Abstract Background Childhood-onset Systemic Lupus Erythematosus (cSLE) is an autoimmune disease associated with fatigue, mood symptoms, and pain. Fortunately, these symptoms are potentially modifiable with psychological intervention such as cognitive-behavioral therapy (CBT). The Treatment and Education Approach for Childhood-onset Lupus (TEACH) program is a CBT intervention developed to target these symptoms for adolescents and young adults with cSLE. This pilot randomized controlled trial (RCT) aims to determine the feasibility and effect of TEACH for youth with cSLE. Adjustments to the study protocol following the COVID-19 pandemic are also described. Methods This two-arm multisite RCT will explore the feasibility (primary outcome) and effect (secondary outcome) of a remotely delivered TEACH protocol. Participants will be randomized to a six-week remotely delivered TEACH program plus medical treatment as usual (TAU) or TAU alone. We will include patients ages 12–22 years presenting to rheumatology clinics from six sites. Validated measures of fatigue, depressive symptoms, and pain will be obtained at baseline and approximately eight and 20 weeks later. Protocol adjustments were also made due to the COVID-19 pandemic, in collaboration with the investigative team, which included patients and caregivers. Conclusions Findings from this multi-site RCT aim to document the feasibility of TEACH and provide an estimate of effect of a remotely delivered TEACH protocol on fatigue, depression, and pain symptoms in youth with cSLE as compared to standard medical treatment alone. This findings may positively impact clinical care for patients with cSLE. Clinical trials.gov registration: NCT04335643.
Youth with rheumatologic diseases have a high prevalence of comorbid mental health disorders. Individuals with comorbid mental health disorders are at increased risk for adverse outcomes related to mental health as well as their underlying rheumatologic disease. Early identification and treatment of mental health disorders has been shown to improve outcomes, but current systems of care fall short in providing adequate mental health services to those in need. Pediatric rheumatologists are uniquely positioned to provide mental health screening and intervention for youth with rheumatologic diseases due to the frequency of patient encounters and ongoing therapeutic relationship with patients and families. However, additional training is likely required for pediatric rheumatologists to provide effective mental health care, and focusing efforts on providing trainees with mental health education is key to building competency. Potential opportunities for improved mental health education include development of clinical guidelines regarding mental health screening and management within pediatric rheumatology settings and incorporation of mental health didactics, workshops, and interdisciplinary clinic experiences into pediatric rheumatology fellowship curricula. Additional steps include mental health education for patients and families and focus on system change, targeting integration of medical and mental health care. Research is needed to better define the scope of the problem, determine effective strategies for equipping pediatric rheumatologists with skills in mental health intervention, and develop and implement sustainable systems for delivery of optimal mental health care to youth with rheumatologic diseases.
Objective To compare major depression risk among young adults with juvenile‐onset and adult‐onset systemic lupus erythematosus ( SLE ), and to determine demographic and health‐related predictors of depression. Methods Young adults with SLE ages 18–45 years (n = 546) in the Lupus Outcomes Study completed annual telephone surveys from 2002–2015, including assessment of depression using the Center for Epidemiologic Studies Depression Scale ( CES ‐D), and self‐report measures of sociodemographics and health characteristics. Juvenile‐onset SLE was defined as age <18 years at diagnosis (n = 115). Repeated‐measures analysis was performed to assess the risk for major depression ( CES ‐D ≥24) at any point in study, and logistic regression was used to assess for recurrent (present on ≥2 assessments) major depression. Results Major depression was experienced by 47% of the cohort at least once during the 12‐year study period. In adjusted analyses, juvenile‐onset SLE patients had an increased risk of having a major depressive episode (odds ratio [ OR ] 1.7 [95% confidence interval (95% CI ) 1.0–2.7]) and recurrent episodes ( OR 2.2 [95% CI 1.2–4.3]), compared to participants with adult‐onset SLE . Older age, lower educational attainment, and physical function, higher disease activity, and a history of smoking were associated with an increased depression risk. Juvenile‐onset SLE patients had a higher risk of major depression across all educational groups. Conclusion Young adults with SLE , particularly those with juvenile‐onset disease, are at high risk for major depression, which is associated with increased disease activity, poorer physical functioning, and lower educational attainment. Early depression intervention in young adults with SLE has the potential to improve both medical and psychosocial outcomes.
There are no validated screening measures for depressive or anxiety disorders in childhood Systemic Lupus Erythematosus (cSLE). We investigated cross-sectionally (1) the prevalence of depressive and anxiety disorder in cSLE. (2) the validity of the Centre for Epidemiologic Studies Depression Scale for Children (CES-DC) and the Screen for Childhood Anxiety and Related Disorders (SCARED) measures in identifyingthese disorders.Participants 8-18 years with cSLE/incipient cSLE completed CES-DC, SCARED, and Quality OfMy Life (QOML) measures. Parents completed the SCARED-Parent measure. Diagnosis was by gold-standard psychiatric interview and determined prevalence of psychiatric disorder. Receiver Operating Characteristics Area under the Curve (ROCAUC) evaluated screening measure diagnostic performance.Ofseventy-two parent-child dyads, 56 interviews were completed. Mean screen scores were: CES-DC = 15 (range 1-49, SD 12), SCARED-C = 22 (range 2-61, SD 14), SCARED-P = 13 (range 0-36, SD 8). Depressive disorder screen positivity (CES-DC ≥ 15) was 35% (vs. prevalence 5%). Anxiety disorder screen positivity (SCARED ≥ 25) was 39% (vs. prevalence 16%). CES-DC ROCAUC = 0.98 and SCARED-C ROCAUC = 0.7 (cut-points 38 and 32 respectively).Diagnostic thresholds for depressive and anxiety disorderscreening measures are high for both CES-DC and SCARED-C in cSLE. Brief focused interview should follow to determine whether psychiatric evaluation is warranted.
Cognitive complaints are common in children with childhood-onset systemic lupus erythematosus (cSLE), but neuropsychiatric lupus (NPSLE) remains challenging to diagnose and treat. To increase understanding of contributing mechanisms, we examined the association between cognitive function, disease measures and structural neuroimaging metrics.
Methods
We examined a cross-sectional sample of 24 patients with cSLE (ages 12-17) meeting ACR or SLICC classification criteria. Patients completed standardized traditional neurocognitive tests quantifying domains of attention and inhibition (CPT-3, Conners' Continuous Performance Test 3rd ed), working memory (WISC-V, Wechsler Intelligence Scale for Children 5th ed), and cognitive flexibility (D-KEFS, Delis-Kaplan Executive Function System). Cognitive impairment was defined as a score of 1.5 standard deviations below the mean in any domain. T1-weighted brain magnetic resonance images (MRI) were obtained using a 3T scanner. Advanced structural MRI analysis was used to extract volume, cortical thickness, and surface area metrics for brain segments. Demographic and disease measures were extracted from medical records. We used Partial Least-Squares Regression (PLS2), to examine the association between cognitive function (continuous outcome) and its potential predictors, comprised of structural brain metrics as well as disease and demographic measures. PLS2 analysis enables description of interactions between multivariate and potentially collinear data with a relatively small sample size. Each predictor's relevance criteria (i.e., stability and significance) were based on the bootstrapped sample distribution of its variable importance in projection (VIP) value, which measures the relative weight of a predictor across all outcome variables.
Results
The mean age of the sample was 15.4 years (standard deviation 1.7), 20/24 (83%) were female, and 16/24 (67% were on non-White race/ethnicity. The median disease duration was 1.8 years (interquartile range 1.0, 3.1). Cognitive impairment was present in 10/24 (42%) of patients; only one subject had a diagnosis of NPSLE. In PSL2 analysis (figure 1), 52 predictors were found to be relevant in the estimation of cognitive function (CI = 95%, VIP > 1.18). Of these, 50 were brain structure variables, with the most highly associated brain measures deriving from the frontal lobe (n=19), temporal lobe (n=11), occipital lobe (n=9) and cingulate cortex (n=7). The surface area and volume of the mid-posterior corpus callosum, total left and bilateral cortical volumes, higher level of CRP and older age of patients at study visit were also found to be relevant predictors of cognitive function.
Conclusions
Objective cognitive impairment was prevalent in >40% of patients with cSLE. Impairment was strongly associated with several structural brain metrics, most of which derived from the frontal lobe. Only one disease-related factor (CRP) and one demographic factor (patient age) were found to be relevant predictors of cognitive function. Our results suggest that computational modeling has the potential to enhance diagnosis of NPSLE. Further study is needed to identify robust disease biomarkers that can be linked to functional and structural brain metrics with the use of machine learning models.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry is a multi-center, observational registry that collects demographic, clinical, and provider- and patient-reported data from patients with pediatric-onset rheumatic diseases in North America, Israel and Italy. This study aimed to describe the demographic features, cumulative clinical manifestations, and treatments of the childhood systemic lupus erythematosus (cSLE) cohort within the CARRA Registry.
Methods
Since 2015, the CARRA Registry has enrolled 10,411 patients at 70 centers. Childhood-onset SLE enrollment began in March 2017. We performed a retrospective cohort study of patients with cSLE enrolled in the US between March 2017 to December 2020. Inclusion criteria for participants in the CARRA cSLE Registry include: 1) diagnosis of cSLE at <18 years based on American College of Rheumatology (ACR) or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) ; 2) enrollment within two years of cSLE diagnosis or at the time of a flare of lupus nephritis; and 3) enrollment prior to 21 years of age. Sociodemographic and clinical data were summarized using descriptive statistics.
Results
The current registry cohort includes 671 participants with cSLE. The majority are female (85%) with mean age at enrollment of 14.3 (SD 2.9) years. The cohort is both ethnically and racially diverse (table 1). Socioeconomic status varies widely, noting 12.5% having a household income below $25,000/year. The median time from symptom onset to diagnosis was two months (interquartile range (IQR) 25 days to 6 months), from diagnosis to enrollment was 5 (IQR 1-15) months, and from enrollment to end of follow up was 14 (IQR 6 to 23) months. At the end of the follow-up period, more than 60% of participants developed nephritis as defined by ACR or SLICC criteria. 6.1% and 10% had neurological manifestations per ACR and SLICC criteria, respectively (table 2). Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at enrollment was a median of 4 (IQR 2-10). Most patients were prescribed hydroxychloroquine. In the first 2-3 years of disease, participants received a variety of immunosuppressive therapies including Mycophenolate Mofetil, Cyclophosphamide, Azathioprine, Rituximab, Belimumab and disease modifying anti-rheumatic drugs such as Leflunomide and Methotrexate. 84% of patients were prescribed either oral or intravenous glucocorticoids during their disease course (table 3).
Conclusions
The CARRA Registry has enrolled a racially and ethnically diverse cohort of cSLE patients in the early course of their disease. These participants exhibit moderate disease activity and although the use of hydroxychloroquine in this cohort is high, a significant proportion of patients are utilizing glucocorticoids at the last study visit. We anticipate enrolling a minimum of 1000 participants with more than ten years of follow-up. This cohort, which is one of the Centers for Disease Control (CDC) funded SLE registries, provides a unique opportunity to describe the natural history, treatments, and outcomes in patients with cSLE.
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