Evaluation of depressive and anxiety symptoms in childhood-onset systemic lupus erythematosus: Frequency, course, and associated risk factors.

BACKGROUND: Depressive and anxiety symptoms are common in childhood-onset systemic lupus erythematosus (cSLE), yet their etiology and course remain unclear. We investigated the frequency of depressive and anxiety symptoms longitudinally in youth with cSLE, and associated socio-demographic and disease factors. METHODS: Participants 8-18 years with cSLE completed baseline measures [demographic questionnaire, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Screen for Childhood Anxiety Related Disorders (SCARED), and psychiatric interview] and follow-up measures (CES-DC and SCARED) > 6 months later. Prevalence of clinically significant depressive (score >15 on CES-DC) or anxiety symptoms (score ≥25 on SCARED) was calculated at baseline and follow-up. Baseline psychiatric interview diagnoses were tabulated. Relationships between socio-demographics (neighborhood-level material deprivation, ethnic concentration, adverse childhood event history, psychiatric condition in a first-degree relative), disease-related factors (disease duration, major organ disease, disease activity, glucocorticoid use, comorbid medical condition) and baseline depressive and anxiety scores, were examined in linear regression models. Factors with univariate associations with p < 0.2 were included in multivariable adjusted models. RESULTS: At baseline, of 51 participants with a mean disease duration of 4.3 years (SD 2.7), 35% (n = 18) and 35% (n = 18) had clinically significant depressive and anxiety symptoms, respectively. Anxiety disorder was diagnosed by psychiatric interview in 14% (n = 7), depressive disorders in 6% (n = 3), and post-traumatic stress disorder in 4% (n = 2). Adverse childhood events and first-degree relative with psychiatric condition were present in 40% (n = 20) and 37% (n = 18), respectively. In multivariable regression analysis, baseline depressive symptoms were positively correlated with neighbourhood-level material deprivation (ß = 4.2, 95% CI [1.0, 7.3], p = 0.01) and psychiatric condition in a first-degree relative (ß = 7.3, 95% CI [2.2, 12.4], p = 0.006). No associations were found between baseline anxiety scores and patient factors. At a median follow-up of 13.5 months (IQR 10.5, 18) for CES-DC (n = 34) and SCARED (n = 44), depressive and anxiety symptoms were persistent (18%, n = 6; 16%, n = 7), and newly present (24%, n = 8; 16% n = 7) at follow-up. CONCLUSION: In this sample, depressive and anxiety symptoms were prevalent and persistent. Depressive symptoms correlated with neighborhood-level material deprivation, and family psychiatric history. These findings support routine psychosocial assessment in cSLE, and provision of appropriate resources.

Towards development of treat to target (T2T) in childhood-onset systemic lupus erythematosus: PReS-endorsed overarching principles and points-to-consider from an international task force.

OBJECTIVES: Application of 'treat-to-target' (T2T) in childhood-onset systemic lupus erythematosus (cSLE) may improve care and health outcomes. This initiative aimed to harmonise existing evidence and expert opinion regarding T2T for cSLE. METHODS: An international T2T Task Force was formed of specialists in paediatric rheumatology, paediatric nephrology, adult rheumatology, patient and parent representatives. A steering committee formulated a set of draft overarching principles and points-to-consider, based on evidence from systematic literature review. Two on-line preconsensus meeting Delphi surveys explored healthcare professionals' views on these provisional overarching principles and points-to-consider. A virtual consensus meeting employed a modified nominal group technique to discuss, modify and vote on each overarching principle/point-to-consider. Agreement of >80% of Task Force members was considered consensus. RESULTS: The Task Force agreed on four overarching principles and fourteen points-to-consider. It was agreed that both treatment targets and therapeutic strategies should be subject to shared decision making with the patient/caregivers, with full remission the preferred target, and low disease activity acceptable where remission cannot be achieved. Important elements of the points-to-consider included: aiming for prevention of flare and organ damage; glucocorticoid sparing; proactively addressing factors that impact health-related quality of life (fatigue, pain, mental health, educational challenges, medication side effects); and aiming for maintenance of the target over the long-term. An extensive research agenda was also formulated. CONCLUSIONS: These international, consensus agreed overarching principles and points-to-consider for T2T in cSLE lay the foundation for future T2T approaches in cSLE, endorsed by the Paediatric Rheumatology European Society.

Genetics of osteonecrosis in children and adults with systemic lupus erythematosus.

OBJECTIVES: Genetics plays an important role in SLE risk, as well as osteonecrosis (ON), a significant and often debilitating complication of SLE. We aimed to identify genetic risk loci for ON in people with childhood-onset (cSLE) and adult-onset (aSLE) SLE. METHODS: We enrolled participants from two tertiary care centres who met classification criteria for SLE. Participants had prospectively collected clinical data and were genotyped on a multiethnic array. Un-genotyped single nucleotide polymorphisms (SNPs) were imputed, and ancestry was inferred using principal components (PCs). Our outcome was symptomatic ON confirmed by imaging. We completed time-to-ON and logistic regression of ON genome-wide association studies (GWASs) with covariates for sex, age of SLE diagnosis, five PCs for ancestry, corticosteroid use and selected SLE manifestations. We conducted separate analyses for cSLE and aSLE and meta-analysed results using inverse-variance weighting. Genome-wide significance was P < 5 × 10-8. RESULTS: The study included 940 participants with SLE, 87% female and 56% with cSLE. ON was present in 7.6% (n = 71). Median age of SLE diagnosis was 16.9 years (interquartile range [IQR]: 13.5, 29.3), with median follow-up of 8.0 years (IQR: 4.2, 15.7). Meta-GWAS of cSLE and aSLE time-to-ON of 4 431 911 SNPs identified a significant Chr.2 SNP, rs34118383 (minor allele frequency = 0.18), intronic to WIPF1 (hazard ratio = 3.2 [95% CI: 2.2, 4.8]; P = 1.0 × 10-8). CONCLUSION: We identified an intronic WIPF1 variant associated with a 3.2 times increased hazard for ON (95% CI: 2.2, 4.8; P = 1.0 × 10-8) during SLE follow-up, independent of corticosteroid exposure. The effect of the SNP on time-to-ON was similar in cSLE and aSLE. This novel discovery represents a potential ON risk locus. Our results warrant replication.

Genetics of longitudinal kidney function in children and adults with systemic lupus erythematosus.

OBJECTIVES: Genome-wide association studies (GWAS) have identified loci associated with estimated glomerular filtration rate (eGFR). Few LN risk loci have been identified to date. We tested the association of SLE and eGFR polygenic risk scores (PRS) with repeated eGFR measures from children and adults with SLE. METHODS: Patients from two tertiary care lupus clinics that met ≥4 ACR and/or SLICC criteria for SLE were genotyped on the Illumina MEGA or Omni1-Quad arrays. PRSs were calculated for SLE and eGFR, using published weighted GWA-significant alleles. eGFR was calculated using the CKD-EPI and Schwartz equations. We tested the effect of eGFR- and SLE-PRSs on eGFR mean and variance, adjusting for age at diagnosis, sex, ancestry, follow-up time, and clinical event flags. RESULTS: We included 1158 SLE patients (37% biopsy-confirmed LN) with 36 733 eGFR measures over a median of 7.6 years (IQR: 3.9-15.3). LN was associated with lower within-person mean eGFR [LN: 93.8 (s.d. 26.4) vs non-LN: 101.6 (s.d. 17.7) mL/min per 1.73 m2; P < 0.0001] and higher variance [LN median: 157.0 (IQR: 89.5, 268.9) vs non-LN median: 84.9 (IQR: 46.9, 138.2) (mL/min per 1.73 m2)2; P < 0.0001]. Increasing SLE-PRSs were associated with lower mean eGFR and greater variance, while increasing eGFR-PRS was associated with increased eGFR mean and variance. CONCLUSION: We observed significant associations between SLE and eGFR PRSs and repeated eGFR measurements, in a large cohort of children and adults with SLE. Longitudinal eGFR may serve as a powerful alternative outcome to LN categories for discovery of LN risk loci.

A decade of progress in juvenile idiopathic athritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

OBJECTIVE: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing a 2005-2010 and a 2017-2021 inception cohorts. METHODS: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan Meier survival analysis and multivariable Cox regression. RESULTS: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for Inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for a good health-related quality of life. CONCLUSION: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient reported outcomes were smaller than improvements in disease activity.

Acute kidney injury requiring kidney replacement therapy in childhood lupus nephritis: a cohort study of the Pediatric Nephrology Research Consortium and Childhood Arthritis and Rheumatology Research Alliance.

BACKGROUND: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited. METHODS: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure. RESULTS: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure. CONCLUSIONS: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

TNF inhibition in vasculitis management in adenosine deaminase 2 deficiency (DADA2).

BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited autoinflammatory disorder caused by a loss of functional ADA2 protein. TNF inhibition (TNFi) has proven to be highly effective in treating inflammatory manifestations. OBJECTIVE: We sought to explore the pathophysiology and the underlying mechanisms of TNF-inhibitor response in these patients. METHODS: We performed Sanger sequencing of the ADA2 gene. We used flow cytometry, intracellular cytokine staining, transcriptome analysis, immunohistochemistry, and cell differentiation experiments to define an inflammatory signature in patients with DADA2 and studied their response to TNF-inhibitor treatment. RESULTS: We demonstrated increased inflammatory signals and overproduction of cytokines mediated by IFN and nuclear factor kappa B pathways in patients' primary cells. Treatment with TNFi led to reduction in inflammation, rescued the skewed differentiation toward the proinflammatory M1 macrophage subset, and restored integrity of endothelial cells in blood vessels. We also report 8 novel disease-associated variants in 7 patients with DADA2. CONCLUSIONS: Our data explore the cellular mechanism underlying effective treatment with TNFi therapies in DADA2. DADA2 vasculitis is strongly related to the presence of activated myeloid cells, and the endothelial cell damage is rescued with anti-TNF treatment.

Causal pathways to health-related quality of life in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

OBJECTIVE: Structural equation modelling was applied to data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort to help elucidate causal pathways to decreased health-related quality of life (HRQoL) in children with JIA. METHODS: Based on published literature and clinical plausibility, a priori models were constructed with explicit root causes (disease activity, treatment intensity) and mediators (pain, disease symptoms, functional impairments) leading to HRQoL [measured by the Quality of my Life (QoML) scale and the Juvenile Arthritis Quality of Life Questionnaire (JAQQ)] at five disease stages: (i) diagnosis, (ii) 3-9 months after diagnosis, (iii) flare, (iv) remission on medications, (v) remission off medications. Following structural equation modelling, a posteriori models were selected based on data fit and clinical plausibility. RESULTS: We included 561, 887, 137, 186 and 182 patients at each stage, respectively. In a posteriori models for active disease stages, paths from disease activity led through pain, functional impairments, and disease symptoms, directly or through restrictions in participation, to decreased QoML scores. Treatment intensity had detrimental effects through psychosocial domains; while treatment side effects had a lesser role. Pathways were similar for QoML and JAQQ, but JAQQ models provided greater specificity. Models for remission stages were not supported by the data. CONCLUSION: Our findings support disease activity and treatment intensity as being root causes of decreased HRQoL in children with JIA, with pain, functional impairments, and participation restrictions being mediators for disease activity; they support psychosocial effects and side effects as being mediators for treatment intensity.

Association of systemic lupus erythematosus (SLE) genetic susceptibility loci with lupus nephritis in childhood-onset and adult-onset SLE.

OBJECTIVE: LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). METHODS: Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. RESULTS: Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). CONCLUSION: We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.

A comparison between childhood and adult onset systemic lupus erythematosus adjusted for ethnicity from the 1000 Canadian Faces of Lupus Cohort.

OBJECTIVE: Childhood-onset SLE (cSLE) manifests differently than adult-onset SLE (aSLE). This study determined whether ethnic differences contribute to the differences in clinical presentation between the two groups. METHODS: This cross-sectional study used data from a multi-centred registry from eight adult and four paediatric Canadian centres gathered at study entry. We compared the frequency of clinical manifestations and autoantibodies between aSLE and cSLE. For those with a significant difference, a multivariable logistic regression was performed, adjusting for ethnicity, SLE onset (cSLE vs aSLE), disease duration and centre. Disease activity and damage between aSLE and cSLE were compared after stratifying by disease duration. RESULTS: Of 552 aSLE subjects, 502 (90.9%) were female and 381 (69.0%) were Caucasian. Mean age at diagnosis was 37.0 ± 13.6 years and disease duration 10.9 ± 9.6 years. Of 276 cSLE subjects, 231 (83.7%) were female and 101 (36.6%) were Caucasian. Mean age at diagnosis was 12.7 ± 3.3 years and disease duration 5.6 ± 8.2 years. In multivariable regression analysis, aSLE was associated with decreased odds of having a neurologic disorder (odds ratio = 0.49) and increased odds of having aCL antibodies (odds ratio = 1.85). Disease activity and damage accrual scores were higher in aSLE than cSLE within the same disease duration strata, although the differences were not clinically significant. Ethnicity was not associated with any differences in clinical manifestations or autoantibody frequency between aSLE and cSLE. CONCLUSIONS: Although a crude comparison of aSLE and cSLE yielded several differences in clinical symptoms and autoantibodies, this difference was not attributable to ethnic differences between aSLE and cSLE.

PANDAS/PANS in childhood: Controversies and evidence.

Since first defined in 1998, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and its later, broader iteration, paediatric acute-onset neuropsychiatric syndrome (PANS), have garnered significant attention and controversy. The role of streptococcal infection in children with explosive onset obsessive-compulsive disorder and new onset tics, the natural history of this entity, and the role of symptomatic and disease-modifying therapies, including antibiotics, immunotherapy, and psychoactive drugs, are all issues that have yet to be definitively addressed. While definitive proof of the autoimmune hypothesis of PANDAS is lacking, given the heightened attention to this entity and apparent rise in use of this diagnostic category, addressing questions around diagnosis, treatment, and etiology is imperative. In this paper, we review current working definitions of PANDAS/PANS, discuss published evidence for interventions related to this entity, and propose a clinical approach to children presenting with acute symptoms satisfying criteria for PANDAS/PANS.

The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

OBJECTIVE: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare. METHODS: We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression. RESULTS: 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. CONCLUSIONS: In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare.

The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort.

OBJECTIVE: To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. METHODS: Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan-Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments. RESULTS: In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46-57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. CONCLUSIONS: Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.

Validation of the systemic lupus erythematosus responder index for use in juvenile-onset systemic lupus erythematosus.

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.

Adolescent Health Care Needs and Relationship to Disease in Patients With Childhood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: Our objective was to characterize adolescent health and psychosocial issues in patients with childhood-onset systemic lupus erythematosus (cSLE) and evaluate demographic and disease characteristics associated with adolescent health. METHODS: We retrospectively examined adolescents aged 12 to 18 years with cSLE seen at the Hospital for Sick Children meeting the American College of Rheumatology/Systemic Lupus International Collaborating Clinics classification criteria, assessed by adolescent medicine in the cSLE clinic between 2018 and 2020. Adolescent health issues were characterized using the Home, Education/Employment, Activities, Diet/Drugs, Sexuality, Suicide/mood (HEADDSS) framework. Issues were classified as presenting and/or identified; adolescent health burden was tabulated as the number of distinct adolescent issues per patient. Multiple Poisson regression models examined associations between patient and disease characteristics (age, sex, material deprivation, disease activity, disease damage, and high-dose glucocorticoid exposure) and adolescent health issues. RESULTS: A total of 108 (60%) of 181 adolescents with cSLE were seen by adolescent medicine, with a median of 2 (interquartile range [IQR] 1-3) visits and a median of 2 (IQR 1-5) adolescent health issues during the study period. Common issues were mood (presenting in 21% vs identified in 50%), sleep (27% vs 2%), school and education (26% vs 1%), and nonadherence (23% vs 8%). Psychoeducation was provided by adolescent medicine to 54% of patients. High-dose glucocorticoids (risk ratio [RR] 1.82, 95% confidence interval [CI] 1.41-2.35, P < 0.001), material deprivation (RR 1.17, 95% CI 1.04-1.30, P = 0.007), and lower SLE Disease Activity Index scores (RR 0.95, 95% CI 0.92-0.98, P = 0.004) were associated with higher adolescent health burden. CONCLUSION: Adolescents with cSLE experience many adolescent issues, especially low mood. High-dose glucocorticoids and social marginalization are associated with greater adolescent health burden. This study highlights the importance of addressing adolescent health needs as part of routine care.

An update on childhood-onset systemic lupus erythematosus.

PURPOSE OF REVIEW: This manuscript will provide a review of studies published in the last year examining the major disease manifestations, comorbidities, biomarkers and therapeutic trials involving childhood-onset systemic lupus erythematosus (cSLE) patients. RECENT FINDINGS: Recent multicenter prospective cohort studies supported previous findings that cSLE patients accrue damage early on their disease. Four studies showed that ethnicity altered disease severity and incidence of both cSLE and lupus nephritis. Description of clinical features and response to therapy in a large group of cSLE patients with neuropsychiatric involvement provided useful information on this feature. Advancement in the field of biomarkers was seen but the new biomarkers are not yet ready for clinical use. A randomized placebo-controlled trial of statins to prevent atherosclerosis progression did not meet its primary endpoint but did show a trend in improvement of carotid intima-media thickness, a surrogate marker of atherosclerosis. No other prospective interventional treatment trials designed specifically for cSLE patients were reported in the past year. SUMMARY: There is an urgent need to better characterize the long-term outcome of cSLE patients and identify early on those at risk of a worse outcome. Advances in the field of biologics and small molecules will hopefully allow better targeted therapies of the cSLE population.