Angelo Ravelli

Recommendations for collaborative paediatric research including biobanking in Europe: a Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative

Innovative research in childhood rheumatic diseases mandates international collaborations. However, researchers struggle with significant regulatory heterogeneity; an enabling European Union (EU)-wide framework is missing. The aims of the study were to systematically review the evidence for best practice and to establish recommendations for collaborative research. The Paediatric Rheumatology European Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) project enabled a scoping review and expert discussion, which then informed the systematic literature review. Published evidence was synthesised; recommendations were drafted. An iterative review process and consultations with Ethics Committees and European experts for ethical and legal aspects of paediatric research refined the recommendations. SHARE experts and patient representatives vetted the proposed recommendations at a consensus meeting using Nominal Group Technique. Agreement of 80% was mandatory for inclusion. The systematic literature review returned 1319 records. A total of 223 full-text publications plus 22 international normative documents were reviewed; 85 publications and 16 normative documents were included. A total of 21 recommendations were established including general principles (1–3), ethics (4–7), paediatric principles (8 and 9), consent to paediatric research (10–14), paediatric databank and biobank (15 and 16), sharing of data and samples (17–19), and commercialisation and third parties (20 and 21). The refined recommendations resulted in an agreement of >80% for all recommendations. The SHARE initiative established the first recommendations for Paediatric Rheumatology collaborative research across borders in Europe. These provide strong support for an urgently needed European framework and evidence-based guidance for its implementation. Such changes will promote research in children with rheumatic diseases.

SHARE – workpackage 5: evidence-based recommendations for diagnosis and treatment of kawasaki disease and henoch schönlein purpura

Kawasaki Disease (KD) and Henoch Schonlein Purpura (HSP) are paediatric vasculitides that can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physician experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimize and disseminate guidelines for diagnosis and management for children and young adults with paediatric rheumatic diseases (PRD) such as KD and HSP within Europe.

SHARE – workpackage 5 : evidence based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus

Childhood-onset systemic lupus erythematosus (cSLE) is a rare multisystem autoimmune disease that often leads to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physician’s experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases such as cSLE.

SHARE – workpackage 5: evidence based recommendations for diagnosis and treatment of the antiphospholipid syndrome

Antiphospholipid syndrome (APS), either primary or secondary to other paediatric rheumatic diseases, is rare in children, but it can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physician’s experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases such as APS.

Comparazione tra esame clinico ed esame ecografico nell’artrite idiopatica giovanile (AIG)

Lo scopo del presente studio e stato quello di comparare la relativa sensibilita dell’esame ecografico articolare rispetto all’esame clinico in pazienti con AIG, poiche a tutt’oggi esistono poche informazioni a riguardo. Sono stati inclusi nello studio tutti i pazienti con diagnosi si artrite idiopatica giovanile secondo la definizione ILAR, osservati consecutivamente presso la clinica Pediatrica del Policlinico San Matteo di Pavia da settembre 2007 ad aprile 2008. I pazienti sono stati sottoposti nella stessa giornata ed in modo indipendente ad esame clinico ed valutazione ecografia di 52 articolazioni. Nell’analisi sono stati inclusi solo i pazienti che presentavano sinovite attiva in almeno una articolazioni in almeno una delle due valutazioni (clinica e/o ecografica). La valutazione clinica ha incluso: numero di articolazioni tumefatte, con dolore e limitazione funzionale, score della tumefazione, dolore, limitazione funzionale, coefficiente di severita articolare, giudizio globale del medico e del genitore sull’attivita di malattia (VAS, 0-10), Juvenile Arthritis Functionality Scale (JAFS), VES, PCR, JADAS52. La valutazione ecografica ha incluso il numero di articolazioni con iperplasia sinoviale, versamento articolare, power-doppler, lo score dei precedenti parametri ed il coefficiente di severita articolare ecografico. L’analisi statistica e stata condotta valutando la concordanza con il kappa di Coehn e la correlazione con il coefficiente di Spearman tra i parametri clinici ed ecografici. 32 pazienti sono stati inclusi nello studio con un totale di 1664 articolazioni esaminate. Un primo risultato ottenuto e che rispetto all’esame clinico, l’ecografia ha classificato un maggior numero di pazienti con poliartrite rispetto all’esame clinico. Tra le valutazioni cliniche ed ecografiche, e stata osservata una maggiore discordanza per le articolazioni del piede, i polsi, le interfalangee prossimali delle mani, nelle quali l’ecografia si e mostrata piu sensibile. La concordanza tra parametri clinici ed ecografici e risultata moderata, in particolare per la tumefazione articolare. E stata evidenziata una buona correlazione tra i parametri clinici ed ecografici per quel che riguarda il numero di articolazioni tumefatte e lo score di tumefazione, il numero di articolazioni attive ed il coefficiente di severita articolare clinico. Inoltre esiste elevata correlazione tra il numero di articolazioni con versamento articolare all’esame ecografico ed il numero di articolazioni attive all’esame clinico.

Grading of joint indices for severity reflects better the burden of joint disease and its impact on child's well-being in juvenile idiopathic arthritis (JIA)

Background and aim The severity of joint disease in JIA can be quantified by counting the number of joints with swelling, tenderness/ pain on motion, and restricted motion, and by calculating, through these parameters, the number of active joints (NAJ). Alternatively, a global articular severity score (GASS) can be obtained by grading symptoms in each joint and summing the scores obtained in all joints. Although the former method is currently preferred, it is unclear which method is more advantageous to capture the impact of joint disease on childs health and wellbeing. We aimed to compare the ability of NAJ and GASS to capture the impact of joint disease on childs health and well-being by assessing their correlation with physicians, parents and patients subjective ratings and functional ability assessment.

Chapter 4 Macrophage Activation Syndrome

Publisher Summary This chapter provides an overview of the clinical features, epidemiology, nomenclature, pathogenesis, diagnosis, and management of macrophage activation syndrome (MAS). MAS is a life-threatening complication of systemic inflammatory disorders seen most commonly in systemic juvenile idiopathic arthritis and is caused by the activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to widespread hemophagocytosis and cytokine overproduction. The clinical presentation of MAS is generally acute and occasionally dramatic. Recent findings in hemophagocytic lymphohistiocytosis, a disease that is clinically very similar to MAS, highlight the possible pathogenetic role of a defective function of cytotoxic lymphocytes. Prompt diagnosis is important. The chapter outlines the preliminary diagnostic guidelines for the syndrome are proposed. Cyclosporine A is effective in patients with corticosteroid resistant MAS, however, it is still unclear whether biologic agents have a role in the treatment of MAS.