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Background/Aims Macrophage activation syndrome (MAS), a form of secondary haemophagocytic lymphohistiocytosis, is a severe, life-threatening complication of rheumatic diseases such as Still’s disease (systemic juvenile idiopathic arthritis or adult-onset Still’s disease) and systemic lupus erythematosus (SLE). Interferon gamma has been implicated in the underlying pathology of both conditions. Standard first-line treatment for MAS is high-dose glucocorticoids (GCs); however, additional treatments are used without a standardised approach in patients who are treatment-refractory. When 9 patients with an inadequate response to high-dose GCs were administered emapalumab in a pilot study (NCT03311854), interferon gamma was rapidly neutralised and MAS was controlled. Emapalumab also had a favourable safety profile. A new study (EMERALD) is currently enrolling patients with MAS in Still’s disease and SLE to further evaluate the efficacy and safety of emapalumab. Methods The open-label, single arm, multicentre, phase 2/3 interventional EMERALD study (NCT05001737) is enrolling paediatric and adult subjects with MAS and an inadequate response to high-dose GCs into two cohorts: MAS in Still’s disease (n = 25) and MAS in SLE (n = 16). Each cohort is a single-arm study comprising two phases: an optional run-in phase and an interventional phase. Key eligibility criteria vary by cohort and phase (Table). During the run-in phase, patients are treated with high-dose GCs and followed until MAS remission or inadequate response, or for a maximum of 12 weeks. Patients enrolled in the interventional phase are treated with intravenous emapalumab (initial dose 6 mg/kg, subsequent doses 3 mg/kg) for 4 weeks or until protocol-defined complete response (CR), then followed up for 1 year. Results The primary endpoint of the study is protocol-defined CR at Week 8 after first emapalumab administration. Secondary efficacy endpoints include GC tapering, survival, time to first CR, overall response (CR and partial response), time to first overall response, MAS recurrence, pharmacokinetic/pharmacodynamic profile of emapalumab and patient-reported outcomes. Safety endpoints include assessments of adverse events, abnormal laboratory parameters and anti-drug antibodies. Conclusion The ongoing EMERALD study is designed to address the unmet need for new efficacious and safe therapies for the treatment of MAS. Disclosure P. Brogan: Consultancies; P.B. has acted as a consultant for Sobi, Novartis, Roche and UCB. A. Grom: Consultancies; A.G. has acted as a consultant for Novartis, AB2 Bio, Novimmune and Sobi. R. Kanceva: Corporate appointments; R.K. is an employee of Sobi. F. De Benedetti: Consultancies; F.D.B. has acted as a consultant for AbbVie, Sobi, Pfizer, Roche, Sanofi, Novartis and Novimmune. Grants/research support; F.D.B has received research grants from AbbVie, Sobi, Pfizer, Roche, Sanofi, Novartis and Novimmune.

Objective To describe the incidence of Kawasaki Disease (kDa) between 2006 and 2021 in England. Methods We identified all cases in hospital episode statistics with an ICD-10 diagnostic code M303 (for kDa) between 1 April 2006 and 31 March 2021. We validated 83 diagnoses using hospital medical records and found >97% accuracy. We calculated incidence rate ratios (IRRs) using Poisson regression and assessed the influence of age, sex, ethnicity and index of multiple deprivation (IMD). We used Office for National Statistics population estimates for England as the denominator. Results We identified a total of 5908 cases of kDa in all children under the age of 16 (mean age 3.8, s.d.=3.2, 95% CI: 3.7, 3.9). Incidence in children aged Conclusions Incidence rates of kDa derived from hospital admission data in England were higher than in studies relying on clinician reporting. We confirm previous findings on the influence of sex and ethnicity on kDa incidence and observe that there was a higher incidence of kDa within more deprived socioeconomic groups.

Objectives Hereditary systemic autoinflammatory diseases are rare genetic disorders, which if untreated, can be complicated by AA amyloidosis leading to renal failure and premature death. Our objective was to find a genetic cause in a British family with a dominantly inherited autoinflammatory disease complicated by AA amyloidosis. Methods The index patient and his sister underwent comprehensive clinical and laboratory assessment including the next-generation sequencing panel targeting autoinflammatory genes. Subsequently, other relatives underwent clinical evaluation and genetic testing. Screening of the SAA1 gene was performed in all symptomatic cases. Results The index case and his sister presented with proteinuria due to AA amyloidosis. They have been suffering from episodes of fever accompanied by severe abdominal and chest pain, arthritis and erythema since childhood. Their father died aged 52 years from complications following a cadaveric renal transplantation. The post-mortem examination demonstrated AA amyloidosis. The index case’s grandmother, two paternal cousins and two of their children described similar symptoms. All symptomatic individuals had excellent responses to colchicine. Next-generation sequencing analysis identified a single MEFV p.P373L variant in the index case, his sister and subsequently, in symptomatic family members. Sequencing of the SAA1 gene revealed all cases were heterozygous for the SAA1.1 allele. Conclusion Typically FMF is an autosomal recessive disorder; nonetheless rare cases of dominantly inherited disease have previously been described. Here we report a novel MEFV variant p.P373L, causing dominant FMF complicated by AA amyloidosis in four generations of a British family.

Objective To describe the presenting clinical features, treatment and outcome in children with eosinophilic granulomatosis with polyangiitis (EGPA) and to define factors that predicted mortality. Methods A retrospective case notes review of patients fulfilling the Chapel Hill Consensus Conference definition and/or ACR criteria for EGPA seen at Great Ormond Street Hospital, London. Demographics, clinical features, histopathology, treatment and outcomes were recorded. Descriptive statistics were expressed as median and range. Fisher's exact test was used for group comparisons. The Paediatric Vasculitis Activity Score and Paediatric Vasculitis Damage Index (PVDI) were calculated. Results Thirteen children (38% female) aged at diagnosis 14.1 (4-15.6) years were identified. The median time to diagnosis was 2 (0-7.3) years. History of asthma was documented in 76%. The most common presenting features were pulmonary (69%), skin (61%), gastrointestinal (46%), cardiac involvement (46%), paranasal sinus abnormality (38%), arthritis/arthralgia (38%) and neurological involvement (15%). Paediatric Vasculitis Activity Score at presentation was 8/63 (2-25/63); ANCA was negative in all 10/13 patients tested. Treatment included corticosteroids in all, combined with CYC in 38% or AZA in 23%. PVDI at 12 (3-48) months follow-up was 3/72 (0-13/72). Relapses were recorded in 46%. Mortality was 15%; cardiomyopathy and PVDI scores ⩾5 significantly associated with mortality risk (P = 0.012). Conclusion EGPA in the paediatric population is a rare and potentially life-threatening vasculitis. Increased awareness is essential to secure a timely diagnosis and to promptly initiate treatment since our data emphasize a high mortality, particularly in those with cardiac involvement and significant accrued damage.

Objective To date there is no uniformly effective treatment for either chronic recurrent multifocal osteomyelitis (CRMO) or synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. We report on our clinical experience of using biologic therapy to treat children with these conditions. Methods Retrospective descriptive case series of four children with refractory disease treated with biologics. Disease activity was assessed at predetermined time points (T = 0, T = 6 weeks and T = 12 months after the start of biologic therapy, and at latest follow-up) using a combination of clinical examination and radiological findings: a 10 cm pain and physician visual analogue scale; the Childhood Health Assessment Questionnaire as an assessment of disability; and changes in markers of systemic inflammation. Results There was an initial improvement in all parameters assessed for all three children treated with TNF-alpha blockade, although the third case had to discontinue the therapy due to a suspected (but unconfirmed) fungal skin infection. Anakinra treatment alleviated the symptoms in the fourth patient at 6 weeks, but there was no sustained response to treatment at 1-year follow-up. Conclusion We present our preliminary experience of using biological therapies to treat children with CRMO and SAPHO in conjunction with other immunosuppression. Further studies are needed to establish the role of these therapies in refractory CRMO and SAPHO.

Objectives. To assess if age and/or age-dependent variations in the levels of two major calcification regulatory proteins, fetuin-A and osteopontin, could be associated with an increased risk of calcinosis in children with juvenile dermatomyositis (JDM). Methods. The frequency of calcinosis was derived from a national UK database of 212 cases of JDM. Serum fetuin-A and plasma osteopontin levels were determined using ELISA in 15 JDM patients with calcinosis and 15 JDM patients without calcinosis. Healthy controls were 19 age-matched children, 24 adolescents and 13 adults. Sixteen patients with juvenile idiopathic arthritis (JIA) were additional paediatric disease controls. Results. Of the 212 JDM cases 10% had calcinosis. Calcinosis patients had younger age of disease onset than those without calcinosis (mean age of 5.3 yrs vs 7.1 yrs, respectively, P ¼ 0.016). No significant difference in fetuin-A or osteopontin could be detected between the two JDM groups. Fetuin-A levels in all groups of children and the adolescent group were much lower than described previously in adults, and there was a significant positive correlation between age and fetuin-A level, and also between osteopontin levels in plasma and serum fetuin-A. Conclusions. Children who develop JDM at an younger age may have increased risk of developing calcinosis. Physiologically low levels of fetuin-A in young children combined with an additional negative acute-phase effect on fetuin-A due to chronic inflammation could explain in part the propensity to develop ectopic calcification observed in JDM patients, and why calcinosis is less frequent in adults with