Shared genomic segments analysis identifies MHC class I and class III molecules as genetic risk factors for juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease encompassing several clinically defined subtypes of varying severity. The etiology of JIA remains largely unknown, but genome-wide association studies (GWASs) have identified up to 22 genes associated with JIA susceptibility, including a well-established association with HLA-DRB1. Continued investigation of heritable risk factors has been hindered by disease heterogeneity and low disease prevalence. In this study, we utilized shared genomic segments (SGS) analysis on whole-genome sequencing of 40 cases from 12 multi-generational pedigrees significantly enriched for JIA. Subsets of cases are connected by a common ancestor in large extended pedigrees, increasing the power to identify disease-associated loci. SGS analysis identifies genomic segments shared among disease cases that are likely identical by descent and anchored by a disease locus. This approach revealed statistically significant signals for major histocompatibility complex (MHC) class I and class III alleles, particularly HLA-A∗02:01, which was observed at a high frequency among cases. Furthermore, we identified an additional risk locus at 12q23.2-23.3, containing genes primarily expressed by naive B cells, natural killer cells, and monocytes. The recognition of additional risk beyond HLA-DRB1 provides a new perspective on immune cell dynamics in JIA. These findings contribute to our understanding of JIA and may guide future research and therapeutic strategies.

Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.

OBJECTIVE: Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes. METHODS: This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. RESULTS: We enrolled 41 patients with SJIA-LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow-up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty-four percent of patients carried the HLA-DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA-LD also showed markedly elevated serum interleukin-18 (IL-18), variable C-X-C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti-IL-1/6 biologics and addition of other immunomodulatory treatments and lung-directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. CONCLUSION: Patients with SJIA-LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.

Prevalence of tissue transglutaminase antibodies and IgA deficiency are not increased in juvenile idiopathic arthritis: a case-control study.

BACKGROUND: The prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1-7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers. METHODS: Serum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher's exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated. RESULTS: 808 JIA cases and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs. 68% p = 0.309). A total of 1.2% of cases were IgA deficient compared to none of the controls (p = 0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA ≥ 4u/mL compared to 3.6% of controls (p = 0.216) (OR = 0.5; 95% C.I = 0.1-1.4); and 0.8% of cases had tTG IgA > 10u/mL compared to 1.4% of controls (p = 0.627) (OR = 0.5; 95%C.I = 0.1-2.9). CONCLUSIONS: Using the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for CD.

Childhood-Onset Lupus Nephritis in the Childhood Arthritis and Rheumatology Research Alliance Registry: Short-Term Kidney Status and Variation in Care.

OBJECTIVE: The goal was to characterize short-term kidney status and describe variation in early care utilization in a multicenter cohort of patients with childhood-onset systemic lupus erythematosus (cSLE) and nephritis. METHODS: We analyzed previously collected prospective data from North American patients with cSLE with kidney biopsy-proven nephritis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from March 2017 through December 2019. We determined the proportion of patients with abnormal kidney status at the most recent registry visit and applied generalized linear mixed models to identify associated factors. We also calculated frequency of medication use, both during induction and ever recorded. RESULTS: We identified 222 patients with kidney biopsy-proven nephritis, with 64% class III/IV nephritis on initial biopsy. At the most recent registry visit at median (interquartile range) of 17 (8-29) months from initial kidney biopsy, 58 of 106 patients (55%) with available data had abnormal kidney status. This finding was associated with male sex (odds ratio [OR] 3.88, 95% confidence interval [95% CI] 1.21-12.46) and age at cSLE diagnosis (OR 1.23, 95% CI 1.01-1.49). Patients with class IV nephritis were more likely than class III to receive cyclophosphamide and rituximab during induction. There was substantial variation in mycophenolate, cyclophosphamide, and rituximab ever use patterns across rheumatology centers. CONCLUSION: In this cohort with predominately class III/IV nephritis, male sex and older age at cSLE diagnosis were associated with abnormal short-term kidney status. We also observed substantial variation in contemporary medication use for pediatric lupus nephritis between pediatric rheumatology centers. Additional studies are needed to better understand the impact of this variation on long-term kidney outcomes.

"There's so much to be done": a qualitative study to elucidate research priorities in childhood-onset systemic lupus erythematosus.

OBJECTIVE: There is a pressing need for high-quality, comprehensive research to describe the natural history, best treatments, access to care and disparities in care for patients with childhood-onset SLE (cSLE). Building on a previously published survey study of cSLE clinicians and researchers to describe research priorities in cSLE, the primary objective of this study was to conduct expert interviews to define high-priority areas for cSLE research. METHODS: Individuals with identified multidisciplinary expertise in cSLE were recruited worldwide using purposive sampling technique. Experts participated in open-ended, semistructured qualitative interviews. Interviews were designed to elicit expert perspectives on research priorities, optimal research approaches, and factors that facilitate and hinder advancing cSLE research. Interviews were digitally recorded, transcribed and de-identified for analysis. Analysis for underlying themes of cSLE expert perspectives was performed using a constant comparative approach. RESULTS: Twenty-nine experts with diverse clinical and research backgrounds participated. Themes emerged within five domains: (1) expanding disease knowledge; (2) investigator collaboration; (3) partnering with patients and families; (4) improving care to optimise research; and (5) overcoming investigator barriers. Choosing a singular area of focus was difficult; experts identified many competing priorities. Despite the numerous priorities that emerged, experts described several existing and potential opportunities for advancing cSLE research. CONCLUSIONS: In addition to the priorities identified by cSLE experts in this study, the opportunities for advancing cSLE research and care that were proposed should be used as a foundation for creation of a cSLE research agenda for both research and funding allocation.

Evaluation of Serious Infection in Pediatric Patients with Low Immunoglobulin Levels Receiving Rituximab for Granulomatosis with Polyangiitis or Microscopic Polyangiitis.

INTRODUCTION: The aim of this work was to assess the impact of prolonged low immunoglobulin (IgG or IgM) serum concentrations on the potential cumulative serious infection (SI) risk in pediatric patients following rituximab treatment for granulomatosis with polyangiitis or microscopic polyangiitis (GPA/MPA) in PePRS. METHODS: Patients aged ≥ 2 to < 18 years received four weekly intravenous rituximab infusions of 375 mg/m2 and concomitant glucocorticoid taper. After 6 months, patients could receive further rituximab and/or other immunosuppressants per investigator discretion. Immunoglobulin levels and SIs were assessed throughout the 4.5-year observation period. Prolonged low IgG or IgM was defined as below the lower limit of normal age-specific reference range for ≥ 4 months. RESULTS: A total of 25 patients were included, of whom 19 (76%) had GPA and six (24%) had MPA; 18 (72%) had newly diagnosed disease and seven (28%) had relapsing disease. All 25 patients completed the rituximab induction regimen; 24 completed ≥ 18 months of follow-up. At month 18, eighteen patients (72%) had prolonged low IgG; 19 (76%), prolonged low IgM; and 15 (60%), both. Seven patients (28%) had nine SIs; one occurred during or after prolonged low IgG only, two during or after prolonged low IgM only, and six during or after concurrent prolonged low IgG and IgM. No patients died or discontinued the study due to SI. All patients had complete and sustained peripheral B-cell depletion for ≥ 6 months. CONCLUSIONS: The majority of pediatric patients who received rituximab for GPA/MPA with prolonged low immunoglobulin levels did not experience SIs. In patients with SIs, these events were manageable, and the number of SIs did not increase over time or with multiple rituximab treatments. These observations are consistent with the rituximab safety profile in adults with GPA/MPA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01750697.

Use of EuroLupus Cyclophosphamide Dosing for the Treatment of Lupus Nephritis in Childhood-onset Systemic Lupus Erythematosus in North America.

OBJECTIVE: Childhood-onset systemic lupus erythematosus (cSLE) has higher rates of lupus nephritis (LN) than adult-onset SLE, often requiring intensive immunosuppression. This study examined North American practices and preferences for the low-dose EuroLupus cyclophosphamide (CYC) protocol, as compared to the high-dose National Institutes of Health (NIH) CYC protocol, to treat LN in cSLE. METHODS: A 35-item Web-based survey was distributed to Childhood Arthritis and Rheumatology Research Alliance (CARRA) and Pediatric Nephrology Research Consortium (PNRC) providers. The survey assessed participant demographics, CYC prescribing practices, perceptions of EuroLupus protocol, and LN vignette treatment decisions; 1 vignette was taken from a 2009 CARRA survey and responses were compared. Multivariable logistic regression analyzed provider factors associated with use of low- vs high-dose CYC. RESULTS: Responses were provided by 185/421 (44%) pediatric rheumatologists (CARRA) and 40/354 (11%) pediatric nephrologists (PNRC). Among respondents who prescribed CYC for pediatric LN over the past year (n = 135), half reported using EuroLupus. When presented with the same vignette about an adolescent with class IV LN, 32% of pediatric rheumatologists chose EuroLupus dosing in 2020, vs 6% in 2009. Provider factors associated with choosing the low-dose regimen were familiarity with the protocol (OR 4.2, P = 0.006) and greater perceived benefit (OR 1.6, P < 0.0001). Pediatric nephrologists had similar responses to the pediatric rheumatology providers. Overall, 78% of respondents perceived EuroLupus protocol efficacy to be equivalent to the high-dose protocol in cSLE LN. CONCLUSION: Pediatric specialists are currently more likely to use low-dose CYC to treat cSLE LN than they were a decade ago. Nevertheless, familiarity with EuroLupus dosing remains low.

Phase IIa Global Study Evaluating Rituximab for the Treatment of Pediatric Patients With Granulomatosis With Polyangiitis or Microscopic Polyangiitis.

OBJECTIVE: To assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). METHODS: The Pediatric Polyangiitis Rituximab Study was a phase IIa, international, open-label, single-arm study. During the initial 6-month remission-induction phase, patients received intravenous infusions of RTX (375 mg/m2 body surface area) and glucocorticoids once per week for 4 weeks. During the follow-up period, patients could receive further treatment, including RTX, for GPA or MPA. The safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy outcomes with RTX were evaluated. RESULTS: Twenty-five pediatric patients with new-onset or relapsing disease were enrolled at 11 centers (19 with GPA [76%] and 6 with MPA [24%]). The median age was 14 years (range 6-17 years). All patients completed the remission-induction phase. During the overall study period (≤4.5 years), patients received between 4 and 28 infusions of RTX. All patients experienced ≥1 adverse event (AE), mostly grade 1 or grade 2 primarily infusion-related reactions. Seven patients experienced 10 serious AEs, and 17 patients experienced 31 infection-related AEs. No deaths were reported. RTX clearance correlated with body surface area. The body surface area-adjusted RTX dosing regimen resulted in similar exposure in both pediatric and adult patients with GPA or MPA. Remission, according to the Pediatric Vasculitis Activity Score, was achieved in 56%, 92%, and 100% of patients by months 6, 12, and 18, respectively. CONCLUSION: In pediatric patients with GPA or MPA, RTX is well tolerated and effective, with an overall safety profile comparable to that observed in adult patients with GPA or MPA who receive treatment with RTX. RTX is associated with a positive risk/benefit profile in pediatric patients with active GPA or MPA.

Diagnosis and Management of Suspected Pediatric Autoimmune Encephalitis: A Comprehensive, Multidisciplinary Approach and Review of Literature.

Autoimmune encephalitis is an increasingly recognized entity in children. When treated promptly, favorable outcomes are seen in a majority of pediatric patients. However, recognition of autoimmune encephalitis in young patients is challenging. Once autoimmune encephalitis is suspected, additional difficulties exist regarding timing of treatment initiation and duration of treatment, as evidence to guide management of these patients is emerging. Here, we review available literature regarding pediatric autoimmune encephalitis and present our institution's comprehensive approach to the evaluation and management of the disease. These guidelines were developed through an iterative process involving both pediatric neurologists and rheumatologists.

A novel transition clinic structure for adolescent and young adult patients with childhood onset rheumatic disease improves transition outcomes.

BACKGROUND: The transition of health care from Pediatric to Adult providers for adolescents and young adults with chronic disease is associated with poor outcomes. Despite the importance of this transition, over 80% of these patients do not receive the services necessary to transition to Adult health care. In 2018, we initiated a transition clinic structure, integrating an Internal Medicine - Pediatrics trained Adult Rheumatologist in a Pediatric Rheumatology clinic to guide this transition. Our goal was to improve transition outcomes. We report the methods of this clinic and its preliminary outcomes. METHODS: For patients referred to the transition clinic, the Adult Rheumatologist assumed medical management and implemented a six-part modular transition curriculum. This curriculum included a Transition Policy, Transition Readiness Assessment, medication review and education, diagnosis review and education, and counseling on differences between Pediatric and Adult-oriented care. Eligible patients and their families were enrolled in a prospective observational outcomes research registry. Initial data from this transition clinic is reported including adherence with certain aspects of the transition curriculum and clinic utilization. RESULTS: The transition clinic Adult Rheumatologist saw 177 patients in 2 years, and 57 patients were eligible for, approached, and successfully enrolled in the registry. From this registry, all patients reviewed the Transition Policy with the Adult Rheumatologist and 45 (78.9%) completed at least one Transition Readiness Assessment. Of the 22 patients for whom transition was indicated, all were successfully transitioned to an Adult Rheumatologist. 17 (77.3%) continued care post-transition with the transition clinic Adult Rheumatologist, and 5 (22.7%) continued care post-transition with a different Adult Rheumatologist. The median time between the last transition clinic visit and first Adult clinic visit was 5.1 months. CONCLUSIONS: Our experience demonstrated the success of our clinic model regarding participation in the transition curriculum and improved clinic utilization data. Our results are an improvement over transition rates reported elsewhere that did not implement our model. We believe that this structure could be applied to other primary care and subspecialty clinics. TRIAL REGISTRATION: This research was approved by the University of Utah Institutional Review Board (IRB) in January 2019 (IRB_00115964). Patients were retrospectively registered if involved prior to this date.

Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort.

Lupus nephritis (LN) is a life-threatening manifestation of systemic lupus erythematosus (SLE) and is more common in children than adults. The epidemiology and management of childhood-onset SLE (cSLE) have changed over time, prompting the need to reassess expected outcomes. The purpose of this study is to use the Childhood Arthritis and Rheumatology Research Alliance (CARRA) prospective registry to validate historical principles of LN in a contemporary, real-world cohort. After an extensive literature review, six principles of LN in cSLE were identified. The CARRA registry was queried to evaluate these principles in determining the rate of LN in cSLE, median time from cSLE diagnosis to LN, short-term renal outcomes, and frequency of rituximab as an induction therapy. Of the 677 cSLE patients in the CARRA registry, 32% had documented LN. Decline in kidney function was more common in Black cSLE patients than non-Black patients (p = 0.04). Black race was associated with worse short-term renal outcomes. In short-term follow up, most children with LN had unchanged or improved kidney function, and end stage kidney disease (ESKD) was rare. Ongoing follow-up of cSLE patients in the CARRA registry will be necessary to evaluate long-term outcomes to inform risk, management, and prognosis of LN in cSLE.

Engaging patients and parents to improve mental health intervention for youth with rheumatological disease.

BACKGROUND: Mental health disorders are common in youth with rheumatological disease yet optimal intervention strategies are understudied in this population. We examined patient and parent perspectives on mental health intervention for youth with rheumatological disease. METHODS: We conducted a mixed methods cross-sectional study, via anonymous online survey, developed by researchers together with patient/parent partners, to quantitatively and qualitatively examine youth experiences with mental health services and resources in North America. Patients ages 14-24 years with juvenile idiopathic arthritis, juvenile dermatomyositis, or systemic lupus erythematous, and parents of patients ages 8-24 with these diseases were eligible (not required to participate in pairs). Participants self-reported mental health problems (categorized into clinician-diagnosed disorders vs self-diagnosed symptoms) and treatments (e.g. therapy, medications) received for the youth. Multivariate linear regression models compared patient and parent mean Likert ratings for level of: i) comfort with mental health providers, and ii) barriers to seeking mental health services, adjusting for potential confounders (patient age, gender, disease duration, and patient/parent visual analog score for disease-related health). Participants indicated usefulness of mental health resources; text responses describing these experiences were analyzed by qualitative description. RESULTS: Participants included 123 patients and 324 parents. Patients reported clinician-diagnosed anxiety (39%) and depression (35%); another 27 and 18% endorsed self-diagnosed symptoms of these disorders, respectively. 80% of patients with clinician-diagnosed disorders reported receiving treatment, while 11% of those with self-diagnosed symptoms reported any treatment. Patients were less comfortable than parents with all mental health providers. The top two barriers to treatment for patients and parents were concerns about mental health providers not understanding the rheumatological disease, and inadequate insurance coverage. Over 60% had used patient mental health resources, and over 60% of these participants found them to be helpful, although text responses identified a desire for resources tailored to patients with rheumatological disease. CONCLUSION: Self-reported mental health problems are prevalent for youth in this sample with rheumatological disease, and obstacles to mental health treatment include disease-related and logistic factors. Strategies are needed to improve acceptance and accessibility of mental health intervention, including routine mental health screening and availability of disease-specific mental health resources.

Differences in Healthcare Transition Views, Practices, and Barriers Among North American Pediatric Rheumatology Clinicians From 2010 to 2018.

OBJECTIVE: Since 2010, the rheumatology community has developed guidelines and tools to improve healthcare transition. In this study, we aimed to compare current transition practices and beliefs among Childhood Arthritis and Rheumatology Research Alliance (CARRA) rheumatology providers with transition practices from a provider survey published in 2010. METHODS: In 2018, CARRA members completed a 25-item online survey about healthcare transition. Got Transition's Current Assessment of Health Care Transition Activities was used to measure clinical transition processes on a scale of 1 (basic) to 4 (comprehensive). Bivariate analyses were used to compare 2010 and 2018 survey findings. RESULTS: Over half of CARRA members completed the survey (202/396), including pediatric rheumatologists, adult- and pediatric-trained rheumatologists, pediatric rheumatology fellows, and advanced practice providers. The most common target age to begin transition planning was 15-17 years (49%). Most providers transferred patients prior to age 21 years (75%). Few providers used the American College of Rheumatology transition tools (31%) or have a dedicated transition clinic (23%). Only 17% had a transition policy in place, and 63% did not consistently address healthcare transition with patients. When compared to the 2010 survey, improvement was noted in 3 of 12 transition barriers: availability of adult primary care providers, availability of adult rheumatologists, and pediatric staff transition knowledge and skills (P < 0.001 for each). Nevertheless, the mean current assessment score was < 2 for each measurement. CONCLUSION: This study demonstrates improvement in certain transition barriers and practices since 2010, although implementation of structured transition processes remains inconsistent.

Development of a Set of Lupus-Specific, Ambulatory Care-Sensitive, Potentially Preventable Adverse Conditions: A Delphi Consensus Study.

OBJECTIVE: Individuals with systemic lupus erythematosus (SLE) are at high risk for infections and SLE- and medication-related complications. The present study was undertaken to define a set of SLE-specific adverse outcomes that could be prevented, or their complications minimized, if timely, effective ambulatory care had been received. METHODS: We used a modified Delphi process beginning with a literature review and key informant interviews to select initial SLE-specific potentially preventable conditions. We assembled a panel of 16 nationally recognized US-based experts from 8 subspecialties. Guided by the RAND-UCLA Appropriateness Method, we held 2 survey rounds with controlled feedback and an interactive webinar to reach consensus regarding preventability and importance on a population level for a set of SLE-specific adverse conditions. In a final round, the panelists endorsed the potentially preventable conditions. RESULTS: Thirty-five potential conditions were initially proposed; 62 conditions were ultimately considered during the Delphi process. The response rate was 100% for both survey rounds, 88% for the webinar, and 94% for final approval. The 25 SLE-specific conditions meeting consensus as potentially preventable and important on a population level fell into 4 categories: vaccine-preventable illnesses (6 conditions), medication-related complications (8 conditions), reproductive health-related complications (6 conditions), and SLE-related complications (5 conditions). CONCLUSION: We reached consensus on a diverse set of adverse outcomes relevant to SLE patients that may be preventable if patients receive high-quality ambulatory care. This set of outcomes may be studied at the health system level to determine how to best allocate resources and improve quality to reduce avoidable outcomes and disparities among those at highest risk.

Disease activity and health-care utilization among young adults with childhood-onset lupus transitioning to adult care: data from the Pediatric Lupus Outcomes Study.

BACKGROUND: Individuals with childhood-onset systemic lupus erythematosus (cSLE) must transfer from pediatric to adult care. The goal of this study was to examine disease activity and health-care utilization among young adults with cSLE who are undergoing or have recently completed the transfer to adult care. METHODS: The Pediatric Lupus Outcomes Study (PLOS) is a prospective longitudinal cohort study of young adults aged 18-30 diagnosed with cSLE. We conducted a cross-sectional analysis comparing 47 participants under the care of pediatric rheumatologists to 38 who had completed transfer to adult care. Demographics, disease manifestations, health- care utilization and transition readiness were compared between groups. RESULTS: Those in the post-transfer group had significantly lower medication usage and were less likely to have seen a rheumatologist in the past year. Disease manifestations, flare rates, and hospitalizations were similar between groups. Nearly a quarter of patients who had transferred to adult care reported difficulties with the process. CONCLUSION: Post-transfer patients had lower health-care utilization as evidenced by less medication usage and lack of rheumatology follow-up, in spite of the fact that disease activity was similar in both groups. Future studies will assess longitudinal changes in disease activity and damage in this population.

Research priorities in childhood-onset lupus: results of a multidisciplinary prioritization exercise.

BACKGROUND: Childhood-onset systemic erythematosus lupus (cSLE) is characterized by more severe disease, widespread organ involvement and higher mortality compared to adult-onset SLE. However, cSLE is largely underfunded to carry out necessary research to advance the field. Few commonly used SLE medications have been studied in children, and important knowledge gaps exist concerning epidemiology, genetics, pathophysiology and optimal treatments for cSLE. METHODS: In order to assess highest cSLE research priority areas, the Lupus Foundation of America (LFA) and Childhood Arthritis and Rheumatology Research Alliance (CARRA) administered a cSLE research prioritization survey to pediatric rheumatologists, dermatologists and nephrologists with expertise in lupus. Members of LFA and CARRA's SLE Committee identified a list of cSLE research domains and developed a 17-item tiered, web-based survey asking respondents to categorize the research domains into high, medium, or low priority areas. For domains identified as high priority, respondents ranked research topics within that category. For example, for the domain of nephritis, respondents ranked importance of: epidemiology, biomarkers, long-term outcomes, quality improvement, etc. The survey was distributed to members of CARRA, Midwestern Pediatric Nephrology Consortium (MWPNC) and Pediatric Dermatology Research Alliance (PeDRA) Connective Tissue Disease group. RESULTS: The overall response rate was 256/752 (34%). The highest prioritized research domains were: nephritis, clinical trials, biomarkers, neuropsychiatric disease and refractory skin disease. Notably, nephritis, clinical trials and biomarkers were ranked in the top five by all groups. Within each research domain, all groups showed agreement in identifying the following as important focus areas: determining best treatments, biomarkers/pathophysiology, drug discovery/novel treatments, understanding long term outcomes, and refining provider reported quality measures. CONCLUSION: This survey identified the highest cSLE research priorities among leading rheumatology, dermatology and nephrology clinicians and investigators engaged in care of children with lupus. There is a strong need for multidisciplinary collaboration moving forward, which was indicated as highly important among stakeholders involved in the survey. These survey results should be used as a roadmap to guide funding and specific research programs in cSLE to address urgent, unmet needs among this population.

Gaps in Mental Health Care for Youth With Rheumatologic Conditions: A Mixed Methods Study of Perspectives From Behavioral Health Providers.

OBJECTIVE: To identify behavioral health provider perspectives on gaps in mental health care for youth with rheumatologic conditions. METHODS: Social workers (n = 34) and psychologists (n = 8) at pediatric rheumatology centers in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an online survey assessing current practices and mental health care needs of youth with rheumatologic conditions. Responses were compared to a published survey of CARRA rheumatologists (n = 119). Thematic analysis of 20 semi-structured interviews with behavioral health providers was performed. RESULTS: One-third of CARRA centers (n = 100) had no affiliated social worker or psychologist. Only 1 behavioral health provider reported current universal mental health screening at their rheumatology clinic, yet routine depression screening was supported by >85% of behavioral health providers and rheumatologists. Support for anxiety screening was higher among behavioral health providers (90% versus 65%; P < 0.01). Interviews illustrated a need for interventions addressing illness-related anxiety, adjustment/coping/distress, transition, parent/caregiver mental health, and peer support. Limited resources, lack of protocols, and patient cost/time burden were the most frequent barriers to intervention. Inadequate follow-up of mental health referrals was indicated by 52% of providers. More behavioral health providers than rheumatologists favored mental health services in rheumatology settings (55% versus 19%; P < 0.01). Only 7 social workers (21%) provided counseling/therapy, and interviews indicated their perceived underutilization of these services. CONCLUSION: Behavioral health providers indicated an unmet need for mental health interventions that address illness-related issues affecting youth with rheumatologic conditions. Implementation of mental health protocols and optimizing utilization of social workers may improve mental health care for these youth.

Adding patient-reported outcomes to a multisite registry to quantify quality of life and experiences of disease and treatment for youth with juvenile idiopathic arthritis.

BACKGROUND: Children with Juvenile Idiopathic Arthritis (JIA) often have poor health-related quality of life (HRQOL) despite advances in treatment. Patient-centered research may shed light on how patient experiences of treatment and disease contribute to HRQOL, pinpointing directions for improving care and enhancing outcomes. METHODS: Parent proxies of youth enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry shared patient-reported outcomes about their child's HRQOL and experiences of disease and treatment burden (pain interference, morning stiffness, history of medication side effects and methotrexate intolerance). Contributions of these measures to HRQOL were estimated using generalized estimating equations accounting for site and patient demographics. RESULTS: Patients (N = 180) were 81.1% white non-Hispanic and 76.7% female. Mean age was 11.8 (SD = 3.6) years, mean disease duration was 7.7 years (SD = 3.5). Mean Total Pediatric Quality of Life was 76.7 (SD = 18.2). Mean pain interference score was 50.1 (SD = 11.1). Nearly one-in-five (17.8%) youth experienced >15 min of morning stiffness on a typical day, more than one quarter (26.7%) reported ≥1 serious medication side effect and among 90 methotrexate users, 42.2% met criteria for methotrexate intolerance. Measures of disease and treatment burden were independently negatively associated with HRQOL (all p-values <0.01). Negative associations among measures of treatment burden and HRQOL were attenuated after controlling for disease burden and clinical characteristics but remained significant. CONCLUSIONS: For youth with JIA, HRQOL is multidimensional, reflecting disease as well as treatment factors. Adverse treatment experiences undermine HRQOL even after accounting for disease symptoms and disease activity and should be assessed routinely to improve wellbeing.