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The aim of this work was to assess the impact of prolonged low immunoglobulin (IgG or IgM) serum concentrations on the potential cumulative serious infection (SI) risk in pediatric patients following rituximab treatment for granulomatosis with polyangiitis or microscopic polyangiitis (GPA/MPA) in PePRS.Patients aged ≥ 2 to 18 years received four weekly intravenous rituximab infusions of 375 mg/mA total of 25 patients were included, of whom 19 (76%) had GPA and six (24%) had MPA; 18 (72%) had newly diagnosed disease and seven (28%) had relapsing disease. All 25 patients completed the rituximab induction regimen; 24 completed ≥ 18 months of follow-up. At month 18, eighteen patients (72%) had prolonged low IgG; 19 (76%), prolonged low IgM; and 15 (60%), both. Seven patients (28%) had nine SIs; one occurred during or after prolonged low IgG only, two during or after prolonged low IgM only, and six during or after concurrent prolonged low IgG and IgM. No patients died or discontinued the study due to SI. All patients had complete and sustained peripheral B-cell depletion for ≥ 6 months.The majority of pediatric patients who received rituximab for GPA/MPA with prolonged low immunoglobulin levels did not experience SIs. In patients with SIs, these events were manageable, and the number of SIs did not increase over time or with multiple rituximab treatments. These observations are consistent with the rituximab safety profile in adults with GPA/MPA.ClinicalTrials.gov identifier, NCT01750697.

The COVID-19 pandemic has led to a rapid increase in the use of telemedicine. This is likely to continue when the social distancing restrictions have been eased. There have been a number of technological advances that have contributed to the roll-out and improved quality of telemedicine consultations. Telemedicine has a number of benefits including facilitating home working for clinicians, reduce travel time for families and allows multidisciplinary team working across different sites. In addition to these clinical benefits there are also the environmental benefits of reduced travel to and from the hospital setting. There are limitations to this change in practice including the need for repeat appointments if a telemedicine facilitated contact is not adequate and the perpetuation of inequality for vulnerable families, the so called "digital divide". Due to the increase in the use of telemedicine it is important that clinicians develop effective consultation practices including appropriate selection of patients, technical setup and consultation tools. In order to ensure trainees are developing appropriate skills in telemedicine, educational opportunities should be developed including structured assessment tools to allow the demonstration of competence in this area.

Background/Aims The Childhood Health Assessment Questionnaire (CHAQ) and 0-10cm visual analogue scale (VAS) for self-reporting global-wellbeing form part of the Core Outcome Variables measuring disease activity in juvenile idiopathic arthritis. However, reported barriers to using paper-based CHAQs include: impacts on consultation time and issues with scoring and transcribing CHAQ data into health records. To address these issues we aimed to develop a digital CHAQ (eCHAQ) for patients attending paediatric rheumatology clinics at Alder Hey Children’s Hospital. Additional objectives included: developing automated invitations to complete eCHAQs; achieving automated scoring and integration of CHAQ data into the hospital’s Electronic Health Record (EHR); investigating the acceptability of the eCHAQ to patients and clinical staff; and studying the effects of the system on CHAQ completion rates. Methods The eCHAQ was developed collaboratively by the Alder Hey Information Technology team, clinicians, and a technology provider, Aire Logic. Acceptability was measured using a patient survey (patient and parent ePROM questionnaire), and a survey (Technology Acceptance Model 2 questionnaire) and focus group involving clinical staff. CHAQ completion rates were measured using a before- after study of data from clinical records. Results The eCHAQ was implemented in April 2021 and approximately 500 eCHAQ invitations are sent monthly. Technical features include automated generation of SMS invitations to complete eCHAQs; automated scoring of CHAQ assessments; and unique URLs (webpage addresses) enabling automated re-integration of CHAQ data into the EHR. Patients/care-givers (n = 24) scored the eCHAQ highly across Likert scale items designed to assess accessibility (median response = 5 [strong agreement]; interquartile range [IQR] = 0); and acceptability (median response = 5 [strong agreement]; IQR = 0). Clinical staff (n = 7; consultants, nurse specialists and occupational therapists) also scored the eCHAQ highly across domains tested using Likert scale items including “Perceived Usefulness” (median response = 7 [strong agreement]; IQR = 0.25) and “Output Quality” (median response = 7 [strong agreement]; IQR = 1). Thematic analysis of a focus group discussion involving 10 members of the Rheumatology MDT identified that strengths of the eCHAQ system included improved access to clinical data, improved data quality and time saved. Concerns relating to access to digital technologies were highlighted. Use of the eCHAQ resulted in a significant increase in the CHAQ completion rate. Before the implementation of the eCHAQ, documentation of a CHAQ score in the EHR occurred in 33/100 (33%) assessed records compared to 47/65 (72%) after the introduction of the eCHAQ system (chi-square = 11.51; p < 0.05). Conclusion Development of a highly-automated digital CHAQ, with integration directly into an NHS EHR, was technically feasible. Introduction of the eCHAQ was found to be highly acceptable to patients and clinical staff and was associated with a significant improvement in CHAQ completion rates. Disclosure M. Neame: None. D. Reilly: None. D. Bond: Other; Employee of private technology provider involved in the development of the reported intervention. A. Puthiyaveetil: None. L. McCann: None. K. Mahmood: None. B. Almeida: None. C.E. Pain: None. V. Furfie: None. G. Cleary: None.

Background Culture-negative infective endocarditis (IE) constitutes approximately 10% of all cases of IE. Bartonella endocarditis is a common cause of culture-negative endocarditis and is associated with a high mortality rate. To date, no cases of Bartonella IE has been reported in association with cryoglobulinemia in the UK. We present a unique case of Bartonella IE causing secondary cryoglobulinemia in a young female. Case presentation A 17-year-old female with a background of pulmonary atresia and ventricular septal defect repaired with a cardiac conduit at the age of 4, presented with a one-year history of weight loss (from 53 to 39 kg) and poor appetite. She subsequently developed a vasculitic rash and haematoproteinuria with decline in renal function, requiring urgent hospital admission. Initial blood tests showed a near normal creatinine, but a raised cystatin C. Renal biopsy showed focal necrotizing glomerulonephritis with no acute tubular necrosis or chronic change. Subsequent blood tests supported a diagnosis of cryoglobulinaemic vasculitis (high rheumatoid factor, low complement, polyclonal gammopathy, Type 3 cryoglobulin). A weak positive PR3 meant there was some uncertainty about whether this could be a primary ANCA-associated vasculitis (AAV). Initial workup for an infectious cause, including multiple blood cultures, were negative. However, an echocardiogram showed definite vegetations on her surgical conduit. The patient did not respond to empirical antimicrobials and so was referred for surgical revision of her conduit. Tissue samples obtained intra-operatively demonstrated Bartonella species. With targeted antimicrobials post-operatively, she improved with resolution of immunologic abnormalities and at last review had a normal renal profile. On reviewing her social history, she had adopted several stray cats in the preceding year; and thus, the cause of the Bartonella infection was identified. Conclusion This is the first reported case of Bartonella endocarditis causing secondary cryoglobulinemia reported in the UK. The key learning points from this case include that Bartonella endocarditis can present as a cryoglobulinaemic vasculitis and should be considered in any differential when the cause of cryoglobulinaemia is not clear and to enquire about relevant exposures especially when culture-negative endocarditis is suspected.

Objectives Data collected during routine clinic visits are key to driving successful quality improvement in clinical services and enabling integration of research into routine care. The purpose of this study was to develop a standardized core dataset for juvenile idiopathic arthritis (JIA) (termed CAPTURE-JIA), enabling routine clinical collection of research-quality patient data useful to all relevant stakeholder groups (clinicians, service-providers, researchers, health service planners and patients/families) and including outcomes of relevance to patients/families. Methods Collaborative consensus-based approaches (including Delphi and World Café methodologies) were employed. The study was divided into discrete phases, including collaborative working with other groups developing relevant core datasets and a two-stage Delphi process, with the aim of rationalizing the initially long data item list to a clinically feasible size. Results The initial stage of the process identified collection of 297 discrete data items by one or more of fifteen NHS paediatric rheumatology centres. Following the two-stage Delphi process, culminating in a consensus workshop (May 2015), the final approved CAPTURE-JIA dataset consists of 62 discrete and defined clinical data items including novel JIA-specific patient-reported outcome and experience measures. Conclusions CAPTURE-JIA is the first ‘JIA core dataset’ to include data items considered essential by key stakeholder groups engaged with leading and improving the clinical care of children and young people with JIA. Collecting essential patient information in a standard way is a major step towards improving the quality and consistency of clinical services, facilitating collaborative and effective working, benchmarking clinical services against quality indicators and aligning treatment strategies and clinical research opportunities.

Objective To assess safety, tolerability, pharmacokinetics, and efficacy of rituximab in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Methods PePRS (Pediatric Polyangiitis Rituximab Study) was a Phase IIa, international, open-label, single-arm study. During the initial 6-month remission induction phase, patients received 4 weekly intravenous rituximab infusions (MabThera/Rituxan® ), 375 mg/m2 body surface area (BSA), and glucocorticoids. During the follow-up period, patients could receive further treatment, including rituximab, for GPA/MPA. Safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy outcomes were evaluated. Results Eleven centers enrolled 25 new-onset or relapsing patients (GPA, 19 [76%]; MPA, 6 [24%]). The median (range) age was 14 (6-17) years. All patients completed the remission induction phase. During the overall study period (≤ 4.5 years), patients received between 4 and 28 infusions of rituximab. All patients experienced ≥ 1 adverse event, mostly Grade 1/2 and primarily infusion-related reactions; 7 patients had 10 serious adverse events and 17 had 31 infection AEs. No deaths were reported. Rituximab clearance correlated with BSA; the BSA-adjusted rituximab dosing regimen resulted in similar exposure in pediatric and adult patients with GPA/MPA. Remission, based on the Pediatric Vasculitis Activity Score, was achieved by 56%, 92%, and 100% of patients by Months 6, 12, and 18, respectively. Conclusion In pediatric patients, rituximab was well tolerated and effective with an overall safety profile comparable with that of rituximab-treated adult patients with GPA or MPA. Rituximab was associated with a positive benefit-risk profile for use in pediatric patients with active GPA or MPA.

Summary Background Juvenile idiopathic arthritis (JIA) is a heterogeneous disease, the signs and symptoms of which can be summarised with use of composite disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score (cJADAS). However, clusters of children and young people might experience different global patterns in their signs and symptoms of disease, which might run in parallel or diverge over time. We aimed to identify such clusters in the 3 years after a diagnosis of JIA. The identification of these clusters would allow for a greater understanding of disease progression in JIA, including how physician-reported and patient-reported outcomes relate to each other over the JIA disease course. Methods In this multicentre prospective longitudinal study, we included children and young people recruited before Jan 1, 2015, to the Childhood Arthritis Prospective Study (CAPS), a UK multicentre inception cohort. Participants without a cJADAS score were excluded. To assess groups of children and young people with similar disease patterns in active joint count, physician's global assessment, and patient or parental global evaluation, we used latent profile analysis at initial presentation to paediatric rheumatology and multivariate group-based trajectory models for the following 3 years. Optimal models were selected on the basis of a combination of model fit, clinical plausibility, and model parsimony. Finding Between Jan 1, 2001, and Dec 31, 2014, 1423 children and young people with JIA were recruited to CAPS, 239 of whom were excluded, resulting in a final study population of 1184 children and young people. We identified five clusters at baseline and six trajectory groups using longitudinal follow-up data. Disease course was not well predicted from clusters at baseline; however, in both cross-sectional and longitudinal analyses, substantial proportions of children and young people had high patient or parent global scores despite low or improving joint counts and physician global scores. Participants in these groups were older, and a higher proportion of them had enthesitis-related JIA and lower socioeconomic status, compared with those in other groups. Interpretation Almost one in four children and young people with JIA in our study reported persistent, high patient or parent global scores despite having low or improving active joint counts and physician's global scores. Distinct patient subgroups defined by disease manifestation or trajectories of progression could help to better personalise health-care services and treatment plans for individuals with JIA. Funding Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and National Institute for Health Research.

Funder: Lauren Currie Twilight Foundation, Funder: Great Ormond Street Hospital Charity; Id: http://dx.doi.org/10.13039/501100001279, Funder: Vasculitis UK; Id: http://dx.doi.org/10.13039/100010876, Objective: Cyclophosphamide (CYC) is used in clinical practice off‐label for the induction of remission in childhood polyarteritis nodosa (PAN). Mycophenolate mofetil (MMF) might offer a less toxic alternative. This study was undertaken to explore the relative effectiveness of CYC and MMF treatment in a randomized controlled trial (RCT). Methods: This was an international, open‐label, Bayesian RCT to investigate the relative effectiveness of CYC and MMF for remission induction in childhood PAN. Eleven patients with newly diagnosed childhood PAN were randomized (1:1) to receive MMF or intravenous CYC; all patients received the same glucocorticoid regimen. The primary end point was remission within 6 months while compliant with glucocorticoid taper. Bayesian distributions for remission rates were established a priori for MMF and CYC by experienced clinicians and updated to posterior distributions on trial completion. Results: Baseline disease activity and features were similar between the 2 treatment groups. The primary end point was met in 4 of 6 patients (67%) in the MMF group and 4 of 5 patients (80%) in the CYC group. Time to remission was shorter in the MMF group compared to the CYC group (median 7.1 weeks versus 17.6 weeks). No relapses occurred in either group within 18 months. Two serious infections were found to be likely linked to MMF treatment. Physical and psychosocial quality‐of‐life scores were superior in the MMF group compared to the CYC group at 6 months and 18 months. Combining the prior expert opinion with results from the present study provided posterior estimates of remission of 71% for MMF (90% credibility interval [90% CrI] 51, 83) and 75% for CYC (90% CrI 57, 86). Conclusion: The present results, taken together with prior opinion, indicate that rates of remission induction in childhood PAN are similar with MMF treatment and CYC treatment, and MMF treatment might be associated with better health‐related quality of life than CYC treatment.

The COVID-19 emergency has been a challenging but innovative time for the National Health Service (NHS) and paediatrics. Enhancing patient care through use of digital technology was already recognised in the NHS long-term plan.1 Remote consultations, working and learning have rapidly accelerated and become established ways of working during the COVID-19 emergency. This rapid deployment must be used to help inform new models of care and training in paediatrics as outlined in a recent the Royal College of Paediatrics and Child Health (RCPCH) project 2040 report.2 Here we consider some of the new remote working and learning opportunities available to trainees, how they can be used and we propose formal integration into future …

Background Measuring the outcomes that matter to children and young people (CYP) with juvenile idiopathic arthritis (JIA), is a necessary precursor to patient-centred improvements in quality of clinical care. We present a two-centre validation of novel JIA patient-reported outcome and experience measures (PROM and PREM) developed as part of the CAPTURE-JIA project. Methods CYP with JIA were recruited from paediatric rheumatology clinics, completing the CAPTURE-JIA PROM and PREM, CHAQ and CHU 9D. A subset participated in face-to-face interviews and completed the PROM/PREM 1 week later. The OMERACT filter was applied and the three domains of validation assessed. Truth assessments included cognitive interviewing, sensitivity analysis and Spearman’s correlations. Discrimination assessments included specificity and reliability testing. Feasibility was assessed using time to form completion and proportion of missing data. Results Eighty-two CYP and their families were recruited; ten cognitive interviews and fifteen PROM/PREM test/retests were conducted. Truth: CYP and parents understood the PROM/PREM and felt important areas were covered. PROM criteria had high sensitivities (> 70%) against similar items on the CHU 9D, with the exception of fatigue (58%). Correlations between similar PROM and CHU 9D criteria were moderate to very strong (coefficients 0.40–0.82.) Discrimination: high specificities (> 70%) on corresponding PROM and CHU 9D domains. Feasibility: median completion times for PROM 60 s (IQR 38–75) and PREM 49 s (IQR 30–60) respectively. Conclusion The CAPTURE-JIA PROM and PREM are valid and feasible in UK paediatric rheumatology clinics. Embedding routine collection into clinical care would be a major step towards improving quality of care.

Background There is a challenging lack of evidence to inform best practice in the routine clinical care of juvenile idiopathic arthritis (JIA). Wide inter-centre variation in the definition and documentation of clinical data items is a major barrier to improvement. In response, we have developed a consensus agreed standardised core dataset called CAPTURE-JIA (n = 62 data items and a ‘data dictionary’ including agreed definitions of terms) designed to support routine collection of high-quality clinical data. The feasibility and acceptability of CAPTURE-JIA in clinical practice is not yet known and was the focus of this pilot study. Methods A purposeful sample of six paediatric rheumatology centres across England was invited to collect the CAPTURE-JIA dataset using paper collection forms (n = 20 patients/centre). The dataset was analysed for missing data. Six focus groups (n = 3-10) explored clinicians’ views on acceptability and feasibility. Results One hundred and twenty-one patients were recruited over three months. The completeness of the dataset was similar across centres, with minor variations. The majority of data items (eg demographics, dates, ILAR type and examination) were >80% completed. However, 14/62 data items received >40% missing data. (Table 1) Further descriptive analyses highlighted incorrect completion of paper forms. Three themes emerged from the focus groups: problematic data items (missing from >10% forms at > 1 centre), format of clinician data forms and the role of digital data collection. Suggested solutions included minor changes to data item definitions and formatting. There were no refinements to the data items. Development of a digital data collection system was identified by all as essential. Due to a lack of clear consensus, the original CAPTURE forms included a number of ways to record joint count data. This proved confusing and a unanimous decision was taken to collect joint count data on all 83 joints in a tabular format. P10 Table 1: CAPTURE JIA data items with >40% missing data Data item % forms with data item missing (if item required) Relevant co-morbidities? 60 Macrophage activation syndrome? 100 Has the ILAR subtype changed? 50 Morning stiffness lasting >15 minutes? 42 History of any form of uveitis? 52 Date started uveitis mediation? 50 Strength of uveitis medication? 83 Counselled prior to new DMARD / biologic? 56 Enrolled in BECS/BCRD if new DMARD / biologic? 48 Joint count (homunculus or table format) 48 Physician assessment of systemic disease activity (VAS) 75 ESR 74 CRP 92 Plasma viscosity 100 Conclusion Paper collection of the CAPTURE-JIA data items is feasible and acceptable in the routine clinical setting, but unlikely to be sustainable in the longer term if collected in duplicate with medical notes. A digital tool in the clinical domain, ideally interlocking with local systems, would offer many advantages, including more complete and time-efficient data collection. Conflicts of Interest The authors declare no conflicts of interest.

Objectives Despite medical advances, life-changing articular damage may still occur in patients with JIA. We report a cohort with destructive arthropathy of the ankle treated by surgical arthrodiastasis. Methods Eight patients (nine ankles) received arthrodiastasis by means of an Ilizarov frame between 2009 and 2013. Patient- and clinician-reported outcome measures were collated prospectively, with retrospective analysis of demographics, disease and pre-surgical treatment. Results Pre-surgery, all patients received IA CS (mean 0.8 injections/year) and MTX (mean diagnosis to treatment 3.8 years; two of eight started within 3 months). Seven of eight patients received biologic drugs. Pain scores improved by 56 and 29% (P Conclusion Arthrodiastasis with an Ilizarov frame is a safe, well-tolerated technique that should be considered as a short-term joint-preserving procedure to improve pain and function when damage has occurred. Delays to systemic medical treatment in this cohort would be considered out-with standard modern practice but, although less prevalent, destructive ankle arthropathy continues to occur in JIA, and we believe this study to be relevant. The ankle is particularly susceptible to damage and, even if localized, should be treated early and aggressively with DMARDs and rapid progression to biologic therapies. Levelof evidence Level IV.

Background:Low immunoglobulin (Ig) levels can occur after rituximab treatment, but the clinical significance is not completely understood. Not all patients (pts) who develop low Ig levels after rituximab are at an increased risk of serious infection (SI), but factors such as pre-existing low Ig levels, prior biologic therapies, history of SI and other disease and age-related factors may increase the risk.Objectives:To assess the risk of SI in pediatric pts with prolonged low IgG or IgM serum concentrations following rituximab treatment for GPA or MPA in a global clinical trial.Methods:In the Phase 2a PePRS study (WA25615), pts aged ≥ 2 to ≤ 18 yrs with GPA or MPA received 4 weekly intravenous rituximab infusions of 375 mg/m2body surface area and concomitant oral glucocorticoid taper. After 6 months, pts could receive further rituximab and/or other immunosuppressants at the investigator’s discretion during a minimum 12-month follow-up phase. Pts with IgG/IgM levels below age-specific reference ranges at baseline were excluded. Ig levels were measured every 4-12 wks. SI occurrence was assessed during/after low IgG or IgM. Prolonged low Ig was defined as IgG or IgM levels < lower limit of normal (LLN) reference range for age for a ≥ 4-month period.Results:All 25 pts completed 4 weekly rituximab infusions and the 6-month Remission Induction Phase; 24/25 pts completed ≥ 18 months of follow-up. 17 pts received additional rituximab treatment on or after Month 6. 11 pts received concomitant immunosuppressants (cyclophosphamide, azathioprine, mycophenolate mofetil) during the study. All pts had a decrease in IgG and IgM mostly after the first rituximab infusion. There was no consistent trend in IgG or IgM levels over time and no clear relationship between low IgG or IgM levels and the number of follow-up rituximab treatments. 18 pts (72%) had prolonged low IgG ≥ 4 months, of whom 5 had IgG levels < LLN at screening and/or baseline; in 7 pts, IgG levels returned to within normal range by study end. During or after prolonged low IgG, 6/18 pts experienced a total of 7 SIs. Three pts received treatment with intravenous Ig. 19 pts (76%) had prolonged low IgM, of whom 5 had IgM levels < LLN at screening and/or baseline. During or after prolonged low IgM levels, 6/19 pts experienced a total of 8 SIs. There were no deaths or study discontinuation due to SI. All pts with prolonged low IgG or IgM had past and/or concomitant treatment with steroids and/or immunosuppressants as potential contributory factors. Analysis of SI onset in relation to timing of low Ig was limited due to protocol-defined time points for Ig assessments.Conclusion:In pediatric pts with GPA/MPA treated with rituximab, there was no consistent pattern in IgG or IgM levels over time. The majority of pts with prolonged low IgG or IgM did not experience any SIs; no increase in the number of SIs was observed over time or with multiple rituximab treatments. While no firm conclusions can be made on a possible relationship between prolonged low IgG or IgM and risk of SI following rituximab due to study limitations (low pt numbers, lack of placebo comparator), these observations are consistent with the known rituximab safety profile in adult pts with GPA/MPA.Disclosure of Interests:Simone Melega Shareholder of: F. Hoffmann-La Roche, Employee of: F. Hoffmann-La Roche, Paul Brogan Grant/research support from: Roche, Novartis, SOBI, Chemocentryx, Novimmune, Consultant of: Roche, SOBI, UCB, Novartis, Speakers bureau: Roche, SOBI, UCB, Novartis, Gavin Cleary Speakers bureau: AbbVie, Aimee Hersh: None declared, Ozgur Kasapcopur: None declared, Satyapal Rangaraj: None declared, Rae Yeung Consultant of: AbbVie, Novartis, Speakers bureau: AbbVie, Novartis, Andrew Zeft: None declared, Jennifer Cooper Employee of: Genentech, Inc., Pooneh Pordeli Shareholder of: Roche, Employee of: Roche, Petra Kirchner Shareholder of: Roche, Employee of: Roche, Patricia Lehane Shareholder of: Roche, Employee of: Roche

Background Rituximab in combination with glucocorticoids (GC) is approved to treat adult patients (pts) with GPA or MPA; however, limited data exist on the safety and efficacy of rituximab in paediatric pts with these potentially life- and organ-threatening diseases. Objectives To report the interim safety, pharmacokinetics (PK) and exploratory efficacy data from the 6 month remission induction phase of a Phase IIa international, open-label, 18 month clinical study of rituximab in paediatric pts with GPA or MPA. Methods Pts aged ≥2 to≤18 years with newly diagnosed or relapsing GPA/MPA received 4 intravenous (IV) rituximab infusions of 375 mg/m 2 body surface area (BSA) on Days 1, 8, 15 and 22 with concomitant GC 1 mg/kg/day (max 60 mg/day) tapered to 0.2 mg/kg/day minimum (max 10 mg/day) by Month 6. All pts received 3 doses of pulse IV methylprednisolone (30 mg/kg/day, max 1 g/day) prior to first rituximab infusion and mandatory prophylaxis for Pneumocystis jiroveci infection. Pts were also pre-medicated with acetaminophen and an antihistamine, 1 hour before each rituximab infusion. Adverse events (AEs) and laboratory data were measured at each study visit (1, 2, 4 and 6 months). Plasma samples for PK analysis were collected throughout the study; clearance and area under the curve (AUC) were calculated using population PK modelling from the RAVE study of rituximab in adult pts with GPA/MPA. 1 For exploratory efficacy assessment, the Paediatric Vasculitis Activity Score (PVAS) was measured at each study visit. Results Of the 25 pts enrolled, 19 (76%) had GPA and 6 (25%) had MPA (median [range] age 14 6–17 years; 80% female). Median (range) disease duration was 0.5 (0.2–0.72) months; 2 pts had received prior cyclophosphamide therapy. All received 4/4 rituximab infusions and completed the 6 month induction phase. By Month 6, all pts had experienced ≥1 AE. The most common AEs by system organ class were infections and infestations in 16 pts (64%). AE terms reported in ≥3 pts are listed in the table 1. Eleven serious AEs occurred in 7 pts (28%), including 3 serious infections (viral gastroenteritis, one lower and one upper respiratory tract infection). 32% of pts had ≥1 infusion related reaction (IRR). No serious IRRs or deaths were reported. The relationship between AUC and BSA was flat and comparable to adult pts. A total of 13 pts (52%) achieved remission by 6 months, defined as PVAS of 0 and GC dose 0.2 mg/kg/day (max 10 mg/day) or PVAS of 0 on 2 consecutive readings≥4 weeks apart irrespective of GC dose. Conclusions In the initial 6 months of this first global clinical trial of rituximab in paediatric pts with GPA/MPA, rituximab was generally safe and well tolerated. The overall safety profile and PK parameters were comparable to adults with GPA/MPA. No new safety signals were observed. However, the study size and interim nature of the analysis limit firm conclusions. The clinical trial and additional efficacy, PK and safety analyses are ongoing. Reference [1] Stone, et al. NEJM 2010;363:221–32. Acknowledgements This study is funded by F. Hoffmann-La Roche. Disclosure of Interest P. Brogan Grant/research support from: Roche, SOBI, Novartis, Chemocentryx, Consultant for: Roche, SOBI, UCB, Speakers bureau: SOBI, Novartis, G. Cleary Speakers bureau: AbbVie, O. Kasapcopur: None declared, S. Rangaraj: None declared, R. Yeung Consultant for: Novartis, Eli Lilly, P. Brunetta Shareholder of: Roche, Employee of: Genentech, Inc., J. Cooper Employee of: Genentech, Inc., P. Pordeli Employee of: Roche, P. Lehane Employee of: Roche

Objective Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. Methods A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Results Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. Conclusion A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services.

Many patients presenting to paediatric rheumatology services require physical therapy. The physiotherapist may take on multiple roles and responsibilities within the team, including diagnostic, therapeutic, disease education, coordinator, patient advocate and facilitator of access to research programmes. As such the physiotherapist will need a background understanding of each disease involving the multi-disciplinary management. In this review, we aim to highlight the importance of the physiotherapist and the roles taken in our multi-disciplinary approach to assessment and treatment of children with rheumatological disorders. Early accurate diagnosis and appropriate management will lead to improved prognosis.

Presentation of suspected pediatric uveitis: Pediatric uveitis is usually managed in specialized ophthalmic centers in the UK. Meaningful data acquisition in these clinics may be helpful in clinical governance, and healthcare planning in a specialty that is gradually changing due to changes in treatment choices.Retrospective analysis of prospectively acquired data in the Liverpool pediatric uveitis database was performed.Analysis of our data, based on 147 patients, with a mean age of 10 years, indicated a female to male ratio of 2:1. 99% of patients were Caucasian. Our data indicates 86% of all patients attending the uveitis clinic were diagnosed with juvenile idiopathic arthritis, followed by intermediate uveitis 5% and idiopathic uveitis 4%. 46% of patients required treatment. Systemic treatment included methotrexate (34%), prednisolone (14%), etanercept (6%), ciclosporin (6%), mycophenolate (3%), and infliximab (1%). Severe visual loss (defined by counting fingers or below vision) was seen in 10 eyes despite appropriately treated chronic uveitis.Our data shows uveitis-related ocular morbidity in a predominantly pediatric Caucasian population. Patients with severe and chronic uveitis may experience significant uveitis-related complications and subsequent visual loss despite aggressive treatment.

Objective The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort. Methods Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n = 198) whose diagnosis fulfilled ≥4 of the ACR criteria for SLE. Results Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4–14.5 years). Male patients were younger than female patients (P < 0.01). Standardized ethnicity data demonstrated a greater risk of juvenile SLE in non-Caucasian UK patients (P < 0.05). Scores on the pediatric adaptation of the 2004 British Isles Lupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of ≥1. Conclusion The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease-associated damage could be seen.

Limping in children is common and may arise from a spectrum of disorders ranging from normal variations in gait development, through to potentially life threatening systemic disease. In this review we take the reader through the normal development of gait, then discuss normal variants of gait in order to identify pathological gait patterns. We aim to provide a framework for the holistic clinical assessment of the limping child and review in more detail some of the commoner diseases associated with limping. Finally some of the commoner pitfalls to establishing a correct diagnosis are presented along with suggestions that may help to improve the diagnostic yield.

Katy was a 6-year-old girl who first presented to the local paediatric minor injuries centre with a history of a swollen, painful right knee. This was of “a couple of days” duration, and the family could not recall any traumatic events in the preceding days. She had a mild upper respiratory tract infection. There was no family history of arthritis, psoriasis or inflammatory bowel disease. The examining practitioner observed Katy walking into the consultation room slowly and with an antalgic gait. She was noted to be rather quiet but did not look toxic. She denied any joint pain when asked specifically. She was rather flushed, but had no rash, and her temperature was 37.5°C. She had a swollen right knee with an effusion. There was no bruising, but the joint was warm to touch and had a reduced range of movement. Remaining detailed systemic examination, including urinalysis, blood pressure and assessment of height and weight that were plotted on appropriate centile charts, was normal. Katy was referred that day to the orthopaedic team at the nearby district general hospital, with possible septic arthritis as the working diagnosis. The examining practitioner was aware that acute septic arthritis is a medical emergency with the potential to cause rapid and irreversible joint damage, so must always be considered in any child with a new presentation of arthritis. Bacterial seeding to the joint via haematogenous transmission is the most frequent pathophysiological process, so he looked specifically for signs of systemic toxicity suggestive of bacterial sepsis. The commonest cause of acute arthritis is reactive arthritis, and there was evidence of an upper respiratory tract infection. Inflammatory joint disease can be associated with other systemic illnesses such as connective tissue disorders and inflammatory bowel disease, signs of which were looked for on detailed multisystem examination, which …

Background Frequent complaints of pain (FCP) are common in high-income countries, affecting about 25% of children, and may have significant adverse consequences including prolonged school absence and disability. Most FCP are unexplained, and the aetiology is poorly understood. This study aimed to identify risk factors for FCP and explore how risk factors explain variation in pain reporting by childhood socioeconomic conditions (SECs). Methods Analysis of the UK Millennium Cohort Study, including 8463 singleton children whose parents provided data throughout the study. At 11 years, mothers were asked whether their child frequently complains of pain. Risk ratios (RR) and 95% CIs for FCP were estimated using Poisson regression, according to maternal education. Other risk factors were explored to assess if they attenuated any association between FCP and SECs. Results 32.3% of children frequently complained of pain. Children of mothers with no educational qualifications were more likely to have FCP than children of mothers with higher degrees (RR 2.06, 95% CI 1.64 to 2.59) and there was a clear gradient across the socioeconomic spectrum. Female sex, fruit consumption, childhood mental health and maternal health measures were associated with childhood FCP in univariable and multivariable analyses. Inclusion of these factors within the model attenuated the RR by 17% to 1.70 (95% CI 1.36 to 2.13). Conclusion In this representative UK cohort, there was a significant excess of FCP reported in less advantaged children that was partially attenuated when accounting for indicators of parental and childhood mental health. Addressing these factors may partially reduce inequalities in childhood FCP.

OBJECTIVE: To determine whether mucocutaneous manifestations are associated with major organ involvement in a UK national cohort of juvenile-onset SLE (JSLE) patients. METHODS: JSLE patients (n = 241) from 15 different centres whose diagnosis fulfilled four or more of the ACR criteria were divided into two groups: those with at least one ACR mucocutaneous criterion (ACR skin feature positive) and those without (ACR skin feature negative) at diagnosis. The relative frequency of skin involvement was described by the paediatric adaptation of the 2004 British Isles Lupus Assessment Group (pBILAG-2004) index. RESULTS: One hundred and seventy-nine patients (74%) had ACR-defined skin involvement with no significant demographic differences compared with those without. ACR skin feature negative patients showed greater haematological (84% vs 67%), renal (43% vs 26%) (P < 0.05) and neurological (16% vs 4%) involvement (P = 0.001). Forty-two per cent of ACR skin feature negative patients had skin involvement using pBILAG-2004, which included maculopapular rash (17%), non-scaring alopecia (15%), cutaneous vasculitis (12%) and RP (12%). ACR skin feature negative patients with moderate to severe skin involvement by pBILAG-2004 showed greater renal and haematological involvement at diagnosis and over the follow-up period (P < 0.05). Higher immunosuppressive drug use in the skin feature negative group was demonstrated. CONCLUSION: Patients who fulfil the ACR criteria but without any of the mucocutaneous criteria at diagnosis have an increased risk of major organ involvement. The pBILAG-2004 index has shown that other skin lesions may go undetected using the ACR criteria alone, and these lesions show a strong correlation with disease severity and major organ involvement.

We report our results with systemic Etanercept in patients with juvenile idiopathic arthritis in a joint ophthalmology-rheumatology clinic at a tertiary hospital.Patients with JIA on Etanercept were identified from a dedicated uveitis database. A retrospective review of electronic and paper-based patient records was performed.Nine patients with JIA and current or previous treatment with Etanercept were identified, including six females and three males. Five patients with previous or current uveitis were noted. A further four were under observation for uveitis and required Etanercept for their joint disease. All nine patients had previously been taking Methotrexate, which had a suboptimal response in controlling arthritis or uveitis. Six out of nine patients did not show any uveitis activity at their last follow-up. Eyes of three patients still show signs of active inflammation in the anterior chamber (two on Etanercept and one off Etanercept). Severely impaired visual acuity (PL) was recorded in both eyes of one patient with long-standing persistent uveitis. Moderate visual loss in one eye of one patient was seen. The remaining seven patients did not show any significant loss of vision. Intraocular inflammation was not induced in any patient started on Etanercept.Etanercept may be useful in controlling JIA-related uveitis or arthritis in a pediatric patient when Methotrexate has had a suboptimal response in controlling the inflammatory activity.

Background Biologic agents may cause auto-antibody formation and drug induced lupus but no paediatric guidelines exist regarding monitoring of auto-antibodies. The UK Royal College of Nursing Guidance advises checking ANA and anti-dsDNA before starting biologic treatment and repeating anti-dsDNA if concerned. The Alder Hey protocol tested an autoantibody profile (Table 1, 2) 3-6 monthly for data entry for the British Paediatric and Adolescent Rheumatology (BSPAR) Biologics and New Drugs Registry (BDNR) and children with day ward IV biologic administration often had automatic antibodies testing 4-6 weekly.

Results Case 1 A 15 year old girl with worsening asthma and rhinitis presented with a persistent 10x6 cm breast lump 6 months after starting Montelukast. Chest X-rays and CT scan were normal, maxillary sinuses congested, with absolute eosinophilia of 2.4 x 10/l, ESR normal, no proteinuria). On needle biopsy, dilated ducts contained necrotic eosinophilic debris, intense infiltrate of eosinophils and plasma cells without granulomatous infiltration or vasculitis. Despite withdrawing Montelukast the mass persisted but treatment with steroids was successful.

Aim Patients with Complex Regional Pain syndromes require multidisciplinary care to be managed effectively. Relief from the symptoms of neuropathic pain often requires the use of centrally acting medications, as well as physiotherapy and psychological support. There is currently no evidence of the relative clinical efficacy or side effect profiles of the medications used for neuropathic pain management. Methods A retrospective audit of paediatric patients with a diagnosis of complex regional pain syndrome attending a tertiary referral clinic (November 2008 – March 2013) was carried out to determine the pattern of medication use for neuropathic pain relief. Results Thirty-two patients were identified, average age at diagnosis 11y 9 m, male gender 25.0% (n = 8). No patient had a validated pain score/tool used at diagnosis. A prescription for a neuropathic pain medication was present in 93.8% (n=30). Physiotherapy was undertaken in 93.8% (n = 30) and psychology input was present in 56.3% (n = 18). The first medication used was Amitriptyline 86.7% (n = 26), combination Amitriptyline and Gabapentin 6.7% (n = 2), Gabapentin 3.3% (n = 1) and Pregabalin 3.3% (n = 1). Over the course of their treatment, the median number of neuropathic pain medications used was 2 (range 1–4), with 46.7% (n = 14) children only requiring a single medication, 33.3% (n = 10) requiring two, and 20% (n = 6) requiring 3+. The number of children receiving each medication is shown in Table 1. At the end of the audit process, 56.7% (n = 17) were still using these medications. Conclusion Amitriptyline is the most commonly used drug for initiating pain therapy in chronic pain, but during treatment there are a number of other medications used. Pharmacologically, the medications used have different modes of action, and hence there is reason to believe that there may be different rates of efficacy in these conditions, and different side effect profiles. Prospective studies are needed in this area to determine the optimal place of each medication in the treatment of neuropathic pain in complex regional pain disorders.

OBJECTIVES: To describe the biologic treatment regimens and report the efficacy and safety of biologic therapies in a multicentre series of children with primary systemic vasculitis (PSV). METHODS: This was a retrospective descriptive case series of children with PSV treated with biologic therapy between February 2002 and November 2007. Primary retrospective outcome assessment measures were: daily corticosteroid dose; Birmingham Vasculitis Activity Score (BVAS); and adverse events (including infection rate). RESULTS: Twenty-five patients median age 8.8 (range 2.4-16) years; 11 male with active PSV (n = 6 with anti-neutrophil cytoplasmic antibody associated vasculitides, n = 11 with polyarteritis nodosa, n = 7 with unclassified vasculitis and n = 1 with Behcet's disease) were treated with biologic agents including infliximab (n = 7), rituximab (n = 6), etanercept (n = 4), adalimumab (n = 1) or multiple biologics sequentially (n = 7). Overall, there was a significant reduction in BVAS from a median of 8.5 (range 5-32) at start of therapy to 4 (range 0-19) at median 32 months follow-up (P = 0.003) accompanied by significant reduction in median daily prednisolone requirement from 1 (range 0.2-2) to 0.25 (range 0-1) mg/kg/day, P = 0.000. For those receiving multiple biologic agents sequentially, a similar clinical improvement was observed with corticosteroid sparing. Infections occurred in 24%, the most severe in those receiving infliximab. CONCLUSION: Our data provide retrospective evidence of efficacy of these agents, and highlight the associated infectious complications. Further multicentre standardization of treatment protocols and data collection to inform clinical trials of biologic therapy in systemic vasculitis of the young is required

CML (Chronic myeloid leukemia) is a myeloproliferative disorder, with dysregulated proliferation and differentiation of granulocytes. CML is rare during childhood, incidence of 1 in 1,000,000 and accounts for less than 5% of childhood leukemia. There are 3 different stages: chronic phase, accelerated phase and blast phase.

Cranio-Osteoarthropathy (COA) is a very rare form of primary hypertrophic osteoarthropathy (HOA). HOA is characterised by digital clubbing, arthropathy, pachyderma and sub-periosteal new bone formation along shafts of long bones. In COA, decreased neurocranium ossification is seen without the pachyderma feature.

Protoplasmic astrocytoma is an extremely rare form of grade II low grade glioma which usually presents as a discrete mass lesion. We describe a 3-year-old female with diffuse protoplasmic astrocytoma with parenchymal involvement and leptomeningeal spread. This tumour proved extremely difficult to diagnose and followed a progressive course. Three superficial biopsies did not give the diagnosis and this was only confirmed 8 months from presentation from a larger fourth biopsy taken deeper from the cerebellum. To our knowledge this case represents the distinct presentation of protoplasmic astrocytoma presenting as extensive diffuse meningeal disease. Pediatr Blood Cancer 2010;54:768–769. © 2009 Wiley-Liss, Inc.

Aims We describe successful arthrodiastasis by the means of an Ilizarov frame in two children with juvenile idiopathic arthritis (JIA) with localised destructive disease despite medical therapy. Methods Case 1 - A 2 year old girl was diagnosed with polyarticular JIA (rheumatoid factor (RF) negative, intermittent antinuclear antibody (ANA) positive). Active symptomatic disease progressed despite combinations of intra-articular steroids, methotrexate (MTX), and biologic agents. Magnetic resonance imaging (MRI) showed erosive change of the left ankle with complete loss of joint space and subtalar joints, and by the age of 13 her mobility was increasingly limited. In order to control pain and prevent permanent arthrodesis, Ilizarov distraction of the left ankle was performed. Case 2 - A 13 year old girl with 10 year history of polyarticular JIA (ANA positive RF negative) developed destructive arthropathy in her right ankle with bone on bone crepitus despite treatment with MTX and etanercept. Serial MR scans showed progressive destructive disease. The patient was treated with cross ankle distracting Ilizarov frame with a perioperative course of intravenous methyprednisolone (IVMP) to control synovitis. She had minor skin sepsis at pin sites. Results In both cases, an improvement has been shown post-operatively in terms of reduced pain and improved function. There is radiological evidence of improvement in both patients. Conclusion JIA is a potentially destructive inflammatory disease. Treatment by a skilled multidisciplinary team with access to disease modifying drugs including biologic therapies usually prevents articular damage and disabling symptoms. Joint destruction is rare, but can significantly impact on the quality of life through pain, deformity, and loss of function. Arthrodiastasis, or joint distraction using an orthopaedic frame, can be used as rescue procedure to avoid arthrodesis in severely painful damaged joints unresponsive to medical therapies.

Background & aims The Medicines and Healthcare Regulatory Authority (MHRA) in the UK runs a national spontaneous reporting system (Yellow Card Scheme) to collect ‘suspected’ Adverse Drug Reactions (ADRs) for all medicines. To increase the data for paediatric medicines, current MHRA advice is to report all suspected ADRs in paediatric patients. Yellow Cards submitted between 2000 and 2009 were analysed for medications commonly used in paediatric rheumatology. Methods Data on all UK spontaneous ‘suspected’ ADRs reported to the MHRA in patients