Whole-body magnetic resonance imaging in the assessment of muscular involvement in juvenile dermatomyositis/polymyositis patients.

OBJECTIVES: Our aim was to demonstrate the benefit of whole-body magnetic resonance imaging (WBMRI) as a diagnostic modality in the detection of muscle activity in juvenile dermatomyositis (JDM)/polymyositis (JPM) patients and to correlate these findings with clinical evaluation, laboratory examinations, nailfold capillaroscopy (NFC), and muscle biopsy. METHOD: Thirty-four patients aged 5.5 to 18.9 years with a diagnosis of JDM/JPM were prospectively evaluated using clinical examination, muscle enzyme determination, the Childhood Myositis Assessment Scale (CMAS), Disease Activity Score (DAS), Manual Muscle Testing (MMT), NFC, and WBMRI. An open muscle biopsy was performed if muscle disease activity was detected on WBMRI. RESULTS: Disease activity was detected in WBMRI in four (11.7%) patients and confirmed by muscle biopsy. All four patients had elevation of at least one muscle enzyme and NFC showed scleroderma patterns in these patients. CONCLUSIONS: WBMRI allows us to evaluate the extent and symmetry of muscle disease and inflammatory activity. NFC is an important additional examination to assess disease activity.

Monitoring and Treatment of Juvenile Idiopathic Arthritis-associated Uveitis: Brazilian Evidence-based Practice Guidelines.

PURPOSE: To present a national guideline for ophthalmologic care and surveillance of juvenile idiopathic arthritis-associated uveitis (JIA-uveitis). METHODS: Review article based on medical literature and the experience of an Expert Committee composed of members of the Brazilian Society of Pediatric Ophthalmology/Brazilian Council of Ophthalmology and the Brazilian Society of Pediatrics/Brazilian Society of Rheumatology. Studies with a high level of evidence were selected by searching the PubMed/Medline database. The final document was approved by the experts. RESULTS: The main recommendations are that children/adolescents with JIA should undergo screening according to their risk factors. Ophthalmological checkups should also consider ocular inflammation and therapy. Topical glucocorticoids should be the first line of therapy, with systemic glucocorticoids acting as bridge treatments in severe uveitis. Methotrexate should be the first-line systemic therapy and anti-tumor necrosis factor (anti-TNF alpha) the second for uncontrolled uveitis. CONCLUSIONS: This evidence-based guideline for JIA-uveitis will be useful for both ophthalmology and rheumatology practice.

A Brazilian registry of juvenile dermatomyositis: onset features and classification of 189 cases.

OBJECTIVE: To describe onset features, classification and treatment of juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) from a multicentre registry. METHODS: Inclusion criteria were onset age lower than 18 years and a diagnosis of any idiopathic inflammatory myopathy (IIM) by attending physician. Bohan & Peter (1975) criteria categorisation was established by a scoring algorithm to define JDM and JPM based on clinical protocol data. RESULTS: Of the 189 cases included, 178 were classified as JDM, 9 as JPM (19.8: 1) and 2 did not fit the criteria; 6.9% had features of chronic arthritis and connective tissue disease overlap. Diagnosis classification agreement occurred in 66.1%. Median onset age was 7 years, median follow-up duration was 3.6 years. Malignancy was described in 2 (1.1%) cases. Muscle weakness occurred in 95.8%; heliotrope rash 83.5%; Gottron plaques 83.1%; 92% had at least one abnormal muscle enzyme result. Muscle biopsy performed in 74.6% was abnormal in 91.5% and electromyogram performed in 39.2% resulted abnormal in 93.2%. Logistic regression analysis was done in 66 cases with all parameters assessed and only aldolase resulted significant, as independent variable for definite JDM (OR=5.4, 95%CI 1.2-24.4, p=0.03). Regarding treatment, 97.9% received steroids; 72% had in addition at least one: methotrexate (75.7%), hydroxychloroquine (64.7%), cyclosporine A (20.6%), IV immunoglobulin (20.6%), azathioprine (10.3%) or cyclophosphamide (9.6%). In this series 24.3% developed calcinosis and mortality rate was 4.2%. CONCLUSION: Evaluation of predefined criteria set for a valid diagnosis indicated aldolase as the most important parameter associated with definite JDM category. In practice, prednisone-methotrexate combination was the most indicated treatment.

Increased concentration of plasma homocysteine in children with systemic lupus erythematosus.

OBJECTIVE: Studies in adults with SLE have evidenced increase of homocysteine related, mainly, to thromboembolic events. The aim of our study was to evaluate plasma homocysteine concentration in children with systemic lupus erythematosus (SLE) and its correlation with renal involvement, serum and erythrocyte folate, vitamin B12, antiphospholipid antibodies, estimated creatinine clearance and dyslipidemia. METHODS: Thirty-two children (29 females) with SLE and 32 healthy controls (29 females) matched for age and sex were included in the study. The mean age of patients and controls was 14.2 years (range from 10 to 18 years). Only one patient presented one thrombotic event. Plasma homocysteine, erythrocyte and serum folate, vitamin B12, lipid profile, antiphospholipid antibodies and estimated creatinine clearance were evaluated. Raised homocysteine concentration was defined as equal or more than 12.9 mol/L. RESULTS: Raised homocysteine concentration was detected in 15 (46.9%) children with SLE with an important statistical difference in relation to control group (p < 0.001). A positive correlation was found between plasma homocysteine concentration and renal involvement (odds ratio 11.1 [95% CI 1.50-82.24], p = 0.01) based on the presence of renal biopsy, abnormalities of urine sediment and/or serum creatinine. However, when we performed the estimated creatinine clearance the correlation with homocysteine concentration was not positive. We did not observe abnormalities in serum and erythrocyte folate and vitamin B12 in our patients. However, they presented significant higher concentrations of TC total cholesterol (p = 0.005) and of LDL low-density lipoprotein (p = 0.02) than controls. CONCLUSION: Elevated plasma homocysteine concentration is frequent in children with SLE. We believe that these results may signalize to the possibility of complications in our patients later in life. Further long-term and prospective studies are needed in order to determine the real role of the homocysteine concentration as a risk factor in children.

Cyclosporine A in juvenile idiopathic arthritis. Results of the PRCSG/PRINTO phase IV post marketing surveillance study.

OBJECTIVE: To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care. METHODS: An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease. RESULTS: A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation. CONCLUSION: This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.

Bone mineral density of Brazilian girls with juvenile dermatomyositis.

We measured bone mineral density (BMD) in girls with juvenile dermatomyositis (JDM) considering multiple factors in order to determine if it could be used as a predictor of reduction in bone mass. A cross-sectional study of lumbar spine BMD (L2-L4) was conducted on 10 girls aged 7-16 years with JDM. A group of 20 age-matched healthy girls was used as control. Lumbar spine BMD was measured by dual-energy X-ray absorptiometry. Weight, height and pubertal Tanner stage were determined in all patients and controls. Duration of disease and mean daily and cumulative steroid doses were calculated for all patients on the basis of their medical charts. JDM activity was determined on the basis of the presence of muscle weakness, cutaneous vasculitis and/or elevation of serum concentration of one or more skeletal muscle enzymes. Seven patients demonstrated osteopenia or osteoporosis. Lumbar BMD was significantly lower in the JDM patients than the age-matched healthy control girls (0.712 vs 0.878, respectively; Student t-test, P = 0.041). No significant correlation between BMD and age, height, Tanner stage, disease duration, corticosteroid use, or disease activity was observed in JDM girls, but a correlation was observed between BMD and weight (Pearson's correlation coefficient, r = 0.802). Patients with JDM may be at risk for a significant reduction in BMD that might contribute to further skeletal fragility. Our results suggest that reduced bone mass in JDM may be related to other intrinsic mechanisms in addition to steroid treatment and some aspects of the disease itself may contribute to this condition.

Nail fold capillaroscopy: normal findings in children and adolescents.

OBJECTIVES: Capillaroscopy is a simple diagnostic method that permits noninvasive in vivo study of the capillary network. Studies designed to standardize capillary normality in children are limited. This article presents the capillaroscopic findings in healthy children and adolescents, thus making the application of this methodology viable for patients in this age range. MATERIAL AND METHODS: Healthy children were recruited from a private elementary school and junior high school. Nail fold capillaroscopy was performed using a stereomicroscope at 16 times magnification, addressing the following parameters: capillary morphology, capillary enlargement, devascularization, microhemorrhage, and subpapillary venous plexus visibility (PVS). These parameters were related to age, sex, ethnicity, and local periungal conditions. RESULTS: The sample comprised 329 individuals with mean age of 8.2 years. We observed atypical capillary morphology in 118 of the studied cases (36%), mainly bizarre capillaries in 90 (27%), meandering capillaries in 32 (10%), and bushy capillaries in 20 (6%). The enlarged capillary phenomenon was uncommon, being observed in 30 cases (9%). The number of capillaries per millimeter varied from five to nine. Deletion areas were detected in only seven individuals (2%). The subpapillary venous plexus was not visualized in 13 (4%) cases. Younger children presented higher PVS scores and fewer capillaries/mm as compared with older children. PVS scores were lower in males and in nonwhite children. Other variables were not associated with sex or ethnicity. CONCLUSIONS: The normal nail fold capillary network in children resembles that observed in adults with some differences, such as a lower number of loops per millimeter, a higher PVS score, and a higher frequency of atypical loops. This information is important for the diagnostic evaluation of children in the context of autoimmune rheumatic diseases.

Evaluation of the 1982 ARA lupus criteria data set in pediatric patients. Committees of Pediatric Rheumatology of the Brazilian Society of Pediatrics and the Brazilian Society of Rheumatology.

OBJECTIVE: Although commonly used, the 1982 revised criteria for the classification of Systemic Lupus Erythematosus (SLE) have not been completely evaluated in pediatric patients. This study was aimed at evaluating the sensitivity and specificity of the 1982 revised criteria when applied to pediatric patients. METHODS: One hundred and three children with SLE and 101 children with other rheumatic diseases were selected from 5 rheumatology centers in Brazil. Diagnosis of SLE by the 1982 criteria were compared with our clinical diagnosis. The diagnosis of other diseases was made according to internationally accepted classification criteria or, when these were not available, according to the physician's own experienced judgement. RESULTS: The median number of criteria fulfilled by the patients with SLE and the controls were 6 and 1, respectively. The most common criteria observed in children with SLE were: abnormal antinuclear antibody titers (94%), arthritis (83%), immunologic disorder (83%), hematologic disorder (70%), malar rash (67%), and photosensitivity (58%). When the immunologic disorder was broken down into its constituent elements, antibodies to dsDNA and Sm were observed in 73.0% (65/89) and 31.4% (15/48), respectively. The sensitivity and specificity observed were 96% and 100%, respectively. CONCLUSION: The 1982 classification criteria can be successfully applied to children with SLE. These criteria may serve as a basis for multi-center collaborative studies on children with SLE.

Association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis in a child.

The authors report the case of a 15-year-old, HLA-B27-positive male patient who presented a rare association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis, which resulted in death. A brief review of the literature is provided.

Copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis.

OBJECTIVE: To evaluate the copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis (JRA), considering the pauci and polyarticular types, the disease activity and duration, the number of inflamed joints and the use of corticosteroids therapy. DESIGN: Cross-sectional study with control group. SETTING: Outpatients of the pediatric rheumatology public health clinic, of the Universidade Federal de São Paulo/Escola Paulista de Medicina, Brazil. SUBJECTS: Forty-one patients with JRA were evaluated and 23 patients' brothers, as a control group. INTERVENTIONS: Copper and zinc intake evaluation by Food Register method. Copper and zinc serum levels by atomic absorption spectrophotometry. RESULTS: The disease activity did not determine difference in copper (P=0.624) and zinc (P=0.705) intake, being predominantly below the Recommended Dietary Allowances. The serum copper in relation to control was statistically greater (P=0.018), showing that the number of inflamed joints is statistically significantly related with its variation (P=0.001). The serum zinc was not different either in relation to control (P=0.940) or to the disease characteristics. CONCLUSIONS: The evaluation of copper intake seems to be of fundamental importance. It may influence the efficiency of the organic serum response. More research is needed to indicate, with security, adequate zinc intake.

Symptomatic cardiac involvement in juvenile rheumatoid arthritis.

In a retrospective study of 172 patients with juvenile rheumatoid arthritis, symptomatic cardiac involvement occurred in 13 (7.6%) patients (11 systemic and 2 polyarticular). There was predominance of the male sex and in most patients the involvement occurred in the initial years of the disease. Pericarditis occurred in seven patients; perimyocarditis in four and myocarditis in two patients. In the follow-up, one of the patients with pericarditis died of an arrhythmia during pericardiocentesis for cardiac tamponade. Among the patients with myocarditis, three died of septicemia during active disease. One of these three patients had myocarditis associated with cardiac tamponade. Among the 172 patients with juvenile rheumatoid arthritis, five children died; four belonged to the symptomatic cardiac involvement group (P less than 0.001). Cardiac involvement, in particular myocarditis and cardiac tamponade, can be regarded as a factor of worse prognosis.

Serum penicillin concentrations after intramuscular administration of benzathine penicillin G in children with rheumatic fever and controls.

Serum and urine penicillin levels were determined in 11 children with rheumatic fever (RF) who were receiving benzathine penicillin G (BPG) prophylactically every 3 weeks and in 10 children without RF who received the drug for the treatment of other infections. The dose given was 600,000 units for children weighing less than 25 kg and 1,200,000 units for those with a weight above 25 kg. Blood and urine samples were collected from both groups before and on days 7, 14 and 21 after BPG administration. Our results showed that: minimum inhibitory concentrations (MICs) of BPG for group A beta-hemolytic streptococci were 0.02 IU/ml or 0.0125 microgram/ml; intramuscular BPG did not give adequate serum levels to block the growth of group A beta-hemolytic streptococci in approximately 24 and 62% of children included in the study on days 14 and 21 after its administration, respectively; BPG metabolism was similar in both groups and did not depend on the underlying disease; serum and urine levels did not vary according to sex and weight; and there was a small correlation between serum and urine levels.

Low density neutrophils in patients with juvenile idiopathic arthritis.

OBJECTIVES: (1) To study the correlation among conventional clinical and laboratory parameters and the relation between the number of lymphocytes and neutrophils (L/N) in cell suspensions from peripheral blood of patients with juvenile idiopathic arthritis (JIA). (2) To evaluate the L/N relation of JIA patients after an 8 year follow-up period. METHODS: Fifty-one JIA patients (25 female, disease course: 19 systemic, 15 polyarticular, 17 pauciarticular) were enrolled in the study. To measure the L/N relation, we used Boyum's method: The leucocyte separation was done by centrifugation of peripheral blood on Ficoll-Hypaque (FH) gradient, and the number of lymphocytes, monocytes, and neutrophils in 500 cells was determined. The following clinical and laboratory parameters were evaluated: disease activity, number of active and limited joints, functional capacity, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP). Twenty-four healthy children were used as controls. We also studied 13/51 patients from our Pediatric Rheumatology Unit who had been evaluated by the same method 8 years before. RESULTS: We observed the lowest L/N relation in patients with active disease, especially those with polyarticular course. A statistical correlation was also observed with the acute-phase reactants (ESR and CRP, p < 0.05). The majority of patients who had presented a low L/N relation at the first evaluation (8 years before) had a worse outcome. CONCLUSION: The measure of L/N relation from peripheral blood could be used as an auxiliary tool in the assessment of the activity and outcome of JIA patients, especially at disease onset.

Use of single photon emission computed tomography and magnetic resonance to evaluate central nervous system involvement in patients with juvenile systemic lupus erythematosus.

The objective of the present study was to identify the single photon emission computed tomography (SPECT) and magnetic resonance (MR) findings in juvenile systemic lupus erythematosus (JSLE) patients with CNS involvement and to try to correlate them with neurological clinical history data and neurological clinical examination. Nineteen patients with JSLE (16 girls and 3 boys, mean age at onset 9.2 years) were submitted to neurological examination, electroencephalography, cerebrospinal fluid analysis, SPECT and MR. All the evaluations were made separately within a period of 15 days. SPECT and MR findings were analyzed independently by two radiologists. Electroencephalography and cerebrospinal fluid analysis revealed no relevant alterations. Ten of 19 patients (53%) presented neurological abnormalities including present or past neurological clinical history (8/19, 42%), abnormal neurological clinical examination (5/19, 26%), and abnormal SPECT or MR (8/19, 42% and 3/19, 16%, respectively). The most common changes in SPECT were cerebral hypoperfusion and heterogeneous distribution of blood flow. The most common abnormalities in MR were leukomalacia and diffuse alterations of white matter. There was a correlation between SPECT and MR (P<0.05). We conclude that SPECT and MR are complementary and useful exams in the evaluation of neurological involvement of lupus.

Bone mineral density in juvenile systemic lupus erythematosus.

We evaluated spine bone mineral density (BMD) in Brazilian children with juvenile systemic lupus erythematosus (JSLE) in order to detect potential predictors of reduction in bone mass. A cross-sectional study of BMD at the lumbar spine level (L2-L4) was conducted on 16 female JSLE patients aged 6-17 years. Thirty-two age-matched healthy girls were used as control. BMD at the lumbar spine was measured by dual-energy X-ray absorptiometry. Weight, height and pubertal Tanner stage were determined in patients and controls. Disease duration, mean daily steroid doses, mean cumulative steroid doses and JSLE activity measured by the systemic lupus erythematosus disease activity index (SLEDAI) were determined for all JSLE patients based on their medical charts. All parameters were used as potential determinant factors for bone loss. Lumbar BMD tended to be lower in the JSLE patients, however, this difference was not statistically significant (P = 0.10). No significant correlation was observed in JSLE girls between BMD and age, height, Tanner stage, disease duration, corticosteroid use or disease activity. We found a weak correlation between BMD and weight (r = 0.672). In the JSLE group we found no significant parameters to correlate with reduced bone mass. Disease activity and mean cumulative steroid doses were not related to BMD values. We did not observe reduced bone mass in female JSLE.

Bone mineral density of the lumbar spine of Brazilian children and adolescents aged 6 to 14 years.

The authors performed a study of bone mass in eutrophic Brazilian children and adolescents using dual-energy X-ray absorptiometry (DXA) in order to obtain curves for bone mineral content (BMC) and bone mineral density (BMD) by chronological age and correlate these values with weight and height. Healthy Caucasian children and adolescents, 120 boys and 135 girls, 6 to 14 years of age, residents of São Paulo, Brazil, were selected from the Pediatric Department outpatient clinic of Hospital São Paulo (Universidade Federal de São Paulo). BMC, BMD and the area of the vertebral body of the L2-L4 segment were obtained by DXA. BMC and BMD for the lumbar spine (L2-L4) presented a progressive increase between 6 and 14 years of age in both sexes, with a distribution that fitted an exponential curve. We identified an increase of mineral content in female patients older than 11 years which was maintained until 13 years of age, when a new decrease in the velocity of bone mineralization occurred. Male patients presented a period of accelerated bone mass gain after 11 years of age that was maintained until 14 years of age. At 14 years of age the mean BMD values for boys and girls were 0.984 and 1.017 g/cm2, respectively. A stepwise multiple regression analysis of paired variables showed that the "vertebral area-age" pair was the most significant in the determination of BMD values and the introduction of a third variable (weight or height) did not significantly increase the correlation coefficient.

Thyroid function and serum prolactin levels in patients with juvenile systemic lupus erythematosus.

OBJECTIVE: To evaluate both thyroid function and serum prolactin levels in patients with juvenile systemic lupus erythematosus (JSLE) and to detect possible correlation with disease activity. METHODS: Forty-two JSLE patients (3-15 years old at disease onset), twenty-two pubertal. All patients were evaluated according their clinical manifestations and disease activity. We determined serum prolactin, thyroid-stimulating hormone (TSH), T4, free T4, T3, thyroid peroxidasis and thyreoglobulin antibodies in all patients and controls. Thyroid ultrasonography was performed in the patients. RESULTS: We did not observe any difference in thyroid hormone and prolactin levels between patients and controls. One patient with JSLE presented with hyperthyroidism and six had thyroid antibodies. We observed abnormalities by ultrasonography in four patients (9.3%), specially heterogeneity of the gland echotexture. We did not find any correlation between prolactin levels, clinical manifestations or disease activity. CONCLUSIONS: Evaluation of thyroid function should not be routine for JSLE patients. Thyroid hormones and prolactin should be measured only in patients with clinical manifestations of hypo- or hyperthyroidism.

Gastroduodenal lesions in children with juvenile rheumatoid arthritis.

BACKGROUND/AIMS: There are few studies about gastrointestinal abnormalities in patients with juvenile rheumatoid arthritis-probably due to the fact that this association is not frequently recognized. The aim of our study was to observe the prevalence of endoscopic gastroduodenal lesions in these patients. METHODOLOGY: Fourteen patients with juvenile rheumatoid arthritis, all of them using non-steroidal anti-inflammatory drugs associated or not with methotrexate, were assessed clinically and by endoscopy. Gastric antrum biopsy and Helicobacter pylori search were also performed. RESULTS: The mean age of the patients was 10.6 years (7 boys). Abdominal pain was observed in 27% of them. Macroscopic endoscopic lesions were found in 43% and infection by Helicobacter pylori in 57%. The correlation between anemia and endoscopic abnormalities was statistically significant (p < 0.05). CONCLUSIONS: Our data show that patients with juvenile rheumatoid arthritis have considerable susceptibility to gastroduodenal lesions, especially if they are using any drug association and present anemia.

Juvenile systemic lupus erythematosus. Neurological involvement.

With the purpose of analyzing the neurological involvement due to systemic lupus erythematosus (SLE), we evaluated 17 female patients who were seen regularly at the hospital and had been diagnosed as having SLE according to classification criteria proposed by the American College of Rheumatology revised in 1982, before the age of 16. Neurological involvement was detected in 12 patients (71%): headache (35%), extrapyramidal syndrome (35%), epileptic syndrome (24%) pyramidal syndrome (24%), peripheral neuropathy (12%) and optic neuritis (6%). The findings of CT scan (58%) and cerebrospinal fluid (50%) were most closely correlated to clinical neurological involvement.