Liza J. McCann

Background/Objectives: Patients with childhood-onset rheumatic diseases may be at additional risk of developing other health conditions. This systematic review aimed to (i) identify and describe the comorbidities associated with three significant childhood-onset rheumatic diseases—Juvenile Idiopathic Arthritis (JIA), Juvenile-onset Systemic Lupus Erythematosus (jSLE), and Juvenile Dermatomyositis (JDM); (ii) describe comorbidity prevalence and incidence reported as apparent in childhood or adulthood, and (iii) compare these comorbidity estimates with control groups. Methods: PubMed, Web of Science, and Scopus databases were systematically searched without restrictions, in accordance with PRISMA guidelines. Where three or more studies reported the same comorbidity, a meta-analysis was performed using random-effect models. The risk of bias and study quality were assessed using an adjusted version of the Newcastle–Ottawa Scale. Results: Comorbidities were reported in 136,072 patients, of which 115,062 (84.56%) presented in childhood. There was significant heterogeneity within the results. The comorbidities presenting in childhood were uveitis (13.95%, 95% CI 11.79–16.43) in JIA patients, chronic kidney disease (48.38%, 95% CI 0.67–99.24) in jSLE patients, and calcinosis (29.70%, 95% CI 25.91–33.81) in JDM patients. The comorbidities identified in adult populations with childhood-onset rheumatic disease were uveitis (14.46%, 95% CI9.76–20.90) in JIA, hypertension (18.30%, 95% CI 7.52–38.16) in jSLE, and calcinosis (40.37%, 19.02–66.11) in JDM patients. Almost all comorbidities that were compared to control groups were more common in patients with childhood-onset rheumatic disease if statistically significant. Conclusions: Uveitis, chronic kidney disease/hypertension and calcinosis were most commonly identified among JIA, jSLE and JDM patients, respectively. Patients with the three childhood-onset rheumatic diseases evaluated in this systematic review were often found to be at higher risk of comorbidities compared to controls. This finding supports the need for the proactive, multidisciplinary management of comorbidities by clinicians and highlights the breadth of disease burden for patients.

Objective: To seek current evidence in support of the adoption of the treat-to-target (T2T) strategy in the management of juvenile dermatomyositis (JDM). Methods: A systematic literature review (SLR) was performed to address 14 research questions formulated by the steering committee (SC) of the project. MEDLINE, Embase, Cochrane Central, and Web of Science databases were searched for clinical trials, observational studies (retrospective and prospective), case reports of > 2 patients, expert recommendations, and systematic reviews published until March 2023. The protocol for the SLR was registered in PROSPERO (CRD42023421254). Quality assessment was performed according to a modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: A total of 2714 articles were retrieved from the databases, with an additional 47 identified through citation searching and 23 flagged by SC members. Of these, 220 were included in the final review. Evidence was strong or moderate for 2 and 22 articles, respectively, and weak for the remaining articles. Although no published study that compared conventional management with a targeted approach was retrieved, useful insights were obtained on specific therapeutic endpoints and optimal timing for their achievement that could be considered in designing the T2T strategy for JDM. Conclusion: This SLR provides a comprehensive overview of the current knowledge that served as the basis for the consensus definition of the overarching principles and recommendations for the T2T strategy in JDM.

Background: Childhood-onset rheumatic diseases, such as juvenile idiopathic arthritis, juvenile-onset lupus and juvenile dermatomyositis, appear to be associated with an increased risk of comorbidities in adulthood compared to the general population. For the first stage of a research project evaluating this topic, we wanted to capture views from young people with juvenile-onset rheumatic disease to ensure that further work was relevant to their lived experience and priorities. This study aimed to determine (i) which comorbidities young people identify as important, (ii) how they access information about their disease, including comorbidity risk, whether (iii) they would like to hear about the risk of comorbidities whilst they are under paediatric care, and (iv) would be motivated to make lifestyle choices to decrease the risk of potential comorbidities. Methods: A topic guide based on the proposed study aims was developed, and PowerPoint slides were prepared to facilitate three focus group discussions to gain insights from young people. Focus groups were conducted via video platform, and the views of young people were assimilated using notetaking and an online interactive polling tool. Results: A total of 18 young people between 10 and 27 years of age participated in the focus groups. Mental health (including depression and anxiety) was described as important comorbidity by 17/18 (94%), followed by obesity or being overweight by 9/18 (50%), heart disease by 7/18 (39%) and stroke by 5/18 (28%) of participants. Young people reported searching United Kingdom National Health Service websites, charity resources, and Google for information on their disease and associated comorbidities. They stated that they would be willing to change their lifestyle to reduce the risk of comorbidities if information were given to them sensitively with clear practical steps for reducing risk. Conclusion: Three groups of young people identified risk of mental health issues, obesity, and cardiovascular morbidities as particularly important to them. They reported searching online platforms related to their disease and increasingly accessed online resources as they transitioned from paediatric to adult care. Participants thought it would be helpful to provide information on young people’s disease and associated comorbidity in a motivational and sensitive way. Clinical trial number: Not applicable.

Objective IgA vasculitis (IgAV) is the most frequently experienced subtype of vasculitis seen in children. Most children fully recover, however, complications including chronic kidney disease are recognised. The aim of this project was to use a best available evidence, group agreement, based approach to develop national recommendations for the initial management of IgAV and its associated complications. Methods A fully representative multiprofessional guideline development group (GDG), consisting of 28 members, was formed and met monthly. Graded recommendations were generated using nationally accredited methods, which included a predefined scope, open consultation, systematic literature review, evidence appraisal, review of national or international guidelines and a period of open consultation. Audit measures and research priorities were incorporated. Results The IgAV GDG met over a 14-month period. A total of 82 papers were relevant for evidence synthesis. For the initial management, four topic areas were identified with five key questions generating six graded recommendations related to classification, specialist referral and musculoskeletal involvement. For the associated complications, five topic areas with 12 key questions generated 15 graded recommendations covering nephritis, gastrointestinal and testicular involvement, atypical disease and follow-up. Open consultation feedback was incorporated. The guidelines were endorsed by the UK Kidney Association and Royal College of Paediatrics and Child Health and are available online. Conclusion Despite IgAV being a rare disease with limited evidence, a national standardised approach to the clinical management for children and young people has been achieved. This should unite approaches to care and act as a foundation for improvement.

Lesley Ann Saketkoo, Antonia Valenzuela, Susan Kim, Liza J McCann, Christian Lood, Dawn M Wahezi, Victoria P Werth, Belina Yi, Helene Alexanderson, Susan Mailla

The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.

Reviews; Authors: L.J. Mccann, P. Livermore, M.G. Wilkinson, L.R. Wedderburn