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.

The effect of nutritional intervention on the lipid profile and dietary intake of adolescents with juvenile systemic lupus erythematosus: a randomized, controlled trial.

Objective This study sought to evaluate the effects of a nutritional intervention on the lipid metabolism biomarkers associated with cardiovascular risk, and their variation over time, in juvenile systemic lupus erythematosus (JSLE) patients. This study also investigated the relationships between these biomarkers and dietary intake, nutritional status, disease variables, and medication used. Methods A total of 31 10- to 19-year-old female adolescents with JSLE for at least six months were analyzed. The participants were randomly allocated to two groups: nutritional intervention or control. The intervention group received verbal and printed nutritional instructions once per month over nine months. Before and after the intervention, the participants underwent assessments of anthropometry; dietary intake; physical activity; socioeconomic status; total cholesterol and fractions; triglycerides; apolipoprotein A (Apo A-I); apolipoprotein B (Apo B); paraoxonase (PON) activity (a) and amount (q); myeloperoxidase (MPO); and small, dense LDL-c (sdLDL) particles. Results After nine months, we found significant reductions in the calorie, carbohydrate, total fat, saturated fat, and trans fat intakes in the intervention compared with the control group over time. The PONa/HDL-c ratio increased by 3.18 U/ml/mg/dl in the intervention group and by 0.63 U/ml/mg/dl in the control group ( p = 0.037). Unlike the intervention group, the sdLDL levels of the control group worsened over time ( p = 0.018). Conclusion The present study detected a reduction in calorie and fat intake, which indicates an improvement of HDL-c function and possible protection against cardiovascular risk for the intervention group.

Low serum concentrations of 25-hydroxyvitamin D in children and adolescents with systemic lupus erythematosus

We evaluated the concentrations of 25-hydroxyvitamin D [25(OH)D] in children and adolescents with juvenile systemic lupus erythematosus (JSLE) and associated them with disease duration and activity, use of medication (chloroquine and glucocorticoids), vitamin D intake, calcium and alkaline phosphatase levels, and bone mineral density. Thirty patients with JSLE were evaluated and compared to 30 healthy individuals, who were age and gender matched. Assessment was performed of clinical status, disease activity, anthropometry, laboratory markers, and bone mineral density. The 30 patients included 25 (83.3%) females and 16 (53.3%) Caucasians, with a mean age of 13.7 years. The mean age at diagnosis was 10.5 years and mean disease duration was 3.4 years. Mean levels of calcium, albumin, and alkaline phosphatase were significantly lower in patients with JSLE compared with controls (P<0.001, P=0.006, and P<0.001, respectively). Twenty-nine patients (97%) and 23 controls (77%) had 25(OH)D concentrations lower than 32 ng/mL, with significant differences between them (P<0.001). Fifteen patients (50%) had vitamin D levels <20 ng/mL and 14 had vitamin D levels between 20 and 32 ng/mL. However, these values were not associated with greater disease activity, higher levels of parathormone, medication intake, or bone mineral density. Vitamin D concentrations were similar with regard to ethnic group, body mass index, height for age, and pubertal stage. Significantly more frequently than in controls, we observed insufficient serum concentrations of 25(OH)D in patients with JSLE; however, we did not observe any association with disease activity, higher levels of parathormone, lower levels of alkaline phosphatase, use of medications, or bone mineral density alterations.

Low serum concentrations of 25-hydroxyvitamin D in children and adolescents with systemic lupus erythematosus.

We evaluated the concentrations of 25-hydroxyvitamin D [25(OH)D] in children and adolescents with juvenile systemic lupus erythematosus (JSLE) and associated them with disease duration and activity, use of medication (chloroquine and glucocorticoids), vitamin D intake, calcium and alkaline phosphatase levels, and bone mineral density. Thirty patients with JSLE were evaluated and compared to 30 healthy individuals, who were age and gender matched. Assessment was performed of clinical status, disease activity, anthropometry, laboratory markers, and bone mineral density. The 30 patients included 25 (83.3%) females and 16 (53.3%) Caucasians, with a mean age of 13.7 years. The mean age at diagnosis was 10.5 years and mean disease duration was 3.4 years. Mean levels of calcium, albumin, and alkaline phosphatase were significantly lower in patients with JSLE compared with controls (P<0.001, P=0.006, and P<0.001, respectively). Twenty-nine patients (97%) and 23 controls (77%) had 25(OH)D concentrations lower than 32 ng/mL, with significant differences between them (P<0.001). Fifteen patients (50%) had vitamin D levels <20 ng/mL and 14 had vitamin D levels between 20 and 32 ng/mL. However, these values were not associated with greater disease activity, higher levels of parathormone, medication intake, or bone mineral density. Vitamin D concentrations were similar with regard to ethnic group, body mass index, height for age, and pubertal stage. Significantly more frequently than in controls, we observed insufficient serum concentrations of 25(OH)D in patients with JSLE; however, we did not observe any association with disease activity, higher levels of parathormone, lower levels of alkaline phosphatase, use of medications, or bone mineral density alterations.

Validation of the Portuguese Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY) in Brazil.

BACKGROUND AND OBJECTIVE: Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY) is a health-related quality of life (HRQOL) assessment tool for pediatric systemic lupus erythematosus (SLE), which has been translated into Portuguese for Brazil. We are reporting preliminary data on cross-cultural validation and reliability of SMILEY in Portuguese (Brazil). METHODS: In this multi-center cross-sectional study, Brazilian children and adolescents 5-18 years of age with SLE and parents participated. Children and parents completed child and parent reports of Portuguese SMILEY and Portuguese Pediatric Quality of Life Inventory (PedsQL™) Generic and Rheumatology modules. Parents also completed the Childhood Health Assessment Questionnaire (CHAQ). Physicians completed the SLE disease activity index (SLEDAI), Physician's Global Assessment of disease activity (PGA) and Systemic Lupus Erythematosus International Collaborating Clinics ACR Damage Index (SDI). RESULTS: 99 subjects (84 girls) were enrolled; 93 children and 97 parents filled out the SMILEY scale. Subjects found SMILEY relevant and easy to understand and completed SMILEY in 5-15 minutes. Brazilian SMILEY was found to have good psychometric properties (validity and reliability), and the child-parent agreement was moderate. CONCLUSION: SMILEY may eventually be used routinely as a research/clinical tool in Brazil. It may be also adapted for other Portuguese-speaking nations offering critical information regarding the effect of SLE on HRQOL for children with SLE.

Factors affecting survival in juvenile systemic sclerosis.

OBJECTIVES: To determine whether demographic, clinical and immunological features may predict the outcome in juvenile SSc (JSSc). METHODS: Clinical and laboratory characteristics of patients with JSSc collected from paediatric rheumatology centres worldwide were analysed. First, univariate tests identified those features significantly related with fatal outcome, and then multivariate logistic regression analysis was applied to determine the predictors of mortality. RESULTS: One hundred and thirty-four patients from 40 centres were eligible for the analysis. Sixteen patients died and a rapidly fatal course was observed in most of them: 4/16 died within 1 yr after diagnosis and 10/16 within 5 yrs. At the moment of diagnosis, patients with poor outcome showed a significantly higher frequency of internal organ involvement, particularly cardiac, respiratory and gastrointestinal systems. No significant difference emerged for entity of skin, vascular and musculo-skeletal involvement, nor for auto-antibodies profile and laboratory tests. Multivariate analysis showed the following factors to be significant predictors of mortality: fibrosis on chest X-rays [odds ratio (OR) 11.2], raised creatinine levels (OR 22.7) and pericarditis (OR 41.3), while a short disease duration at diagnosis conferred protection (OR 0.3). CONCLUSIONS: All patients with JSSc and fatal outcome were affected by the diffuse form of the disease, and most of them showed a very rapid progression and early signs of internal organ involvement. This suggests that, in children, SSc may have two possible courses: a rapid development of internal organ failure leading to severe disability and eventually to death, or a slow course of the disease with lower mortality.

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.

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.

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 percent) presented neurological abnormalities including present or past neurological clinical history (8/19, 42 percent), abnormal neurological clinical examination (5/19, 26 percent), and abnormal SPECT or MR (8/19, 42 percent and 3/19, 16 percent, 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

The Brazilian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the cross-cultural adaptation and validation into Brazilian-Portuguese of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children regardless the underlying disease. The Brazilian CHAQ was revalidated, while the CHQ has been derived from the Portuguese version. A total of 471 subjects were enrolled: 157 patients with JIA (27% systemic onset, 38% polyarticular onset, 9% extended oligoarticular subtype, and 26% persistent oligoarticular subtype) and 314 healthy children. The CHAQ discriminated clinically healthy subjects from JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and lower overall well-being scores when compared to their healthy peers. Also the CHQ discriminated clinically healthy subjects from JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being score when compared to their healthy peers. In conclusion the Brazilian versions of the CHAQ-CHQ are reliable and valid tools for the combined physical and psychosocial assessment of children with JIA.

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.

The value of echocardiography in the diagnosis and followup of rheumatic carditis in children and adolescents: a 2 year prospective study.

OBJECTIVE: To evaluate echocardiographic/Doppler findings in patients with rheumatic fever whether or not clinical manifestations of carditis were present, and the followup of these findings 24 months after the acute phase. METHODS: Twenty-two patients with rheumatic fever (13 boys, 9 girls, mean age 11.0 years) were evaluated at baseline (at diagnosis) and after 3 and 6 mo of disease. Eighteen patients were reevaluated 24 mo later. The assessment included physical and cardiac examination, electrocardiogram, chest radiography, and color ECHO/Doppler performed blindly by different investigators. The control group included 15 healthy children. RESULTS: We observed clinical carditis in 8 patients (36.4%): Group 1, all with ECHO abnormalities. We observed no clinical cardiac manifestations in 14 patients (Group 2), but 5 (35.7%) had positive ECHO/Doppler abnormalities that persisted at least 6 mo in followup assessments. Mitral and aortic were the most frequently involved valves. In Group 1 we observed normalization of the ECHO/Doppler in 3 patients, improvement in 2, no change in 2, and worsening in one. Twelve of 14 patients without clinical carditis were reevaluated, including the 5 patients with ECHO/Doppler abnormalities during the initial evaluations; normalization or improvement was observed in 2 patients, no change in 2, and worsening in one. We observed no ECHO/Doppler abnormalities in the control group. CONCLUSION: This blind prospective study suggests the existence of asymptomatic carditis in some patients with rheumatic fever and the role ECHO/Doppler investigation could play in diagnosis and followup.