5 patients), rheumatic fever (2 patients), spondyloarthropathy, polyarticular JIA, Crohn’s disease, Prader–Willi disease, diabetes mellitus, Moyamoya and primary immunodeficiency. 7 (9.9%) patients presented 10 atypical manifestations, such as pyoderma gangrenosum, erythema nodosum, myositis, chorea, enthesitis, episcleritis, uveitis, hepatomegaly, splenomegaly and necrosis of extremities. Our study emphasizes the main misdiagnoses, associated diseases and atypical manifestations that occur in patients with j-TA and warns of the features that may alert paediatricians to this diagnosis, such as constitutional symptoms and elevated inflammatory markers.

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.

Tratamento da tuberculose latente em pacientes com doenças reumáticas juvenis: uma revisão sistemática

INTRODUCTION Children and adolescents with rheumatic diseases receiving TNF blockers are at risk for the activation of latent Mycobacterium tuberculosis infection (LTBI). Although LTBI treatment is indicated in this group, there are different therapeutic regimens in the literature, without a definite consensus. OBJECTIVES To review in the literature therapeutic schemes used and indicated for the treatment of LTBI in these patients. METHODS Systematic review of the literature, using health databases, selecting studies that addressed the treatment of LTBI in patients with juvenile rheumatic diseases using TNF blockers, from 1990 to 2015. All study designs were considered. RESULTS A total of 162 studies were identified through the electronic databases and one was found through a manual search by the author, totaling 163 articles. We excluded studies that did not meet the mentioned inclusion criteria, and included a retrospective cohort study and two prospective cohort studies. The three studies addressed treatment with isoniazid (INH) for 9 months and one of them also addressed INH treatment associated with rifampicin for 3 months. CONCLUSIONS Only one case of LTBI activation was observed; there was good treatment adherence and absence of complications during follow-up. More studies are necessary to evaluate the response to the other available therapeutic regimens, with better tolerability assessment and a larger sample. However, the results showed that INH therapy for 9 months and INH therapy plus rifampicin for 3 months had a low rate of LTBI activation and complications.