Search

Objective To determine the utility and acceptability for depression and anxiety screening of adolescents and young adults (AYA) with childhood-onset SLE (cSLE) in the pediatric rheumatology setting. Methods AYA with cSLE, ages 12-21, from 8 collaborating sites, were consecutively screened for depression and anxiety with the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic and disease characteristics were collected, as well as patient-reported outcome measures using the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric profile-25. Acceptability of screening was assessed with post-screening surveys completed by AYA and parents. Chi square and Wilcoxon rank-sum tests examined the relationship between patient characteristics and history of previous screening. Spearman correlations examined relationships between screening scores, PROMIS domains, and other disease factors. Results Among 106 AYA screened, 64 (60%) had been previously screened, 25 (24%) by general pediatricians. Thirty-two (30%) AYA screened positive, including 24% for depression, 17% for anxiety, and 14% had suicidal ideation. Depression and anxiety symptom severity were highly correlated with increased PROMIS domain scores for fatigue and pain interference, and moderately correlated with increased pain severity, decreased mobility and peer relationships. Eighty-six percent of AYA and 95% of parents expressed comfort with screening in the pediatric rheumatology setting. Conclusion Depression, anxiety, and suicidal ideation are common among AYA with cSLE, and symptoms are correlated with important patient-reported outcomes. Mental health screening in the pediatric rheumatology setting was highly acceptable among AYA with cSLE and their parents.

Objective A working group was established to develop a core domain set (CDS) for Chronic Nonbacterial Osteomyelitis (CNO) and Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) following the OMERACT filter 2.1. Methods A scoping review to identify disease-related manifestations was performed, followed by a special interest group (SIG) session at OMERACT2020 to begin the CNO/SAPHO CDS framework. Results Candidate items were identified from the scoping review and most fell under Life Impact and Pathophysiology Manifestation core areas. A SIG agreed on the need to develop a CDS for CNO and SAPHO (100%) and for children and adults (91%). Conclusion Based on candidate items identified, qualitative research and Delphi surveys will be performed as next steps.

Background The impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examined the impact of community poverty level, a key social determinant of health, on time from patient reported symptom onset to first pediatric rheumatology visit among pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods This is a cohort study of pJIA patients in the CARRA registry who lived in the United States from July 2015–February 2020. The primary exposure was community poverty level derived by geocoding patient addresses. The primary outcome was time to first rheumatology appointment. Kaplan-Meier analysis was performed to analyze time to first rheumatologist visit, stratified by community poverty and family income. Log-rank tests were used to identify differences between groups. Adjusted cox proportional-hazards models were used to determine the relationship between community poverty level and time from onset of disease symptoms to date first seen by rheumatologist. Results A total of 1684 patients with pJIA meeting study inclusion and exclusion criteria were identified. Median age of onset of pJIA was 7 years (IQR 3, 11), 79% were female, 17.6% identified as minority race and/or ethnicity, and 19% were from communities with ≥20% community poverty level. Kaplan-Meier analysis by community poverty level (p = 0.6). The Cox proportional hazards model showed that patients with ≥20% community poverty level were 19% less likely (adjusted HR 0.81, 95% CI 0.67–0.99, p = 0.038) to be seen by a rheumatologist compared to patients with Conclusion In this study of pJIA patients in the CARRA registry, increased community poverty level is associated with longer time to presentation to a pediatric rheumatologist after symptom onset.

IntroductionProspective comparative effectiveness research in chronic nonbacterial osteomyelitis (CNO) is lacking.ObjectivesStudy objectives were to: 1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, 2) the feasibility of usingchronic nonbacterialosteomyelitis international registry (CHOIR) data for comparative effectiveness research, and 3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR.MethodsConsenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants.Results140 (76%) CHOIR participants enrolled between August 2018 and September 2020 received at least one CTP regimen. Baseline characteristics from the three groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement. The CDAS significantly decreased after initiating second-line treatments from median 12 (8-15.5) to 5 (3-12). While second-line treatments were well tolerated, psoriasis was the most common adverse event.ConclusionThe CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future comparative effectiveness research.Key messagesThechronic nonbacterialosteomyelitis international registry (CHOIR) provides comprehensive prospective data for comparison of treatment effectivenessThe clinical disease activity score (CDAS) has content and construct validity to assess CNO

Purpose of review The aim of this article is to review recent findings regarding the diagnosis and treatment of chronic recurrent multifocal osteomyelitis (CRMO). Recent findings An adequate understanding of pathophysiology along with the new advances in MRI imaging make it possible to determine the extent of disease and establish early treatment. TNF-α inhibitors and bisphosphonates have shown to be a well-tolerated and efficient treatment for CRMO providing both symptomatic relief and normalization of bone morphology. Summary The results of recent studies suggest that a better knowledge of the genetic and molecular factors will allow early diagnosis and the development of more effective individualized treatments in the future.

OBJECTIVE To document the need for additional Food and Drug Administration (FDA)-approved medications for the treatment of juvenile idiopathic arthritis (JIA). METHODS The electronic medical records of JIA patients treated at Cincinnati Children's Hospital Medical Center (CCHMC) and data from JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry were included in this study. Unmet medication need was defined in 2 ways: (a) the presence of chronically uncontrolled JIA, defined as a physician global assessment of JIA activity ≥3 (on a 0-10 scale, where 0 = inactive) OR ≥3 joints with active arthritis OR a patient global assessment of well-being ≥3 (on a 0-10 scale, where 0 = very well), despite sequential use of ≥2 biologic disease-modifying antirheumatic drugs (bDMARDs); and (b) the use of ≥1 bDMARD not approved for any JIA category. RESULTS At CCHMC, 829 of 1,599 JIA patients (52%) were treated with ≥1 bDMARD, and 304 (19%) had been exposed to ≥1 unapproved bDMARD. In the CARRA Registry, 4,766 of 7,379 children (65%) had received ≥1 bDMARD, and 1,122 (15%) had been prescribed ≥1 unapproved bDMARD. Of those children treated with ≥2 bDMARDs for whom complete data were available, 52% (255 of 487) at CCHMC and 45% (527 of 1,159) in the CARRA Registry had chronically uncontrolled JIA despite the use of ≥2 bDMARDs. CONCLUSION Despite the availability of bDMARDs currently approved for JIA, there is persistent need for additional therapies to control JIA signs and symptoms. Since FDA approval is critical to ensure access to bDMARDs, the study and licensing of new medications is critical to address the unmet medication need and to further improve JIA outcomes.

Joint pain is a common symptom in children and adolescents. While there are many causes of joint pain in children, most of these are acute or not related to underlying joint inflammation. Chronic arthritis, however, can be one of the reasons behind the joint pain. The most common causes of chronic arthritis in children are categorized under juvenile idiopathic arthritis (JIA). The purpose of this review is to highlight the most important clinical features, work-up, and medical management of the different subtypes of JIA.

Background/objective Patients with juvenile idiopathic arthritis (JIA) often present with signs and symptoms suggestive of serious bacterial infection (SBI). Procalcitonin (PCT) is a biomarker that is elevated in SBI. We conducted a comparative cohort study to test the hypothesis that PCT levels will differ between active JIA, quiescent JIA, and bacteremic patients and healthy controls. Methods From October 2016 to May2018, consecutive children 6 months to 18 years of age with (a) active untreated JIA, (b) quiescent JIA, and (c) healthy elective presurgical candidates were recruited from clinics at a musculoskeletal specialty hospital. Juvenile idiopathic arthritis was defined according to the International League of Associations for Rheumatology criteria. Clinical data and serum samples meeting the same criteria were included from a prior study. Consecutive bacteremic patients were identified over the same period. Procalcitonin and other common measures of inflammation were measured. Descriptive statistics and univariate logistic analyses were performed. Results Ninety-two study subjects were recruited. Erythrocyte sedimentation rate, C-reactive protein (CRP), and PCT levels were all elevated in bacteremic patients in comparison to the other groups. Erythrocyte sedimentation rate and CRP both had wide ranges that overlapped between groups; however, the PCT concentration was 0.15 μg/mL or greater in 1 of 59 patients with JIA, whereas it was 0.15 μg/mL or less in only 1 bacteremic patient. Conclusions Our study indicates that serum erythrocyte sedimentation rate, CRP, and PCT levels are all biomarkers that can be used to distinguish SBI versus active JIA at presentation. However, PCT is the most accurate, with the least overlap between patients with infection and noninfectious inflammatory arthritis. This finding can help clinicians direct therapy.

Spondyloarthritis (SpA) is a blanket term encompassing entities such as enthesitis-related arthritis, nonradiographic axial SpA, and ankylosing spondylitis. These diseases share many clinical features, including a predilection for inflammation of the entheses and the sacroiliac joints. The nomenclature is based on the evolution of the classification of the disease and the age of the patient. SpA has a prevalence of approximately 1% of the population of the United States, with 10% to 20% of patients experiencing the onset during childhood. Children with onset of arthritis before age 16 years are classified as having juvenile idiopathic arthritis. Children with enthesitis and/or sacroiliitis are further classified as belonging to the enthesitis-related arthritis subtype of juvenile idiopathic arthritis. The initial manifestations can be subtle and will usually include a peripheral pattern of arthritis and enthesitis. It may take several years for axial disease to develop in children. Except for an association with the human leukocyte antigen (HLA-B27) serotype, there are no laboratory markers for the disease, and the radiographic findings are often negative. A careful clinical evaluation for evidence of inflammation in the entheses and the joints and a search for comorbidities are required. Magnetic resonance imaging facilitates the early detection of sacroiliitis, an important feature that may be clinically silent. Because recent studies indicate that earlier introduction of therapy can help achieve better outcomes, rapid identification and treatment of children with SpA is essential.

Long-term photophobia in children that has no obvious cause is uncommon and presents a diagnostic dilemma. It may produce significant discomfort and result in social isolation and school absence. We present the case of a 5-year-old boy who presented with chronic photophobia due to interstitial keratitis that was the result of Lyme disease.

Juvenile idiopathic arthritis is a group of heterogeneous chronic inflammatory arthropathies occurring in childhood without a known cause. This article discusses the key clinical features of juvenile idiopathic arthritis and treatment updates for oligoarthritis, polyarthritis, enthesitis-related arthritis, psoriatic arthritis, and systemic arthritis. Paradigm changes in management include the earlier use of biologic agents and the introduction of biosimilars and targeted synthetic disease modifying agents like tofacitinib. This review summarizes recent developments while considering potential areas for improvement and study.

Objective The objectives were: 1) to explore the discordance between the Patient Global Health Assessment (PtGA) scores, the Physician Global Health Assessment (PhGA) scores, and Pain scores; and 2) to explore whether the PtGA during disease remission is associated with future disease flare in pJIA. Methods Data from an NIH funded clinical trial (NCT00792233) evaluating flare were used (N = 137). PtGA, PhGA, and Pain scores were assessed. Flare was defined as any active arthritis. Spearman’s correlation coefficients were calculated, and multivariable logistic regression was performed. Results 122 patients had records of flare status, of which 63 developed flare, and 42 of these patients had a visit immediately prior to flare. For study subjects with a visit immediately prior to flare, the PtGA, pain scores, and PhGA all increased at time of flare. For every unit increase in PtGA and Pain scores, there was a 9% and 23% higher odds of developing flare, respectively (p = 0.76, p = 0.40). For every unit increase in the PhGA score, there was a substantially lower odds of developing flare (p = 0.05). Conclusion Our results demonstrate that the PtGA and Pain scores are strongly correlated with each other and increased at the visit prior to flare, while the PhGA scores are not. Further, the PtGA and Pain score have some predictive value for flare, while the PhGA does not. These findings highlight the value of patient input in medical care and decision-making, and support the development and use of more sophisticated PROs in the care of JIA patients.

Mucosal-associated lymphoid tissue (MALT) lymphoma is rare in the pediatric population, but primary Sjogren syndrome is a well-established risk factor for this malignancy. This report describes 2 cases of MALT lymphoma in children with Sjogren syndrome. A 15-year-old girl developed MALT lymphoma of the parotid gland as the presenting symptom of Sjogren syndrome. In the second case, a 15-year-old boy with known Sjogren syndrome presenting mainly with arthritis was diagnosed with MALT lymphoma, also of the parotid gland. With early diagnosis and treatment, outcomes in pediatric MALT lymphoma are generally encouraging. Pediatric oncology specialists should be aware of the association of MALT lymphoma with Sjogren syndrome and have a high index of suspicion for this malignant complication.

Objective.To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ).Methods.Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112;ClinicalTrials.gov,NCT00642460) and pcJIA (n = 188;ClinicalTrials.gov,NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts.Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8–16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3–8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial.Conclusion.Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.

Telehealth is an extraordinary advancement of modern medicine. It has increased access to care for underserved populations and, in the case of pediatric rheumatology, has expanded the reach of a limited work force. During the Coronavirus Disease 2019 (COVID-19) pandemic, telehealth has radically changed the way healthcare workers have been able to deliver care while maintaining social distance. In addition to the infectious havoc of COVID-19, the pandemic has further altered the psychosocial milleu of our society which directly impacts the wellness and safety of our pediatric rheumatology patients. These psychosocial factors may be difficult to assess and triage solely using telehealth. The objective of this short review is to educate practitioners on the psychosocial concerns exacerbated by the COVID-19 pandemic and to discuss the possible hurdles in utilization of telehealth to care for our vulnerable patient population.

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.

BACKGROUND. Undifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments. METHODS. Sixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing. RESULTS. Thirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS. CONCLUSIONS. In patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression. Fil: de Jesus, Adriana A.. National Institute Of Allergy And Infectious Diseases; Estados Unidos Fil: Hou, Yangfeng. Shandong University; China Fil: Brooks, Stephen. National Institute Of Arthritis And Musculoskeletal And Skin Diseases; Estados Unidos Fil: Malle, Louise. cahn School of Medicine at Mount Sinai; Estados Unidos Fil: Biancotto, Angelique. No especifíca; Fil: Huang, Yan. National Institute Of Allergy And Infectious Diseases; Estados Unidos Fil: Calvo, Katherine R.. National Institutes of Health; Estados Unidos Fil: Marrero, Bernadette. No especifíca; Fil: Moir, Susan. No especifíca; Fil: Oler, Andrew J.. National Institute Of Allergy And Infectious Diseases ; Estados Unidos Fil: Deng, Zuoming. National Institute Of Arthritis And Musculoskeletal And Skin Diseases; Estados Unidos Fil: Montealegre Sanchez, Gina A.. National Institute Of Allergy And Infectious Diseases ; Estados Unidos Fil: Ahmed, Amina. No especifíca; Fil: Allenspach, Eric. Washington State University; Estados Unidos Fil: Arabshahi, Bita. Virginia Commonwealth University; Estados Unidos Fil: Behrens, Edward. University of Pennsylvania; Estados Unidos Fil: Benseler, Susanne. University of Calgary; Canadá Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bout Tabaku, Sharon. No especifíca; Fil: Brescia, AnneMarie C.. No especifíca; Fil: Brown, Diane. No especifíca; Fil: Burnham, Jon M.. University of Pennsylvania; Estados Unidos Fil: Caldirola, Maria Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina Fil: Carrasco, Ruy. No especifíca; Fil: Chan, Alice Y.. University of California; Estados Unidos Fil: Cimaz, Rolando. Università degli Studi di Milano; Italia Fil: Dancey, Paul. Janeway Children's Hospital And Rehabilitation Centre; Canadá Fil: Dare, Jason. University of Arkansas for Medical Sciences; Estados Unidos Fil: DeGuzman, Marietta. Baylor College Of Medicine; Estados Unidos Fil: Dimitriades, Victoria. No especifíca; Fil: Ferguson, Ian. University of Yale. School of Medicine; Estados Unidos Fil: Ferguson, Polly. University of Iowa; Estados Unidos Fil: Finn, Laura. University of Washington; Estados Unidos Fil: Gattorno, Marco. No especifíca; Fil: Grom, Alexei A.. No especifíca; Fil: Hanson, Eric P.. No especifíca; Fil: Hashkes, Philip J.. No especifíca; Fil: Hedrich, Christian M.. University of Liverpool; Reino Unido Fil: Herzog, Ronit. University of New York; Estados Unidos Fil: Horneff, Gerd. Universitat zu Köln; Alemania Fil: Jerath, Rita. Augusta University; Estados Unidos Fil: Kessler, Elizabeth. University of Missouri; Estados Unidos Fil: Kim, Hanna. No especifíca; Fil: Kingsbury, Daniel J.. No especifíca; Fil: Laxer, Ronald M.. University Of Toronto. Hospital For Sick Children; Canadá Fil: Lee, Pui Y.. Children's Hospital Boston; Estados Unidos Fil: Lee Kirsch, Min Ae. Technische Universität Dresden; Alemania Fil: Lewandowski, Laura. No especifíca; Fil: Li, Suzanne. Hackensack University Medical Center; Estados Unidos Fil: Lilleby, Vibke. Oslo University Hospital; Noruega Fil: Mammadova, Vafa. Azerbaijan Medical University; Azerbaiyán Fil: Moorthy, Lakshmi N.. Robert Wood Johnson Medical School; Estados Unidos Fil: Nasrullayeva, Gulnara. Azerbaijan Medical University; Azerbaiyán Fil: O'Neil, Kathleen M.. Riley Hospital for Children; Estados Unidos Fil: Onel, Karen. Hospital for Special Surgery; Estados Unidos Fil: Ozen, Seza. Hacettepe University; Turquía Fil: Pan, Nancy. Hospital for Special Surgery; Estados Unidos Fil: Pillet, Pascal. Children Hospital Pellegrin-Enfants; Francia Fil: Piotto, Daniela G.P.. Universidade Federal de Sao Paulo; Brasil Fil: Punaro, Marilynn G.. University of Texas; Estados Unidos Fil: Reiff, Andreas. University of Nebraska; Estados Unidos Fil: Reinhardt, Adam. University of Nebraska; Estados Unidos Fil: Rider, Lisa G.. No especifíca; Fil: Rivas Chacon, Rafael. Nicklaus Children’s Hospital; Estados Unidos Fil: Ronis, Tova. Children’s National Health System; Estados Unidos Fil: Rösen Wolff, Angela. Technische Universität Dresden; Alemania Fil: Roth, Johannes. Children’s Hospital of Eastern Ontario; Canadá Fil: Mckerran Ruth, Natasha. Medical University of South Carolina; Estados Unidos Fil: Rygg, Marite. Norwegian University of Science and Technology; Noruega Fil: Schmeling, Heinrike. University of Calgary; Canadá Fil: Schulert, Grant. Children’s Hospital Medical Center; Estados Unidos Fil: Scott, Christiaan. University of Cape Town; Sudáfrica Fil: Seminario, Gisella. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Shulman, Andrew. University of California at Irvine; Estados Unidos Fil: Sivaraman, Vidya. Nationwide Children’s Hospital; Estados Unidos Fil: Son, Mary Beth. Boston Children’s Hospital; Estados Unidos Fil: Stepanovskiy, Yuriy. Shupyk National Medical Academy for Postgraduate Education; Ucrania Fil: Stringer, Elizabeth. Dalhousie University Halifax; Canadá Fil: Taber, Sara. Hospital for Special Surgery; Estados Unidos Fil: Terreri, Maria Teresa. Universidade Federal de Sao Paulo; Brasil Fil: Tifft, Cynthia. No especifíca; Fil: Torgerson, Troy. University of Washington; Estados Unidos Fil: Tosi, Laura. Children’s National Health System; Estados Unidos Fil: van Royen Kerkhof, Annet. Wilhelmina Children’s Hospital Utrech; Países Bajos Fil: Wampler Muskardin, Theresa. New York University School of Medicine; Estados Unidos Fil: Canna, Scott W.. University of Pittsburgh; Estados Unidos Fil: Goldbach Mansky, Raphaela. National Institute Of Allergy And Infectious Diseases ; Estados Unidos

Background/objective The importance of patient-reported outcomes, like the Patient-Reported Outcomes Measurement Information System (PROMIS) measures, is increasingly recognized both in clinical care and in research. While "short forms" have been studied in juvenile idiopathic arthritis (JIA), study of PROMIS computer adaptive tests (CATs) in JIA is limited. This cross-sectional study evaluates whether PROMIS CATs correlate with disease activity in patients with JIA. Methods A convenience sample of patients with JIA (N = 44) was recruited from a single center. Patients and parents completed pediatric and parent proxy PROMIS CATs. Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71) and the Childhood Health Assessment Questionnaire (CHAQ). Correlation of the CAT T scores with disease activity was assessed using Spearman correlation coefficients. Results Forty-four of 80 eligible subjects (29 patients and 15 parents) completed all or some PROMIS CATs. Pain interference and mobility CATs correlated moderately with JADAS-71. Nearly all correlations with the JADAS-71 were weakened when the patient global was removed. Pain interference, mobility, and fatigue were strongly correlated with the CHAQ. Among parent proxy CATs, only mobility and depressive symptoms correlated strongly with the CHAQ. Conclusions Only pain interference and mobility PROMIS CATs showed strong correlation with standard disease activity measures in JIA, and nearly all correlations were weakened when the patient global was removed. Correlations of the CATs with the CHAQ were stronger than correlations with the JADAS-71, indicating that although the CHAQ is no longer routinely used it may be a better measure of health-related quality of life in routine clinical care.

The pediatric rheumatic diseases represent a broad group of diseases that range in severity and duration. In this chapter we aim to highlight the major similarities and differences between pediatric onset rheumatic diseases and their adult counterparts. Certain diseases are restricted to childhood and therefore may be unfamiliar to the adult rheumatologist. Even in diseases which are felt to be similar irrespective of age of presentation, the unique features of growth and development in childhood may present particular changes to both diagnosis and management of these illnesses.

Background: Children with systemic lupus erythematosus (cSLE) with kidney involvement face considerable morbidity and mortality. Commonly used methods for assessing kidney involvement in cSLE, such as renal function tests, are non-specific and provide a limited picture of disease activity. Kidney biopsy, the mainstay to assess disease class and chronicity as well as response to treatment, is an invasive procedure. The field of transcriptomics has identified markers that have helped our understanding of cSLE pathogenesis. Objectives: Transcriptional profiling of urinary cells has the potential to provide us with non-invasive biomarkers and has not been studied thus far. Our aim is to evaluate intracellular urinary transcripts in cSLE. Methods: Using the Human Inflammation v2 panel on the nanoString nCounter platform, expression of 255 genes was profiled from 82 urinary pellets (all from 43 cSLE with differing classes of lupus nephritis). Results: Healthy control samples yielded low quantities of RNA and were excluded from further analysis. The patient’s raw transcript counts were normalized and the use of unsupervised learning analysis revealed robustness among classes with higher disease activity (higher SLE Disease Activity Index (SLEDAI) scoring). Statistical analysis (ANOVA) showed that Classes III or IV + V (mixed nephritis; highest average SLEDAI) display robust interferon and inflammasome-related signatures in comparison to other classes. Interestingly, samples from cSLE with no known nephritis also displayed an interferon signature, although less intense than the mixed class. Some transcripts such as C3 (complement 3) were uniquely dysregulated in the mesangial class. Therapeutically targetable pathways were identified in a number of patients (specifically in the mixed class). Conclusion: These studies are currently being extended in order to confirm the value of urinary transcriptional profiling as a source of biomarkers and to identify potential therapeutic targets in cSLE. References: [1] Pascual, et al., “Understanding Human Autoimmunity and Autoinflammation Through Transcriptomics,” Annu Rev Immunol, 2017 Apr 26;35:337-370. doi: 10.1146/annurev-immunol-051116-052225 [2] Bennett L, Palucka AK, Arce E, et al. Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood. The Journal of Experimental Medicine. 2003;197(6):711-723. doi:10.1084/jem.20021553. [3] Banchereau R, Hong S, Cantarel B, Baldwin N, Baisch J, et al. 2016. Personalized immunomonitoring uncovers molecular networks that stratify lupus patients. Cell 165:551–65 [4] Chiche L, Jourde-Chiche N, Whalen E, Presnell S, Gersuk V, et al. 2014. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol. 66:1583–95 [5] Brunner H.I., Bennett M.R., Gulati G., Abulaban K., Klein-Gitelman M.S., Ardoin S.P., Tucker L.B., Devarajan P. Urine biomarkers to predict response to lupus nephritis therapy in children and young adults (2017) Journal of Rheumatology, 44 (8), pp. 1239-1248. Acknowledgement: Childhood Arthritis and Rheumatology Research Alliance Disclosure of Interests: None declared

Background Mental health conditions are common in youth with systemic lupus erythematosus (SLE), yet intervention strategies are understudied. We used a patient-engaged approach to investigate the mental health needs of youth with SLE. Methods An anonymous online survey examined beliefs and experiences with mental health for youth with SLE. Eligible youth ages 14–24 years had a diagnosis of SLE and reported specific treatment for the condition. Parents of youth 8–24 years meeting the above criteria were also eligible to participate. The survey was developed in collaboration with patient and parent advisors, the Childhood Arthritis and Rheumatology Research Alliance (CARRA), and the Patients, Advocates, and Rheumatology Teams Network for Research and Service (PARTNERS). Participants were recruited through the Lupus Foundation of America and CARRA clinics. We tabulated youth responses for i) self-reported prevalence of mental health problems, categorized into mutually exclusive clinician-diagnosed disorders and self-diagnosed symptoms, and ii) mean Likert ratings (0=low, 4=high) for the impact of disease related-factors on their mental health. We also compared youth and parent responses using regression models to examine comfort level with potential mental health providers. Results 102 respondents included 59 patients (58%) and 43 (42%) parents. Youth had a mean age of 20.9 (standard deviation, SD=3.4) years, and mean disease duration of 6.9 (SD 4.0) years. History of a mental health problem was reported by 21 youth (36%), of which 66% said that their rheumatologist was unaware. Clinician-diagnosed anxiety was reported by 19%, depression by 12%, and adjustment disorders by 19%; another 17%, 8% and 10% had self-reported symptoms of these disorders, respectively. Mean Likert ratings by youth indicated that disease aspects most impacting mental health were worry about disease impact on the future at 3.0 (SD 1.2), worry about having a flare at 2.9 (1.2), and worry about medication side effects at 2.8 (1.3). Youth and parents felt most comfortable discussing mental health concerns with rheumatologists and primary care providers, and least comfortable with social workers and school counselors (figure 1). Conclusions Youth with SLE have high rates of diagnosed and undiagnosed mental health problems, which are impacted by their disease. Mental health intervention strategies in rheumatology settings may improve mental health education, screening and treatment for these youth. Funding Source(s): The Childhood Arthritis and Rheumatology Research Alliance

ObjectiveTo investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).MethodsIn a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.ResultsLD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.ConclusionsA rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

Pediatric rheumatology is an exciting and rewarding career area. However, challenges when attracting trainees to this field include practice often occurring in smaller groups compared with general pediatrics, available positions requiring relocation, and fluctuation in funding resulting in uncertainty regarding training positions. Having critical mass in pediatric divisions is important to ensure adequate mentoring and people power to produce scholarly work, reduce on-call frequency and mitigate faculty absences that result in unplanned addition of clinical work. Compensation has historically lagged behind that of general pediatrics. Increased research opportunities through organized networks, patient and parent engagement, and the increasing recognition of pediatric rheumatologists as contributing to scholarship has heightened the profile of pediatric rheumatology nationally and internationally.

Objective Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histologic LN activity. Methods We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n = 47) at the time of kidney biopsy. Histologic LN activity was measured by the National Institutes of Health activity index (NIH-AI) and the tubulointerstitial activity index (TIAI). High LN-activity status (versus moderate/low) was defined as NIH-AI scores >10 (versus ≤10) or TIAI scores >5 (versus ≤5). RAIL algorithms that predicted LN-activity status for both NIH-AI and TIAI were derived by stepwise multivariate logistic regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined. Results The differential excretion of 6 UBMs (neutrophil gelatinase–associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin, and kidney injury molecule 1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activity (NIH-AI) status with >92% accuracy and LN-activity (TIAI) status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71% and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. Conclusion The RAIL is a robust and highly accurate noninvasive measure of LN activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation.

Objective.To identify targets for improving mental healthcare of adolescents with systemic lupus erythematosus (SLE) by assessing current practices and perceived barriers for mental health intervention by pediatric rheumatology clinicians.Methods.Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed a Web-based survey assessing current mental health practices, beliefs, and barriers. We examined associations between provider characteristics and the frequency of barriers to mental health screening and treatment using multivariable linear regression.Results.Of the 375 eligible CARRA members, 130 responded (35%) and 119 completed the survey. Fifty-two percent described identification of depression/anxiety in adolescents with SLE at their practice as inadequate, and 45% described treatment as inadequate. Seventy-seven percent stated that routine screening for depression/anxiety in pediatric rheumatology should be conducted, but only 2% routinely used a standardized instrument. Limited staff resources and time were the most frequent barriers to screening. Respondents with formal postgraduate mental health training, experience treating young adults, and practicing at sites with very accessible mental health staff, in urban locations, and in Canada reported fewer barriers to screening. Long waitlists and limited availability of mental health providers were the most frequent barriers to treatment. Male clinicians and those practicing in the Midwest and Canada reported fewer barriers to treatment.Conclusion.Pediatric rheumatology clinicians perceive a need for improved mental healthcare of adolescents with SLE. Potential strategies to overcome barriers include enhanced mental health training for pediatric rheumatologists, standardized rheumatology-based mental health practices, and better integration of medical and mental health services.

Objective To validate clinical indices of lupus nephritis activity and damage when used in children against the criterion standard of kidney biopsy findings. Methods In 83 children requiring kidney biopsy, the Systemic Lupus Erythematosus Disease Activity Index renal domain (SLEDAI-R), British Isles Lupus Assessment Group index renal domain (BILAG-R), Systemic Lupus International Collaborating Clinics (SLICC) renal activity score (SLICC-RAS), and SLICC Damage Index renal domain (SDI-R) were measured. Fixed effects and logistic models were calculated to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low-to-moderate versus high lupus nephritis activity (National Institutes of Health [NIH] activity index [AI]) score: ≤10 versus >10; tubulointerstitial activity index (TIAI) score: ≤5 versus >5; or the absence versus presence of lupus nephritis chronicity (NIH chronicity index) score: 0 versus ≥1. Results There were 10, 50, and 23 patients with ISN/RPS class I/II, III/IV, and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with lupus nephritis activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between lupus nephritis activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture lupus nephritis chronicity was 23.5% and 91.7%, respectively. Despite being designed to measure lupus nephritis activity, SLICC-RAS and SLEDAI-R scores significantly differed with lupus nephritis chronicity status. Conclusion Current clinical indices of lupus nephritis fail to discriminate ISN/RPS class in children. Despite its shortcomings, the SLEDAI-R appears best for measuring lupus nephritis activity in a clinical setting. The SDI-R is a poor correlate of lupus nephritis chronicity.

To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN).In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy.Adiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient (r) = - 0.49; p 0.0001] but not proteinuria (r = 0.20; p 0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p 0.01], combinations of osteopontin and adiponectin levels showed moderate accuracy [AUC = 0.75; p = 0.003] in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP.In combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline.• Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis. • Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance. • Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.

Background Children and adolescents with rheumatic diseases are at risk for psychosocial challenges related to illness, treatment, and normal development and should receive psychosocial screening. Psychosocial assessments have been successfully utilised in other paediatric specialties, including oncology and gastroenterology. A common psychosocial screening tool is the HEEADSSS (home environment, education/employment, eating, activities, drugs, sexuality, suicide/depression, and safety). This tool is easy to remember, quickly administered, and modifiable for younger children. Objectives We conducted a quality improvement project aimed to increase psychosocial screening by providers in a single paediatric rheumatology clinic by instituting standardised follow up templates for juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) including the HEEADSSS assessment. Methods The quality improvement intervention evaluated in this study involved the creation of disease specific follow up note templates inclusive of the HEEADSSS assessment and introduction of the templates to the paediatric rheumatology fellows clinic. Charts of patients with an ICD-10 diagnosis of JIA or SLE were reviewed during a 3 month window prior to (February-April 2017) and after (October-December 2017) the intervention. Charts were reviewed for presence of 2 elements of the HEEADSSS assessment documented within the previous 12 months: smoking exposure (all patients) and sexual activity (ages 11 years and up). The proportion of patients with completed HEEADSSS assessment components pre- and post-intervention were compared using Fisher’s exact test. Results Chart review included 36 patients pre- and 42 post-intervention (table 1). There was an increase in assessment of both measures in the period immediately following the intervention. Assessment of smoking exposure increased from 0.0% to 21.4% (p=0.003) with greater but not significant improvement in SLE versus JIA patients (29.4% versus 16.4%, p=0.45). Assessment of sexual activity in patients 11 years and older increased from 13.0% to 37.5% (p=0.09), although this comparison may be underpowered due to decreased sample sizes. Conclusions Introduction of standardised note templates with the HEEADSSS assessment has resulted in preliminary improvement in psychosocial screening by providers in a single paediatric rheumatology clinic as demonstrated by improved rates of screening for smoking exposure and a trend towards improved screening rates for sexual activity. Additional studies are needed to confirm these findings, and future studies will assess whether the improvement seen is sustained and whether usage of this template can be expanded to other paediatric patient populations. Acknowledgements We thank the EMR team for helping develop the note templates and the fellows for adopting these templates. Disclosure of Interest None declared

Background Patients with JIA often present with signs and symptoms suggestive of infection. However, differentiation of infectious from non-infectious presentation in routine clinical care is challenging. Procalcitonin (PCT) is a serum biomarker elevated in the setting of bacterial infection, but whether it can reliably differentiate infection from disease flare in patients with JIA is unknown.[1 Objectives To test the hypothesis that PCT levels will differ between active JIA, quiescent JIA, bacteremic patients and healthy controls. Methods From 10/16–4/17, consecutive children 6 months – 18 years with a) active untreated JIA b) quiescent JIA and c) healthy pre-surgical candidates were recruited from a musculoskeletal specialty hospital. JIA was defined according to ILAR criteria. Patients with active JIA despite treatment were excluded, to avoid confounding by treatment. Consecutive bacteremic patients were identified from an associated paediatric intensive care unit over the same period. Descriptive statistics and univariate logistic analyses were performed as appropriate. Results Patient characteristics are summarised in Table 1; bacteremic patients were younger. PCT was elevated in bacteremic patients, and was undetectable in all other subjects (Table 2). There were trends towards higher ESR and CRP in bacteremic patients, but these were not statistically significant. Conclusions Serum PCT levels appear to be a reliable biomarker to distinguish infection vs. active JIA at presentation, and can aid in directing therapy. However, PCT does not appear useful to assess disease activity in JIA. Further studies are needed to assess utility of serum PCT measurement in differentiating JIA flares from less severe infections. Reference [1] Milcent K, et al., “Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants,”JAMA Pediatrics170, no. 1 (2016): 62–69; Mohsen A, et al., “Predictive Values for Procalcitonin in the Diagnosis of Neonatal Sepsis,” Electronic Physician 7, no. 4 (2015): 1190–95. Disclosure of Interest None declared

Background: The importance of patient-reported outcomes is increasingly recognized both in clinical care and in research. PROMIS is an NIH-supported collection of patient-reported outcome measures, covering a variety of domains that are designed without disease specificity. While ‘short forms’ have been studied in juvenile idiopathic arthritis (JIA), PROMIS computer adaptive tests (CATs) have not. Objectives: This study evaluates whether PROMIS CATs correlate with disease activity in patients with JIA. Methods: A convenience sample of patients with JIA (N=21) were recruited from a single center. Patients aged 10–17 years completed all available pediatric PROMIS CATs, and parents of patients aged 2–9 years completed all available parent proxy PROMIS CATs (fatigue, pain interference, peer relations, anxiety, depressive symptoms, and mobility). Correlation of the CATs t-scores with disease activity, as measured by the Juvenile Disease Activity Score-71 (JADAS-71), (0–101, higher being worse) was evaluated using Spearman correlation coefficients. Results: All families approached completed the PROMIS CATs: 13 patients and 8 parents (table 1). Median age was 12.7 years (range 1.3 – 18.6 years), and mean JADAS-71 score was 9.58 (SD 2.07). 69% of patients completed PROMIS CATs remotely via smartphone. Anxiety (r=0.74, p=0.006), depressive symptoms (r=0.84, p Conclusions: Our results demonstrate that the PROMIS CATs are feasible to administer in an outpatient pediatric rheumatology setting. Anxiety, depressive symptoms, and pain interference were significantly correlated with disease activity, even though mean disease activity was relatively low. This underscores the negative effect on quality of life of even mild disease. Parent proxy CATs showed poor correlations with disease activity, suggesting parents are inaccurate in assessing important aspects of their child’s health. Larger prospective studies are needed to evaluate the sensitivity of PROMIS CATS to change in disease activity over time. Disclosure of Interest: None declared

Background JIA is a chronic autoimmune disease that poses many challenges. There is increasing recognition of the importance of patient-reported outcomes (PROs) and newer PROs are being developed and more widely utilised both in clinical care and in research, However, their performance and reliability remain unclear. Objectives This study seeks to evaluate: 1 performance of the patient global health assessment (PGA) compared to standard disease activity measures in children with JIA, 2 correlations of the PGA with socioeconomic status (SES) in JIA, and 3 relationship between PGA and physician global health assessment in JIA. Methods A convenience sample of patients with JIA (n=47) aged 2–18 were recruited from a single centre. Patients aged ≥10 years completed the questionnaire, and parents of patients aged 2–9 completed a proxy questionnaire for their child. Correlations between 1 the PGA and disease activity, as measured by the Juvenile Disease Activity Score-71 (JADAS-71), 2 the PGA and physician global health assessment, and 3 the physician global health assessment and the JADAS-71 were evaluated using Spearman correlation coefficients. PGAs were compared by age, sex, insurance status, race, and ethnicity; and differences between PGA and physician global health assessments were compared using Wilcoxon rank-sum tests. Results 16 parents and 31 patients completed the assessments (table 1). There was a moderate correlation between PGA and JADAS-71 (r=0.503, p Conclusions Our results demonstrate that physician global health assessment had a stronger correlation with standard disease activity measures than the PGA. These scores were higher in patients who were non-White race, Hispanic, and had Medicaid insurance; however, these were not statistically significant. These data indicate that the PGA is fairly stable across groups, and can be used reliably for disease monitoring. Disclosure of Interest None declared

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.

Objective Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product-based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4-year (2008–2012) EDSSP. Methods Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6-month period. Reporting rates were calculated per 100 person-years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution. Results Thirty-seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person-years (95% CI 0.95–1.19). The rates for SAEs and IMEs were 0.54 per 100 person-years (95% CI 0.45–0.63) and 0.53 per 100 person-years (95% CI 0.49–0.62), respectively. Conclusion The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product-based registry.

OBJECTIVE To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). METHODS In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. RESULTS Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36). CONCLUSION Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.

OBJECTIVE To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. METHODS In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. RESULTS Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). CONCLUSION Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.

Objective The nuclear oncoprotein DEK is an autoantigen associated with juvenile idiopathic arthritis (JIA), especially the oligoarticular subtype. DEK is a secreted chemotactic factor. Abundant levels of DEK and DEK autoantibodies are found in inflamed synovium in JIA. We undertook this study to further characterize the nature of DEK autoantibodies in screening serum samples from 2 different cohorts that consisted mostly of patients with JIA. Methods DEK autoantibody levels were analyzed in sera from 33 JIA patients, 13 patients with other inflammatory conditions, and 11 healthy controls, as well as in 89 serum samples from JIA patients receiving anti-tumor necrosis factor (anti-TNF) therapy. Recombinant His-tagged full-length DEK protein (1-375 amino acids [aa]) and the 187-375-aa and 1-350-aa His-tagged DEK fragments made in a baculovirus system were used for enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The C-terminal 25-aa fragment of DEK was expressed in a glutathione S-transferase-tagged vector. ELISA results were calculated as area under the curve by the trapezoidal rule. Results DEK autoantibody levels were significantly higher in patients with polyarticular JIA than in those with oligoarticular JIA, and were higher in patients with polyarticular JIA who had more active disease after cessation of anti-TNF therapy. Immunoblotting against the C-terminal 25-aa fragment of DEK confirmed that this section of the DEK molecule is the most immunogenic domain. Conclusion DEK autoantibody levels are higher in patients with polyarticular JIA than in those with oligoarticular JIA, and higher in patients who have disease flares after cessation of anti-TNF therapy. The C-terminal 25-aa fragment is the most immunogenic portion of DEK. These findings are significant with respect to the nature of DEK autoantibodies, their contribution to JIA pathogenesis, and their implications for JIA management.