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Introduction/Background Sarcoidosis is a rare multisystemic inflammatory disorder with 2 distinct presentations in childhood. A monogenic form associated with mono-allelic mutation in NOD2 presents with the triad of uveitis, rash and arthritis in children less than 4-years (early-onset sarcoidosis). The other presentation affects older children with similar presentation to adults, with greater pulmonary and lymph node involvement. Histopathological evidence of non-caseating granulomas is essential for the diagnosis but does not exclude alternative diagnoses. We report a 17-month-old infant, who presented with atypical features suggestive of sarcoidosis, but was subsequently found to have a rare cardiac angiosarcoma driving an exaggerated granulomatous reaction. Description/Method A previously healthy 17-month-old girl born to non-consanguineous Caucasian parents presented with recurrent fever for 3-months, associated with lethargy, weight loss and worsening anemia. Examination revealed an irritable febrile child, weight on 5th centile, with muffled heart sounds; there were no skin lesions, no lymphadenopathy, and no arthritis. Investigations showed severe anemia (Hb 46g/L), leukocytosis (WBC 24/L), thrombocytosis (662/L), high inflammatory markers (CRP >300mg/L, ESR 160mm/hr), high ferritin (600ug/L). CT thorax with cardiac angiogram revealed a large intra-atrial septal mass, extensive pulmonary nodules, bilateral hilar and mediastinal lymphadenopathy and pericardial effusion. She was managed with broad-spectrum antibiotics, blood transfusions and pericardiocentesis with endomyocardial biopsy. Extensive infectious workup, including TB from pericardial exudate, was negative. Serum angiotensin-converting enzyme was normal, with no blasts in blood film; eye examination was unremarkable. The endomyocardial biopsy was inconclusive, so underwent lung and lymph node biopsies, which were initially reported as revealing florid multiple non-necrotising granulomas, but no evidence of malignant cells. Whole-exome sequencing was performed, result pending at that stage. Differential diagnosis included malignancy, infection, immunodeficiency or autoimmune disorder including sarcoidosis, in light of histopathology. With malignancy and infection felt to be excluded, she was managed empirically for atypical sarcoidosis and treated with IV methylprednisolone 30mg/kg followed by tapering steroid and anti-TNF; IL-1 was added later. However, there was no clinical response with ongoing fever, irritability and static inflammatory markers (CRP∼300mg/L). Immunomodulating medications were subsequently stopped. Repeat chest imaging revealed progression of pulmonary findings and increasing cardiac mass. Open-heart bypass surgery with debulking of cardiac mass and further biopsies. Histopathology revealed an extremely rare primary cardiac malignant vascular tumour, angiosarcoma, with loss of SMARCB1 protein staining. Retrospective review and specific staining with SMARCB1 of initial lung biopsy subsequently confirmed that the granulomatous reaction was in response to micro-metastases of tumour throughout the lungs. Discussion/Results The differential diagnosis of granulomatous disease in paediatric patients is very broad. Ultimately, the diagnosis of cancer driving and exaggerated immunological response was provided by a combination of very invasive surgical biopsy of the heart; combined with whole exome sequencing. Whole exome sequencing revealed 2 distinct genetic diagnoses which fully explained the phenotype: heterozygosity for a stop mutation in SMARCB1 (p.R158X) consistent with Rhabdoid Tumour Predisposition Syndrome Type 1; and homozygosity for the hypomorphic PRF1 p.A91V mutation explaining low (but not absent) intracellular perforin levels and exaggerated granulomatous immunological response to tumour. The rare angiosarcoma detected is scarcely reported in the literature, but entirely compatible with the type of cancer associated with RTPS1. Hypomorphic perforin mutation probably explains the exaggerated but frustrated granulomatous immunological response to tumour in this case. Key learning points/Conclusion This case serves to remind us that granulomas can occur in response to malignancy in children. Lack of response to immunosuppression with ongoing severe systemic inflammation in this case provided an important clue to the need for more invasive diagnostic biopsies. Particular challenges relates to the time it takes to obtain genetic test results; but in this case whole-exome sequencing resolved the phenotype fully. Patients with rare and unusual presentations may have more than one genetic diagnosis, with a blending of phenotypes thereafter. Screening of other family members for the mutation associated with RTPS1 is ongoing.

Introduction/Background MDA5-positive juvenile dermatomyositis (JDM) represents a distinct clinical phenotype associated with skin and oral ulceration, milder muscle involvement and a higher incidence of interstitial lung disease (ILD) and severe rapidly progressive ILD (RP-ILD). Description/Method The objectives were to describe the presenting clinical characteristics of patients with MDA5-positive JDM, the incidence of ILD and risk factors associated with development of RP-ILD. Retrospective clinical notes review of patients with MDA5-positive JDM managed at Great Ormond Street Hospital (GOSH) over a 24-year period. Discussion/Results Demographics Twenty-five patients were managed at our centre with MDA5-positive JDM. One additional patient was excluded as no notes available. Sixty-four % females. Sixty % were White British, 20% Black African, 8% Mixed, 8% Asian, 8% European and 4% South Asian. Median age of presentation was 10.0 years (IQR 6.9,12.3). Diagnostic delay was significant, with median 14 weeks (8,26) between initial symptoms and diagnosis. 24% of this cohort were also Ro-52 positive. Presentation: All patients had skin involvement; 52% ulcerating skin disease, 64% heliotrope rash and 100% Gottrons papules on initial presentation. Forty-four % had peri-ungal changes, 35% digital pitting/infarcts and 64% nailfold changes. 40% had peri-orbital oedema. Muscle involvement was present in all, with median CMAS 40/52 (36,44) and MMT8 57/80 (51,62). Eighty-eight % had arthritis; initial active joint count was available for 16 patients with median 5.5 joints (3,16). 40% had gastrointestinal symptoms; fever, weight loss and mouth ulcers were present in 52%, 52% and 60% respectively. Twenty-four % had respiratory symptoms at diagnosis. Interstitial lung disease: 52% were diagnosed with ILD and a further 20% had abnormal pulmonary CT scans not thought to be diagnostic of ILD. 13% (2 patients) had RP-ILD; both of whom died despite immunosuppression and extracorporeal membrane oxygenation. There were no other deaths amongst this cohort. No respiratory involvement was identified in 28%. Of 19 patients who had a CT chest at diagnosis, 84% were abnormal. Only 1 patient developed respiratory involvement during disease course whilst on treatment; the other 93% with ILD had evidence of ILD at diagnosis. Out of 58 putative variables, 4 risk factors were associated with development of RP-ILD which reached statistical significance, a further 3 factors were significantly protective, as is shown in Table 1. 2 patients had pneumocystis pneumonia (PCP), both of whom required intensive care and one associated with death. Key learning points/Conclusion Skin and muscle involvement were identified in all patients, with the majority also presenting with ulcerating skin disease, oral ulceration and arthritis. The majority of this cohort had lung involvement and 2 patients died of RP-ILD. Four risk factors were found to be predictive of RP-ILD and a further 3 protective factors were identified. Rapid deterioration of respiratory symptoms was associated with PCP, while ILD was unlikely to develop whilst on treatment if not present at diagnosis. These findings need to be validated in a larger cohort of patients.

Introduction/Background Embedding research into clinical practice has many benefits, with research-active healthcare settings reporting better clinical outcomes and improved staff recruitment and retention. This is recognised by the NHS who aim to ‘build the capacity and capability of our current and future workforce to embrace and actively engage with research’. In spite of this, clinical academic capacity across the NHS remains challenging; the number of consultants working in clinical academia has declined in recent years and there is concern about lack of academic progression for non-medical professions. Reported barriers include clinical pressures and lack of dedicated time, individual skill and confidence. Description/Method Our aim was to gather information about research exposure across the Paediatric Rheumatology multidisciplinary team (MDT), including paediatric trainees (rheumatology grid, rheumatology spin and level 2 trainees), clinical nurse specialists (CNS), advanced nurse practitioners (ANPs) and Allied Health Professionals (AHPs). We initially sought to identify if trainees were receiving adequate research opportunities during their training. A pilot questionnaire was distributed, and results collated and presented at the Spring Clinical Studies Group (CSG) annual meeting. Feedback was received from both questionnaire respondents and the CSG. Following this, we modified and broadened the scope of the questionnaire to include the Paediatric Rheumatology MDT, with the aim of comparing experiences across the MDT. This was developed using an online survey platform with the link distributed via email and messaging groups for trainees, AHPs and CNSs. The aims of the modified questionnaire were to; 1. Understand the current research experience across the paediatric rheumatology MDT and identify barriers and ways to support participation in research. 2. Identify if individuals wanted more exposure to research and what specific research skills they would like to develop. Discussion/Results There were 34 respondents: 14 (41%) paediatric trainees (7 grid, 2 spin, 2 post-CCT fellows, 3 level-2 trainees), 14 (41%) CNS, 4 (12%) AHPs and 2(6%) ANPs. Across the MDT, 19 respondents (56%) agreed they had adequate opportunity to be involved in research, of which 7 (21%) strongly agreed. In terms of research exposure, 22 (65%) have undertaken postgraduate degrees, 5 (15%) PhD, 9 (26%) MSc, 5 (15%) diploma and 6 (18%) postgraduate certificate. Eight-respondents (24%) had taken time out to develop research skills. Research experience:  18 respondents (53%) have been on the delegation-log for clinical trials. 20 (59%) have contributed to data collection for National Registries. 23 (68%) have given a poster/oral presentation at national/international conferences and 15 (44%) have published in peer-reviewed journals - the majority trainees (n = 11,73%). Research training:  51% report adequate training in critical appraisal, 48% in literature review and 40% in consent; fewer reported adequate training in designing research projects (21%), ethics applications (21%) and statistical analysis (23%). Further training would be desirable in: • designing research projects (68%); • discussing research with patients (65%); • statistical analysis (49%); • critical appraisal (40%); • literature search (37%). Future research involvement:  94% would like more opportunities to be involved in research. In the future, 63% would like allocated research time, 6% to be mainly academic (1 CNS, 1 trainee) and 12% to be full-time clinical (1 spin, 1 level-2 trainee, 2 CNS). Barriers to research:  Free text answers were used to gather information and common themes identified included lack of: • time/heavy clinical commitment (60%); • supervision/support from seniors (9%); • local resources (9%); • research funding (9%); • awareness of projects (12%); • research skills (9%). Encourage participation in research:  Common suggestions included: • protected research time during training/career (35%); • further research training (21%); • earlier awareness of projects/trials (18%); • Increased support from more experienced colleagues (15%); • improved collaboration/networking (12%). Key learning points/Conclusion This survey provides an interesting insight into the research experience throughout the Paediatric Rheumatology MDT. It is encouraging that within the Rheumatology MDT 56% of respondents reported that they have had adequate opportunities to be involved in research and the majority have presented or published their research. However, 94% have reported they would like more opportunities to be involved in research. Lack of time was reported as the most common barrier to research involvement; this finding is consistent with the British Society for Rheumatology’s 2019 ‘Paediatric State of Play’ report. Additionally, significant numbers report they would like further training in research skills. Academic writing for publication was noted as a particular area of concern for nurses and AHPs. We advocate for further research opportunities throughout the MDT. For Rheumatology trainees, it was suggested that research skills be incorporated into the curriculum, with dedicated time allocated to gain experience and contribute to research. All members of the MDT may benefit from research skills training courses, although this would need to be carefully considered, given lack of time and resources were common barriers reported by respondents. Several professionals reported lack of support or supervision from seniors and suggested the benefit of mentoring networks. A weakness of this study is the relatively low number of respondents; the survey remains open and we intend to collect further data to maximise representation across the MDT. Additionally, there is potential bias, with individuals with a research interest possibly more likely to contribute, meaning research experience may be over-represented by this sample of the MDT. Also, representation from AHPs was limited compared to paediatric trainees and CNS. Further work is needed to understand research experience across the MDT, however this initial survey is a valuable first step in encouraging discussion of MDT participation in research.