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The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol [1]. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence (NICE) accreditation.

Objective To summarize evidence regarding efficacy of anti-TNFα in childhood chronic uveitis, refractory to common DMARDs. Methods An updated systematic search was conducted between November 2012 and January 2020. Studies investigating the efficacy of anti-TNFα therapy, in children of ages Results We identified 1677 articles of which 37 articles were eligible. Three were randomized controlled trials, one on ETA and two on ADA, and were excluded from pooled analysis. From the observational studies, a total of 487 children were identified: 226 received ADA, 213 INF and 48 ETA. The proportion of responding children was 86% (95% CI: 76%, 95%) for ADA, 68% (95% CI: 50%, 85%) for INF and 36% (95% CI: 9%, 67%) for ETA. Pooled analysis showed clear differences (χ2 = 32.2, P Conclusion This meta-analysis, consistent with recent randomized controlled trial data, suggests the efficacy of ADA and INF in childhood chronic uveitis treatment. However, ADA results were superior to those of INF in this clinical setting.

Chronic recurrent multifocal osteomyelitis (CRMO) is an auto-inflammatory disorder affecting the skeleton of children and adolescents. Whole-body MRI (WBMRI) is key in the diagnosis and follow-up of CRMO. Imaging protocols should include sagittal short Tau inversion recovery of the spine, imaging of the hands and feet, and T1 images for distinguishing normal bone marrow. CRMO lesions can be metaphyseal, epiphyseal and physeal—potentially causing growth disturbance and deformity. Spinal lesions are common, important and can cause vertebral collapse. Lesion patterns include multifocal tibial and pauci-focal patterns that follow a predictable presentation and course of disease. Common pitfalls of WBMRI include haematopoietic marrow signal, metaphyseal signal early on in bisphosphonate therapy and normal high T2 signal in the hands and feet. Pictorial reporting assists in recording lesions and follow-up over time. The purpose of this paper is to review the different WBMRI protocols, imaging findings, lesion patterns and common pitfalls in children with CRMO

Background/Aims The evidence base underlying the management of children and young people (CYP) with paediatric rheumatic diseases (PRDs) is inadequate, with many critical outstanding questions warranting investigation. The aim of this study was to elicit multidisciplinary PRDs research priorities, through consultation with patients, carers and healthcare professionals. Methods This study was led by the UK NIHR CRN Children/Versus Arthritis Paediatric Rheumatology CSG (referred to as ‘the CSG’) and its Topic Specific Groups (TSGs). The CSG is a multidisciplinary group with strong patient/parent representation, supporting the development of clinical studies in the UK. Research priority ideas were sought from paediatric rheumatologists, trainees, allied healthcare professional (AHP), nurses, patients, parents and charities, through online surveys and face-to-face meetings. Research ideas were categorised as disease-specific or broad/general. They were grouped into sub-themes, duplicates/questions that had already been answered were removed, and similar submissions combined. A modified Delphi process was undertaken, including online research priority ranking, and an online consensus workshop to derive top PRD research priorities. Results The initial consultation yielded 304 research priority ideas; 25% from patients/parents, 22% from the CSG, 18% from TSGs, 13% from AHPs, 11% from trainees, 11% from Nurses. 55 disease-specific and 37 broad/general research priorities were voted upon in the first online survey, yielding a top 11 general broad research priorities. The top 10 disease specific priorities were discussed at the online Delphi priority setting workshop, and two online surveys were held during the workshop to determine their final ranking. Two of the disease-specific priorities were combined, leading to a top 9 (see Table). Disease specific proprieties related to clinical trials in JIA (n = 3) / Juvenile Dermatomyositis (n = 1) / Chronic Recurrent Multifocal Osteomyelitis (n = 1) / Juvenile Systemic Lupus Erythematosus (n = 1) Scleroderma (n = 1), management of JIA in adulthood (n = 1) and chronic pain (n = 1). Conclusion UK consensus-based PRD research priorities have been derived, underpinned by collaboration with patients/carers and healthcare professionals, helping to guide funding bodies to improve the evidence base in PRD’s. Disclosure E.M.D. Smith: None. N. Egbivwie: None. K. Cowan: None. A.V. Ramanan: None. C.E. Pain: None.

Objectives To assess the achievability and effect of attaining low disease activity (LDA) or remission in childhood-onset SLE (cSLE). Methods Attainment of three adult-SLE derived definitions of LDA (LLDAS, LA, Toronto-LDA), and four definitions of remission (clinical-SLEDAI-defined remission on/off treatment, pBILAG-defined remission on/off treatment) was assessed in UK JSLE Cohort Study patients longitudinally. Prentice–Williams–Petersen gap recurrent event models assessed the impact of LDA/remission attainment on severe flare/new damage. Results LLDAS, LA and Toronto-LDA targets were reached in 67%, 73% and 32% of patients, after a median of 18, 15 or 17 months, respectively. Cumulatively, LLDAS, LA and Toronto-LDA was attained for a median of 23%, 31% and 19% of total follow-up-time, respectively. Remission on-treatment was more common (61% cSLEDAI-defined, 42% pBILAG-defined) than remission off-treatment (31% cSLEDAI-defined, 21% pBILAG-defined). Attainment of all target states, and disease duration (>1 year), significantly reduced the hazard of severe flare (P 0.05). Attainment of all targets reduced the hazards of new damage (P Conclusions This is the first study demonstrating that adult-SLE-derived definitions of LDA/remission are achievable in cSLE, significantly reducing risk of severe flare/new damage. Of the LDA definitions, LLDAS performed best, leading to a statistically comparable reduction in the hazards of severe flare to attainment of clinical remission.

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome, which if not promptly treated, can lead rapidly to critical illness and death. HLH is termed macrophage activation syndrome (MAS) when associated with rheumatic disease (where it is best characterized in systemic JIA) and secondary HLH (sHLH) when associated with other triggers including malignancy and infection. MAS/sHLH is rare and coupled with its mimicry of other conditions, is underrecognized. These inherent challenges can lead to diagnostic and management challenges in multiple medical specialties including haematology, infectious diseases, critical care and rheumatology. In this review we highlight the pathogenesis of MAS/sHLH including its underlying triggers, key clinical features and diagnostic challenges, prognostic factors and current treatments in adults.

Background Background Corticosteroids (CS) are widely used for rapid-action or induction treatment in children and young people (CYP) with juvenile idiopathic arthritis (JIA). Given a lack of evidence base on CS induction regimen for CYP with JIA, and since criteria for choosing CS are based on healthcare professional (HCP) preference, further research is needed (1). Methods A national electronic survey was undertaken among HCPs across the UK as part of the Steroid Induction Regimen for Juvenile Idiopathic Arthritis (SIRJIA) study. We aimed to establish the opinions of HCPs current practice regarding the clinical criteria for commencing CS treatment Results A total of 39 (24%) responses were received from 162 HCPs. These included 22 (56%) NHS consultants, five (13%) grid trainees, eight (21%) clinical nurse specialists and four other HCPs (10%). The most common treatments newly diagnosed JIA or a disease flare were intra-articular IACS or a combination of DMARDs and IAS (except for systemic JIA and oligoarticular JIA). The majority of HCPs 17 would treat new and flaring CYP the same with 53% choosing a different regime or not answering. The key criteria HCPs used for commencing CS and choosing route of administration were rapid induction of remission (31 (89%)), high disease activity (31 (89%)), severity of systemic JIA (30 (86%)) and level of inflammation (28 (80%)), see Table 1. The main determinants of route of administration was disease severity disease subtype. The majority of HCPs (52-72%) would consider entering CYP with JIA into a trial randomising to modes of administration. P14 Table 1 Reasons of CS Choice Number N = 39 Percentage % High Disease Activity 35 89.7 Rapid induction of remission 34 87.18 Severity of Systemic JIA 34 87.18 Level of inflammation 32 82.5 Severe Uveitis 30 76.92 JIA subtype 27 68.21 Targeting Specific Joints 26 66.67 Level of Disability 18 46.15 Level of pain 16 41.03 Long-standing Disease 11 28.1 Patient reluctance to take DMARDS 8 20.5 Conclusion The results from this national survey of clinical practice showed varying practices in the management of new CYP with JIA and those that are flaring. The majority of HCPs who completed this survey, indicated that they would be prepared to consider entering CYP into a trial that randomised to the four CS delivery methods. Conflicts of Interest The authors declare no conflicts of interest.

Poster presentation Tuesday 8 October Background Haemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) is a hyperinflammatory syndrome which can complicate sepsis, malignancy or autoimmune/autoinflammatory disease, potentially leading to critical illness and death at all ages. A previous service evaluation of children with ferritin > 10,000 μg/L, which is highly specific for HLH/MAS, reported mortality of 33% and in 44% there was no documented evidence that HLH had been considered by clinicians. The condition may present to generalists, specialists and intensivists and prompt recognition and treatment can be life-saving. A consensus for the management of HLH in older children and adults has not been defined. The aim of this ongoing project is to identify current practice and improve the evidence-base for diagnosis and treatment of HLH. Methods A national cross-specialty group was established in June 2018 including paediatric and adult specialists in rheumatology, haematology, oncology, immunology, infectious diseases, virology, nephrology and intensive care. Clinicians, scientists, pharmacists and data management experts have been incorporated. The group, which numbers over 50 professionals, has met on three occasions to set clinical and research priorities and is supported by Histiocytosis UK, a charity representing patients with HLH. Results The group agreed these priorities: To complete a retrospective service evaluation of adult patients with ferritin > 10,000 μg/L identified over a 3-year period using a standardised proforma established in the previous paediatric cohort [provisionally, this has identified over 200 adults with a mortality rate of 39%]To provide education to clinicians across the UK to improve recognition of HLH [in progress]To develop guidance for investigation of suspected HLH [in progress]To link local multi-specialty teams experienced in managing HLH to create a national network [in progress]To conduct a retrospective, observational study of the use and outcomes of anakinra treatment in HLHTo establish a national registry for HLH as part of the UK Histiocytosis Registry (UKHR) using the REDCap online portal for data collection. Patients with definite and probable HLH, including those with MAS secondary to rheumatological conditions, will be eligible for recruitment. Baseline demographic and clinical data, investigations which contribute to the HLH 2004 criteria and H score, and underlying diagnoses will constitute a minimal dataset. Treatments, and responses, and long-term follow-up data will be recorded. In addition to data collection, with the appropriate consents, biological samples will be available for genetic and histopathological analysis and cellular samples for in vitro studies. Conclusion HLH/MAS is an under-recognised condition with high mortality. A national cross-specialty, all-age collaboration has established priorities to improve clinical care and advance research. Development of a registry, with collection of biological samples, will facilitate investigation of disease pathogenesis and help to stratify patients with a view to future clinical trials. Conflicts of Interest The authors declare no conflicts of interest.

This editorial refers to ‘Efficacy and safety of tocilizumab in a real-life observational cohort of patients with polyarticular juvenile idiopathic arthritis’, by Minna-Maija Grönlund et al., on pages 732 741.

Many paediatric rheumatic diseases result from the abnormal activation or control of the immune system. Biologic drugs, which are synthesised within a biological system, have been designed to target specific molecules involved in cytokine signalling or cell–cell interactions. The past 15 years have seen a revolution in the range of effective treatments for rheumatic diseases, particularly juvenile idiopathic arthritis (JIA). As a result, the target of inactive disease and minimal long-term disease-associated damage is increasingly becoming achievable. In this article we review evidence from recent trials of the use of biologic drugs in the treatment of systemic JIA, juvenile dermatomyositis and juvenile systemic lupus erythematosus. We also highlight novel agents currently undergoing investigation which may broaden our therapeutic armamentarium over the coming decade. Key to these developments are well-designed multicentre controlled clinical trials and long-term safety monitoring as part of international drug registries.

OBJECTIVE The aim of this study was to describe the efficacy of pamidronate therapy on disease activity in children with chronic non-bacterial osteitis (CNO) using whole body MRI (WB-MRI). METHODS Clinical assessment and WB-MRI were obtained in 11 children before and after 1 year of pamidronate therapy using a 1.5 T MRI scanner and short tau inversion recovery sequences. The images were reported by a paediatric radiologist. RESULTS WB-MRI identified 75 lesions in 11 patients; 16 of these lesions had not been detected by clinical examination. Follow-up MRI after 1 year of pamidronate showed complete resolution of inflammation in 45 lesions, moderate improvement in 10 lesions and no change in 20 lesions. Two new lesions developed while on treatment. CONCLUSION WB-MRI allows a more accurate assessment of the disease extent in CNO than clinical examination alone and is useful in the objective measurement of treatment efficacy. Pamidronate appears to be an effective treatment in children with CNO unresponsive to NSAIDs.

Objective. To assess the safety and efficacy of US-guided CS injection done by a paediatric rheumatologist into the TM joints (TMJs) in children with JIA. Methods. Children with JIA presenting to the rheumatology clinic were assessed for TMJ arthritis. Triamcinolone hexacetonide was injected in children with active arthritis assessed by MRI using US guidance under general anaesthesia by the same paediatric rheumatologist trained in the procedure. Efficacy and safety were assessed post-injection by patient-guided symptoms and physical examination. Results. Thirty-eight children (34 girls) with JIA who had TMJ injection done between January 2009 and January 2011 were included in the analysis. Mean age was 12.25 (± 3.55) (range 518) years. The mean disease duration was 4.54 (± 2.73) (range 1.511.1) years. Symptoms pre-injection were pain in 17/38 (44.7%), jaw deviation in 14/38 (36.8%), restricted jaw movement in 13/38 (34.2%) and chewing dysfunction in 7/38 (18.4%). Five (12.5%) children had micrognathia. A total of 63 joints were injected. The injection was efficacious in 58/63 (92.06%) joints. All 17 (100%) children had resolution of pain, and chewing dysfunction improved in 5/7 (71.4%). Jaw deviation improved in 13/14 (92.8%). In the 5/63 (7.9%) injections that were not efficacious, two children with both TMJs injected (four joints) had persisting stiffness with chewing dysfunction and one had persistent jaw deviation. One child developed a scar at the site of injection. Conclusion. US-guided CS injection into the TMJ done by a paediatric rheumatologist trained in the procedure is safe with a high rate of success.

Objective. To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of severe refractory juvenile localized scleroderma (JLS). Methods. A retrospective chart review was performed in patients with JLS who had been treated with MMF after the failure of a combination of MTX and corticosteroids for at least 4 months, or whose JLS had concomitant severe extracutaneous manifestations. Outcome was assessed through clinical examination and thermography. Adverse events were recorded. Results. Ten patients (six females and four males) were enrolled in the study. JLS clinical subtypes were deep morphoea (two patients with disabling pansclerotic morphoea), generalized morphoea (three patients), linear scleroderma (five patients) affecting the limbs in two and face in three patients (en coup de sabre). The age at onset of disease was 8 (range 2–16) years, and the disease duration at the time of treatment with MMF was 18 (range 8–62) months. All MMF-treated patients experienced clinical improvement that allowed withdrawal or reduction of doses of corticosteroids and MTX. Over a follow-up of 27 (range 6–36) months, mild abdominal discomfort was reported in only one patient. Conclusions. MMF appears to be effective in arresting disease progression in severe or MTX-refractory JLS and is generally well tolerated. Further controlled studies are needed to confirm these data.

Objective. To investigate the involvement of neuroendocrine candidate genes in the aetiopathogenesis of juvenile idiopathic arthritis (JIA). Methods. Single-nucleotide polymorphisms and intragenic microsatellite markers within five neuroendocrine candidate genes (CRH, CBG, CYP19, ESR1, PRL) were investigated in 463 clinically characterized UK Caucasian JIA patients and a panel of 276 unrelated, healthy UK Caucasian controls. Results. None of the polymorphisms investigated showed any statistically significant associations with JIA. Conclusions. The lack of association with polymorphisms of these neuroendocrine genes suggests that they are not involved in susceptibility to JIA.

Sir, Early-onset sarcoidosis (EOS) is often diagnosed if there is granulomatous involvement of an organ or sometimes as a diagnosis of exclusion in a child presenting with fever, rash and swollen joints. Recent evidence points to the fact that EOS is synonymous with juvenile systemic granulomatous disease (JSGD), also eponymously known as Blau syndrome (BS) or Jabs disease [1, 2]. They share clinical features of uveitis, dermatitis and arthritis, and are caused by inherited (BS) or sporadic (EOS) mis-sense mutations in the NACHT [NAIP (neuronal apoptosis inhibitory protein), CIITA (MHC Class II transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TP1 (telomerase-associated protein)] protein domain of the NOD2 (CARD15) gene, a major orchestrator during innate immune responses [1, 3]. Granulomatous disease of any origin may cause a panuveitis characterized by inflammation in the anterior and vitreous chambers and also the choroid or retina. We report a case of JSGD with a novel mutation and highlight the difficulty in distinguishing between granulomatous inflammation and infection in ocular inflammation. The importance of this is magnified when anti-TNF-α agents are implicated. We also speculate on mechanisms by which infection and inflammation may share a similar clinical profile. A 15-month-old Caucasian male, C.P., presented with a 2-week history of spiking fevers, a follicular, erythematous rash and symmetrical polyarthritis affecting the small joints of hand, ankles, knees and wrists and hips (Fig. 1). He had normocytic anaemia (7 g/dl), normal ferritin and elevated ESR and CRP (100 mm; 200 mg/l). Autoantibodies including RF and ANA were negative and infection was excluded. Biopsies were not taken from skin or SF. Fig. 1 Synovitis of the ankles and follicular rash. A clinical diagnosis of systemic-onset JIA was made initially followed by treatment with MTX, IVIG and anakinra alongside frequent, intermittent courses of oral, IA and i.v. CS therapy for recurrences of rash and arthritis over the next 4 years. Consequently, etanercept and MTX were instituted when C.P. was 6 years old. Etanercept was stopped upon developing bilateral anterior uveitis [4]. In order to control both ocular disease and arthritis, adalimumab was started but 8 weeks later, C.P. was admitted as an emergency with papilloedema, headache and raised CSF pressure, CSF leucocyte count and protein. Investigations for tuberculosis were negative including CSF PCR, CSF and blood culture, ELISpot™ (Mabtech, Nacka, Sweden) IFN-γ-release assay (IGRA) and TST (tuberculin skin test). Despite negative results, he was treated empirically with a full course of quadruple therapy for tuberculous meningitis and adalimumab was stopped. Ocular inflammation relapsed during anti-tuberculous therapy with reduction of vision attributable to panuveitis [4] with choroidal infiltrate; this responded to oral CS and MTX. Aqueous fluid was sampled under general anaesthetic for MTb PCR but the sample volume was insufficient. At this stage, we revised the differential to consider inflammatory granulomatous diseases as neither granulomatous ocular disease nor recurrent rash are consistent with a diagnosis of JIA. Venous blood samples from C.P. and his biological parents were obtained for genomic DNA extraction and genotyping of the NOD2 exonic regions. This analysis revealed a novel, de novo heterozygous mutation at position c.1558 C > T in exon 4 encoding the amino acid substitution H520Y in C.P., confirming a diagnosis of JSGD. Following reported success with infliximab and its more potent TNF-α blockade, C.P. was restarted on infliximab after 9 months of anti-tuberculous therapy normal lung imaging and repeated negative ELISpot™. C.P. is now 8 years old, he remains in drug-induced remission for joint and ocular disease and has vision of 6/5 in both eyes.