BackgroundThere is a lack of published evidence on the importance of methotrexate (MTX) dose and route of administration on both its efficacy and adverse events in children with Juvenile Idiopathic Arthritis (JIA). We aimed to document our clinical practice based on the treat-to-target approach in order to support the concept that better therapeutic effect achieved with an optimal dose of parenteral MTX is associated with clinically acceptable adverse effects comparable to those reported for oral treatment.MethodsStudy inclusion criteria were indication of new MTX therapy for active arthritis in confirmed JIA patients younger than 18 years. Eligible patients were evaluated prospectively every 3 months for 1 year using standardized instruments for treatment response (American College of Rheumatology Pediatric (ACRPedi) response, Juvenile Arthritis Disease Activity Score (JADAS) 71, Clinically Inactive Disease (CID)) and adverse events (laboratory monitoring, Methotrexate Intolerance Severity Score (MISS)). MTX responders had to achieve at least ACRPedi 70 response. MTX intolerance was defined by MISS ≥ 6.ResultsIn 45/55 patients (81.8 %) MTX was started as subcutaneous injection. The initial median weekly dose was 14.4 mg/m2 in parenteral and 11.7 mg/m2 in oral administration. MTX therapy was effective in the level of ACRpedi70 and CID in 50.9 % and 30.9 % of patients at month 6 and in 70.9 % and 56.4 % after 12 months of the treatment, respectively. MTX intolerance at 6 and 12 months was noted in 25.5 % and 30.6 %, respectively. Management of intolerance included change in the dose and/or route of administration, education and councelling. Adverse events led to MTX withdrawal in 5 patients (9 %) due to toxicity (n = 3) and intolerance (n = 2). We did not find any significant predictive factors for either MTX therapeutic response or intolerance.ConclusionSubcutaneous MTX weekly dose around 15 mg/m2 is associated not only with a high response rate within the first 12 months of treatment, but also with a relatively low rate of significant adverse effects that would lead to the treatment termination. It allows early recognition of MTX non-responders and addition of biologic therapy. Sustainability of therapeutic effect and longer-term evolution of adverse events will be addressed by an ongoing extension of the study.

ObjectiveTo quantify the impact of inflammatory brain diseases in the pediatric population on health-related quality of life, including the subdomains of physical, emotional, school and social functioning.MethodsThis was a multicenter, observational cohort study of children (< 18 years of age) diagnosed with inflammatory brain disease (IBrainD). Patients were included if they had completed at least one Health Related Quality of Life Questionnaire (HRQoL). HRQoL was measured using the Pediatric Quality of Life Inventory Version 4.0 (PedsQL) Generic Core Scales, which provided a total score out of 100. Analyses of trends were performed using linear regression models adjusted for repeated measures over time.ResultsIn this study, 145 patients were included of which 80 (55%) were females. Cognitive dysfunction was the most common presenting symptoms (63%), and small vessel childhood primary angiitis of the CNS was the most common diagnosis (33%). The mean child’s self-reported PedsQL total score at diagnosis was 68.4, and the mean parent’s proxy-reported PedsQL score was 63.4 at diagnosis. Child’s self-reported PedsQL scores reflected poor HRQoL in 52.9% of patients at diagnosis. Seizures or cognitive dysfunction at presentation was associated with statistically significant deficits in HRQoL.ConclusionPediatric IBrainD is associated with significantly diminished health-related quality of life. Future research should elucidate why these deficits occur and interventions should focus on improving HRQoL in the most affected subdomains, in particular for children presenting with seizures and cognitive dysfunction.

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BackgroundCyclophosphamide (CYC) has been a mainstay in the treatment of severe childhood primary systemic vasculitis. Although major organ involvement is rare in IgA vasculitis (IgAV), CYC is among therapeutic options in moderate and severe IgAV nephritis.(1) No specific recommendations are available for cerebral vasculitis of IgAV.ObjectivesTo describe disease course and treatment response in 2 patients with severe IgAV with CNS and renal involvement.MethodsCase reports with disease assessments using Paediatric Vasculitis Activity Score (PVAS).(2)ResultsBoth children were Caucasian boys with unremarkable previous history aged 4 (Patient 1) and 8 (Patient 2) years. In both cases the initial typical presentation included purpura and abdominal pain in both, arthritis in Patient 1 and haematuria in Patient 2. After 2 weeks of prednisone therapy for severe gastrointestinal (GIT) symptoms Patient 1 was admitted for right-sided weakness and facial palsy. His brain MRI revealed an ischaemic lesion. His PVAS reached 21/63 for skin, abdominal, renal (haematuria) and CNS systems. When Patient 2 was admitted for abdominal symptoms he developed a focal epileptic paroxysm. His brain MRI was compatible with cerebral vasculitis. His nephritic-nephrotic syndrome prompted renal biopsy showing mesangioproliferative nephritis with IgA deposits. His PVAS was 27/63 for skin, abdominal, renal (hypertension, haematuria, proteinuria) and CNS systems. Both patients received 3 doses of intravenous methylprednisolone 30 mg/kg followed by oral prednisone 1 mg/kg with subsequent tapering and 3 doses of CYC 500mg/m2(monthly i.v.). At follow-up 3 months after the 1st CYC dose both patients fully recovered neurologically. Patient 2 was on prednisone (0.2 mg/kg) and ACE inhibitor and his urine was negative for the first time, PVAS=0. Patient 1 had been developing significant proteinuria during prednisone withdrawal and his PVAS counted 10/63 for renal disease. Prednisone was re-instituted and ACE inhibitor added while renal biopsy has been pending.ConclusionIn both cases therapy with corticosteroids and CYC led to the full recovery of CNS disease but did not prevent progression of nephritis in Patient 1. Response of Patient 2 nephritis to CYC appeared satisfactory at 3 months visit but would require confirmation after full prednisone withdrawal. Although generally benign, when IgAV presents with major organ involvement its treatment is challenging. Further research is needed in order to gather better evidence to support treatment recommendations.References[1] özen S, et al. Europen consensus-based recommendations for diagnosis and treatment of IgA vasculitis – the SHARE initiative. Rheumatology (Oxford) 2019, in print[2] Doležalová P, et al. Disease activity assessment in childhood vasculitis: development and preliminary validation of the Paediatric Vasculitis Activity Score (PVAS). Ann Rheum Dis 2013 72(10):1628-33Disclosure of InterestsNone declared