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.

Correlation between the Modified Systemic Lupus Erythematosus Disease Activity Index 2000 and the European Consensus Lupus Activity Measurement in juvenile systemic lupus erythematosus.

Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p < 0.001). Similarly, Spearman correlation between the activity indices was also high ( rs > 0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.

Chronic active disease pattern predicts early damage in juvenile systemic lupus erythematosus.

OBJECTIVE: The objective of this article is to assess disease activity patterns and their relationship to damage, death and growth failure in a cohort of juvenile lupus. METHODS: Chronic active, relapsing-remitting and long quiescent activity patterns were retrospectively classified according to longitudinal scores of both the Modified SLEDAI-2K and ECLAM. The Pediatric SLICC/ACR Damage Index (Ped-SDI) was scored at the last visit in patients followed more than six months. Survival analysis was performed considering death, damage and growth failure, and stratified according to disease activity patterns. Cox model analysis identified predictors for damage and growth failure among onset clinical variables. RESULTS: Thirty-seven patients with 11 years mean age at diagnosis and 3.2 years mean follow-up were studied. According to the Modified SLEDAI-2K, activity pattern was 67.5% relapsing-remitting, 29.8% chronic active and 2.7% long quiescent and by ECLAM, 45.9%, 48.7% and 5.4%, respectively. The five-year survival was 90%. Damage accrued in 62.5% and growth failure in 31.3%. Chronic active cases progressed to damage earlier than relapsing-remitting (log-rank test, p < 0.05). Damage was associated with disease duration (p < 0.0001), thrombocytopenia (p < 0.05) and alopecia (p < 0.004). Growth failure was associated with disease duration (p < 0.007) and renal failure (p < 0.007). CONCLUSION: Damage was observed in nearly two-thirds of patients, and occurred earlier in the chronic active pattern. Disease duration, thrombocytopenia and alopecia at onset predicted damage.

Probability of remission of juvenile idiopathic arthritis following treatment with steroid joint injection.

OBJECTIVES: Steroid joint injection is indicated as starting treatment for juvenile idiopathic arthritis, but its effect as single treatment has not been explored. Our aim was to estimate arthritis remission probability after single or repeated injections. METHODS: Conduct a retrospective analysis of inactive arthritis status, remission on medication and remission off medication, estimating cumulative probability and mean time to survival, from the first joint injection session to the last follow-up visit or disease-modifying anti-rheumatic drugs initiation. Remission and time to achieve remission status after single or repeated injections were compared. RESULTS: Seventy-seven patients with 4-year medium follow-up and 254 treated joints, were reviewed. Eighty-three percent of the individuals had oligoarticular subtype and 57% had persistent oligoarticular course. Overall, 26% achieved remission off medication status, 4% remission on medication and 38% initiated disease-modifying anti-rheumatic drugs. Survival analysis resulted in mean time of achieving inactive disease status, remission on medication and off medication of 8, 11 and 56 months, respectively. The cumulative probability of remission off medication was 2% at 12 months, 8% at 24 months and 18% at 36 months. Frequency of inactive disease, remission on medication and remission off medication status decreased proportionally following repeated joint injections in comparison with the frequency of the same status for those receiving single treatment. CONCLUSIONS: The dropout rates due to anti-rheumatic drugs initiation indicated limited long-term benefits of intra-articular steroids for juvenile idiopathic arthritis.

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.

Clinical presentation and salivary gland histopathology of paediatric primary Sjögren's syndrome.

OBJECTIVES: Explore the presentation, diagnostic criteria and exocrine gland histopathology of paediatric primary Sjögren's syndrome (PPSjS). METHODS: A case series of 8 children is reported and American-European Consensus Group (AECG-2002) criteria were examined, as well as minor labial salivary and lachrymal gland biopsies, which were scored by a pathologist blinded to outcome. For all cases, connective tissue diseases and parotid-related infectious disease were excluded. RESULTS: Age at onset varied from 5-13 years old; 6 were females, all followed from diagnosis up to the last visit (1-10 years). The main features at presentation were recurrent tender parotid swelling and sialectasis imaging, with decreased salivary function assessed by Tc-99 scintigraphy. Mild sicca symptoms were observed in 4/8 cases. Systemic features, including fatigue, myalgia, arthritis, tenosynovitis, joint contractures, transient Raynaud's and high ESR, were recorded at onset. Autoantibody profile was unremarkable for diagnosis, while lymphocytic infiltration of labial salivary glands and sialectasis were observed in all biopsies (8/8). In lachrymal glands, massive lymphocytic infiltration and lymphocytic gastritis were observed during complementary assessment. Flares were treated with low dose steroids and long-term use of hydroxychloroquine (5/8), although only 3/8 fulfilled AECG-2002 diagnostic criteria, throughout the disease course. CONCLUSIONS: PPSjS is rare, slowly progressive and its early presentation is variable. Standardised diagnostic algorithms should include recurrent parotid swelling and early diagnosis should rely mostly on salivary and lachrymal gland histopathology in this age group.

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.