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ObjectivePatients with Kawasaki disease (KD) with coronary artery enlargement at diagnosis are at the highest risk for persistent coronary artery aneurysms (CAAs) and may benefit from primary adjunctive anti-inflammatory therapy beyond intravenous immunoglobulin (IVIG). We evaluate the effect of primary adjunctive corticosteroid therapy on outcomes in patients with CAA at diagnosis.DesignSingle-centre, retrospective review.PatientsPatients with KD diagnosed within 10 days of fever onset and with baseline CA z-score ≥2.5.InterventionsPrimary treatment with IVIG (n=162) versus IVIG plus corticosteroids (n=48).Main outcome measuresTreatment resistance (persistent fever >36 hours after initial treatment), CAA regression rate.ResultsOf the 92 patients with KD who received corticosteroids at our institution from 2012 to 2019, 48 met the inclusion criteria for primary adjunctive therapy. The corticosteroid group was younger and had larger baseline CAAs compared with historical controls. Demographics and laboratory values were otherwise similar between groups. The corticosteroid group had a less treatment resistance (4% vs 30%, p=0.003) and a greater improvement in C reactive protein. After adjusting for baseline CA z-score, age and baseline bilateral versus unilateral CAA, the corticosteroid group had a higher odds of (OR 2.77 (1.04, 7.42), p=0.042) and a shorter time to CAA regression (HR 1.94 (1.27, 2.96), p=0.002).ConclusionPrimary adjunctive corticosteroid therapy is associated with decreased initial treatment resistance, greater improvement in inflammatory markers and higher likelihood of CAA regression in patients who have CAA at diagnosis. Multi-centre, randomised controlled trials are needed to confirm the benefits of corticosteroids in patients with CAA at diagnosis and to compare corticosteroids with other adjunctive therapies.

ObjectiveMacrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) characterised by a vicious cycle of immune amplification that can culminate in overwhelming inflammation and multiorgan failure. The clinical features of MAS overlap with those of active sJIA, complicating early diagnosis and treatment. We evaluated adenosine deaminase 2 (ADA2), a protein of unknown function released principally by monocytes and macrophages, as a novel biomarker of MAS.MethodsWe established age-based normal ranges of peripheral blood ADA2 activity in 324 healthy children and adults. We compared these ranges with 173 children with inflammatory and immune-mediated diseases, including systemic and non-systemic JIA, Kawasaki disease, paediatric systemic lupus erythematosus and juvenile dermatomyositis.ResultsADA2 elevation beyond the upper limit of normal in children was largely restricted to sJIA with concomitant MAS, a finding confirmed in a validation cohort of sJIA patients with inactive disease, active sJIA without MAS or sJIA with MAS. ADA2 activity strongly correlated with MAS biomarkers including ferritin, interleukin (IL)-18 and the interferon (IFN)-γ-inducible chemokine CXCL9 but displayed minimal association with the inflammatory markers C reactive protein and erythrocyte sedimentation rate. Correspondingly, ADA2 paralleled disease activity based on serial measurements in patients with recurrent MAS episodes. IL-18 and IFN-γ elicited ADA2 production by peripheral blood mononuclear cells, and ADA2 was abundant in MAS haemophagocytes.ConclusionsThese findings collectively identify the utility of plasma ADA2 activity as a biomarker of MAS and lend further support to a pivotal role of macrophage activation in this condition.

Background:Juvenile Localized Scleroderma (jLS) is a rare pediatric inflammatory disease of skin and underlying tissues that may cause significant functional impairment and disfigurement. Management approaches vary and an optimum treatment regimen is lacking. In 2012, a group of jLS researchers of Childhood Arthritis and Rheumatology Research Alliance (CARRA) proposed consensus treatment plans (CTPs), aimed to streamline the approach to care for jLS patients.Objectives:This study aimed to evaluate a large jLS patient cohort seen over a 21-year period in a single tertiary care pediatric hospital in the USA, in order to examine treatments utilized and determine parameters for systemic therapy initiation.Methods:This retrospective cohort study included jLS patients with disease onset in childhood (≤18-years of age) who were seen in rheumatology, dermatology, or combined rheumatology-dermatology clinics from 1999-2020, with ≤ 3 years of follow-up. Data on demographics, disease characteristics, therapies prescribed, and treatment trends were analyzed.Results:Of the 270 jLS patients identified, 101 fulfilled the inclusion criteria. The primary reason for exclusion was Table 1.Demographic and Disease CharacteristicsAll Patients(n=101)On Systemic Therapy(n=63)No Systemic Therapy(n=38)p valueAge-onset (Y), median (IQR)7.5 (6.4)9 (6)7 (4)NSAge-diagnosis(Y), median (IQR)9 (7.9)10 (6.7)9 (3.7)NSDiagnostic delay(M), median (IQR)10 (2.9)12 (13)7.5 (17)NSFollow-up (M), median (IQR)74 (69.3)65 (44.5)78 (47.7)NSSubtype Linear563917NS Face29209NS Circumscribed23419 Mixed220NS Generalized201820.004Extracutaneous Involvement191810.001Clinic type Dermatology29227 Rheumatology211920.003 Combined51429The majority of patients who were on systemic immunomodulatory therapy were treated with methotrexate (59/63, 93.6 %) and/or systemic corticosteroids (21/63, 33 %). 5 patients were treated with hydroxychloroquine, 2 of which were also on methotrexate. 6 patients on methotrexate were either switched to or had mycophenolate mofetil added as concomitant therapy. The most common adverse effects observed in methotrexate-treated patients were gastrointestinal complaints (12/61, 19.7%) and fatigue (7/61, 11.5%). The median treatment duration was 50 months (IQR: 33.5). Patients were more likely to receive systemic therapy if they were followed in rheumatology or combined rheumatology-dermatology clinics as compared to dermatology clinics. Finally, 78% of patients with jLS received systemic treatment after 2013 (a year after publication of the CARRA jLS CTP) as compared to 55% of patients prior to 2013 (p < 0.05).Conclusion:This jLS cohort is one of the largest reported from a single center and reflects an increase in the use of systemic therapy since publication of CARRA CTPs in 2012. Further studies on long-term treatment outcomes and therapeutic approaches utilized when first-line treatment failures occur are warranted.References:[1]Li SC, Torok KS, Pope E, et al. Development of consensus treatment plans for juvenile localized scleroderma: a roadmap toward comparative effectiveness studies in juvenile localized scleroderma. Arthritis Care Res (Hoboken). 2012;64(8):1175-1185.Disclosure of Interests:Bugra Egeli: None declared, Johnathan Dallas: None declared, Edwin Anderson: None declared, Michelle Min: None declared, Daniel Mazori: None declared, Stephen Gellis: None declared, Mary Beth Son: None declared, Robert Sundel: None declared, Ruth Vleugels: None declared, Fatma Dedeoglu Consultant of: Novartis

Background:The introduction of biologics has transformed care for children with systemic juvenile idiopathic arthritis (SJIA). Differences in treatment approaches between countries and how they have changed over time are not well studied.Objectives:We contrast the initial features, treatment and 12-month outcome in SJIA across 10 JIA registers in Europe and North America.Methods:Data were extracted locally from 10 Registers including manifestations at diagnosis, medication use over first year and outcomes (Physician Global Assessment (PGA), active joint count (AJC)) at 12 months. Data was compared before/after 2012 to assess change over time. Weighted (w) means were used to adjust for varying number of patients/Register.Results:1,149 patients; 553 had medication data for 2012-2018; primarily female and Caucasian; median age at diagnosis 5.3-8 years. Median duration of symptoms prior to first visit varied (0-3.3 months). Glucocorticoid (GC) use was common in the first year (w_average 72% (range 33-96%)). Biologic use included IL-1, IL-6 and TNF inhibitors. The proportion of patients treated with biologics, primarily anakinra, increased after 2012 (Table 1). W_mean PGA and AJC at the 12±3 month visit were 1.55 and 1.57, respectively (Table 2). At one year, the proportion of patients prescribed GC varied (w_mean 40%, range 26-60%).Conclusion:Analysis of SJIA patients across 10 countries show that time to first rheumatology visit was highly variable. Although local factors influence treatment decisions, biologic use increased after 2011; anakinra most common. Nearly 75% of patients were prescribed steroids within the first year but seemed to decrease after 1 year. More study is needed on long-term outcomes in SJIA patients within this modern era.1: Medication Usage within First Year (pre/post 2012 where available)Glucocorticoids (IV+PO)%Methotrexate%Biologic%Anti-IL-1%Anakinra%Tocilizumab%USA2010-2011n=922563333330USA2012-2018n=91501771705717Canada2005-2010n=8876601710100UK2001-2011n=69787110330UK2012-2018n=31485829191919Portugal2008-2011n=7342364330Portugal2012-2018n=19744732161621Sweden2009-2015n=50964662302830Denmark1997-2011n=83864013662Denmark2012-2018n=325012.575636319Turkey2000-2011n=71937758423720Turkey2012-2018n=11498524032289Germany2000-2011n=27173621376Germany2012-2018n=249574727191020Norway1997-2011n=26816212448Norway2012-2018n=510060100202080Finland2006-2011n=12424217008Finland2012-2018n=1225880082: Clinical Outcomes at 12 Months -all yearsAJCMedian [IQR]PGAMedian [IQR]GC Use, %USA0 [0, 0]0 [0,0]47Canada0 [0, 2]0.1 [0, 2.7]41UK0 [0, 0]0.5 [0, 1.7]53Portugal0 [0, 0]0.3 [0, 1]53Sweden0 [0, 0.5]0 [0, 0.5]31Denmark0 [0, 0]-26Turkey4 [2, 7]4 [3, 7]60Germany0 [0, 1]0 [0,2]36Norway0 [0, 0]0.5 [0, 2]45Finland0 [0, 0]0 [0, 0]33Disclosure of Interests:Mary Beth Son: None declared, Yukiko Kimura Consultant of: Genetech, Kristiina Aalto: None declared, Lillemor Berntson: None declared, Johnathan Dallas: None declared, Ciaran Duffy: None declared, Mia Glerup: None declared, Jaime Guzman: None declared, Troels Herlin: None declared, Petteri Hovi: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Jens Klotsche: None declared, Bo Magnusson: None declared, Vanessa McItyre: None declared, Ellen Nordal: None declared, Seza Özen: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Betül Sözeri: None declared, Timothy Beukelman Consultant of: UCB, Novartis