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Objective: Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time., Methods: Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K., Results: There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years., Conclusion: Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

Objective The objective of this article is to examine the quality, content, and readability of information and resources in the English language and accessible on the internet by pediatric patients with systemic lupus erythematosus (SLE) and their families in North America. Methods Keywords relevant to SLE were generated by an undergraduate student, a first-year medical student, and a third-year pediatric resident, and a search was conducted across five commonly used search engines. Quality of information found was evaluated independently by an undergraduate student, a graduate student, a first-year medical student, and a third-year pediatric resident using the DISCERN tool. Two pediatric rheumatologists assessed website accuracy and completeness. Readability of websites was determined using the Flesch-Kincaid grade level and Reading Ease score. Results Out of 2000 websites generated in the search, only 34 unique websites met inclusion criteria. Only 16 of these websites had DISCERN scores above 50% (fair quality). Overall quality of website information was fair with mean ±standard deviation (SD) DISCERN quality score of 44 ± 7 (range: 30-56). Only nine websites of 34 had DISCERN scores above 50 (>66%, indicating greater quality) and were further assessed for completeness. Flesch-Kincaid grade level was 11 ± 1 (mean±SD) and reading ease score was 39 ± 10 (mean±SD, range of 11-61). Conclusion Our study highlights the need for more complete, readable information regarding the unique needs of pediatric patients with childhood-onset SLE and their families.

Objective: This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE)., Methods: Obesity was defined as a body mass index (BMI) ≥ 95 th percentile according to the Sex-specific Center for Disease Control BMI-For-Age Charts and determined in a multicenter cohort of jSLE patients. In this secondary analysis, the domain and summary scores of the Pediatric Quality of Life (PedsQL) Inventory and the Child Health Questionnaire (CHQ) of obese jSLE patients were compared to those of non-obese jSLE patients as well as historical obese and non-obese healthy controls. Mixed-effects modeling was performed to evaluate the relationship between obesity and HRQOL measures., Results: Among the 202 jSLE patients, 25% (n = 51) were obese. Obesity had a significant negative impact on HRQOL in jSLE, even after adjusting for differences in current corticosteroid use, disease activity, disease damage, gender and race between groups. Obese jSLE patients had lower physical functioning compared to non-obese jSLE patients, and to non-obese and obese healthy controls. Compared to their non-obese counterparts, obese jSLE patients also had worse school functioning, more pain, worse social functioning and emotional functioning. Parents of obese jSLE patients worry more. The CHQ scores for obese jSLE patients were also worse compared to non-obese jSLE patients in several other domains., Conclusion: Our study demonstrates the detrimental effects of obesity on patient-reported outcomes in jSLE. This supports the importance of weight management for the therapeutic plan of jSLE., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Objectives: This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE)., Methods: The SRI considers changes in the SELENA-SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA-SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined., Results: The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change., Conclusions: The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation.

Objective: To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE)., Methods: We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data., Results: In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials., Conclusion: Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE., (Copyright © 2013 by the American College of Rheumatology.)

Objective: To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE)., Methods: One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models., Results: Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score., Conclusion: Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity.

Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS proteins for detecting activity of LN over time. Using surface-enhanced or matrix-assisted laser desorption/ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), alpha1-acid-glycoprotein (AGP), lipocalin-type prostaglandin-D synthetase (L-PGDS), albumin, and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African American) and 30 controls with juvenile idiopathic arthritis. All urinary PS proteins were significantly higher with active vs. inactive LN or in patients without LN (all p < 0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 mo before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001), and L-PGDS (p < 0.01) occurred, indicating that these PS proteins are biomarkers of LN activity and may help anticipate the future course of LN.

Objective: To evaluate corticosteroid prescribing patterns in childhood-onset systemic lupus erythematosus (SLE), comparing four academic pediatric rheumatology practices., Methods: Patients with childhood-onset SLE (n=72) treated at four large pediatric rheumatology centers were studied at 3-month intervals for 18 months. Information on medication use, disease activity as measured by the SLEDAI and the SLAM; and disease damage by the SLICC/ACR Damage Index was collected., Results: At the time of enrollment, patients at each center were similar for disease duration, age, frequency of renal involvement and disease damage. Prednisone (mean 9 mg/day) was continued during 72% of periods of inactive disease for at least 3 months (SLEDAI=0). Centers differed in the use of intravenous pulse methylprednisolone (p<0.0001). Even when adjusted for between-center differences in patient weight, race and disease activity, centers also significantly differed in the dose of prednisone (p<0.05). The center with the largest between-patient variability in the dose of prednisone prescribed to its patients showed the smallest between-patient variance in patient disease activity., Conclusions: Corticosteroids are commonly used for the treatment of childhood-onset SLE, even when the disease is inactive. There appears to be important between-center differences in the use of intravenous and oral corticosteroids for childhood-onset SLE therapy that cannot be explained by patient disease activity corticosteroid prescribing patterns influence disease control. Further studies are needed to determine whether differences in practice patterns lead to significant differences in longer-term disease outcomes with childhood-onset SLE.

The objective of this study is to examine the clinical features and outcomes of patients with systemic lupus erythematosus (SLE) whose disease began in adolescence [juvenile-onset SLE (jSLE)] compared with adult-onset patients [adult-onset SLE (aSLE)] from a large multiethnic cohort. Systemic lupus erythematosus patients of African-American, Caucasian, or Hispanic ethnicity and >or=1 year follow-up were studied in two groups: jSLE (diagnosed at

Approximately 15% of patients with systemic lupus erythematosus (SLE) will have the onset of their disease in childhood or adolescence. Due to the broad range of possible clinical features of SLE, the diagnosis may be difficult to make in a general pediatric or community setting. The common symptoms of SLE in children and adolescents include fever, fatigue, weight loss, arthritis, rash and renal disease. SLE is more common in non-Caucasian ethnic groups and should be considered in the differential diagnosis of a multisystem disease in these patients. In this article, the classification criteria for SLE are discussed, and an approach to making an accurate and timely diagnosis of this disease is considered.

The childhood rheumatic diseases are a group of chronic disorders with variable courses, morbidity, and outcomes ranging from complete remission to long-term disability. The major childhood rheumatic disorders are juvenile idiopathic arthritis (systemic onset, polyarticular, oligoarticular, enthesitis-related, psoriatic), juvenile dermatomyositis, systemic lupus erythematosus, and the vasculitides. In this review, the current status of outcomes measurement application to pediatric rheumatology will be discussed.

Nearly 15% of patients with systemic lupus erythematosus (SLE) present during adolescence; it is therefore highly likely that a pediatrician will care for a young adult with SLE in his or her practice. The author stresses the importance of an individualized medical treatment plan that suits the patient and disease stage, as well as the clinician's obligation to provide clear and accurate information to adolescents and their parents. Guidelines to facilitate patient compliance and understanding are also offered.

Objective: To determine the incidence of anti-hsp90 and 70 antibodies in children with SLE, juvenile dermatomyositis and juvenile chronic arthritis., Methods: We utilized a previously described ELISA to detect the presence of antibodies to mammalian hsp90 and 70 in 33 children with SLE, 55 with juvenile chronic arthritis (JCA) and 11 with dermatomyositis. Sera from 19 children with non-autoimmune conditions served as controls., Results: Antibodies reactive with hsp90 and/or 70 were detected in 35% of the children with SLE, and the numbers of children with SLE who have raised IgG anti-hsp90 antibodies (24%) is very similar to our adult onset cases, although the prevalence of IgM antibodies is much smaller. However, serum antibodies to hsp70 were as infrequent in children with SLE or JCA as in adults with SLE or RA, although IgG antibodies to hsp70 were detected in 50% of the synovial fluid of JCA patients., Conclusion: The incidence of antibodies to hsp90 in childhood-onset SLE resembles that described in adult onset disease suggesting that, despite clinical differences between the two, a subset of each may share a similar pathological mechanism of disease.

This study examines the differences which may distinguish systemic lupus erythematosus (SLE) presenting in adult life or childhood. A common database was established, with analysis of clinical, serological and outcome features of a cohort of patients with SLE, with disease diagnosed before the age of 16 (n = 39) or after the age of 16 (n = 165). Disease onset was generally more severe in the childhood-onset patients. Cardiopulmonary disease was more common in the older-onset group, but major haematological manifestations were more frequent in the childhood-onset group. Serologically, anti-DNA, anti-Sm and anti-RNP antibodies and a low C3 were all found more frequently in the younger patients. Twice as many adult-onset cases had died at the time of the last follow-up (10 vs 5%), but this group had been followed for a longer period (average 7.5 yr, S.D. 3.9 for adults vs average 4.8 yr, S.D. 3.2 for children). However, the younger patients were twice as likely (82 vs 40%) to require high-dose prednisone, although the requirement for immunosuppressive agents was similar in the two groups. Clinicians should anticipate that children with SLE have a more severe disease onset than adults in general.

Neuropsychological assessments of adults with SLE have shown cognitive impairment, sequential processing deficits, memory loss, increased incidence of left handedness, learning disabilities and emotional distress compared with healthy individuals or subjects with other medical conditions. Neuropsychological testing regarding these variables in children and adolescents with SLE has been infrequently reported. For this study, eight children with SLE (age 9-17 years at diagnosis) were assessed with neuropsychological testing at a median of 10.5 months (range 1 week to 30 months) after diagnosis. Tests included Wechsler Intelligence Scale for Children-Revised or Wechsler Adult Intelligence Scale-Revised, Wide Range Achievement Test-Revised, Standard Binet Intelligence Scale Fourth Edition Memory Subtests or Wechsler Memory Scale (all mean = 100 +/- 15) and Gates MacInitie Reading Comprehension Test, Achenbach Child Behavior Checklist and Achenbach Youth Self Report. Mean intellectual scores were in the low average range (Wechsler Full Scale mean = 85.0 +/- 11.9, Verbal Scale mean 85.2 +/- 13.9, Performance Scale mean = 88.0 +/- 13.9). Academic achievement was globally depressed (reading recognition mean = 79.5 +/- 22.0, spelling mean = 78.9 +/- 23.5), especially in arithmetic (mean = 70.5 +/- 14.9). Children with SLE averaged 5 years behind grade placement in reading comprehension. Visual memory was also depressed in patients with SLE. Behavior ratings failed to demonstrate any significant aberrations in the test subjects.

The recent description of a lupus-like disease in normal mice after injections of human mAb that bind DNA and carry the common Id 16/6 Id has excited much attention. In an effort to reproduce this model we have performed two experiments using eight human mAb three of which bear the 16/6 Id. Despite using an injection protocol very similar to that of the original authors and waiting for up to 1 yr we were unable to detect any autoantibodies or any evidence of renal disease. We suspect that our failure to reproduce the model may be due to differences in either or both the batches of CFA used, or in the animal house environments. It supports the view that a mosaic of effects is required to induce clinical expression of an autoimmune disease.

Id-16/6 is an idiotypic marker found in both IgM and IgG antibodies, as well as in the tissue lesions of patients with SLE. The prototypic Id-16/6+ mAb is 18/2, whose VH3-derived H chain is encoded by an unmutated germ-line gene. We found that the H chains of VH3-derived Id-16/6+ antibodies contain the major determinants of Id-16/6. Moreover, B cell clones from which those antibodies were harvested produce RNA that hybridized under conditions of high stringency to oligonucleotide probes corresponding to the CDR of the VH segment of 18/2. Western blots of Id-16/6+ mAbs with anti-Id confirmed the association of the Id with H chains. Id-16/6 can identify a subgroup of VH3-derived antibodies we have termed the 18/2 CDR family. However, Id-16/6 can also be expressed in some antibodies unrelated to the 18/2 CDR family. No characteristic Ag-binding specificity was found among the members of the 18/2 CDR family. The principal phenotypic feature shared by all known members of the family is Id-16/6.