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Introduction/Background Patients attend rheumatology daycare either for regular infusions or one episode depending on their treatment. A typical day for a child would involve observations, having a cannula put in and having the infusion before returning home. Due to the COVID-19 pandemic, there had been some changes to the day care pathway in our hospital including: only one parent being allowed to attend with their child; a strict timing schedule; COVID-19 testing prior to attending appointments. We felt it is vital to know the young person and the family’s perspectives of their experience at day care. Description/Method A special study module (SSM) medical student conducted a feedback survey over a 2 month period (December 2021 and January 2022). The aims and objectives were focused on the following: Whether the patients are receiving an appropriate level of care to optimise their experience at day-care.was their treatment given in a timely manner?Were there any delays, if so the reasons and actions taken to mitigate. 2 questionnaires were used, one for the patient and one for the parent/carers. The questionnaires were provided to the patient/carers during their admission by the admitting nursing staff. The medical student collected the questionnaires at the end of the day. Discussion/Results 39 patients attended the daycare during this period. 9 completed questionnaires were received. • Feedback from parents/carers: - Carers (100%) said they were happy with how they had appointment dates and most appointments took their availability and preferences into consideration. Due to COVID, families were notified of their appointment time only one day prior; this was highlighted as an area for improvement to ensure enough notice for the appointment time. - All parents (100%) agreed that they received enough information regarding their child’s appointment at daycare and this was delivered in an understandable manner. - 77.8% (7 out of 9) of parents did not experience long waiting times at their appointment. 22.2% (2 out of 9) parents said there were long waiting times at their appointment, and they were made aware of the reasons regarding the wait. The main reasons highlighted was busy ward with lots of patients. - 2 out of 7 parents indicate the care provided has remained the same pre- and post-pandemic. 3 out of 7 patients felt that their care has improved due to the following reason: treatment was completed more quickly; wards looked less busy as there were limited patients present at one time; there was a reduced length of stay compared to pre-COVID. • Children’s questionnaires: - 100% (9 out of 9) children were happy with the care received at daycare. - 22.2% (2 out of 9) children reported being worried/anxious due to having bloods and cannula taken (1) and missing school (1). - 5 out of 9 children had play therapist input and they all found it helpful. Key learning points/Conclusion Despite the COVID pandemic restrictions, all young people and families had a positive experience during their day care treatments. Effective communication and engaging the patients and families, and providing appropriate explanations to any delays in treatment is vital. The overall experience has provided an opportunity to reflect on the systems to manage the day care treatments, which we presume has been the case in many centres. Allied health professionals like play therapists and youth teams provide immense support to the young people who are attending day care for regular treatments. Provision of these services to all young people if appropriate will enable positive experiences to the patients. Limitation of this survey was a small sample size with the response rate of only 23%. Further survey over an extended period may provide more insight in this area.

Introduction/Background Juvenile dermatomyositis is a rare inflammatory disease with a reported incidence of 0.8–4.1 per million children per year. It presents with a constellation of symptoms and signs of inflammation of skin and muscle, and is associated with significant morbidity if untreated. Juvenile systemic sclerosis (JSSc) is an even rarer rheumatological condition of childhood with significant risk of internal organ involvement, especially cardiopulmonary disease. We herewith present the case of a 7-year-old boy with history of hypothyroidism associated with a PAX8 gene variant who presented with clinical features of an overlap of Systemic Sclerosis with JDM with supportive autoantibody profile. Description/Method A 7-year-old boy presented with a history of restricted range of movements in his hands – noted due to difficulties with pen grip – and calcinosis. He reported symptoms of fatigue, intolerance to cold with colour changes to hands and feet, stiffness of movements particularly in the morning, and infrequent episodes of choking. His past medical history was significant for hypothyroidism secondary to a paternally inherited PAX8 missense mutation, and there is a family history of Raynaud’s and hypothyroidism. A detailed examination identified diffusely swollen hands with sclerodactyly, calcinosis of his elbows and fingertips, and limited flexion of his fingers and wrists. He also had telangiectasia of his upper eyelids, Gottron’s papules over his knees and elbows, and sluggish circulation in his hands and feet. He had evidence of mild proximal muscle weakness. His investigations revealed mild elevation of muscle enzymes with normal inflammatory markers. His autoantibody profile showed a moderately positive ANA titre of 1600 with a nucleolar pattern, and was positive for anti-NXP2 and anti-SCL-100 antibodies MRI scan of the pelvis showed no evidence of myositis, echocardiogram was normal and a high-resolution CT scan of chest was normal with no features of interstitial lung disease. The overall picture was one of Systemic Sclerosis/JDM overlap with CREST syndrome. He was commenced on induction therapy with IV Methylprednisolone and Cyclophosphamide in view of the calcinosis. After three cycles of Cyclophosphamide and weaning course of oral corticosteroids, his energy levels are significantly improved and he has better overall mobility with no significant proximal muscle weakness (Childhood Myositis Assessment Scale score 49/53). However, flexion of his fingers remains limited albeit better; he has ongoing fingertip calcinosis but fewer lesions over his elbows. He has been commenced on weekly subcutaneous Methotrexate as he completes Cyclophosphamide. Discussion/Results This patient had an unusual medical history of early onset thyroid dysfunction, the genetic testing for which revealed a missense PAX8 gene variant [c.49G>Ap.(Gly17Arg)] (also present in his father, who is euthyroid). This was classified as being of uncertain significance, although felt to clinically be the most likely cause for his hypothyroidism. There was no evidence to suggest that PAX8 gene mutations increased the risk of autoimmune conditions. There is evidence that PAX8 gene mutations, when expressed on malignant cells, may confer resistance to chemotherapy, which made us rethink the plan to commence him on Cyclophosphamide. However, we were reassured that in constitutional variants, there is no increased risk of cancer, and no known history of resistance to Cyclophosphamide. This patient also demonstrated an interesting antibody pattern, as he was positive for anti-NXP2 antibodies (indicating high risk for calcinosis) and anti-SCL-100 antibodies, which are associated with a clinical subset of patients with overlap of Systemic Sclerosis and JDM and associated with extensive extra-muscular features. He had two distinct clinical phenotypes of calcinosis, which is probably explained by the presence of two autoantibodies that increase the risk of calcinosis. Key learning points/Conclusion Although JDM has bimodal age group for presentation in childhood, only 3% of systemic sclerosis are seen in childhood, which makes this an extremely unusual presentation, given the age, gender and the overlap features (clinical and immunological). We explored whether this rare presentation could be linked to the underlying PAX8 gene mutations, but we could not find any association. With the clinical diagnosis of systemic sclerosis, it was important to rule out cardiopulmonary complications. The other consideration was regarding the choice of therapeutic agent - whether the germline PAX8 gene variants could increase the risk of malignancies or cause resistance to chemotherapeutic agents like Cyclophosphamide, for neither of which we could find any evidence. Extensive calcinosis cutis in this patient could be explained by the presence of two risk factors (CREST syndrome and JDM with NXP2 antibodies).

Introduction/Background COVID-19 disease, caused by SARS-CoV-2 virus, first emerged as a presentation of severe respiratory disease in 2019. Although children exhibit mild disease, concerns were raised about serious infection in immunocompromised children. The current national guidance recommends that immunocompromised children between 12 and 18 years of age should be offered three primary doses of the Pfizer BioNTech vaccine, 8 weeks apart, followed by a booster dose within 3 months. This audit looked at the awareness and uptake of this regime in young persons on immunosuppression. This information was disseminated to families during clinical contacts and automatic replies sent out from the team mailbox. Description/Method To collect the data for the audit, we used an anonymous questionnaire to capture the following information: • Diagnosis • Immunomodulatory/Immunosuppressive treatment • Their awareness of the regime for COVID vaccine (number of doses and interval) • Number of vaccines taken • If not taken, why? The questionnaires were handed out to 31 patients attending Paediatric Rheumatology day-care and outpatient clinics over a two-week period for their response. There were no non-responders. Patients who were not on any immunosuppressant medication were excluded. The split of their diagnoses and medications are summarised in tables 1 and 2: Patients with JIA (55%) unsurprisingly dominated the cohort, followed by JSLE, JDM and scleroderma. Only 3/31 patients (10%) were on any form of systemic steroid therapy (all on oral Prednisolone less than 0.5 mg/kg). Majority of the patients (21/31 – 68%) were on Methotrexate, either on its own, or in combination with one of the biologic agents (one scleroderma patient was on MTX + MMF). 14/21 (45%) patients were on one of the biologic agents, of which only one patient was on Rituximab. Discussion/Results The results showed that only 6/31 (19%) of patients/their carers knew the correct number (3 + 1) of COVID vaccines recommended in this cohort. 18/31 (58%) patients had received the vaccine, of which 4 patients refused further doses due to side effects they had experienced following the first dose. Of the 13 young people who did not take the vaccine, 9 patients (29%) were unsure whether they need the vaccine. They did not know the benefits of the vaccine and were afraid it either could have a negative effect on immunocompromised children or just were not aware of the guidelines. The other 4 (13%) participants did not want to take the vaccine due to their own personal beliefs. Although concerns were raised about serious COVID-19 infection in immunocompromised children, there is currently very little evidence to suggest that the infection rate and severity of COVID-19 infection in children treated with Methotrexate or biologic agents is higher or the treatment needs to be discontinued or the doses adjusted. There is some emerging evidence to suggest that adults on Rituximab and to a lesser extend Mycophenolate may have increased risk of developing severe outcomes from COVID-19, which has not been replicated in children. The recommendation for third primary dose is based on preliminary results from UK studies of real-world vaccine effectiveness (VE) in persons who are immunosuppressed, suggesting a modest reduction in VE against symptomatic COVID-19. There is also emerging evidence that COVID vaccination significantly reduces the risk of Paediatric Inflammatory Multisystem Syndrome (PIMS-TS) in 12 – 18 year olds. Key learning points/Conclusion Despite the notion that the team had disseminated information on the vaccine regime to patients, only one fifth of the patients/carers knew the exact regime for COVID vaccine recommended in this group of young people. Just under 60% of the patients took the vaccine, with the rest choosing not to have it due to a mixture of lack of information and personal choice. The action plan was drawn up to: 1. enquire about and document vaccination status, and provide advice and information during every clinical contact; 2. include COVID vaccine in education sessions by nursing team; 3. include the information as default in all clinic letters; 4. reaudit in six months.

Systemic connective tissue diseases (CTDs) are characterised by the presence of autoantibodies and multiorgan involvement. Although CTDs are rare in children, they are associated with pulmonary complications, which have a high morbidity and mortality rate. The exact pathophysiology remains unclear. The pleuropulmonary complications in CTD are diverse in their manifestations and are often complex to diagnose and manage. The most common CTDs are discussed. These include juvenile systemic lupus erythematosus, juvenile dermatomyositis, juvenile systemic sclerosis, Sjögren's syndrome and mixed connective tissue disease. We describe the clinical features of the pleuropulmonary complications, focusing on their screening, diagnosis and monitoring. Treatment strategies are also discussed, highlighting the factors and interventions that influence the outcome of lung disease in CTD and pulmonary complications of treatment. Early detection and prompt treatment in a multidisciplinary team setting, including respiratory and rheumatology paediatricians and radiologists, is paramount in achieving the best possible outcomes for these patients., Pleuropulmonary complications of CTD, though rare in paediatrics, can be associated with high morbidity and mortality. Joint management by respiratory and rheumatology paediatricians is recommended. Treatment includes steroids and other immunomodulators. https://bit.ly/2MCvEpp

Case report - Introduction 15 year old girl with the diagnosis of granulomatosis polyangiitis (GPA) managed with induction regimen of intravenous cyclophosphamide and whilst on maintenance mycophenolate mofetil (MMF) developed multiple cavitating lung lesions with the large cavity abutting pulmonary vein and bilateral segmental pulmonary embolism (PE) posing complex management dilemmas. Case report - Case description 15-year-old girl presented with being unwell for 3 months with malaise, lethargy, joint pains, significant weight loss (10 kg), mouth ulcer and significant hearing loss. Investigations showed anaemia, raised inflammatory markers, and impaired kidney function (estimated glomerular filtration rate eGFR 40). Her ANCA was positive, hearing test showed significant mixed hearing loss and CXR was normal. The renal biopsy confirmed pauci-immune ANCA associated glomerulonephritis with 70% crescents. She was initially managed with intravenous pulse of steroids followed by oral weaning regime, double filtration plasmapheresis and commenced on induction regimen of intravenous cyclophosphamide. She received 6 doses of cyclophosphamide 500 mg/m2 and following good recovery with normalising kidney function; was commenced on maintenance MMF. At this point she developed new onset earache, sore throat, and hoarseness of voice with raised inflammatory markers and worsening symptoms despite antibiotics. This was presumed to a flare of vasculitis and hence was given further pulse of steroids and increased the dose of MMF. The ENT assessment did not reveal any subglottic stenosis. After few weeks, symptoms recurred with cough/hoarseness of voice and associated tiredness. Bloods showed raised inflammatory markers; CXR revealed cavitating lung lesions and a CT chest was arranged. CT chest showed apical sub pleural lung nodule and a large thick-walled cavity measuring 6.6x 4.4 cm abutting the pulmonary vein on the right side and bilateral segmental pulmonary emboli. The child was systemically stable with no respiratory distress and oxygen saturations were 100% in air. Case report - Discussion The management of GPA was further complicated by the pulmonary embolism and cavitating lung lesions abutting pulmonary vein. The management included escalation of immunosuppression with pulse of steroids, further dose of cyclophosphamide and commence Rituximab .The key challenges with the immediate management were risk of bleeding associated with the anticoagulation, treating the pulmonary embolism, risk of diffuse alveolar haemorrhage and managing the patient in a safe setting equipped with all the expertise required. The child was screened for cardiolipin antibodies on multiple occasions and these were negative. An ECHO was done to look for evidence of clot at the end of central line tip, but this was normal. Deep venous thrombosis of legs was ruled out by Doppler scanning. There was no clear source of emboli identified. Although there is emerging evidence for increased incidence of vascular events in GPA adult patients, the data on vascular events in children with GPA is scarce. Merkel and co-workers reported a high occurrence of pulmonary embolism (PE) and deep venous thrombosis (DVT) among GPA patients included in a randomized therapeutic trial (WeCLOT study) 1 .FAURSCHOU et al. reported that GPA was associated with a much lower relative risk of stroke than of pulmonary embolism and deep venous thrombosis; the risk of venous thromboembolic events among GPA patients was increased during early as well as late follow up periods. Currently there are no significant data on the use of antiplatelet and/or anticoagulant therapy in AAV. Following extensive multidisciplinary discussion with respiratory, haematology, cardiology, cardiothoracic surgical and paediatric intensive care teams, and the child was anticoagulated with close monitoring in paediatric high dependency unit and immunosuppression escalated alongside. Case report - Key learning points This case highlights the risk of thromboembolic events in children with GPAProposed mechanisms in the literature for thrombosis in vasculitis at molecular level would probably explain the episode in the absence of source identifiedMultidisciplinary team approach is crucial for management of complex patientsThere were few challenges due to geographical location of the patient and the regional variation of subspecialty cover provided for their local District General HospitalFor discussion- Role of Rituximab early in GPA?

Background The BSPAR section council consensus-based guidance is the most widely used guideline on the use of methotrexate. This recommends that varicella immunity status is checked prior to commencing methotrexate and to consider immunisation if the child is non-immune. It also suggests considering checking measles status and testing for TB in high risk patients. We aim to evaluate our practice of screening paediatric rheumatological patients prior to commencing them on methotrexate. All patients in our centre have methotrexate teaching with a clinical nurse specialist prior to commencing treatment. Methods This study included paediatric patients who were prescribed methotrexate in all forms (subcutaneous, intravenous and orally) for rheumatological conditions and uveitis during a 2-year period (2016 – 2018) regardless of when it was first commenced. Digital health records were accessed to obtain the data retrospectively. Patients were excluded if they had been started on methotrexate prior to joining our centre, or were lost to follow up during the study period or if the required data was unavailable. Results 123 patients were identified to have been prescribed methotrexate during the 2-year study period and 102 patients were included in the study. 28 patients were commenced on methotrexate during 2016 /17 and others were commenced anytime between 2008 -2015. 91 (89%) patients had their varicella status checked prior to commencing methotrexate and 7 patients were checked after treatment was commenced. It was not checked in 4 patients (1 sample rejected and not repeated). Of those checked 20 patients were non-immune and 16 were vaccinated. 57 patients had had measles serology checked, 31 of these prior to commencing methotrexate. 35 patients had TB Quantiferon checked prior to methotrexate being started and 39 after. There were no positive results and 6 (8%) indeterminate of which 5 were repeated and 4 were negative. Of the indeterminate results 4 samples were taken prior to commencing methotrexate and 2 after. Conclusion This study shows that local adherence to checking varicella status prior to commencing methotrexate and vaccinating non-immune patients is good. Routine practice for checking measles, hepatitis and TB is varied. The data was captured over a 2-year period but actually included practice of methotrexate commencement over 9 years and thus time span and change in doctors will have contributed to the variation in practice. We believe some results from outreach clinics were not captured. All four tests are often carried out if it is felt the patient is likely to go on to require biologics. An updated guideline would help streamline the pre-DMARD screening and may limit the number of unnecessary investigations. Conflicts of Interest The authors declare no conflicts of interest.

Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab 10 Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months) 7 Number of patients on rituximab monotherapy 2 Number of patients who are 6 months post-treatment 1 Number of patients with other risk factors for PCP 1 (hypogammaglobulinaemia) Number of patients who are eligible for prophylaxis, as per the guideline 8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia) Number of patients on cotrimoxazole 7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest.

Objective.We aimed to establish the prevalence and clinical associations of anti-HMG-CoA-reductase (anti-HMGCR) in a large UK cohort with juvenile myositis.Methods.There were 381 patients investigated for anti-HMGCR using ELISA.Results.Anti-HMGCR autoantibodies were detected in 4 patients (1%). These children had no or minimal rash and significant muscle disease. Muscle biopsies were considered distinctive, with widespread variation in fiber size, necrotic fibers, and chronic inflammatory cell infiltrates; all had prolonged elevation of creatine kinase and all ultimately received biologic therapies.Conclusion.Anti-HMGCR in UK children with myositis are associated with severe disease that is poorly responsive to standard treatment.