HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. METHODS: We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. RESULTS: The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. CONCLUSIONS: The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.

Fatigue in children with juvenile idiopathic arthritis: reliability of the "Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale".

The aim of the study was (1) to translate the "Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale" (PedsQL-Fatigue) into Brazilian Portuguese language and culture and evaluate its reliability and (2) to measure fatigue among patients with juvenile idiopathic arthritis (JIA): (1) Translation of the PedsQL-Fatigue by two bilingual researchers; (2) Backtranslation into English assessed by the authors of the original version; (3) Pilot study with five patients followed in the Pediatric Rheumatology Outpatient Clinic and their parents; and (4) Field study and assessment of measurement properties (internal consistency, reproducibility, and construct validity). In this stage, the scale was administered to 67 patients with JIA and 63 healthy individuals, aged from 2 to 18 years old, matched by age (from 2 to 4, 5 to 7, 8 to 12, and from 13 to 18 years old). Cronbach's alpha coefficient ranged from 0.6 to 0.8 for children and parents, indicating the instrument's good internal consistency. The scale's construct validity was confirmed by a satisfactory Spearman's coefficient between the PedsQL-Fatigue and the generic PedsQL 4.0 (0.840 for the children and 0.742 for the parents). Reproducibility was also adequate (0.764 for the children and 0.938 for the parents). No differences were found between the scores obtained by the JIA group and control group, though lower scores were observed among patients with clinically active JIA when compared to those without clinical activity. The PedsQL-Fatigue is a valid and reliable tool, and that can be used to measure fatigue among patients with JIA.

Do patients with juvenile idiopathic arthritis in remission exhibit active synovitis on joint ultrasound?

The aim of the study was to assess the presence and characteristics of subclinical synovitis using power Doppler (PD) ultrasonography on patients with juvenile idiopathic arthritis (JIA) in clinical remission and compare the findings with those of healthy children. A cross-sectional study was carried out involving the clinical (physical exam, functional capacity and laboratory tests) and ultrasonography evaluation of 34 joints (synovial fluid/hypertrophy, PD signal and bone erosion). Subclinical synovitis was defined as the presence of synovial hypertrophy/joint effusion with or without any PD signal. Thirty-six patients (11.5 ± 3.74 years) and 36 controls (sex and age matched) were evaluated (2,448 joints). Twenty-seven patients were in remission on medication (mean duration: 1.8 ± 2.2 years). Subclinical synovitis was detected in 41.7% patients and 11.1% controls (p = 0.003). Erosion was detected in three patients (8.3%). Subclinical synovitis was found in 38/1,224 (3.1%) joints in the patients (most affected: radiocarpal wrist, anterior elbow and tibiotalar ankle) and 8/1,224 (0.6%) joints in the controls (most affected: radiocarpal wrist). Differences in subclinical synovitis between patients and controls were found in the elbows (p = 0.033) and ankles (p = 0.006). A greater frequency of subclinical synovitis was found in patients with the extended oligoarticular or polyarticular subtypes (p = 0.013), those at an older age at disease onset (p = 0.007) and using methotrexate (p = 0.049). Patients with JIA in remission exhibit subclinical synovitis more frequently than controls. Subclinical synovitis was more frequent in patients with the polyarticular involvement and those at an older age at disease onset.

Health related quality of life of children with rheumatic heart diseases: reliability of the Brazilian version of the Pediatric Quality of Life Inventory™ Cardiac Module scale.

BACKGROUND: This study aimed to translate the 'Pediatric Quality of Life Inventory™ (PedsQL™ 3.0) Cardiac Module' into Portuguese, adapt it to Brazilian culture, and assess its psychometric properties (validity and reproducibility), and to calculate health-related quality of life scores on the PedsQL 4.0 and PedsQL™ 3.0 Cardiac Module Scales for a group of patients 5 to 18 years old with rheumatic heart disease. METHODS: The methods suggested by the authors of the original version of the questionnaire included 1) translation by an expert panel; 2) translation back into English and revision by the authors of the original version; 3) pilot study with seven children and parents in each of three age ranges (5 to 7, 8 to 12, and 13 to 18 years old); and 4) assessment of the measurement properties. In this stage, the PedsQL™ 3.0 Cardiac Module and the PedsQL 4.0 Generic Scale were applied to a sample comprising 109 children and adolescents with rheumatic heart disease and their parents or caregivers. The version for parents or caregivers was administered separately on the same day. RESULTS: The values of Cronbach's alpha for all scales assessed in the questionnaire (heart problems and treatment [symptoms], problems with perceived physical appearance, treatment anxiety, cognitive problems, and communication problems) varied from 0.6 to 0.8, indicating good internal consistency. Correlation was found between the scores for the Cardiac Module and the Generic Scale (0.36-0.86), demonstrating convergent validity (Spearman's correlation coefficient, p < 0.01). The symptoms, problems with perceived physical appearance, and cognitive and communication problem domains were able to distinguish between groups of patients with mild and moderate/severe heart disease (Student's t-test, p < 0.05). The intraclass correlation of the interobserver reproducibility was adequate (0.76 to 0.94 among the patients [children/adolescents] and 0.76 to 0.84 among their caregivers). The correlation between the patients' scores and their parents' scores varied from 0.50 to 0.86 (Pearson's correlation coefficient, p < 0.01). CONCLUSIONS: The Brazilian version of the PedsQL™ 3.0 Cardiac Module was shown to be reliable. The application of this questionnaire in practice will be very useful for all professionals charged with the care of children and adolescents with heart diseases.

Dyslipidemia in pediatric systemic lupus erythematosus: the relationship with disease activity and plasma homocysteine and cysteine concentrations.

OBJECTIVE: To evaluate the presence of dyslipidemia and plasma concentrations of homocysteine (Hcy) and cysteine (Cys) in adolescents with juvenile systemic lupus erythematosus (SLE) and relate these findings to disease activity (Systemic Lupus Erythematosus Disease Activity Index, SLEDAI) and cardiovascular risk factors. METHODS: A cross-sectional controlled study including 26 female adolescents with SLE and 26 healthy controls was conducted. We evaluated SLEDAI, medications, anthropometric data, dietary intake, lipid profile, proteinuria, Hcy, Cys, folic acid, vitamin B12, and high-sensitivity C-reactive protein levels. RESULTS: Dyslipidemia was observed in 46.2% of the patients and in 19.2% of the controls. The SLE group had a higher Cys concentration and a lower high-density lipoprotein cholesterol concentration compared with the controls. In the multivariate analysis only Hcy was significantly and independently associated with the presence of dyslipidemia in the juvenile SLE group; an increase of 1 µmol/l in the Hcy concentration doubled the chance of dyslipidemia (OR: 2.1; 95% CI: 1.1-4.9; p = 0.030). The Cys concentration was correlated with Hcy, total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations. CONCLUSION: We observed the presence of cardiovascular risk factors in adolescents with juvenile SLE. The early identification of biochemical alterations allows the development of intervention strategies that may lower the risk of cardiovascular disease.

Immune response and tolerability of varicella vaccine in children and adolescents with systemic lupus erythematosus previously exposed to varicella-zoster virus.

OBJECTIVES: The aim of the present paper is to evaluate the immune response and tolerability of varicella vaccine in children and adolescents with systemic lupus erythematosus previously exposed to varicella-zoster virus. METHODS: We performed a prospective and controlled study on a group of 54 SLE patients that were chosen at random to be or not to be vaccinated (28 were vaccinated and 26 were not). Twenty-eight healthy controls, of matching age and sex were also vaccinated. All were submitted to a questionnaire, physical evaluation and laboratory assays: lymphocyte immune-phenotyping by flow cytometry, plasma varicella zoster virus (VZV) serology by ELISA and in vitro interferon gamma (IFNγ) production by T-cells after stimulus with VZV antigen. They were evaluated before vaccination and at 30, 45, 180 and 360 days afterwards. RESULTS: We did not observe any differences in the frequency of adverse events in both vaccinated groups. At study entry, all individuals were seropositive for VZV antibodies. The serum VZV antibody titres similarly increased after vaccination. The frequency of flares and the SLEDAI score were also similar among the patients. Thirty days after vaccination the production of IFNγ specific to VZV was lower in the SLE group compared to healthy controls. In the follow-up we observed 4 cases of herpes zoster in the SLE unvaccinated group, but no zoster in the vaccinated group. CONCLUSIONS: The varicella vaccine was well tolerated in SLE group, who had pre-existing immunity to varicella. The varicella vaccine immunogenicity measurement by serum antibody titres was appropriate. The incidence of HZ was lower in the vaccinated lupus group.

[Health-related quality of life of the children of health professionals]. / Qualidade de vida relacionada à saúde de filhos de profissionais da área de saúde.

In this study, we measured the health-related quality of life (HRQOL) and fatigue of the children of health professionals, aged between two and eleven years, and assessed the daytime and sleep habits of these children and their parents. The study included children from a public school. Data regarding demographics and daily habits were collected. The HRQOL, sleep habits and fatigue were measured using questionnaires. A total of 249 parents participated - 63.5% reported getting an adequate amount of sleep, while 47.4% woke up feeling tired. The children's mean age was 5.6 years - 62.2% watched television in their rooms, 50% used the computer (> 4 hours/day) and 27.8% engaged in extracurricular physical exercise. The sleep score was 45.8 ± 12.2. The HRQOL scores were higher in the physical and lower in the emotional aspects. We found that poorer sleep on the part of both children and parents may be related to the children's lower HRQOL. We conclude that the inadequate habits of parents as well as children, are related to a decrease in HRQOL, particularly regarding the emotional aspect.

EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria.

OBJECTIVES: To validate the previously proposed classification criteria for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). METHODS: Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis

Detection of multifocal osteonecrosis in an adolescent with dermatomyositis using whole-body MRI.

Osteonecrosis is a well-recognized complication of corticosteroid use resulting in significant morbidity, often requiring surgical intervention. Whole-body MRI is a promising method that allows imaging of the whole patient in a reasonable time without the use of ionizing radiation. This technique has the potential for evaluating nonmalignant multifocal skeletal disease like osteonecrosis. This case highlights the value of whole-body MR in an adolescent with dermatomyositis who developed multifocal osteonecrosis.

PAIN PERCEPTION AND PAIN COPING MECHANISMS IN CHILDREN AND ADOLESCENTS WITH JUVENILE FIBROMYALGIA AND POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS. / PERCEPÇÃO E ENFRENTAMENTO DA DOR EM CRIANÇAS E ADOLESCENTES COM FIBROMIALGIA JUVENIL E ARTRITE IDIOPÁTICA JUVENIL POLIARTICULAR.

OBJECTIVE: To measure and compare musculoskeletal pain in patients with juvenile fibromyalgia (JFM) and polyarticular juvenile idiopathic arthritis (JIA), and to evaluate and compare pain perception and pain coping mechanisms in these patients. METHODS: In this cross sectional study, we evaluated 150 children and adolescents, and their respective parents, from 3 different groups: JFM, polyarticular JIA, and healthy controls. Pain intensity and pain coping mechanisms were measured using specific questionnaires. Pain perception was evaluated according to three illustrations simulating situations that might cause pain: a shot, a bicycle fall, and social isolation. The patients' parents also filled out the questionnaires and provided a pain score that matched their child's perception of pain for each illustration. RESULTS: The highest pain scores, the lowest pain coping strategy scores, the highest pain perception scores for all three illustrations, and the worse health related to quality of life indicators were observed in the JFM group, when compared to the JIA and control groups. The same pattern was observed with their parents. CONCLUSIONS: Patients with JIA and JFM behave differently in relation to pain perception and the development pain coping mechanisms. Pain should be evaluated from different perspectives for an individualized and efficient treatment of patients.

OBJETIVO: Mensurar e comparar a dor musculoesquelética em pacientes com fibromialgia juvenil (FMJ) e em pacientes com artrite idiopática juvenil poliarticular (AIJ); e avaliar e comparar a percepção e o enfrentamento da dor. MÉTODOS: Foram avaliados, em estudo transversal, 150 crianças e adolescentes (e seus respectivos pais), divididos em três grupos: FMJ, AIJ e controles saudáveis. A mensuração e o enfrentamento da dor foram realizados por meio de instrumentos específicos. Para a avaliação da percepção da dor, desenvolveram-se três vinhetas com simulação de situações que pudessem gerar dor: aplicação de injeção, queda de bicicleta e isolamento social. Os pais e os pacientes responderam individualmente quanto à percepção da dor em cada situação. RESULTADOS: As maiores notas de dor, os menores escores de enfrentamento da dor, as maiores notas para a percepção da dor nas vinhetas e os piores índices de qualidade de vida relacionada à saúde foram observados nos pacientes com FMJ, quando comparados aos pacientes com AIJ e aos controles. O mesmo padrão foi observado com os respectivos pais. CONCLUSÕES: Pacientes com AIJ e FMJ se comportam diferentemente em relação à percepção da dor e ao desenvolvimento de técnicas para o enfrentamento da dor. A dor deve ser avaliada sob diferentes perspectivas para um planejamento mais individualizado e efetivo do tratamento desses pacientes.

Quality of life of children and adolescents from São Paulo: reliability and validity of the Brazilian version of the Pediatric Quality of Life Inventory version 4.0 Generic Core Scales.

OBJECTIVES: To evaluate the reliability and validity of the Brazilian version of the Pediatric Quality of Life Inventory (PedsQL 4.0) Generic Core Scales and measure the quality of life of healthy children and adolescents and patients with rheumatic diseases. METHODS: We followed the translation methodology proposed by the developer of the original English version of the PedsQL 4.0. The instrument was administered by interviews in two groups: 240 apparently healthy children and adolescents from São Paulo (SP, Brazil) and 105 patients with chronic rheumatic diseases matched by age, as well as their respective parents or caregivers. The parent proxy-report was administered to the children's parents or caregivers separately on the same day. RESULTS: Cronbach's alpha values were between 0.6 and 0.9 for all dimensions, demonstrating adequate internal consistency. Patients with rheumatic diseases reported significantly lower PedsQL scores on all dimensions when compared to the healthy control group (p < 0.0001). Construct validity of the Brazilian Portuguese version of the PedsQL 4.0 was also confirmed. Parent proxy-report of patients with rheumatic diseases highly correlated with child self-report for physical functioning (r = 0.77, p < 0.001) and school functioning (r = 0.73, p < 0.001). Lower correlations were observed for emotional and social functioning (r = 0.40 and 0.59, respectively, p < 0.001). CONCLUSIONS: The tool demonstrated reliability, validity, and the administration was fast and easy. Quality of life in patients with rheumatic diseases was significantly lower than in the healthy control group, supporting the necessity of a comprehensive approach to rheumatic disease management, focused on the psychosocial dimensions.

Endothelial function analysis and atherosclerotic risk factors in adolescents with systemic lupus erythematosus.

UNLABELLED: Atherosclerosis is considered an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). Endothelial dysfunction represents an important factor in the onset of atherosclerosis. OBJECTIVE: To assess endothelial function and the risk factors for atherosclerosis in adolescents with SLE. SUBJECTS: Thirty-five adolescents with SLE aged between 10-18 years and 27 age- and sex-matched controls. METHODS: Endothelial function was assessed using a high-resolution ultrasound device (Philips ATL, HDI-3000 model) with a linear array transducer (4.0-7.0 MHz). Measures of diameter and flow were performed at rest, during reactive hyperemia and after glyceryl trinitrate. Total cholesterol and fractions, triglycerides, creatinine, fasting glucose, anticardiolipin antibodies, lupus anticoagulant and plasma homocysteine, as well as, cumulative oral corticoid dose were considered in order to establish the risk factors for atherosclerosis. RESULTS: No significant difference was found between the two groups regarding endothelial function. Although dilation at 90" after cuff deflation had been smaller in patients than in controls, the difference was not statistically significant. Patients had higher levels of total cholesterol (p = 0.02), VLDL (p = 0.01), triglycerides (p = 0.01), and homocysteine (p < .001) compared with controls. Sixty eight percent of our patients showed hyperhomocysteinemia, yet, we did not find any correlation between these values and flow-mediated dilation. CONCLUSION: According to our results, adolescents with SLE do not present alterations in endothelial function as assessed by ultrasound. However, these patients did demonstrate risk factors such as dyslipidemia and hyperhomocysteinemia for the development of atherosclerosis.

Henoch-Schönlein purpura: recurrence and chronicity.

OBJECTIVES: To describe a group of patients treated at our service for Henoch-Schönlein purpura, with emphasis on recurrent and chronic cases, and to compare clinical and demographic characteristics of patients with monocyclic and recurrent disease. METHODS: Data on 67 patients who had been treated since disease onset were analyzed. Twelve patients were excluded because they failed to return for follow-up consultations after less than 3 months, leaving a total of 55 children in the study sample. Recurrence was defined as the presence of a fresh episode after a period of at least 3 months without symptoms, and cases were defined as chronic when cutaneous, abdominal and renal manifestations persisted for a period of 12 months or more. RESULTS: Recurrence was observed in 8/55 patients (14.4%) and four cases were chronic (7.2%). In 29/55 patients (52.7%), infection was identified as the trigger factor. A monocyclic clinical course was observed in 43 patients (26 of whom were girls, with a mean age of 5.4 years). Gastrointestinal and renal involvement was observed in 55.8 and 20.9% of patients, respectively. Among the 12 patients with recurrent or chronic Henoch-Schönlein purpura, three had arthritis, four exhibited signs and symptoms of abdominal involvement and seven of kidney disease: microscopic hematuria in five, macroscopic hematuria in one and hematuria with proteinuria in one other. Late onset was the only variable related to recurrence (p < 0.05). CONCLUSIONS: As is observed in medical literature, monocyclic cases are more common among children with early onset disease. Patients with Henoch-Schönlein purpura should be followed over the long term, since recurrent and chronic cases account for more than 20% of the total.

Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors.

OBJECTIVES: To analyze selective COX 2 inhibitor nonsteroidal anti-inflammatory drugs (NSAID) in terms of their mechanism of action, principal indications, posology and most common adverse effects. SOURCES: MEDLINE and LILACS databases and Food and Drug Administration (FDA) and National Agency for Sanitary Vigilance (ANVISA - Agência Nacional de Vigilância Sanitária) websites. The most important articles were selected and preference was given to articles published within the last 5 years. SUMMARY OF THE FINDINGS: The principal indications for NSAID are for control of pain and acute and chronic inflammation. There is no overwhelming evidence that demonstrates the superiority of one NSAID over another in terms of effectiveness. To date none of the COX 2 inhibitors has been liberated for use in the pediatric age group. Only meloxicam and etoricoxib can be prescribed for adolescents (13 and 16 years, respectively). Selective COX 2 inhibitors are indicated for patients with adverse effects that have proven to be associated with nonselective NSAID use. Selective COX 2 inhibitors can be prescribed in some cases of allergy to aspirin, but they must be used with care. Principal adverse effects include cardiovascular events and thrombotic phenomena. CONCLUSIONS: Selective COX 2 inhibitors are medicines that have been used in certain well-defined clinical situations and which may offer certain advantages over nonselective NSAID. Nevertheless, taking into consideration the higher cost involved and the potential for adverse cardiovascular effects, they should be employed only in accordance with strict criteria.

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 Takayasu's 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.

Diagnosis of malignancies in children with musculoskeletal complaints.

CONTEXT: Musculoskeletal complaints may be associated with neoplasias as an initial manifestation of the disease. When these symptoms predominate at the onset of the disease, the differential diagnosis includes several rheumatic diseases. OBJECTIVE: To assess the frequency, clinical features and types of cancer manifested in children presenting with musculoskeletal complaints over a seven-year period. TYPE OF STUDY: Retrospective. SETTING: Discipline of Allergy, Clinical Immunology and Rheumatology, Universidade Federal de São Paulo-Escola Paulista de Medicina. METHODS: The medical records of patients with musculoskeletal complaints and final diagnosis of malignant disease were reviewed. The data collected were: age when symptoms initially presented, age at diagnosis, clinical features presented, laboratory findings, and the initial and final diagnoses. RESULTS: A final diagnosis of cancer was found in nine out of 3,528 patients (0.25%) whose initial symptom was musculoskeletal pain. The mean time between disease onset and final diagnosis was five months. The most common features presented were pauciarticular arthritis or arthralgia involving the large joints. Juvenile rheumatoid arthritis was the most frequent initial diagnosis, in four out of nine patients. Anemia was the most frequent initial hematological change. Six out of eight patients had an increased erythrocyte sedimentation rate. The lactate dehydrogenase level was raised in five out of eight patients. The malignancies found included acute lymphocytic leukemia, acute myeloid leukemia, lymphoma, neuroblastoma and Ewing's sarcoma. DISCUSSION: The frequency of neoplasia in patients with musculoskeletal pain resembled reports in the literature. Consumptive symptoms were not the warning signal in most of our patients. In subsidiary tests, progressive anemia was the most common finding, although the peripheral blood cell count may continue to be normal for weeks or months after symptom onset. CONCLUSION: Malignancy always needs to be ruled out in cases of children with musculoskeletal complaints. Uncharacteristic clinical manifestations and nonspecific laboratory tests may cause difficulty in the final diagnosis, and rigorous investigation should be performed.

Are temporomandibular joint signs and symptoms associated with magnetic resonance imaging findings in juvenile idiopathic arthritis patients? A longitudinal study.

The aims of this longitudinal study were to perform a comprehensive clinical evaluation of temporomandibular joint (TMJ) and to investigate the association between the clinical and magnetic resonance imaging (MRI) findings in the TMJs of patients with juvenile idiopathic arthritis (JIA). Seventy-five patients with JIA participated in this study. All patients underwent a rheumatological examination performed by a paediatric rheumatologist, a TMJ examination performed by a single dentist and an MRI with contrast of the TMJs. These examinations were scheduled on the same date. The patients were examined again 1 year later. Twenty-eight (37.3 %) patients reported symptoms at the first evaluation and 11 (14.7 %) patients at the second evaluation. In relation to signs, 35 (46.7 %) of the patients presented at least one sign at the first evaluation and 29 (38.7 %) at the second. Intense contrast enhancement of TMJ was significantly associated with disease activity (p < 0.001) at the first evaluation and a trend to significance was observed at the second (p = 0.056), with poly/systemic subtypes (p = 0.028 and p = 0.049, respectively), with restricted mouth opening capacity (p = 0.013 and p = 0.001, respectively), with the presence of erosions at both evaluations (p = 0.0001 and p < 0.0001, respectively) and with altered condylar shape at the second evaluation (p = 0.0005). TMJ involvement is highly prevalent in JIA patients, with asymptomatic children presenting severe structural alterations of the TMJ. The TMJ should always be evaluated in JIA patients, even in the absence of signs and symptoms.

Rheumatic fever and post-streptococcal arthritis.

Rheumatic fever resulting from group A beta-haemolytic Streptococcus infection continues to be a prevalent disease and an important cause of morbidity and mortality in developing countries. Molecular mimicry and CD4 T lymphocytes, interleukins and adhesion molecules play a crucial role in the pathogenesis of this disease. Arthritis, followed by carditis and chorea, are the main manifestations of the disease. Evidence of asymptomatic carditis has been increasing; however, abnormality identified by echo-Doppler evaluation is not considered as a criterion for diagnosis of rheumatic carditis. Benzathine penicillin is still the best therapeutic option for the treatment of streptococcal infection and secondary prophylaxis, due to its efficacy and low cost.

Frequency of antinuclear antibodies in healthy children and adolescents.

Sera from 214 healthy children and adolescents (108 females [50.4%]) aged 6 months to 20 years (mean 8.7 years) and from 116 patients with rheumatic diseases were assayed for antinuclear antibody (ANA) by indirect immunofluorescence (IIF) by using HEp-2 cells as substrate. Twenty-seven healthy children (12.6%) presented a positive ANA test; there was no difference between genders, and we observed a trend for higher frequency of ANA >/= 1/80 among children between 5 years and 10 years. Eight of the 27 healthy children with positive ANA test were reevaluated 36 months later, and none of them had developed any rheumatic disease, though the sera remained positive in 2 of them. ANA was present in 42/116 patients (36.2%). In daily medical practice ANA determination should be required only in individuals with clinical signs and symptoms suggestive of autoimmune disease.