Lucia M. Campos

Pediatric Antiphospholipid Syndrome: Clinical and Immunologic Features of 121 Patients in an International Registry

OBJECTIVES. The purpose of this study was to obtain data on the association of antiphospholipid antibodies with clinical manifestations in childhood and to enable future studies to determine the impact of treatment and long-term outcome of pediatric antiphospholipid syndrome. PATIENTS AND METHODS. A European registry extended internationally of pediatric patients with antiphospholipid syndrome was established as a collaborative project of the European Antiphospholipid Antibodies Forum and Lupus Working Group of the Pediatric Rheumatology European Society. To be eligible for enrollment the patient must meet the preliminary criteria for the classification of pediatric antiphospholipid syndrome and the onset of antiphospholipid syndrome must have occurred before the patients 18th birthday. RESULTS. As of December 1, 2007, there were 121 confirmed antiphospholipid syndrome cases registered from 14 countries. Fifty-six patients were male, and 65 were female, with a mean age at the onset of antiphospholipid syndrome of 10.7 years. Sixty (49.5%) patients had underlying autoimmune disease. Venous thrombosis occurred in 72 (60%), arterial thrombosis in 39 (32%), small-vessel thrombosis in 7 (6%), and mixed arterial and venous thrombosis in 3 (2%). Associated nonthrombotic clinical manifestations included hematologic manifestations (38%), skin disorders (18%), and nonthrombotic neurologic manifestations (16%). Laboratory investigations revealed positive anticardiolipin antibodies in 81% of the patients, anti-β2-glycoprotein I antibodies in 67%, and lupus anticoagulant in 72%. Comparisons between different subgroups revealed that patients with primary antiphospholipid syndrome were younger and had a higher frequency of arterial thrombotic events, whereas patients with antiphospholipid syndrome associated with underlying autoimmune disease were older and had a higher frequency of venous thrombotic events associated with hematologic and skin manifestations. CONCLUSIONS. Clinical and laboratory characterization of patients with pediatric antiphospholipid syndrome implies some important differences between antiphospholipid syndrome in pediatric and adult populations. Comparisons between children with primary antiphospholipid syndrome and antiphospholipid syndrome associated with autoimmune disease have revealed certain differences that suggest 2 distinct subgroups.

The Ped-APS Registry: the antiphospholipid syndrome in childhood

In recent years, antiphospholipid syndrome (APS) has been increasingly recognised in various paediatric autoimmune and nonautoimmune diseases, but the relatively low prevalence and heterogeneity of APS in childhood made it very difficult to study in a systematic way. The project of an international registry of paediatric patients with APS (the Ped-APS Registry) was initiated in 2004 to foster and conduct multicentre, controlled studies with large number of paediatric APS patients. The Ped-APS Registry is organised as a collaborative project of the European Forum on Antiphospholipid Antibodies and Juvenile Systemic Lupus Erythematosus Working Group of the Paediatric Rheumatology European Society. Currently, it documents a standardised clinical, laboratory and therapeutic data of 133 children with antiphospholipid antibodies (aPL)-related thrombosis from 14 countries. The priority projects for future research of the Ped-APS Registry include prospective enrolment of new patients with aPL-related thrombosis, assessment of differences between the paediatric and adult APS, evaluation of proinflammatory genotype as a risk factor for APS manifestations in childhood and evaluation of patients with isolated nonthrombotic aPL-related manifestations.

Dental and facial characteristics of patients with juvenile idiopathic arthritis

OBJECTIVEnIt has been shown that the temporomandibular joint is frequently affected by juvenile idiopathic arthritis, and this degenerative disease, which may occur during facial growth, results in severe mandibular dysfunction. However, there are no studies that correlate oral health (tooth decay and gingival diseases) and temporomandibular joint dysfunction in patients with juvenile idiopathic arthritis. The aim of this study is to evaluate the oral and facial characteristics of the patients with juvenile idiopathic arthritis treated in a large teaching hospital.nnnMETHODnThirty-six patients with juvenile idiopathic arthritis (26 female and 10 male) underwent a systematic clinical evaluation of their dental, oral, and facial structures (DMFT index, plaque and gingival bleeding index, dental relationship, facial profile, and Helkimos index). The control group was composed of 13 healthy children.nnnRESULTSnThe mean age of the patients with juvenile idiopathic arthritis was 10.8 years; convex facial profile was present in 12 juvenile idiopathic arthritis patients, and class II molar relation was present in 12 (P =.032). The indexes of plaque and gingival bleeding were significant in juvenile idiopathic arthritis patients with a higher number of superior limbs joints involved (P =.055). Anterior open bite (5) and temporomandibular joint noise (8) were present in the juvenile idiopathic arthritis group. Of the group in this sample, 94% (P =.017) had temporomandibular joint dysfunction, 80% had decreased mandibular opening (P = 0.0002), and mandibular mobility was severely impaired in 33% (P =.015).nnnCONCLUSIONnThis study confirms that patients with juvenile idiopathic arthritis a) have a high incidence of mandibular dysfunction that can be attributed to the direct effect of the disease in the temporomandibular joint and b) have a higher incidence of gingival disease that can be considered a secondary effect of juvenile idiopathic arthritis on oral health.

Distrofia simpático-reflexa

OBJECTIVE: To describe eight patients with reflex sympathetic dystrophy in terms of clinical and laboratory characteristics and treatment. DESCRIPTION: Eight children (four girls) with reflex sympathetic dystrophy were retrospectively analyzed. The diagnosis of reflex sympathetic dystrophy was based on the presence of pain in the distal extremities, local edema, vasomotor instability and impairment of sensibility. Two patients had associated systemic lupus erythematosus, one had juvenile idiopathic arthritis and one had Glanzmanns thrombasthenia. Mean age was 11.5 years. Most of the patients had lower extremity involvement (7/8). The most important clinical signs were pain, edema and vasomotor instability in the affected extremity (8/8), functional impairment (7/8), and impaired sensibility (3/7). The erythrocyte sedimentation rate was abnormal in three patients and the bone scans in five. All patients received non-steroidal anti-inflammatory drugs and physical therapy with improvement of the symptoms in seven patients, until six months of treatment. Three patients were submitted to acupuncture with good response. One patient had a severe disease and received tricyclic antidepressants, with improvement more than one year after. COMMENTS: Reflex sympathetic dystrophy should be included as part of the differential diagnosis of limb pains of childhood, so that physicians can make an earlier diagnosis and prevent functional impairment.

A Multicenter Study of Invasive Fungal Infections in Patients with Childhood-onset Systemic Lupus Erythematosus.

Objective. To study the prevalence, risk factors, and mortality of invasive fungal infections (IFI) in patients with childhood-onset systemic lupus erythematosus (cSLE). Methods. A retrospective multicenter cohort study was performed in 852 patients with cSLE from 10 pediatric rheumatology services. An investigator meeting was held and all participants received database training. IFI were diagnosed according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria (proven, probable, and possible). Also evaluated were demographic, clinical, and laboratory data, and disease activity [SLE Disease Activity Index 2000 (SLEDAI-2K)], cumulative damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), treatment, and outcomes. Results. IFI were observed in 33/852 patients (3.9%) with cSLE. Proven IFI was diagnosed in 22 patients with cSLE, probable IFI in 5, and possible IFI in 6. Types of IFI were candidiasis (20), aspergillosis (9), cryptococcosis (2), and 1 each disseminated histoplasmosis and paracoccidioidomycosis. The median of disease duration was lower (1.0 vs 4.7 yrs, p < 0.0001) with a higher current SLEDAI-2K [19.5 (0–44) vs 2 (0–45), p < 0.0001] and current prednisone (PRED) dose [50 (10–60) vs 10 (2–90) mg/day, p < 0.0001] in patients with IFI compared with those without IFI. The frequency of death was higher in the former group (51% vs 6%, p < 0.0001). Logistic regression analysis revealed that SLEDAI-2K (OR 1.108, 95% CI 1.057–1.163, p < 0.0001), current PRED dose (OR 1.046, 95% CI 1.021–1.071, p < 0.0001), and disease duration (OR 0.984, 95% CI 0.969–0.998, p = 0.030) were independent risk factors for IFI (R2 Nagelkerke 0.425). Conclusion. To our knowledge, this is the first study to characterize IFI in patients with cSLE. We identified that disease activity and current glucocorticoid use were the main risk factors for these life-threatening infections, mainly in the first years of disease course, with a high rate of fatal outcome.

Prática de vacinação em crianças com doenças reumáticas

INTRODUCAO/OBJETIVOS: Avaliar a pratica clinica com relacao a verificacao do cartao vacinal e a indicacao de vacinas especificas em pacientes com doencas reumaticas pediatricas em uso de diferentes drogas, e evidenciar a possivel associacao entre frequencia de vacinacao e tempo de pratica clinica dos reumatologistas pediatricos do estado de Sao Paulo. MATERIAL E METODOS: Um questionario foi enviado para os reumatologistas pediatricos do Departamento de Reumatologia da Sociedade de Pediatra de Sao Paulo. Esse instrumento incluiu questoes sobre tempo de pratica em Reumatologia Pediatrica, vacinacao de pacientes com Lupus Eritematoso Sistemico Juvenil (LESJ), artrite idiopatica juvenil (AIJ), dermatomiosite juvenil (DMJ) e imunizacao de acordo com os tratamentos utilizados. RESULTADOS: Cartao de vacinacao foi visto por 100% dos profissionais na primeira consulta e por 36% anualmente. Vacinas de agentes vivos nao foram recomendadas para pacientes com LESJ, AIJ e DMJ em 44%, 64% e 48%, respectivamente. Os profissionais foram divididos em dois grupos: A ( 16 anos, n = 13). Nenhuma diferenca estatistica foi observada no uso de vacinas de agentes vivos e vacinas de agentes inativos ou componentes proteicos em relacao ao tratamento nos dois grupos (P > 0,05). Alem disso, os grupos foram similares em relacao a opiniao sobre a gravidade de imunossupressao em pacientes com LESJ, AIJ e DMJ com ou sem atividade e a terapeutica utilizada (P > 0,05). CONCLUSOES: A frequencia de vacinacao por reumatologistas pediatricos de Sao Paulo e baixa, especialmente apos a primeira consulta, e nao e influenciada pelo tempo de pratica profissional.

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.

Exposure to air pollutants increased disease activity in childhood‐onset systemic lupus erythematosus patients

To investigate the association between exposure to air pollutants in the Sao Paulo metropolitan area and disease activity in juvenile‐onset systemic lupus erythematosus (SLE) patients.

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

OBJECTIVEnTo describe the clinical and angiographic characteristics of Takayasus arteritis in Brazilian children and adolescents.nnnMETHODSnA 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.nnnRESULTSnOf 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.nnnCONCLUSIONnThis 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.

Doença periodontal em doenças reumáticas pediátricas

Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity.