Assessing Pediatric Rheumatology Fellow Competence in the Milestone Era: Past, Present, and Future.

Starting in 2015, pediatric rheumatology fellowship training programs were required by the Accreditation Council for Graduate Medical Education to assess fellows' academic performance within 21 subcompetencies falling under six competency domains. Each subcompetency had four or five milestone levels describing developmental progression of knowledge and skill acquisition. Milestones were standardized across all pediatric subspecialties. As part of the Milestones 2.0 revision project, the Accreditation Council for Graduate Medical Education convened a workgroup in 2022 to write pediatric rheumatology-specific milestones. Using adult rheumatology's Milestones 2.0 as a starting point, the workgroup revised the patient care and medical knowledge subcompetencies and milestones to reflect requirements and nuances of pediatric rheumatology care. Milestones within four remaining competency domains (professionalism, interpersonal and communication skills, practice-based learning and improvement, and systems-based practice) were standardized across all pediatric subspecialties, and therefore not revised. The workgroup created a supplemental guide with explanations of the intent of each subcompetency, 25 in total, and examples for each milestone level. The new milestones are an important step forward for competency-based medical education in pediatric rheumatology. However, challenges remain. Milestone level assignment is meant to be informed by results of multiple assessment methods. The lack of pediatric rheumatology-specific assessment tools typically result in clinical competency committees determining trainee milestone levels without such collated results as the foundation of their assessments. Although further advances in pediatric rheumatology fellowship competency-based medical education are needed, Milestones 2.0 importantly establishes the first pediatric-specific rheumatology Milestones to assess fellow performance during training and help measure readiness for independent practice.

Postdischarge Glucocorticoid Use and Clinical Outcomes of Multisystem Inflammatory Syndrome in Children.

Importance: Minimal data are available regarding the postdischarge treatment of multisystem inflammatory syndrome in children (MIS-C). Objectives: To evaluate clinical characteristics associated with duration of postdischarge glucocorticoid use and assess postdischarge clinical course, laboratory test result trajectories, and adverse events in a multicenter cohort with MIS-C. Design, Setting, and Participants: This retrospective cohort study included patients with MIS-C hospitalized with severe illness and followed up for 3 months in an ambulatory setting. Patients younger than 21 years who were admitted between May 15, 2020, and May 31, 2021, at 13 US hospitals were included. Inclusion criteria were inpatient treatment comprising intravenous immunoglobulin, diagnosis of cardiovascular dysfunction (vasopressor requirement or left ventricular ejection fraction ≤55%), and availability of complete outpatient data for 3 months. Exposures: Glucocorticoid treatment. Main Outcomes and Measures: Main outcomes were patient characteristics associated with postdischarge glucocorticoid treatment, laboratory test result trajectories, and adverse events. Multivariable regression was used to evaluate factors associated with postdischarge weight gain (≥2 kg in 3 months) and hyperglycemia during illness. Results: Among 186 patients, the median age was 10.4 years (IQR, 6.7-14.2 years); most were male (107 [57.5%]), Black non-Hispanic (60 [32.3%]), and Hispanic or Latino (59 [31.7%]). Most children were critically ill (intensive care unit admission, 163 [87.6%]; vasopressor receipt, 134 [72.0%]) and received inpatient glucocorticoid treatment (178 [95.7%]). Most were discharged with continued glucocorticoid treatment (173 [93.0%]); median discharge dose was 42 mg/d (IQR, 30-60 mg/d) or 1.1 mg/kg/d (IQR, 0.7-1.7 mg/kg/d). Inpatient severity of illness was not associated with duration of postdischarge glucocorticoid treatment. Outpatient treatment duration varied (median, 23 days; IQR, 15-32 days). Time to normalization of C-reactive protein and ferritin levels was similar for glucocorticoid duration of less than 3 weeks vs 3 or more weeks. Readmission occurred in 7 patients (3.8%); none was for cardiovascular dysfunction. Hyperglycemia developed in 14 patients (8.1%). Seventy-five patients (43%) gained 2 kg or more after discharge (median 4.1 kg; IQR, 3.0-6.0 kg). Inpatient high-dose intravenous and oral glucocorticoid therapy was associated with postdischarge weight gain (adjusted odds ratio, 6.91; 95% CI, 1.92-24.91). Conclusions and Relevance: In this multicenter cohort of patients with MIS-C and cardiovascular dysfunction, postdischarge glucocorticoid treatment was often prolonged, but clinical outcomes were similar in patients prescribed shorter courses. Outpatient weight gain was common. Readmission was infrequent, with none for cardiovascular dysfunction. These findings suggest that strategies are needed to optimize postdischarge glucocorticoid courses for patients with MIS-C.

Active Surveillance With Seroprevalence-based Infection Rates Indicates Racial Disparities With Pediatric SARS-CoV-2 Requiring Hospitalization in Mississippi, March 2020-February 2021.

BACKGROUND: Racial disparities in SARS-CoV-2 infection, hospitalization, and multisystem inflammatory syndrome in children (MIS-C) have been reported. However, these reports have been based on incomplete data relying on passive reporting, unknown catchment populations, and unknown infection prevalence. We aimed to characterize population-based incidence of MIS-C and COVID-19 hospitalizations among non-Hispanic Black and White children using active surveillance based on seroprevalence-based cumulative incidence of pediatric SARS-CoV-2 infection in a defined catchment 16-county area of Mississippi. METHODS: Active, population-based surveillance for MIS-C and acute COVID-19 hospitalizations meeting clinical and laboratory criteria was conducted by adjudicating clinicians at the major pediatric referral hospital for Mississippi, University of Mississippi Medical Center, from March 2020, to February 2021. Race-stratified SARS-CoV-2 seroprevalence was estimated using convenience samples from persons <18 years to calculate cumulative SARS-CoV-2 infections in the population. RESULTS: Thirty-eight MIS-C cases and 74 pediatric acute COVID-19 hospitalizations were identified. Cumulative incidence of MIS-C was 4.7 times higher among Black compared with White children (40.7 versus 8.3 cases per 100,000 SARS-CoV-2 infections). Cumulative incidence of COVID-19 hospitalization was 62.3 among Black and 33.1 among White children per 100,000 SARS-CoV-2 infections. CONCLUSIONS: From the same catchment area, active surveillance, and cumulative incidence of infection estimated by seroprevalence, we show strikingly higher incidence of SARS-CoV-2-hospitalization and MIS-C in non-Hispanic Black children compared with White children before COVID-19 vaccination introduction in children. These disparities in SARS-CoV-2 manifestations cannot be accounted for by differences in exposure or testing. Targeted vaccine interventions will lessen disparities observed with SARS-CoV-2 manifestations in children.

Joint injection practice variations in pediatric rheumatology - a global survey and call for action.

BACKGROUND: Intraarticular injections (IAI) were first reported in adult rheumatology in the 1950s and subsequently gained acceptance as a safe and efficacious treatment in Juvenile idiopathic arthritis (JIA). IAIs are now widely performed and recommended as the initial or only treatment of oligoarticular JIA and ancillary treatment of actively inflamed joints in other varieties of JIA. However, the performance of the procedure is currently not guided by standardized recommendations, and several practice variations are observed. METHODS: This worldwide survey of pediatric rheumatologists (with 48.5% response from Pediatric Rheumatology International Trials Organization [PRINTO and Pediatric Rheumatology Collaborative Study Group [PRCSG] members) captures the differences in pre-procedural, procedural and post-procedural protocols and practices observed across the globe and asks the necessity of developing consensus in this area of Pediatric Rheumatology. RESULTS: This worldwide survey of Pediatric Rheumatologists had a response rate of just under 50% and the views of about 42% who routinely performed the procedure. It captured the differences in IAI protocols and practices observed across the globe. Significant variations in practice were noted in use of Local anesthesia, choice, and dose of therapeutic agent for the intraarticular injection and use of ultrasound to guide injections. While some practice variations may be explained by institutional protocols in different parts of the world, the clinical implications of these are largely unknown and beg the need for further studies. CONCLUSIONS: Given these practice variations, the authors recommend further studies to explore the cost and clinical implications and subsequently work towards developing consensus plans to ensure uniformity in this widely used procedure in Pediatric Rheumatology.

Aspirin Dose in Kawasaki Disease: The Ongoing Battle.

OBJECTIVE: Kawasaki disease (KD) is an acute childhood vasculitis that may result in coronary aneurysms. Treatment of KD with a single infusion of 2 gm/kg intravenous immunoglobulin (IVIG) is well established, but acetylsalicylic acid (ASA) dose remains controversial. Our primary objective was to determine the difference in the incidence of IVIG resistance between 2 ASA doses. Our secondary objective was to compare the duration of hospital stay and the incidence of coronary artery aneurysm. METHODS: We reviewed charts of patients with KD from 2 Canadian centers to assess the impact of ASA dose on IVIG resistance (operationally defined as administration of a second dose of IVIG). Both centers used standard IVIG dosing, but center 1 used low-dose ASA from diagnosis (3-5 mg/kg/day) while center 2 used initial high-dose ASA (80-100 mg/kg/day). RESULTS: There were no significant differences in baseline characteristics between the 2 centers. Retreatment with a second dose of IVIG was required in 28 of 122 patients (23%) treated with low-dose ASA, and in 11 of 127 patients (8.7%) treated with high-dose ASA in center 1 and center 2, respectively (P = 0.003). After adjusting for confounders, low-dose ASA was associated with higher odds of IVIG resistance (OR 3.2 [95% confidence interval 1.1, 9.1]). The mean duration of hospital stay was 4.1 and 4.7 days, respectively (P = 0.37). Coronary artery aneurysms were seen in 2 of 117 and 6 of 125 patients from centers 1 and 2, respectively (P = 0.28). CONCLUSION: Low-dose ASA was associated with 3-times higher odds of IVIG retreatment compared to high-dose ASA, with no significant difference in duration of hospital stay or incidence of coronary artery aneurysms.

Aspirin Dose and Prevention of Coronary Abnormalities in Kawasaki Disease.

BACKGROUND: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA to be used. We aimed to evaluate the noninferiority of ASA at an antiplatelet dose in acute KD in preventing coronary artery (CA) abnormalities. METHODS: This is a multicenter, retrospective, nonrandomized cohort study including children 0 to 10 years of age with acute KD between 2004 and 2015 from 5 institutions, of which 2 routinely use low-dose ASA (3-5 mg/kg per day) and 3 use high-dose ASA (80 mg/kg per day). Outcomes were CA abnormalities defined as a CA diameter with a z score ≥2.5. We assessed the risk difference of CA abnormalities according to ASA dose. All subjects received ASA and intravenous immunoglobulin within 10 days of fever onset. RESULTS: There were 1213 subjects included, 848 in the high-dose and 365 in the low-dose ASA group. There was no difference in the risk of CA abnormalities in the low-dose compared with the high-dose ASA group (22.2% vs 20.5%). The risk difference adjusted for potential confounders was 0.3% (95% confidence interval [CI]: -4.5% to 5.0%). The adjusted risk difference for CA abnormalities persisting at the 6-week follow-up was -1.9% (95% CI: -5.3% to 1.5%). The 95% CI of the risk difference of CA abnormalities adjusted for confounders was within the prespecified 5% margin considered to be noninferior. CONCLUSIONS: In conjunction with intravenous immunoglobulin, low-dose ASA in acute KD is not inferior to high-dose ASA for reducing the risk of CA abnormalities.

Revisiting the role of steroids and aspirin in the management of acute Kawasaki disease.

PURPOSE OF REVIEW: Kawasaki disease is an acute multisystem childhood vasculitis with a predilection for the coronary arteries. The role of corticosteroids and acetyl salicylic acid (ASA) in the treatment of acute Kawasaki disease are matters of ongoing debate and changing attitudes from one extreme to the other. Recent work has provided new evidence to guide our thinking about these two therapeutic agents, which will be the focus of this review. RECENT FINDINGS: Corticosteroids are effective and well tolerated in Kawasaki disease, both as initial adjunctive treatment in those at high-risk for poor outcome, and as rescue therapy after failed intravenous immunoglobulin (IVIG).Higher doses of ASA (> 30 mg/kg/day) in the acute phase of Kawasaki disease, have no clear benefit over antiplatelet doses in improving coronary outcome. SUMMARY: Corticosteroids should be used in patients at high-risk for poor coronary outcome, and in patients who fail IVIG. The absence of widely applicable and validated risk-scoring systems in Kawasaki disease outside of Japan remains a limiting factor to identify high-risk children. Current evidence does not demonstrate any advantage of high-dose over low-dose ASA in the acute phase of Kawasaki disease, in preventing coronary artery aneurysms.

The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus.

OBJECTIVES: Clinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life. METHODS AND RESULTS: By harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosus (SLE). CONCLUSIONS: This case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course.

Modified regimen of etanercept for tumor necrosis factor receptor associated periodic syndrome (TRAPS) like illness.

BACKGROUND: TRAPS, an autosomal dominant autoinflammatory disorder occurs due to mutations of the TNFRSF1A gene. Mutation negative TRAPS (TRAPS like illness) is also known. Anti TNF molecules (etanercept) is the mainstay of therapy. CASE CHARACTERISTICS: A 11-year-old boy with a 5 year clinical profile indicative of a TRAPS like illness and with negative mutation studies is described. He has been followed up for nearly 2 years after starting etanercept. OUTCOME: He had sustained response to etanercept which has subsequently been titrated (0.4 mg/kg subcutaneously every 23-24 days) to keep him symptom free. MESSAGE: Mutation negative cases of TRAPS can be diagnosed with a high index of suspicion. Treatment with etanercept is expensive but possibly intervals between doses could be titrated to reduce cost.