Adolescent Rheumatology Research Articles

Research priority setting for paediatric rheumatology in the UK.

The evidence base that underlies the management of children and young people with paediatric rheumatic diseases is deficient. In this field, there are many crucial unanswered questions. The UK Paediatric Rheumatology Clinical Studies Group, supported by UK National Institute for Health Research Clinical Research Network: children and Versus Arthritis, elicited ideas for research priorities from paediatric rheumatologists, trainees, allied health-care professionals, nurse specialists, patients, parents of patients, carers, and charities. These ideas were collected through online surveys and face-to-face meetings. A modified Delphi process was used, which included online research priority ranking surveys and a consensus workshop. A longlist of 55 disease-specific research priorities and 37 general research priorities were voted on in the first survey. A list of 11 top general research priorities was produced. The top ten disease-specific research priorities were discussed in depth at a Delphi workshop to determine their final ranking. This Health Policy paper will help to guide clinicians, academics, and funding bodies to prioritise research in paediatric rheumatic diseases, specifically in areas of unmet patient needs.

OA31 Youth-led development of an animated film to aid recruitment to a national youth advisory group for adolescent and young adult rheumatology

Background/AimsYour Rheum is a national youth advisory group for adolescent and young adult rheumatology, to ensure meaningful involvement of young people at all stages of research. It was established in 2016 as a result of nationwide research, which reported that young people with rheumatic conditions wanted to be actively involved and had clear opinions of how they wanted to be involved and the priorities for such research. Young people ageing-out of the group remains challenging in view of the national nature of the group and was further compounded by the impact of the COVID-19 pandemic, which prevented the face-to-face meetings of the group. The aim of this project was to develop a short animation detailing what Your Rheum is about to encourage young people to join.MethodsContent for the animation was gathered at a virtual Your Rheum meeting and via an online survey sent to members. A smaller group of members (n = 4) then worked with the Your Rheum facilitator and a national animation company, More Than Minutes, to create a script, storyboard, to choose imagery, colour schemes and discuss a voiceover. The animation was subsequently revised in the light of feedback from the young people.ResultsKey areas of content included: who can get involved in Your Rheum and membership; the different ways the group works with researchers for example group virtual and face-to-face activities, individual online activities; examples of different projects and topics of research discussed; why it is important to involve young people in research; how to contact the Your Rheum team. It was important to ensure the animation imagery was bright, fun and highlighted diversity. Language used in the film had to be clear and simple to understand, to enable young people from the age of 11 years upwards to relate. Subtitles on the video were also an important feature. The animation was successfully launched in September 2021 - [https://youtu.be/Y8OqmEJZ9Eo]ConclusionIt is important to harness the experience and opinions of young people at all stages of research including recruitment strategies and dissemination, as this can result in resources that truly resonant with this age group.Disclosure L.E. Lunt: None. M. Purvis: None. S. Gnanenthiran: None. P. Zing: None. J.E. McDonagh: Consultancies; Consultancy fees from Pfizer (2018) and CSL-Behring (2021).

P027 Challenges and opportunities in embedding quality data into routine clinical practice using electronic health record systems

Abstract Background/Aims The emergence of the electronic health record system (EHRS) creates opportunities for standardising clinical data which can be used for service improvement and research. However, there are also challenges related to EHRS use particularly with respect to data quality and availability. In this project, our goal is to enhance the use of EHRS to enable timely access to reliable high quality clinical data which can be used for research and Quality Improvement. We aimed to improve the entry of structured clinical data starting with problem list, medication list and core outcome variables by 70% within 12 months. Methods We audited our current practice and developed an improvement strategy to incorporate standardized documentation into our adolescent and young adult (AYA) rheumatology clinics. We initially extracted a baseline report for AYA patients to establish our baseline data quality and availability. We also compared structured data to narrative data. Then we organised meetings to develop a shared understanding of the challenges. Subsequent departmental meetings were organised to prioritise and then agree on actions which were summarised in a driver diagram. Then we ran 5 cycles of change and measured data over time including the weekly proportion of clinic encounters using standardised problem lists, medication lists, core outcomes variables. We also measured the use of Smart tools built within our EHRS. Smart-Tools are processes that enable efficiency through easier ordering, navigation and documentation in an EHRS. Using the patient interface ‘MyCare’, we engaged with our patients to encourage them to prepare for their appointment including updating their medication list and completing health questionnaires. Results Initial audit comparing structured and narrative data, revealed poor quality data with 50% of problem lists documented in a structured manner. Of those, 20% were not entered correctly. 70% of medication lists were entered in a non-structured manner. 80% of those with structured medication lists were entered inaccurately. There was no structured documentation of core outcomes variables or joint examination in all encounters which was also inconsistently entered in the free text. Over the last 12 months, 5 cycles of change were implemented testing a number of interventions including developing clinic encounters templates and smart tools within EHRS. The weekly entry of structured problem list improved from 50% to 98%. The Smart-Phrase use and AYA template weekly use rate improved from 0% to 70% and the entry of core outcome variables has improved from 0% to 30% of cases. Conclusion This project supports the feasibility of implementing standardized data into routine clinical practice that can be used for research and service improvement. This has created an opportunity to improve data quality and accuracy. Most importantly, this work has facilitated a standardisation of clinical practice and better engagement between clinicians and patients. Disclosure A. Bouraoui: None. C. Fisher: None. D. Sen: None.

OA43 Development of a national across specialty multi-disciplinary team for management of hyper-inflammatory conditions during the SARS-CoV-2 pandemic

Abstract Background/Aims Effective multi-specialty team working is extremely beneficial in management of children with hyper-inflammatory conditions. With the recognition of paediatric inflammatory multisystem syndrome (PIMS) it became apparent a standardised process for discussion of patients would be beneficial. This includes urgent discussion, with access to multiple specialties, and sharing knowledge and experience in a novel condition. Delivering equitable healthcare including access to expertise, specific treatments and research is challenging in Scotland due to its geography. This is facilitated by successful clinical networks (Scottish Paediatric & Adolescent Rheumatology Network [SPARN] and Scottish Paediatric& Adolescent Infection & Immunology National Managed Clinical Network [SPAIIN]) and a well-established paediatric transport service (ScotSTAR). Our aim was to develop a multi-specialty multi-disciplinary team (MDT) for management of patients with hyper-inflammatory conditions. Methods Narrative account of MDT and service development Results We identified a core group of individuals with an interest in inflammatory disorders from different centres and specialties across Scotland including Rheumatology, Infectious Diseases, Cardiology, Intensive Care, Academic Paediatrics, Pharmacists and Clinical Nurse Specialists. Three priorities emerged from initial planning stages: urgent discussions around patient management, peer-to-peer learning and information sharing, and effective prioritisation of research. We designed a written framework and referral pathway, including criteria for acute cardiology involvement, ScotSTAR transfer and intensive care. An electronic proforma was designed to guide MDT discussion, medico-legal documentation and audit purposes. Table 1 describes characteristics of the first nine patients discussed. A particular strength was in diagnostics and consideration of differentials; among patients referred we identified those with haematological malignancy, systemic lupus erythematosus and non-accidental injury. Regular peer-review sessions were held, for reflection on cases and their management in both secondary and tertiary care settings. Clinicians throughout Scotland were encouraged to join via SPARN and SPAIIN networks. Conclusion This multi-specialty MDT has been and continues to be beneficial for management of hyper-inflammatory patients. We will review the process but hope the MDT will prove to continue to be beneficial for future patients. The authors would like to acknowledge all members of the MDT. Disclosure K. McLellan: None. L. Reilly: None. L. Pollock: None. O. Swann: None. C. Anderson: None. N. Martin: None. M. Brennan: None. R. Hague: None. J. Walsh: None.

P167 COVID-19 perniosis, a differential diagnosis to consider in adolescent patients presenting with chilblain-like lesions

Background/AimsChilblain-like lesions (perniosis) have been reported frequently during COVID-19 pandemic in children and adolescents with no history of exposure to cold temperatures or underlying autoimmune conditions. Patients with these skin changes reported mild COVID-19 symptoms or previous contact with confirmed COVID-19 cases before they became symptomatic. In the majority of cases, a causal relationship between SARS-CoV-2 infection and chilblain-like lesion has not been proven.MethodsRetrospective review of patients with chilblain-like lesions, possibly secondary to SARS-CoV-2 infection, presenting to a tertiary Adolescent Rheumatology service between January and August 2021.ResultsWe identified five, male, adolescent patients (mean age, 16 years old) who presented with new onset of chilblain-like lesions affecting fingers, toes and heels in December 2020, which coincided with the peak of second wave of COVID-19 infection. One month prior to skin changes occurrence, 3 out of 5 patients experienced mild respiratory COVID-19-like symptoms and the rest of the patients were asymptomatic but were in contact with COVID-19 positive cases following outbreaks in schools. 1 of 3 symptomatic patients had a positive COVID-19 PCR test prior to skin manifestations. 2 out of 4 patients with heel lesions had deep, full thickness skin loss heel ulcers and 2 of 5 patients had superficially ulcerated lesions on a finger and toes, respectively, resulting in inability to attend school. None of the patients had any other symptoms or signs to suggest an underlying autoimmune connective tissue disorder. Demographics, clinical features and serological data are summarised in Table 1. One patient underwent a biopsy of heel ulcer which was histologically consistent with perniosis. In two patients (40%) chilblain like lesions resolved spontaneously within 2 months. Three patients (60%), with progressive ulcerated lesions, required various combinations of treatments with aspirin, calcium channel blockers (nifedipine), topical or oral steroids and hydroxychloroquine with complete resolution of symptoms within 6 months.ConclusionChilblain-like lesions, including heel involvement associated with mildly symptomatic COVID-19 infection, have been reported before. Our mini-case series raises awareness of ulcerating chilblain like lesions possibly secondary to COVID-19 in adolescent patients, which require early recognition and instigation of treatment leading to better patient’s outcomes. P167 Table 1Demographics, clinical, laboratory findings of patientsCaseAgeLesion locationCOVID-19 symptomsSARS-CoV-2 PCR / SARS-CoV-2 AbAutoimmune profile/ complement levelsTreatment/ skin symptoms resolution (months)116Fingers, toes, heelsNoNA/ NegativeANA positive (1:80) ENA negative anti-dsDNA normal, C3, C4 normalAspirin, prednisolone, nifedipine, hydroxychloroquine /6216fingers heels, toesNoNA/ NegativeANA negativePrednisolone, nifedipine/6318Toes, heelsrespiratoryPositive/NAANA negativeNil/1416Fingers, toesrespiratoryNegative/ NegativeANA positive (1:320) ENA negative anti- dsDNA normal C3, C4 normalNil/2516Fingers, toes, heelsrespiratoryNA/ NegativeANA negativenifedipine/6NA: not available, PCR: polymerase chain reaction, SARS-CoV-2: severe acute respiratory syndrome coronavirus 2Disclosure N. Gak: None. V. Choida: None. M. Leandro: None. D. Sen: None. C. Ciurtin: None. C. Fisher: None.

Working Towards a Treat-to-Target Protocol in Juvenile Proliferative Lupus Nephritis - A Survey of Pediatric Rheumatologists and Nephrologists in Germany and Austria.

BackgroundTo describe treatment practices for juvenile proliferative lupus nephritis (LN) class III and IV of pediatric rheumatologists and nephrologists in Germany and Austria in preparation for a treat-to-target treatment protocol in LN.MethodsSurvey study by members of the Society for Pediatric and Adolescent Rheumatology (GKJR) and the German Society for Pediatric Nephrology (GPN) on diagnostics and (concomitant) therapy of LN.ResultsFifty-eight physicians completed the survey. Overall, there was a considerable heterogeneity regarding the suggested diagnostics and management of juvenile proliferative LN. Increased urinary protein excretion, either assessed by 24 h urine collection or spot urine (protein-creatinine ratio), and reduced estimated glomerular filtration rate were specified as important parameters for indication of kidney biopsy to diagnose proliferative LN and monitoring of therapy. Corticosteroids were generally proposed for induction and maintenance therapy, most often in conjunction with either mycophenolate mofetil (MMF) or cyclophosphamide (CP) as steroid-sparing immunosuppressants. MMF was clearly preferred over CP for induction therapy of LN class III, whereas CP and MMF were equally proposed for LN class IV. MMF was most often recommended for maintenance therapy in conjunction with oral corticosteroids and continued for at least 3 years and 1 year, respectively, after remission. Hydroxychloroquine was widely accepted as a concomitant measure followed by renin-angiotensin system inhibitors in cases of arterial hypertension and/or proteinuria.ConclusionThe majority of pediatric rheumatologists and nephrologists in Germany and Austria propose the use of corticosteroids, most often in combination with either MMF or CP, for treatment of proliferative LN in children. The considerable heterogeneity of responses supports the need for a treat-to-target protocol for juvenile proliferative LN between pediatric rheumatologists and nephrologists.

2019 ACR/EULAR classification criteria and therapy in predicting organ damage accrual in patients with childhood-onset systemic lupus erythematosus: A retrospective study over the last 29 years.

We explored damage occurrence in patients with childhood-onset SLE (cSLE) and aimed to predict the risk of organ damage occurrence in time. The retrospective study included patients treated for cSLE at the Centre of Reference for Pediatric and Adolescent Rheumatology of the Republic Croatia over a 29-year period. The disease development of 97 patients (77 females) with cSLE was examined. The median (Q1, Q3) follow-up time was 6.5 (2.3, 12.0) years. SDI was determined at 5 time points (6, 12, 24, 36 months, and last follow-up). Thirty-eight patients (48%) had organ damage at the last follow-up. Prepubertal group of patients showed higher SLEDAI scores at the disease onset, while post-pubertal group had significantly lower proportion of patients with relapses. We estimated the time from the first symptom to the moment of damage and our findings suggest that it is unlikely that organ damage will occur in 50% of patients in the first 6years since the diagnosis. The number of 2019 ACR/EULAR classification criteria at the time of diagnosis associated with SDI determined after 1year of the follow-up period. The patients who received higher doses of glucocorticoids accumulated damage faster and mycophenolate mofetil was found to be a more frequent therapy in patients with SDI ≥3. Knowing that damage will most likely happen after the first 6years after diagnosis in 50% of patients enables physicians to better predict damage occurrence. High number of 2019 ACR/EULAR criteria and treatment with glucocorticoids in childhood-onset SLE are associated with damage accrual and these findings could enable us to detect patients which should be closely monitored for higher risk of damage development.

Infection with SARS-CoV-2 causes flares in patients with juvenile idiopathic arthritis in remission or inactive disease on medication

BackgroundFlares of juvenile idiopathic arthritis (JIA) have been described in the context of various infections. Flares of rheumatic diseases in adults have been described following infection with SARS-CoV-2 in several cohorts. So far, the effect of infection with SARS-CoV-2 on the course of JIA is unknown.MethodsThe database of the German Center for Pediatric and Adolescent Rheumatology was searched for patients with confirmed infection with SARS-CoV-2 and subsequent disease flare, admitted from July 2020 until June 2021. cJADAS-27, ESR and C-reactive protein, as well as uveitis activity, medication at the time of flare and treatment of flare was extracted. Patient cases were described individually.ResultsOut of 988 patients admitted, five patients with remission off medication (n = 2) or inactive disease on medication (n = 3) were identified, with flare symptoms up to four weeks after infection with SARS-CoV-2.ConclusionsFlares can occur after infection with SARS-CoV-2 in patients with JIA in remission or inactive disease on medication. Treating physicians need to be aware of this fact, especially when counseling patients with rheumatic diseases about the respective dangers of COVID-19 and vaccination against SARS-CoV-2.

Favorable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases

BackgroundDifferences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and juvenile systemic lupus erythematosus (JSLE) against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group.MethodsSera were collected from JIA (n = 118), JDM (n = 49), and JSLE (n = 30) patients and from healthy control (n = 54) children and adolescents prior to the coronavirus disease 19 (COVID-19) pandemic. We used sensitive flow-cytometry-based assays to determine titers of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and we compared them with respective titers in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C).FindingsDespite immune dysfunction and immunosuppressive treatment, JIA, JDM, and JSLE patients maintained comparable or stronger humoral responses than healthier peers, which was dominated by immunoglobulin G (IgG) antibodies to HCoV-OC43 spike, and harbored IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM, and JSLE patients, which argues against increased exposure.ConclusionsConsequently, autoimmune rheumatic diseases and their treatment were associated with a favorable ratio of spike to nucleoprotein antibodies.FundingThis work was supported by a Centre of Excellence Centre for Adolescent Rheumatology Versus Arthritis grant, 21593, UKRI funding reference MR/R013926/1, the Great Ormond Street Children’s Charity, Cure JM Foundation, Myositis UK, Lupus UK, and the NIHR Biomedical Research Centres at GOSH and UCLH. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust.

POS1321 MENTAL HEALTH SCREENING IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS

Background:Mental disorders often begin in the vulnerable phase of adolescence and young adulthood. Young people with chronic diseases are particularly at risk. Early recognition of mental health problems is necessary in order to be able to support those affected in a timely and adequate manner. By implementing a web-based generic screening tool for mental health in routine care, patients with juvenile idiopathic arthritis (JIA) and mental health conditions can be identified and provided with targeted treatment.Objectives:To investigate the prevalence of mental health conditions in young people with JIA in routine rheumatology care.Methods:Mental health screening is implemented as an add-on module to the National Paediatric Rheumatology Database (NPRD). The current data was gathered over a period of 24 months. Patients complete the screening tool which includes the Patient Health Questionnaire1 (PHQ-9, score 0-27) and the Generalized Anxiety Disorder scale2 (GAD-7, score 0-21) via a web-based questionnaire. The cut-off for critical values in PHQ-9 and GAD-7 were defined as values ≥ 10. Simultaneously, other data, such as sociodemographic data, disease activity (cJADAS10, score 0-30), functional status (CHAQ, score 0-3) were collected as well.Results:The analysis included 245 patients (75% female) with a mean age of 15.7 years and a mean disease duration of 8.8 years. 38.8% of the patients had oligoarthritis (18.0% OA, persistent/20.8% OA, extended) and 23.3% RF negative polyarthritis. At the time of documentation 49 patients (30.6%) had an inactive disease (cJADAS10 ≤ 1) and 120 (49.4%) no functional limitations (CHAQ = 0). In total, 53 patients (21.6%) had screening values in either GAD-7 or PHD-9 ≥10. Patients with critical mental health screening values showed higher disease activity and more frequent functional limitations than inconspicuous patients (cJADAS10 (mean ± SD): 9.3 ± 6 vs. 4.9 ± 4.9; CHAQ: 0.66 ± 0.6 vs. 0.21 ± 0.42). When compared to males, females were significantly more likely to report either depression or anxiety symptoms (11.7% vs. 24.9%, p = 0.031).17.6% of all patients with valid items for these data reported to receive psychological support, meaning psychotherapeutic support (14.5%) and/or drug therapy (8.6%). Among those with a critical mental health screening score, 38.7% received psychological support (psychotherapeutic support (35.5%) and/or drug therapy (16.1%)).Conclusion:Every fifth young person with JIA reported mental health problems, however, not even every second of them stated to receive psychological support. The results show that screening for mental health problems during routine adolescent rheumatology care is necessary to provide appropriate and targeted support services to young people with a high burden of illness.

O14 Frequency and site of clinically unsuspected synovitis on whole-body MRI in juvenile idiopathic arthritis

Abstract Background/Aims Magnetic resonance imaging can facilitate the diagnosis of JIA, but is also increasingly used for monitoring disease activity in individual joints. This prospective study aims to measure the frequency of subclinical synovitis on whole-body MRI, in adolescent patients with JIA. Methods JIA patients were recruited from a tertiary adolescent and young adult rheumatology clinic, between September 2019 and August 2020. All patients were examined by a senior rheumatology registrar, before undergoing a contrast enhanced whole-body MRI scan. Patients were assigned to a clinically active or inactive group, depending on their active joint count (AJC); active patients had AJC≥ 1, while the clinically inactive patients had an AJC =0. The post-contrast, water-only mDixon images were assessed for synovitis by one radiologist, blinded to clinical information. Only joints that were definitely abnormal were counted as synovitic. Eighty-one joints per patient were examined with both methods. The presence of subclinical synovitis in a patient was defined as synovitis in one or more joints on MRI, which were not active clinically. Results Thirty-two patients aged 15 to 24 were included in the analysis. The patient characteristics and the frequency of subclinical synovitis are summarised in the table. Subclinical synovitis was detected in a similar proportion of JIA patients in both active and inactive groups (46.7% vs. 41.2%, P = 0.76). The most frequent region with subclinical synovitis was the hindfoot, detected in 22% (7/32) of JIA patients and 17.2% (11/64) of hindfoot joints assessed by MRI. The second most common joint with clinically unsuspected inflammation was the knee, found in 19% (6/32) of JIA patients and 14% (9/64) knee joints. Similarly, 16% (5/32) of the adolescent patients had active disease in the hip, ankle or midfoot joints. The frequency of elbow involvement was also considerable, with 12% (7/58) of joints with subclinical synovitis in 14% (4/29) of JIA patients. Conclusion In conclusion, 43.8% of JIA patients had subclinical synovitis on whole-body MRI scan with no significant difference between the clinically active vs. inactive JIA patients. Large joints were predominantly affected. Further research is required to validate our findings in a larger cohort of JIA patients. Disclosure V. Choida: None. C. Ciurtin: None. T.J.P. Bray: None. D. Sen: None. C. Fisher: None. M. Leandro: None. M.A. Hall-Craggs: None.

It’s Not Lupus! An Incidental Finding of Anomalous Right Coronary Artery Arising from the Pulmonary Artery in an Adolescent Rheumatology Patient

It’s Not Lupus! An Incidental Finding of Anomalous Right Coronary Artery Arising from the Pulmonary Artery in an Adolescent Rheumatology Patient

Long COVID in the skin: a registry analysis of COVID-19 dermatological duration

Long COVID in the skin: a registry analysis of COVID-19 dermatological duration

Young Minds: Mental Health and Transitional Care in Adolescent and Young Adult Rheumatology.

Consideration of the mental health and emotional wellbeing is an important component of health care for all young people, irrespective of setting. Mental health disorders are common during adolescence and young adulthood and young people with rheumatic musculoskeletal diseases (RMD) are not exempt. For such young people, risks of poor outcomes are related to both mental health as well as their RMD. Times of change during adolescence and young adulthood—transitions—are potentially vulnerable life stages for young people with RMD and warrant specific attention in health care provision. Such transitions include those occurring at puberty, during education, training, and employment, socially with moves away from the parental home, as well as from child to adult-centered health services. There is great potential for rheumatology professionals to support young people with RMD at these transitions in view of their frequent encounters and ongoing therapeutic relationships. In this review, we aim to assess the impact of mental health on RMD during adolescence and young adulthood with particular reference to transitional care provision and how rheumatology professionals can be involved in addressing mental health issues during this time of change.

Results of the systematic literature search as basis for the "Evidence-based treatment recommendations for familial Mediterranean fever patients with insufficient response or intolerability to colchicine" of the Society for Pediatric and Adolescent Rheumatology and the German Society for Rheumatology

HintergrundDas familiäre Mittelmeerfieber (FMF) ist eine in Deutschland eher seltene genetisch bedingte Erkrankung des Kindes- und Erwachsenenalters, die durch rezidivierende Fieberschübe sowie Peritonitis, Pleuritis und Arthritis charakterisiert ist. Die etablierte Therapie mit Kolchizin ist für die meisten Patienten wirksam und verträglich. Einige Patienten sprechen aber auf diese Therapie nicht ausreichend an bzw. vertragen diese nicht. Für diese Patienten kommen Biologika in Betracht. Die Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) und die Deutsche Gesellschaft für Rheumatologie (DGRh) sind übereingekommen, gemeinsame Empfehlungen für diese spezielle klinische Situation zu entwickeln.ZielDurchführung einer systematischen Literaturrecherche (SLR) auf Basis der 2016 publizierten EULAR(European League Against Rheumatism)-Empfehlungen als Grundlage für die Entwicklung von evidenzbasierten Therapieempfehlungen für FMF-Patienten mit unzureichendem Ansprechen bzw. Unverträglichkeit auf Kolchizin.MethodenDie SLR wurde mit Referenzen aus verschiedenen Datenbanken und als Aktualisierung der bis zum Jahr 2014 durchgeführten SLR der EULAR durchgeführt, wobei die Artikel zwischen dem 01.01.2015 und dem 31.12.2017 publiziert worden sein mussten. Für die Vorselektion wurde das werkzeug Rayyan und für die Erstellung der Evidenztabellen die Klassifikation des Oxford Centre for Evidence Based Medicine 2009 benutzt.ErgebnisseDie Suche ergab 360, nach Dublettenabgleich noch 263 Treffer. Insgesamt 88 Publikationen wurden ein- (34%) und 102 ausgeschlossen (39%), bei weiteren 73 war eine Sichtung der Vollpublikation notwendig (28%), und 43 wurden intensiver diskutiert. Schlussendlich blieben 64 Publikationen (24%) übrig. Insgesamt wurden 4 Fall-Kontroll-Studien, 31 Kohortenstudien, 8 Fallserien, 7 kontrollierte Studien (davon 5 s), 10 Übersichtsarbeiten sowie 4 Metaanalysen und systematische Reviews akzeptiert.DiskussionDie SLR wurde wissenschaftlich exakt, transparent und nach internationalen Standards durchgeführt. Die SLR erwies sich als gute Grundlage für die Konsentierung der 5 übergeordneten Prinzipien und der 10 Empfehlungen, sodass die gemeinsame Aktivität von GKJR und DGRh erfolgreich und sogar zeitnah abgeschlossen werden konnte. Die Empfehlungen sind eine solide Basis, Patienten jeden Alters mit FMF gut zu behandeln. Dabei spielen die Erklärungen zum Problem der Kolchizinresistenz eine wichtige Rolle.Zusatzmaterial onlineDie Online-Version dieses Beitrags (10.1007/s00393-020-00886-0) enthält die Evidenztabellen, Tabellen zum Verzerrungsrisiko (RoB) sowie die Übersicht der Suchstrategien. Folgende Inhalte finden Sie online: Tab. 2a: Evidenztabelle für alle zitierten Fall-Kontroll-Studien, Studiencharakteristika; Tab. 2b: Evidenztabelle für alle zitierten Kohortenstudien, Studiencharakteristika; Tab. 2c: Evidenztabelle für alle zitierten Fallserien, Studiencharakteristika; Tab. 2d: Evidenztabelle für sämtliche zitierte kontrollierte Studien (inklusive s), Studiencharakteristika; Tab. 2e: Evidenztabelle für alle zitierten Übersichtsarbeiten, Studiencharakteristika; Tab. 2f: Evidenztabelle für alle zitierten Metaanalysen und systematischen Reviews, Studiencharakteristika; Tab. 3a: Verzerrungsrisiko für sämtliche zitierte Kohortenstudien nach der Newcastle-Ottawa-Skala (Risiko für Bias); Tab. 3b: Verzerrungsrisiko für sämtliche zitierte Fall-Kontroll-Studien nach der Newcastle-Ottawa-Skala (Risiko für Bias); Suchstrategien (Supplement). Beitrag und Zusatzmaterial stehen Ihnen auf www.springermedizin.de zur Verfügung. Bitte geben Sie dort den Beitragstitel in die Suche ein, das Zusatzmaterial finden Sie beim Beitrag unter „Ergänzende Inhalte“.

Disease-associated and patient-specific immune cell signatures in juvenile-onset systemic lupus erythematosus: patient stratification using a machine-learning approach.

SummaryBackgroundJuvenile-onset systemic lupus erythematosus (SLE) is a rare autoimmune rheumatic disease characterised by more severe disease manifestations, earlier damage accrual, and higher mortality than in adult-onset SLE. We aimed to use machine-learning approaches to characterise the immune cell profile of patients with juvenile-onset SLE and investigate links with the disease trajectory over time.MethodsThis study included patients who attended the University College London Hospital (London, UK) adolescent rheumatology service, had juvenile-onset SLE according to the 1997 American College of Rheumatology revised classification criteria for lupus or the 2012 Systemic Lupus International Collaborating Clinics criteria, and were diagnosed before 18 years of age. Blood donated by healthy age-matched and sex-matched volunteers who were taking part in educational events in the Centre for Adolescent Rheumatology Versus Arthritis at University College London (London, UK) was used as a control. Immunophenotyping profiles (28 immune cell subsets) of peripheral blood mononuclear cells from patients with juvenile-onset SLE and healthy controls were determined by flow cytometry. We used balanced random forest (BRF) and sparse partial least squares-discriminant analysis (sPLS-DA) to assess classification and parameter selection, and validation was by ten-fold cross-validation. We used logistic regression to test the association between immune phenotypes and k-means clustering to determine patient stratification. Retrospective longitudinal clinical data, including disease activity and medication, were related to the immunological features identified.FindingsBetween Sept 5, 2012, and March 7, 2018, peripheral blood was collected from 67 patients with juvenile-onset SLE and 39 healthy controls. The median age was 19 years (IQR 13–25) for patients with juvenile-onset SLE and 18 years (16–25) for healthy controls. The BRF model discriminated patients with juvenile-onset SLE from healthy controls with 90·9% prediction accuracy. The top-ranked immunological features from the BRF model were confirmed using sPLS-DA and logistic regression, and included total CD4, total CD8, CD8 effector memory, and CD8 naive T cells, Bm1, and unswitched memory B cells, total CD14 monocytes, and invariant natural killer T cells. Using these markers patients were clustered into four distinct groups. Notably, CD8 T-cell subsets were important in driving patient stratification, whereas B-cell markers were similarly expressed across the cohort of patients with juvenile-onset SLE. Patients with juvenile-onset SLE and elevated CD8 effector memory T-cell frequencies had more persistently active disease over time, as assessed by the SLE disease activity index 2000, and this was associated with increased treatment with mycophenolate mofetil and an increased prevalence of lupus nephritis. Finally, network analysis confirmed the strong association between immune phenotype and differential clinical features.InterpretationMachine-learning models can define potential disease-associated and patient-specific immune characteristics in rare disease patient populations. Immunological association studies are warranted to develop data-driven personalised medicine approaches for treatment of patients with juvenile-onset SLE.FundingLupus UK, The Rosetrees Trust, Versus Arthritis, and UK National Institute for Health Research University College London Hospital Biomedical Research Centre.

Temporomandibular joint involvement in patients with juvenile idiopathic arthritis: a retrospective chart review

Objective To study the proportion of patients with temporomandibular joint (TMJ) involvement among patients with juvenile idiopathic arthritis (JIA), as well as associated clinical characteristics and signs/symptoms. Method We performed a retrospective chart review on consecutive patients followed in the Hamburg Centre for Paediatric and Adolescent Rheumatology Eilbek between January 2010 and July 2012. TMJ involvement was diagnosed based on clinical examination; a subgroup of patients was also assessed by magnetic resonance imaging (MRI). Results The study included 2413 patients with JIA (52.1% girls, mean age at JIA onset 9.5 years). The most frequent JIA category was oligoarthritis (46.6%), followed by enthesitis-related arthritis (ERA; 38.1%). TMJ involvement was diagnosed in 843/2413 patients (34.9%) (677 MRI-confirmed, four not MRI-confirmed, no MRI examination in 162). Female gender (p = 0.017), higher number of additional joints with active arthritis (p < 0.001), anti-nuclear antibody (ANA) positivity (p = 0.005), higher age (p = 0.020), and oligoarthritis (persistent and extended; p = 0.043) were significantly associated with TMJ involvement. Human leucocyte antigen-B27-positive patients were less likely to have TMJ involvement (p = 0.023). Pain on palpation and pain while chewing were statistically significantly associated with TMJ involvement (p = 0.008 and p = 0.020, respectively). Conclusions Based on our findings, to identify TMJ involvement special attention should be paid to JIA patients with female gender, ANA positivity, and oligoarthritis, as well as those with a higher number of additional joints with active arthritis; and regular examinations of the TMJ should be performed.

Frequency of biologic switching and the outcomes of switching in children and young people with juvenile idiopathic arthritis: a national cohort study.

SummaryBackgroundInformation is scarce about biological disease-modifying antirheumatic drug (DMARD) switching patterns in children and young people (aged ≤16 years) with juvenile idiopathic arthritis in an era of many biologic therapies. The best choice of biologic to use if the first biological DMARD is not beneficial also remains unclear. We aimed to quantify and characterise biologic switching patterns in children and young people with juvenile idiopathic arthritis, and to compare the effectiveness of using a second tumour necrosis factor inhibitor (TNFi) versus non-TNF is following failure of a first TNFi biologic in routine clinical practice.MethodsOur study population comprised patients with juvenile idiopathic arthritis who were enrolled in two parallel UK cohort studies (the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study [BSPAR-ETN] and the Biologics for Children with Rheumatic Diseases [BCRD] study) between Jan 1, 2004, and April 11, 2019. Data on disease characteristics and DMARD therapy were collected at the time of initiation of a first biologic, at 6 months, at 1 year, and annually thereafter. Biologic switching patterns were described in all patients who started their first biologic from Jan 1, 2010, onwards. Among patients who started treatment with their first biologic from Jan 1, 2004, onwards, had polyarticular course juvenile idiopathic arthritis (extended oligoarthritis or polyarthritis [positive or negative for rheumatoid factor]), and who had started a second biologic, we assessed changes in outcome variables at 6 months compared with baseline and compared the proportion of patients who achieved an American College of Rheumatology Pediatric (ACR Pedi) 90 response and minimal disease activity at 6 months on the basis of the class of the second biologic (a second TNFi vs non-TNFi biologic). Changes in outcome variables at 6 months were compared using linear regression or logistic regression, adjusted for propensity quintiles to account for confounding by indication. We used multiple imputation to account for missing data.FindingsBetween Jan 1, 2004, and April 11, 2019, 2361 patients were enrolled on initiation of biologic therapy. From Jan 1, 2010, onwards, 1152 patients started their first biologic, most of whom started treatment with TNFis (1050 [91%]). The median follow-up was 2·2 years (IQR 1·1–3·8). During this time, 270 (23%) of 1152 patients started a second biologic, 61 (5%) started a third biologic, and 11 (1%) started a fourth biologic. Among 240 patients with polyarticular-course juvenile idiopathic arthritis, 194 (81%) started a second TNFi and 46 (19%) started a non-TNFi after an initial TNFi had failed. Choice of second treatment (second TNFi vs non-TNFi biologic) did not affect the proportion of patients who achieved an ACR Pedi 90 response (adjusted odds ratio [OR] 2·5, 95% CI 0·8–7·9; p=0·11) or minimal disease activity (adjusted OR 1·6, 95% CI 0·6–3·8; p=0·33).InterpretationFor many children and young people with juvenile idiopathic arthritis, treatment with a first or second biologic is not beneficial. We found no evidence that switching to a second non-TNFi biologic was more beneficial than a second TNFi.FundingVersus Arthritis and The British Society for Rheumatology.

Laying the groundwork: Building relationships for public and patient involvement in pre-clinical paediatric research.

ContextPublic and patient involvement is increasingly becoming an expectation of research funders and policy makers. Not all areas of health research are public‐facing. Here, we outline an approach for building the skills and developing the relationships required for downstream public and patient involvement in pre‐clinical adolescent rheumatology research.ObjectiveTo design a methodology for improving researcher‐adolescent communications specifically aimed at mutual relationship building for PPI. Deliberate and effective preparation in advance of research involvement to improve the downstream success of that involvement.DesignA research seminar and research skills workshop conducted entirely in ‘plain English’ for adolescents and their siblings aged 10‐20. Upskilling of pre‐clinical researchers for effective public involvement.Setting and participantsStudy co‐design between the voluntary charity Irish Children's Arthritis Network and the academic research centre UCD Centre for Arthritis Research. Fifteen adolescents aged 10‐20 years old living with arthritis, four pre‐clinical researchers and one qualitative researcher investigating adolescent or paediatric arthritis.Main variables studiedRelationship building and communications for effective downstream public involvement in pre‐clinical and laboratory research.ResultsThe methodology outlined here was received extremely positively. Both researchers and adolescents living with arthritis felt more comfortable communicating, more knowledgeable about juvenile arthritis and research, and more able to engage in co‐operative dialogue.DiscussionEngaging early, considering the needs of the community and developing appropriate involvement methodology can enable involvement in pre‐clinical research.ConclusionsDedicating resources to building relationships and skills necessary for co‐operative research involvement can overcome some of the barriers to public involvement in pre‐clinical and laboratory‐based research.

P01 Incidence of juvenile idiopathic arthritis in the United Kingdom: estimates from a national primary care dataset

Poster presentation Tuesday 8 October Background Juvenile idiopathic arthritis (JIA) is the most common childhood onset inflammatory arthritis. The last estimates of incidence of JIA in the UK are from nearly 30 years ago, prior to international classification consensus and the emergence of paediatric and adolescent rheumatology as a specialty. The aim of this study was to estimate incidence of JIA from primary care records in the UK since 2000. Methods The study used data from the Clinical Practice Research Datalink (CPRD), a database of UK primary care records broadly representative of the UK in terms of age, gender and ethnicity. A pre-defined list of JIA Read codes were used to identify incident cases annually from 2000-2018. Incidence rates (IR) with 95% confidence intervals(CI) were calculated and stratified by age and gender. The denominator was the population of CPRD &lt;16 years old on the 31st December each year. Direct standardisation, applying Office for National Statistics population data, was used to estimate the UK IR. IRs in 5-year groupings were calculated 2000-2015 to identify change over time. Results Between 2000-2018, there were 1927 incident cases of JIA, from a total of 23,328,676 children &lt;16 years old in CPRD. The total IR (95% CI) was 8.26 (7.90-8.64) per 100,000 population; for females and males respectively it was 9.83 (9.27-10.43) and 6.78 (6.33-7.27) per 100,000. Age-adjusted direct standardisation to the UK population estimated a total IR of 9.66 per 100,000 person-years. By age group, there appeared to be a lower incidence in middle childhood compared to early childhood and adolescents, as well as infancy where lower rates may be due to difficulties recognising the disease (Table 1). IRs over time did not appear to change. P01 Table 1: Incidence rates by age group Age (years) Denominator Cases IR (95% CI) Per 100,000 0-2 1739417 113 6.5 (5.40-7.81) &gt;2-6 5763003 534 9.27 (8.51 – 10.08) &gt;6-12 9464988 693 7.32 (6.80-7.90) &gt;12-15 6361268 587 9.22 (8.51-10.01) Conclusion This is the first study to provide contemporary UK estimates of the incidence of JIA for nearly 30 years. JIA was more common in females compared to males, and in early childhood and adolescence compared to other age groups. Incidence appeared to be stable over fifteen years. These data provide important information for patients, their families and healthcare providers; in addition, they are vital for appropriate resource planning and service provision in paediatric and adolescent rheumatology. Conflicts of Interest The authors declare no conflicts of interest.