Search

Objective Lung disease (LD) is an increasingly recognized complication of systemic juvenile idiopathic arthritis (sJIA). As there are no currently available guidelines for pulmonary screening in sJIA, we sought to develop such an algorithm at our institution. Methods A multidisciplinary workgroup was convened, including members representing rheumatology, pulmonary, stem cell transplantation, and patient families. The workgroup leaders drafted an initial algorithm based on published literature and experience at our center. A modified Delphi approach was used to achieve agreement through three rounds of anonymous, asynchronous voting and a consensus meeting. Statements approved by the workgroup were rated as appropriate with moderate or high levels of consensus. These statements were organized into the final approved screening algorithm for LD in sJIA. Results The workgroup ultimately rated 20 statements as appropriate with a moderate or high level of consensus. The approved algorithm recommends pulmonary screening for newly diagnosed patients with sJIA with clinical features that the workgroup agreed may confer increased risk for LD. These “red flag features” include baseline characteristics (young age of sJIA onset, human leukocyte antigen type, trisomy 21), high disease activity (macrophage activation syndrome [MAS], sJIA‐related ICU admission, elevated MAS biomarkers), respiratory symptoms or abnormal pulmonary examination findings, and features of drug hypersensitivity‐like reactions (eosinophilia, atypical rash, anaphylaxis). The workgroup achieved consensus on the recommended pulmonary work‐up and monitoring guidelines. Conclusion We developed a pulmonary screening algorithm for sJIA‐LD through a multidisciplinary consensus‐building process, which will be revised as our understanding of sJIA‐LD continues to evolve.

Abstract Background Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an immunologic syndrome characterized by widespread neutrophilic infiltration. Histiocytoid Sweet syndrome (H-SS) is a histopathologic variant of SS. While SS most commonly occurs in adults, this case report discusses an infant patient who presented with H-SS. Case presentation Through a multidisciplinary approach, this patient was also found to have very early onset inflammatory bowel disease (VEO-IBD) and Mevalonate kinase-associated disease (MKAD). While prior case studies have characterized an association between VEO-IBD and MKAD, there is no literature describing the association of all three diagnoses this case: H-SS, VEO-IBD and MKAD. Initiation of canakinumab in this patient resulted in successful control of the disease. Conclusions This case highlights the importance of a multidisciplinary approach to rare diagnoses, and collaboration during cases with significant diagnostic uncertainty.

Objective Black and Hispanic children with pediatric lupus (pSLE) have higher morbidity and mortality than non‐Hispanic White children. The extent to which differences in outcomes are due to treatment disparities, including medication use, is unknown. We aimed to determine whether medication use in pSLE is associated with race and ethnicity in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods Patients with pSLE enrolled in the CARRA Registry from 2017 to 2020 were included. Multivariable mixed‐effect logistic regression, adjusted for site of care, was used to compare use of antimalarials, high‐dose oral glucocorticoids, and rituximab in Black and Hispanic children. Results We identified 639 children with pSLE, of whom 480 had at least 1 year of follow‐up. At enrollment, 89% of patients were prescribed an antimalarial and 50% were on high‐dose glucocorticoids. Of those with 1 year of follow‐up, 12% received rituximab. Nephritis, shorter disease duration, and higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores were associated with high‐dose glucocorticoid use. Antimalarial use was higher among those with nephritis and lower in children with no insurance. Rituximab use was associated with Black race in the fixed‐effects model but not when adjusted for site of care. Conclusion We identified differences in medication use by race and insurance status. Site of care was associated with the racial differences observed in rituximab use. Further research is needed to optimize pSLE treatments particularly where use is highly variable, including glucocorticoid dosing and use of rituximab, and understand the impact of practice variation on disparities in pSLE outcomes.

Abstract Adolescents and young adults (AYA) with rheumatologic diseases are at high risk for poor outcomes and gaps in care when transitioning from pediatric to adult care. However, tools for evaluating transition readiness and assessing the impact of transition interventions are limited. We implemented a written transition policy at our pediatric rheumatology center and evaluated preparation for transition among AYA 16 and older before and after distribution. 31 of 77 patients completed the follow-up survey (response rate 40%). Patient report of transition counseling increased following written transition policy implementation, though these results were not statistically significant in our small cohort. Most follow-up respondents (n = 19, 61%) had not yet completed care transfer; 4 (13%) had arranged a visit with an adult rheumatologist and 8 (26%) had fully transitioned to adult care. Those who successfully completed care transfer were older, had completed higher levels of education, and had significantly higher baseline transition preparation scores compared to those with no transfer arranged or planned visit only. Our single-center pilot study demonstrated that longitudinal assessment of transition preparation is feasible and that scores are significantly associated with care transfer outcomes. Tracking transition preparation over time may provide practices with information on areas of highest need for transition guidance and predict successful transfer among AYA with rheumatologic disease.

Objective Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS‐C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS‐C definitions and differing disease severity between cohorts underlay discrepant results. Methods The Overcoming COVID‐19 Public Health Surveillance Registry (OC‐19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS‐C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC‐19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts. Results Of 349 OC‐19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC‐19 patients had WHO‐defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC‐19 patients were more often admitted to intensive care (61.0% vs 44.8%, P

Abstract During the critical early stages of an emerging pandemic, limited availability of pathogen-specific testing can severely inhibit individualized risk screening and pandemic tracking. Standard clinical laboratory tests offer a widely available complementary data source for first-line risk screening and pandemic surveillance. Here, we propose an integrated framework for developing clinical-laboratory indicators for novel pandemics that combines population-level and individual-level analyses. We apply this framework to 7,520,834 clinical laboratory tests recorded over five years and find clinical-lab-test combinations that are strongly associated with SARS-CoV-2 PCR test results and Multisystem Inflammatory Syndrome in Children (MIS-C) diagnoses: Interleukin-related tests (e.g. IL4, IL10) were most strongly associated with SARS-CoV-2 infection and MIS-C, while other more widely available tests (ferritin, D-dimer, fibrinogen, alanine transaminase, and C-reactive protein) also had strong associations. When novel pandemics emerge, this framework can be used to identify specific combinations of clinical laboratory tests for public health tracking and first-line individualized risk screening.

T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides.

Abstract Background Despite timely administration of IVIG, some patients with Kawasaki disease (KD) develop rapidly progressive or giant coronary artery aneurysms (CAA). Case presentation We describe our experience using cyclophosphamide (CYC) for the treatment of such cases as well as a review of the literature on the use of CYC in KD. Through a retrospective chart review of our KD population, we identified ten children treated for KD with intravenous CYC (10 mg/kg/dose) for one or two doses. Seven patients were male, the median age was 2.0 years (range 4 months − 5 years). All patients received initial IVIG between day 4–10 of illness. Other anti-inflammatory treatments administered before CYC included second IVIG (n = 9), corticosteroids (n = 10), infliximab (n = 4), cyclosporine (n = 2), and anakinra (n = 1). Median illness day at administration of the first CYC dose was 22.5 days (range:10–36 days). The primary indication for treatment with CYC for all patients was large or giant CAA and/or rapid progression of CAA. Three patients received a second dose of CYC (10 mg/kg) for progressively enlarging CAA. CAA did not progress after final CYC treatment. One patient with a history of neutropenia in infancy developed severe neutropenia 9 days after treatment with CYC, which recovered without intervention or complications. No patient developed infections or other serious toxicity from CYC. Conclusion In KD patients with severe and progressive enlargement of CAA despite anti-inflammatory therapy, CYC seemed to arrest further dilation and was well-tolerated. Future multicenter studies are needed to confirm our findings in this subgroup of KD patients.

Background: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians)

Oligoarticular juvenile idiopathic arthritis (oligo JIA) is the most common form of chronic inflammatory arthritis in children, yet the cause of this disease remains unknown. To understand immune responses in oligo JIA, we immunophenotyped synovial fluid T cells with flow cytometry, bulk RNA-Seq, single-cell RNA-Seq (scRNA-Seq), DNA methylation studies, and Treg suppression assays. In synovial fluid, CD4+, CD8+, and γδ T cells expressed Th1-related markers, whereas Th17 cells were not enriched. Th1 skewing was prominent in CD4+ T cells, including Tregs, and was associated with severe disease. Transcriptomic studies confirmed a Th1 signature in CD4+ T cells from synovial fluid. The regulatory gene expression signature was preserved in Tregs, even those exhibiting Th1 polarization. These Th1-like Tregs maintained Treg-specific methylation patterns and suppressive function, supporting the stability of this Treg population in the joint. Although synovial fluid CD4+ T cells displayed an overall Th1 phenotype, scRNA-Seq uncovered heterogeneous effector and regulatory subpopulations, including IFN-induced Tregs, peripheral helper T cells, and cytotoxic CD4+ T cells. In conclusion, oligo JIA is characterized by Th1 polarization that encompasses Tregs but does not compromise their regulatory identity. Targeting Th1-driven inflammation and augmenting Treg function may represent important therapeutic approaches in oligo JIA.

Background Accurate prediction of coronary artery aneurysms (CAAs) in patients with Kawasaki disease remains challenging in North American cohorts. We sought to develop and validate a risk model for CAA prediction. Methods and Results A binary outcome of CAA was defined as left anterior descending or right coronary artery Z score ≥2.5 at 2 to 8 weeks after fever onset in a development cohort (n=903) and a validation cohort (n=185) of patients with Kawasaki disease. Associations of baseline clinical, laboratory, and echocardiographic variables with later CAA were assessed in the development cohort using logistic regression. Discrimination (c statistic) and calibration (Hosmer‐Lemeshow) of the final model were evaluated. A practical risk score assigning points to each variable in the final model was created based on model coefficients from the development cohort. Predictors of CAAs at 2 to 8 weeks were baseline Z score of left anterior descending or right coronary artery ≥2.0, age 40‐fold greater in the validation cohort (odds ratio, 44.0; 95% CI, 10.8–180 [P

BackgroundAccurate risk prediction of coronary artery aneurysms (CAAs) in North American children with Kawasaki disease remains a clinical challenge. We sought to determine the predictive utility of baseline coronary dimensions adjusted for body surface area (z scores) for future CAAs in Kawasaki disease and explored the extent to which addition of established Japanese risk scores to baseline coronary artery z scores improved discrimination for CAA development. Methods and ResultsWe explored the relationships of CAA with baseline z scores; with Kobayashi, Sano, Egami, and Harada risk scores; and with the combination of baseline z scores and risk scores. We defined CAA as a maximum z score (zMax) ≥2.5 of the left anterior descending or right coronary artery at 4 to 8 weeks of illness. Of 261 patients, 77 patients (29%) had a baseline zMax ≥2.0. CAAs occurred in 15 patients (6%). CAAs were strongly associated with baseline zMax ≥2.0 versus