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Objectives To evaluate the long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency during the open label extension (weeks 41–113) of the randomized controlled CLUSTER trial. Methods During a 72-week period, patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks. The disease activity was evaluated every 8 weeks using physician global assessment and counting the number of flares. Concentrations of CRP and serum amyloid A protein were measured. The safety was studied by determination and classification of observed adverse events. The safety and efficacy were analysed separately in three subgroups of patients receiving a cumulative dose of less than Results Of the 74 patients who started the CLUSTER study, 66 entered Epoch 4 and 65 completed it. During the 72-week period, 42 (64%) patients experienced no flares, while 13 (20%) had one flare, as compared with a median of 12 flares per year reported at baseline. Low physician global assessment scores were seen at the end of the study for all groups with >90% reporting minimal disease activity or none at all. Median CRP concentrations were consistently equal or lower than 10 mg/l, while median serum amyloid A concentrations remained only slightly above the normal range of 10 mg/l. The study showed no new or unexpected adverse events. Conclusion Canakinumab proved effective to control disease activity and prevent flares in mevalonate kinase deficiency during the 72-week study period. No new safety concerns were reported. Trial registration NCT02059291. https://clinicaltrials.gov.

T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single-cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1+ TOX+ EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+ TOX+ BHLHE40+ population of CD4+ , and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation in situ. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.

T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single-cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1

Lupus nephritis (LN) occurs in 50%–60% of patients with childhood-onset systemic lupus erythematosus (cSLE), leading to significant morbidity. Timely recognition of renal involvement and appropriate treatment are essential to prevent renal damage. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative aimed to generate diagnostic and management regimens for children and adolescents with rheumatic diseases including cSLE. Here, we provide evidence-based recommendations for diagnosis and treatment of childhood LN. Recommendations were developed using the European League Against Rheumatism standard operating procedures. A European-wide expert committee including paediatric nephrology representation formulated recommendations using a nominal group technique. Six recommendations regarding diagnosis and 20 recommendations covering treatment choices and goals were accepted, including each class of LN, described in the International Society of Nephrology/Renal Pathology Society 2003 classification system. Treatment goal should be complete renal response. Treatment of class I LN should mainly be guided by other symptoms. Class II LN should be treated initially with low-dose prednisone, only adding a disease-modifying antirheumatic drug after 3 months of persistent proteinuria or prednisone dependency. Induction treatment of class III/IV LN should be mycophenolate mofetil (MMF) or intravenous cyclophosphamide combined with corticosteroids; maintenance treatment should be MMF or azathioprine for at least 3 years. In pure class V LN, MMF with low-dose prednisone can be used as induction and MMF as maintenance treatment. The SHARE recommendations for diagnosis and treatment of LN have been generated to support uniform and high-quality care for all children with SLE.

Introduction/AbstractT lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro1–29. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA)30–33. However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the heterogeneity of synovial T lymphocytes in JIA patients by single cell RNA-sequencing. We identify subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1+TOX+EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+TOX+BHLHE40+ population of CD4+, and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.

Objectives IgA vasculitis (IgAV, formerly known as Henoch–Schönlein purpura) is the most common cause of systemic vasculitis in childhood. To date, there are no internationally agreed, evidence-based guidelines concerning the appropriate diagnosis and treatment of IgAV in children. Accordingly, treatment regimens differ widely. The European initiative SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) aims to optimize care for children with rheumatic diseases. The aim therefore was to provide internationally agreed consensus recommendations for diagnosis and treatment for children with IgAV. Methods Recommendations were developed by a consensus process in accordance with the EULAR standard operating procedures. An extensive systematic literature review was performed, and evidence-based recommendations were extrapolated from the included papers. These were evaluated by a panel of 16 international experts via online surveys and subsequent consensus meeting, using nominal group technique. Recommendations were accepted when ⩾80% of experts agreed. Results In total, 7 recommendations for diagnosis and 19 for treatment of paediatric IgAV were accepted. Diagnostic recommendations included: appropriate use of skin and renal biopsy, renal work-up and imaging. Treatment recommendations included: the importance of appropriate analgesia and angiotensin-converting enzyme inhibitor use and non-renal indications for CS use, as well as a structured approach to treating IgAV nephritis, including appropriate use of CS and second-line agents in mild, moderate and severe disease along with use of angiotensin-converting enzyme inhibitors and maintenance therapy. Conclusion The SHARE initiative provides international, evidence-based recommendations for the diagnosis and treatment of IgAV that will facilitate improvement and uniformity of care.

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, multisystem and potentially life-threatening autoimmune disorder with significant associated morbidity. Evidence-based guidelines are sparse and management is often based on clinical expertise. SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimise and disseminate management regimens for children and young adults with rheumatic diseases like cSLE. Here, we provide evidence-based recommendations for diagnosis and treatment of cSLE. In view of extent and complexity of cSLE and its various manifestations, recommendations for lupus nephritis and antiphospholipid syndrome will be published separately. Recommendations were generated using the EULAR (European League Against Rheumatism) standard operating procedure. An expert committee consisting of paediatric rheumatologists and representation of paediatric nephrology from across Europe discussed evidence-based recommendations during two consensus meetings. Recommendations were accepted if >80% agreement was reached. A total of 25 recommendations regarding key approaches to diagnosis and treatment of cSLE were made. The recommendations include 11 on diagnosis, 9 on disease monitoring and 5 on general treatment. Topics included: appropriate use of SLE classification criteria, disease activity and damage indices; adequate assessment of autoantibody profiles; secondary macrophage activation syndrome; use of hydroxychloroquine and corticosteroid-sparing regimens; and the importance of addressing poor adherence. Ten recommendations were accepted regarding general diagnostic strategies and treatment indications of neuropsychiatric cSLE. The SHARE recommendations for cSLE and neuropsychiatric manifestations of cSLE have been formulated by an evidence-based consensus process to support uniform, high-quality standards of care for children with cSLE.

Objectives The European initiative Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) aimed to optimize care for children with rheumatic diseases. Systemic vasculitides are very rare in children. Consequently, despite recent advances, paediatric-specific information is sparse. The lack of evidence-based recommendations is an important, unmet need. This study aimed to provide recommendations for diagnosing and treating children with rare forms of childhood systemic vasculitis. Methods Recommendations were developed by a consensus process in accordance with the European League Against Rheumatism standard operating procedures. A systematic literature review informed the recommendations, which were devised and evaluated by a panel of experts via an online survey, and two consensus meetings using nominal group technique. Recommendations were accepted when ⩾ 80% of experts agreed. Results Ninety-three relevant articles were found, and 78 recommendations were accepted in the two consensus meetings. General, cross-cutting recommendations and disease-specific statements regarding the diagnosis and treatment of childhood-onset PAN, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and Takayasu arteritis are provided. Conclusion These Single Hub and Access point for paediatric Rheumatology in Europe recommendations were formulated through an evidence-based consensus process to support uniform, high-quality standard of care for children with rare forms of paediatric systemic vasculitis.

In the past decades, we have gained important insights into the mechanisms of disease and therapy underlying chronic inflammation in juvenile idiopathic arthritis (JIA). These insights have resulted in several game-changing therapeutic modalities for many patients. However, additional progress still has to be made with regard to efficacy, cost reduction, minimization of side effects, and dose-tapering and stop strategies of maintenance drugs. Moreover, to really transform the current therapeutic strategies into personalized medicine, we need validated biomarkers to translate increased insights into clinical practice. In this article, we describe recent developments in JIA research and outline how clinical innovations need to go hand in hand with basic discoveries to really effect care for patients. Facilitating the transition from bench to bedside is crucial for addressing the major current challenges in JIA management. When successful, it will set new standards for a safe, targeted, and personalized medicine in JIA.

ObjectivesThe European Single Hub and Access point for paediatric Rheumatology in Europe initiative aimed to optimize care for children with rheumatic diseases. Kawasaki disease (KD) is the most common cause of acquired heart disease in children and an important cause of long-term cardiac disease into adulthood. Prompt diagnosis and treatment of KD is difficult due to the heterogeneity of the disease but is crucial for improving outcome. To date, there are no European internationally agreed, evidence-based guidelines concerning the diagnosis and treatment of KD in children. Accordingly, treatment regimens differ widely. The aim of this study is to provide consensus-based, European-wide evidence-informed recommendations for diagnosis and treatment of children with KD.MethodsRecommendations were developed using the EULAR’s standard operating procedures. An extensive systematic literature search was performed, and evidence-based recommendations were extrapolated from the included papers. These were evaluated by a panel of international experts via online surveys and subsequently discussed in three consensus meetings, using nominal group technique. Recommendations were accepted when ⩾80% agreed.ResultsIn total, 17 recommendations for diagnosis and 14 for treatment of KD in children were accepted. Diagnostic recommendations included laboratory and imaging workup for complete as well as incomplete KD. Treatment recommendations included the importance of early treatment in both complete and incomplete KD, use of intravenous immunoglobulin, aspirin, corticosteroids for high-risk cases, and other treatment options for those with resistant disease.ConclusionThe Single Hub and Access point for paediatric Rheumatology in Europe initiative provides international evidence-based recommendations for diagnosing and treating KD in children, facilitating improvement and uniformity of care.

During the last decade research has focused on the application of FOXP3+ regulatory T cells (Tregs) in the treatment of autoimmune disease. However, thorough functional characterization of these cells in patients with chronic autoimmune disease, especially at the site of inflammation, is still missing. Here we studied Treg function in patients with juvenile idiopathic arthritis (JIA) and observed that Tregs from the peripheral blood as well as the inflamed joints are fully functional. Nevertheless, Treg-mediated suppression of cell proliferation and cytokine production by effector cells from the site of inflammation was severely impaired, because of resistance to suppression. This resistance to suppression was not caused by a memory phenotype of effector T cells or activation status of antigen presenting cells. Instead, activation of protein kinase B (PKB)/c-akt was enhanced in inflammatory effector cells, at least partially in response to TNFα and IL-6, and inhibition of this kinase restored responsiveness to suppression. We are the first to show that PKB/c-akt hyperactivation causes resistance of effector cells to suppression in human autoimmune disease. Furthermore, these findings suggest that for a Treg enhancing strategy to be successful in the treatment of autoimmune inflammation, resistance because of PKB/c-akt hyperactivation should be targeted as well.

Autoinflammatory diseases are characterised by fever and systemic inflammation, with potentially serious complications. Owing to the rarity of these diseases, evidence-based guidelines are lacking. In 2012, the European project Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate regimens for the management of children and young adults with rheumatic diseases, facilitating the clinical practice of paediatricians and (paediatric) rheumatologists. One of the aims of SHARE was to provide evidence-based recommendations for the management of the autoinflammatory diseases cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and mevalonate kinase deficiency (MKD). These recommendations were developed using the European League Against Rheumatism standard operating procedure. An expert committee of paediatric and adult rheumatologists was convened. Recommendations derived from the systematic literature review were evaluated by an online survey and subsequently discussed at a consensus meeting using Nominal Group Technique. Recommendations were accepted if more than 80% agreement was reached. In total, four overarching principles, 20 recommendations on therapy and 14 recommendations on monitoring were accepted with >= 80% agreement among the experts. Topics included (but were not limited to) validated disease activity scores, therapy and items to assess in monitoring of a patient. By developing these recommendations, we aim to optimise the management of patients with CAPS, TRAPS and MKD.

8th International Congress of Familial Mediterranean Fever and Systemic Autoinflammatory Diseases

Despite a rapidly accumulating clinical experience with autologous stem cell transplantation (ASCT) as a treatment for severe refractory autoimmune disease, data on the mechanisms by which ASCT induces immune tolerance are still very scarce. In this study it is shown that ASCT restores immunologic self-tolerance in juvenile idiopathic arthritis (JIA) via 2 mechanisms. First, ASCT induces a restoration of the frequency of FoxP3 expressing CD4+CD25bright regulatory T cells (Tregs) from severely reduced numbers before ASCT to normal levels after ASCT. This recovery is due to a preferential homeostatic expansion of CD4+CD25+ Tregs during the lymphopenic phase of immunereconstitution, as measured by Ki67 and CD44 expression, and to a renewed thymopoiesis of naive mRNA FoxP3 expressing CD4+CD25+ Tregs after ASCT. Second, using artificial antigen-presenting cells to specifically isolate self-reactive T cells, we demonstrate that ASCT induces autoimmune cells to deviate from a proinflammatory phenotype (mRNA interferon-γ [IFN-γ] and T-bet high) to a tolerant phenotype (mRNA interleukin-10 [IL-10] and GATA-3 high). These data are the first to demonstrate the qualitative immunologic changes that are responsible for the induction of immune tolerance by ASCT for JIA: the restoration of the CD4+CD25+ immune regulatory network and reprogramming of autoreactive T cells.

Cryopyrin-associated periodic syndromes (CAPS) is a group of rare monogenetic autoinflammatory disorders. Evidence-based guidelines are lacking 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 pediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases.

Background FOXP3+ regulatory T cells (Treg) are critical in maintaining self tolerance and are therefore considered important targets for the treatment of autoimmune disease. However, environmental factors at the site of autoimmune inflammation, such as enhanced costimulatory potential of antigen presenting cells (APC) and increased proinflammatory cytokine production, can negatively affect Treg function, thereby limiting effectiveness of these Treg targeted approaches. Aim Here we studied the phenotype of APC present at the site of inflammation in patients with Juvenile Idiopathic Arthritis (JIA) and investigated whether these cells can interfere with Treg mediated suppression. Methods Mononuclear cells were isolated from peripheral blood (PB) of healthy controls (HC) and from paired PB and synovial fluid (SF) of JIA patients. The phenotype of APC was analysed using flow cytometry. In vitro suppression assays were performed to study T cell activation and Treg mediated suppression in the presence of SF and PB derived APC. Results Monocytes from the site of inflammation displayed a more pro-inflammatory phenotype, with significantly increased costimulatory molecule expression, compared to monocytes from PB. In line with this pro-inflammatory phenotype, SF APC induced enhanced proliferation of effector cells and decreased suppression of effector cell proliferation in the presence of Treg. Conclusions APC from the site of inflammation have an enhanced stimulatory capacity that interferes with Treg mediated suppression. Therefore, this increased stimulatory potential should be targeted as well, in order for a Treg enhancing approach to be fully effective in the treatment of autoimmune inflammation.

Since a decade autologous stem cell transplantation (ASCT) is successfully performed to treat patients with severe autoimmune disease. However, the mechanism of action of this intervention remains largely unknown. Scarce data from animal studies and human clinical trials indicate that, besides extensive immune ablation, restoration of regulatory immune networks is of critical importance. This review focuses on the role of naturally occurring and induced regulatory T cells in controlling immune reconstitution and restoration of immune tolerance and in preventing relapses of disease following ASCT.

Background The paediatric vasculitides are a group of rheumatic diseases characterized by blood vessel inflammation. Several vasculitic syndromes can be distinguished based on the size of the involved vessels as well as the specific symptoms. Incidence of these syndromes is low and evidence-based paediatric guidelines are lacking. SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) is a project that aims to develop European evidence-based guidelines for diagnosis and treatment of these and other rare paediatric rheumatic diseases (PRD). Objectives To develop evidence-based recommendations for diagnosis and treatment of paediatric vasculitides, i.e. Kawasaki Disease (KD), Henoch Schonlein Purpura (HSP), Polyarteritis Nodosa (PAN), Granulomatosis with Polyangiitis (GPA), Eosinophilic granulomatosis with Polyangiitis (EGPA) and Takayasu9s Arteritis (TA). Methods A systematic review of literature was conducted (results presented at PReS 2014), from which evidence-based recommendations were derived. A European expert committee evaluated these recommendations, both by online surveys and by discussion using the nominal group technique1 during several in-person consensus meetings in Genoa (Italy, March ’14, results presented at PReS 2014), Utrecht (the Netherlands, January ’15) and Barcelona (Spain, March ’15). Recommendations were accepted for the final guidelines if more than 80% agreement was reached. Results Evidence from literature and expert opinion led to the formulation of recommendations for the different paediatric vasculitides. Adding to the 44 statements accepted with more than 80% consensus in Genoa, an additional 78 statements were accepted in Utrecht. Included statements ranged across different topics, including criteria for diagnosis, referral indications, clinical and laboratory parameters, imaging and treatment of the different vasculitic syndromes. Statements for discussion in Barcelona will focus on general and interdisciplinary aspects of care for children with vasculitis and other PRDs. Conclusions SHARE aims to provide minimal standards of care for PRD. We present the final recommendations for diagnosis and treatment of paediatric vasculitides. These recommendations will contribute to a more uniform and evidence-based foundation for diagnosis and treatment of KD, HSP, PAN, GPA, EGPA and TA in children. References Harvey N, Holmes CA. Nominal group technique: an effective method for obtaining group consensus. Int J Nurs Pract. 2012; 18:188-94 Acknowledgements This project is supported by a grant from European Agency for Health and Consumers (EAHC), grant number 2011 1202. Disclosure of Interest None declared

Background Systemic onset Juvenile Idiopathic Artritis (sJIA) is considered an autoinflammatory disease, with increased circulating neutrophil counts and extremely high serum levels of S100 proteins and interleukin (IL)-18. We have previously shown that upon stimulation with S100 proteins and ATP, peripheral blood mononuclear cells (PBMCs) of healthy donors produce high levels of IL-1β and IL-18; however this cytokine production is decreased in PBMCs of sJIA patients with active disease and partly restored when patients are in remission. 1 Given the observed hyporesponsiveness of PBMCs from sJIA patients, we hypothesized that neutrophils might play an important role in the inflammatory cascade of sJIA. Objectives Our objective was to investigate the role of neutrophils in sJIA, with a focus on the relation between neutrophils, S100 proteins and IL-18. Methods We determined ex vivo cell frequencies of patients at disease onset, patients with inactive disease and healthy controls by flow cytometric analysis, using fluorescent beads for absolute counts. Neutrophils from healthy donors were sorted and subsequently primed with S100 proteins in a time series up to 20 hours with or without Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) for the last 10 minutes. Elastase and cytokine levels in supernatant were measured by Luminex, neutrophil activation markers were analysed by flow cytometry. Results Patients with new onset sJIA had significantly elevated neutrophil counts compared to healthy controls and patients with inactive disease. Immature neutrophils (CD16 dim CD62L + ) and normally matured neutrophils (CD16 + CD62L + ) were significantly higher in patients with new onset sJIA compared to healthy controls or patients with inactive disease, while hypersegmented neutrophils (CD16 + CD62L dim ) were comparable between patients and controls. Given the high serum levels of S100 proteins in active sJIA, we investigated if neutrophils could be activated by these proteins. Priming with S100A9 before stimulation with fMLP increased activation and degranulation of specific granules and secretory vesicles compared to unprimed cells. This was reflected by an increased expression of CD11b, CD66b and CD35. Upon stimulation with S100A9, we observed an increase in elastase secretion in the culture supernatant, as well as a minor increase in IL-6, IL-18 and TNF-α. Conclusions Patients with new onset sJIA have increased neutrophil counts. S100 proteins prime neutrophils and enhance degranulation upon a second stimulus such as fMLP. We are now exploring whether IL-18 or other pro-inflammatory mediators elevated in sJIA plasma can also prime neutrophils. Further, we will investigate whether ex vivo neutrophils from sJIA patients are more activated or respond differently to stimulation compared to patients with inactive disease or healthy controls. References N. Ter Haar, D. Holzinger, W. de Jager, R. Scholman, S. de Roock, B. Vastert. IL-18 production upon s100 stimulation is reduced in active sJIA patients compared to sJIA patients in remission and healthy controls. Pediatric Rheumatology 2014, 12(Suppl 1):O24 Acknowledgements We would like to acknowledge D. Holzinger, T. Vogl, D. Foell and J. Roth for providing the S100 proteins. Disclosure of Interest None declared

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.

Familial Mediterranean Fever (FMF) is a disease that starts in childhood and can lead to significant morbidity. In 2012, a European initiative called SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) has been launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. For FMF, attention was focused on genetics.

Mevalonate kinase deficiency (MKD) is a rare hereditary autoinflammatory syndrome that can lead to significant morbidity. Evidence-based guidelines are lacking 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 pediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases.

Systemic onset Juvenile Idiopathic Artritis (sJIA) is considered to be an autoinflammatory disease. The S100-proteins S100A8, S100A9 and S100A12 in serum and interleukin (IL)-18 in plasma are extremely elevated in sJIA patients and have been proposed to be useful biomarkers for diagnosis, disease activity and response to therapy. Moreover, sJIA patients seem to have a defective IL-18 NK cell axis as NK cell lytic function is impaired in spite of high IL-18 levels. However, it is still unknown how the inflammatory S100 proteins and IL-18 relate to each other, and to the defective NK cell lytic function.

Juvenile Dermatomyositis is a rare Pediatric Rheumatic Disease, associated with 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 pediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases.

In the following a brief commentary is given on a new European project that aims to provide the European countries with recommendations for the care of children and yound adults with rheumatic diseases. These recommendations will be based on surveys sent to PRINTO members and systematic literature reviews. Surveys on current local standard of care and best practice will be send to PRINTO members in EU member states. The success of this project largely largely depends on information provided by individual centers from our existing PRINTO and PReS networks. We would therefore like to ask your collaboration in completing and returning these surveys which will be circulated March April 2013.

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.

Methotrexate (MTX) is a cornerstone and safe disease-modifying anti-rheumatic drug (DMARD) in the treatment of juvenile idiopathic arthritis (JIA). Despite its safety, MTX intolerance occurs frequently, leading to non-compliance, thus hampering efficacy and potentially leading to early discontinuation.

A need for evidence-based guidelines for the management of paediatric rheumatic diseases (PRD) has been recognised. In 2012 the European Agency for Health and Consumers signed the contract for a new European initiative SHARE: Single Hub and Access point for paediatric Rheumatology in Europe (project number 2011 1202).