Eileen M. Baildam

The clinical progression of JIA is unpredictable. Knowing who will develop severe disease could facilitate rapid intensification of therapies. We use genetic variants conferring susceptibility to JIA to predict disease outcome measures. A total of 713 JIA patients with genotype data and core outcome variables (COVs) at diagnosis (baseline) and 1 year follow-up were identified from the Childhood Arthritis Prospective Study (CAPS). A weighted genetic risk score (GRS) was generated, including all single nucleotide polymorphisms (SNPs) previously associated with JIA susceptibility (P-value < 5×10⁻⁰⁸). We used multivariable linear regression to test the GRS for association with COVS (limited joint count, active joint count, physician global assessment, parent/patient general evaluation, childhood HAQ and ESR) at baseline and change in COVS from baseline to 1 year, adjusting for baseline COV and International League of Associations of Rheumatology (ILAR) category. The GRS was split into quintiles to identify high (quintile 5) and low (quintile 1) risk groups. Patients in the high-risk group for the GRS had a younger age at presentation (median low risk 7.79, median high risk 3.51). No association was observed between the GRS and any outcome measures at 1 year follow-up or baseline. For the first time we have used all known JIA genetic susceptibility loci (P=−08) in a GRS to predict changes in disease outcome measured over time. Genetic susceptibility variants are poor predictors of changes in core outcome measures, it is likely that genetic factors predicting disease outcome are independent to those predicting susceptibility. The next step will be to conduct a genome-wide association analysis of JIA outcome.

Background: In the UK, juvenile idiopathic arthritis is the most common inflammatory disorder in childhood, affecting 10 : 100,000 children and young people aged < 16 years each year, with a population prevalence of around 1 : 1000. Corticosteroids are commonly used to treat juvenile idiopathic arthritis; however, there is currently a lack of consensus as to which corticosteroid induction regimen should be used with various disease subtypes and severities of juvenile idiopathic arthritis. Objective: The main study objective was to determine the feasibility of conducting a randomised controlled trial to compare the different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis. Design: This was a mixed-methods study. Work packages included a literature review; qualitative interviews with children and young people with juvenile idiopathic arthritis and their families; a questionnaire survey and screening log to establish current UK practice; a consensus meeting with health-care professionals, children and young people with juvenile idiopathic arthritis, and their families to establish the primary outcome; a feasibility study to pilot data capture and to collect data for future sample size calculations; and a final consensus meeting to establish the final protocol. Setting: The setting was rheumatology clinics across the UK. Participants: Children, young people and their families who attended clinics and health-care professionals took part in this mixed-methods study. Interventions: This study observed methods of prescribing corticosteroids across the UK. Main outcome measures: The main study outcomes were the acceptability of a future trial for children, young people, their families and health-care professionals, and the feasibility of delivering such a trial. Results: Qualitative interviews identified differences in the views of children, young people and their families on a randomised controlled trial and potential barriers to recruitment. A total of 297 participants were screened from 13 centres in just less than 6 months. In practice, all routes of corticosteroid administration were used, and in all subtypes of juvenile idiopathic arthritis. Intra-articular corticosteroid injection was the most common treatment. The questionnaire surveys showed the varying clinical practice across the UK, but established intra-articular corticosteroids as the treatment control for a future trial. The primary outcome of choice for children, young people, their families and health-care professionals was the Juvenile Arthritis Disease Activity Score, 71-joint count. However, results from the feasibility study showed that, owing to missing blood test data, the clinical Juvenile Arthritis Disease Activity Score should be used. The Juvenile Arthritis Disease Activity Score, 71-joint count, and the clinical Juvenile Arthritis Disease Activity Score are composite disease activity scoring systems for juvenile arthritis. Two final trial protocols were established for a future randomised controlled trial. Limitations: Fewer clinics were included in this feasibility study than originally planned, limiting the ability to draw strong conclusions about these units to take part in future research. Conclusions: A definitive randomised controlled trial is likely to be feasible based on the findings from this study; however, important recommendations should be taken into account when planning such a trial. Future work: This mixed-methods study has laid down the foundations to develop the evidence base in this area and conducting a randomised control trial to compare different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis is likely to be feasible. Study registration: Current Controlled Trials ISRCTN16649996. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 36. See the NIHR Journals Library website for further project information.

Patient recruitment can be very challenging in paediatric studies, especially in relatively uncommon conditions, such as juvenile idiopathic arthritis (JIA). However, involving children and young people (CYP) in the design of such trials could promise a more rapid trajectory towards making evidence-based treatments available. Studies involving CYP are advocated in the literature but we are not aware of any early stage feasibility studies that have qualitatively accessed the perspectives of parents and CYP with a long term condition to inform design and conduct of a trial. In the context of a feasibility study to inform the design of a proposed randomised controlled trial of corticosteroid induction regimen in JIA, we explored families’ perspectives on the proposed trial and on JIA trials generally. We analysed interviews with 27 participants (8 CYP aged 8–16 years and 19 parents) from four UK paediatric rheumatology centres. CYP had recently received corticosteroids to treat JIA. Audio-recorded interviews were transcribed and analysed thematically, drawing on the Framework Method. Both parents and CYP were capable of engaging with the logic of the proposed trial but pointed to challenges with its design. Treatment preferences influenced willingness to participate in the proposed trial. The preferences of older children and their parents often differed, with CYP being more willing to participate in the proposed trial than parents. Families’ current treatment preferences were largely informed by past positive and negative treatment experiences. Some participants also indicated that their treatment preferences were influenced by those of their clinicians. Previous research has typically focused on deficits in patients’ understandings of trials. We found that both parents and CYP understood trial concepts and were able to identify potential flaws in the proposed trial. We propose recommendations to optimise the design of a planned corticosteroid induction regimen trial in JIA. Accessing both parents’ and CYP’s perspectives helps to identify and address recruitment challenges, which will ultimately optimise informed consent and future recruitment.

Objectives: To investigate the suitability of the revised Illness Perception Questionnaire ( IPQ ‐R) for use with adolescents with a long‐term pain condition and to validate a new questionnaire for use with this age group. Design: A three‐phase mixed‐methods study. Methods: Phase 1 comprised in‐depth qualitative analyses of audio‐recorded cognitive interviews with 20 adolescents with juvenile idiopathic arthritis who were answering IPQ ‐R items. Transcripts were coded using framework analysis. A content analysis of their intended responses to individual items was also conducted. In Phase 2, a new questionnaire was developed and its linguistic and face validity were assessed with 18 adolescents without long‐term conditions. In Phase 3, the construct validity of the new questionnaire was assessed with 240 adolescents with juvenile idiopathic arthritis. A subset of 43 adolescents completed the questionnaire a second time to assess test–retest reliability. All participants were aged 11–16 years. Results: Participants described both conceptual and response format difficulties when answering IPQ ‐R items. In response, the Pain Perception Questionnaire for Young People ( PPQ ‐ YP ) was designed which incorporated significant modifications to both wording and response formats when compared with the IPQ ‐R. A principal component analysis of the PPQ ‐ YP identified ten constructs in the new questionnaire. Emotional representations were separated into two constructs, responsive and anticipatory emotions. The PPQ ‐ YP showed high test–retest reliability. Conclusions: Symptom beliefs appear to be more salient to adolescents with a long‐term pain condition than beliefs about the illness as a whole. A new questionnaire to assess pain beliefs of adolescents was designed. Further validation work may be needed to assess its suitability for use with other pain conditions. Statement of contribution: What is already known on this subject? Versions of the adult Revised Illness Perception Questionnaire ( IPQ ‐R) have been adapted for adolescents and children by changing item wording; however, research to assess the degree to which the underlying IPQ ‐R constructs are relevant to adolescents with a long‐term condition had not been performed. What the present study adds? In adolescents, beliefs about symptoms of their condition are more salient than beliefs about the illness as a whole. Question response formats for children and young people need to take account of age‐specific abilities. A new questionnaire has been designed for adolescents with pain. It is theoretically congruent with the CS ‐ SRM .

Background: Sarcoidosis is a multisystemic granulomatous disease with diverse and often non-specific symptoms during childhood. The clinical manifestations sometimes include endocrinopathies related to sarcoid infiltration of various endocrine organs, but more commonly due to the associated autoimmune endocrine disorders. There are only a few reports of multiple autoimmune and non-autoimmune endocrine problems occurring simultaneously in patients with sarcoidosis. We report a girl with probable sarcoidosis who also had Hashimoto’s thyroiditis, Type 1 diabetes (T1D) and secondary adrenal insufficiency. Case Presentation: A 9-year-old girl previously diagnosed with autoimmune hypothyroidism and vitamin D deficiency, presented with hypercalcemic pancreatitis after initiating vitamin D supplementation that lead to a diagnosis of probable sarcoidosis. Secondary adrenal insufficiency and T1D were subsequently diagnosed. Her angiotensin converting enzyme levels on 2 occasions were 106 and 135 nmol/mL/min (normal range 10 - 43). All investigations conducted to exclude several infectious and malignant conditions that may mimic sarcoidosis were negative. The patient showed a good response to treatment with hydrocortisone, levothyroxine, insulin and methotrexate. Conclusions: To our knowledge, ours is the youngest ever patient reported in the literature with sarcoidosis to develop multiple autoimmune and non-autoimmune endocrinopathies. Keywords: Sarcoidosis; Hypercalcemia; Pancreatitis; Type 1 Diabetes; Hashimoto’s Thyroiditis; Adrenal Insufficiency

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Background Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DAS) score for juvenile idiopathic arthritis (JIA), including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR. We have shown in previous work that the ESR is not routinely assessed in all patients with JIA; this reduces the feasibility of JADAS use in clinical practice. Objectives To determine whether exclusion of the ESR from JADAS (labelled JADAS3 followed by 10, 27 or 71 respectively) influences correlation with single markers of disease activity (DA), in a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods The JADAS 10, 27 and 71 and JADAS3-10, -27 and -71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 71 and JADAS3-71 with single markers of DA was determined for all ILAR subtypes (Spearman’s rank statistic). Results 354/1041 (34%) children had all four variables and 562/1041 (54%) children had three variables (ie without ESR) available at baseline. 994 (95%) had AJC available, 811 (78%) PGA, 694 (67%) PGE and 647 (62%) ESR. Median age at disease onset was 6.8 years (IQR 2.8-10.8), median disease duration at diagnosis was 5.2 mths (IQR 2.5-10.9) and 64% were female. Correlation for the whole cohort between JADAS3-71 and both JADAS3-27 and -10 was 0.99. Median JADAS3-71 ranged from 5.9-16.7/91 across the subtypes (Table 1). Correlation of JADAS 71 with JADAS3-71 was high, both for the whole cohort (0.96) and within individual ILAR subtypes (range 0.91 to 0.99). Table 1 Correlation of JADAS 71 and JADAS3-71 with single markers of DA was similar between subtypes with the exception of the ESR; this may simply be a reflection of the variation in the frequency of measurement of the ESR between subgroups. Conclusions Correlation of single DA markers with JADAS3-71 was moderate to good across all ILAR subtypes. JADAS3 is potentially a valid surrogate for JADAS in the clinical setting when the ESR is unavailable. Further validation studies are required to determine whether JADAS and JADAS3 reflect changes in DA over time. Disclosure of Interest None Declared

Adult rheumatologists in the UK have historically provided a significant contribution to clinical care for children with rheumatic disease. However, changes in postgraduate training have resulted in adult rheumatology trainees no longer being trained in paediatric rheumatology (PRh), and accordingly, they will be ill-equipped to manage children when incumbent adult rheumatology specialists retire. The objectives of this work were to ascertain the number of UK adult rheumatologists currently involved in PRh care and to inform future workforce planning. As part of the British Society for Rheumatology annual consultant workforce survey, additional questions relating to PRh were included. A questionnaire was sent to 584 adult rheumatologists, of whom 403 (69%) responded to questions about PRh; of these, 75 of 403 (19%) reported seeing children and many will retire in the next 5 and 10 years (13/75 (18%) and 35/75 (48%), respectively). The majority (58/75, 78%) reported having separate clinics for children, often alongside other health care professionals (mostly consultant paediatrician, paediatric rheumatologist, or allied health professional). Notably, 4 of 75 (5%) adult rheumatologists had clinical sessions seeing children without any paediatric input. The median (IQR) number of paediatric consultations by adult rheumatologists per month was 10 (6, 15), equating to a total 931 paediatric consultations per average month. Many UK adult rheumatologists are involved in managing paediatric rheumatic disease and many will retire over the next 10 years. This will result in a shortfall in clinical provision as their replacements in adult rheumatology will not have had appropriate PRh training. This projected shortfall needs to be addressed in future workforce planning.

Objective.: There have been few studies of quality of life in childhood scleroderma and these focused predominantly on self-perception and the influence of skin lesions. Our cross-sectional study aimed to describe the influence of childhood scleroderma on physical function and quality of life in relation to clinical and demographic measures.Methods.: Children with either localized scleroderma or systemic sclerosis (SSc) attending pediatric rheumatology clinics, together with their parents or guardians, were asked to complete a set of 4 validated measures. Clinical and demographic data were provided by consultant pediatric rheumatologists.Results.: In total, 28 children and their parents/guardians participated in the study (68% female, median age 13 yrs; 86% localized scleroderma, 14% SSc). The median Child Health Assessment Questionnaire (CHAQ) score was 0.1 (range 0–3, 0 indicating no impairment), the median Child Dermatology Life Quality Index (CDLQI) score was 5 (range 0–30, 0 indicating no impairment), and the median Child Quality of Life Questionnaire (CQOL) function score was 26 (range 0–105, 0 indicating no impairment). Family activity, measured by the Child Health Questionnaire (CHQ-PF50), was also moderately impaired by scleroderma, with a median score of 83 (0–100, 100 indicating no impairment).Conclusion.: Scleroderma had only a moderate effect on quality of life and physical function as measured by the 4 validated instruments. Although a small number of children reported greater impairment, this is an encouraging finding, given its potential disfiguring and debilitating effects.