MASTERCLASS

Royal College of Physicians of IrelandNo. 6 Kildare St, Dublin 2

Thursday and Friday, 6-7 May 2010

European Masterclass on Rheumatology

Welcome

Dr John Donohoe President, RCPI

Dear Delegates,

Welcome to Ireland; welcome to Dublin; welcome to the Royal College of Physicians of Ireland.

I am very pleased to be welcoming you to the third RCPI European Masterclass on Rheumatology, which brings together experts in emerging or controversial topics and provides a forum for in depth review of the topic and, importantly, provides opportunity for all participants to address the issues.

The organisers of the meeting recognise the complexity and the sensitivity of the issues to be dealt with. I am, therefore, very pleased to warmly welcome all of our presenters both from Ireland and, very particularly, those coming from abroad and to welcome all the delegates. I hope that you will find this meeting educationally beneficial and helpful in shaping your practice.

I want to thank the Faculty of Fellows of the College – Prof Michael Molloy, Prof Douglas Veale and Dr Paul O’Connell – who have constructed the programme. I am particularly grateful to Bristol-Myers Squibb for providing an unrestricted educational grant to support this meeting, and for their continued support of superior quality educational programmes.

We hope you enjoy your visit to Dublin and to an institution which fostered the golden age of Irish Medicine dominated by Graves, Stokes, Cheyne and Corrigan amongst others. We hope you will enjoy the blend of history and modern medicine.

Fáilte Romhat.

Dr John Donohoe President Royal College of Physicians of Ireland

Programme Chairpersons

This meeting is approved for 5 CME credits by the Royal College of Physicians of Ireland

Prof Douglas VealeConsultant Rheumatologist St Vincent’s University Hospital, Dublin, Ireland

Prof Veale will co-chair Session 1

Douglas Veale is Adjunct Professor of Medicine, UCD, Consultant Rheumatologist and Medical Director of Research at St Vincent’s University Hospital, principal investigator at the Conway Institute of Biomolecular and Biomedical Research in Dublin and Director of Translational Research for The Dublin Academic Health Care (DAHC) Medical Centre.

A graduate of the Royal College of Surgeons in Ireland (1984), Prof Veale completed his training at The Jervis Street Charitable Infirmary, Dublin, and the Waterford Regional Hospital. He commenced specialist and General Internal Medicine training in 1988 at Beaumont Hospital and St Vincent’s University Hospital achieving an MD degree by thesis in 1992. After 3 years as lecturer in Medicine, Prof Veale completed his training in the University of Dundee and Ninewells Hospital, receiving JCHMT(UK) accreditation in 1994. He was then appointed Senior Lecturer in Rheumatology at Leeds University, where he established with colleagues a premiere Early Arthritis Programme and Academic Musculoskeletal Centre, until his appointment at St Vincent’s University Hospital in 2001.

Prof Veale is a Fellow of the Royal College of Physicians of Ireland and the Royal College of Physicians of London. He is a Member of the American College of Rheumatology, the Irish and British Societies of Rheumatology, and the Society of Irish and American Rheumatologists, among others. He is an invited speaker at national and international meetings and a member of several advisory groups including The Health Research Board of Ireland and Arthritis Research Campaign (UK). The main focus of Prof Veale’s research is Translational Medicine of early inflammatory diseases including Rheumatoid arthritis, Psoriatic arthritis, Psoriasis and systemic sclerosis to understand the cellular and molecular mechanisms of angiogenesis and cartilage degradation, in addition to Biomarker Development.

Thursday, May 6, 2010TIME EVENT

20:00 Dinner for speakers, chairs and delegates at Dobbins Restaurant, Dublin

Friday, May 7, 2010TIME TITLE SPEAKER CHAIRPERSON

9:00 – 9:30 Registration

9:30 – 9:45 Welcome by Dr John Donohoe, President, Royal College of Physicians of Ireland

9:45 – 10:15 T-cell modulation in RAProf Vivianne Malmstrom, Karolinksa Institute, Sweden

Prof Douglas Veale,St Vincent’s University Hospital, Dublin, Ireland

10:15 – 10:45Management of children with juvenile idiopathic arthritis

Dr Nicolino Ruperto,Istituto Giannina Gaslini, Italy

Dr Orla Killeen,Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland

10:45 – 11:00 Discussion

11:00 – 11:15 Coffee Break

11:15 – 11:45

Progressive multifocal leukoencephalopathy: relevance to the rheumatologist

Dr Eamonn Molloy,St Vincent’s University Hospital, Dublin, Ireland

Prof Geraldine McCarthy, Mater Misericordiae University Hospital, Dublin, Ireland

11:45 – 12:15

Revealing the picture beneath: how novel imaging techniques have changed our approach to RA

Prof Walter Grassi,Università Politecnica delle Marche, Italy

Dr David Kane,AMNCH, Tallaght, Dublin, Ireland

12:15 – 12:30 Discussion

12:30 – 13:30 Lunch

13:30 – 14:00The new world of autoinflammatory diseases

Dr Richard Siegel, NIH/National Institute of Arthritis, Musculoskeletal & Skin Diseases, USA

Prof Michael Molloy,Cork University Hospital, Ireland

14:00 – 14:30DXA in 2010: Diagnostic test or fracture risk predictor

Dr John Carey, Merlin Park University Hospital, Galway, Ireland

Dr Alexander Fraser,Mid-Western Regional Hospital Limerick, Ireland

14:30 – 14.45 Discussion

14:45 – 15.15 Panel discussion led by Prof Michael Molloy

15:15 – 15.30 Close of session – Dr John Donohoe

Chairpersons

Geraldine McCarthy graduated in Medicine from University College Dublin, National University of Ireland. Having trained in General Internal Medicine in Ireland, she completed her Fellowship in Rheumatology at the Medical College of Wisconsin in 1991 where she was mentored by Drs Daniel McCarty, Lawrence Ryan, Robert Wortmann and Herman Cheung. During her Fellowship training, she developed her interest in calcium crystal deposition diseases and received a post-doctoral fellowship from the Arthritis Foundation to pursue her research programme which she has continued since then.

Prof McCarthy’s research is focused on the biological effects of calcium-containing crystals in degenerative joint disease as well as in atherosclerosis and breast cancer and has been facilitated by funding from many sources. These include the National Institutes of Health, American Federation for Aging Research, US Department of Defence and the Wellcome Trust. She was promoted to Associate Professor of Medicine at the Medical College of Wisconsin in 1996 where she remained until her return to Dublin, Ireland in 1998. At this time, she moved her laboratory to the Royal College of Surgeons in Ireland, where she was appointed Associate Professor of Molecular and Cellular Therapeutics. Part of her research programme continues at the RCSI and she teaches in Medicine and Pharmacy there. She was appointed Consultant in Rheumatology at the Mater Misericordiae University Hospital, Dublin in 1999 where she runs a busy clinical practice and has established a clinical research programme. She teaches as part of the University College Dublin Faculty of Medicine where she has been appointed Clinical Professor of Medicine. She is the author of over 90 publications and has spoken at many national and international meetings. She has established many national and international collaborations. She has been winner of several research and teaching awards and has mentored medicine and science graduates in clinical practice and in research.

Prof Geraldine McCarthyConsultant Rheumatologist Mater Misericordiae University Hospital, Dublin, Ireland

Prof McCarthy will co-chair Session 2

Dr Orla Killeen, Paediatric Rheumatologist Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland

Dr Killeen will co-chair Session 1

Orla Killeen qualified from UCG (NUI) Galway in 1996. She trained in General Paediatrics in Our Lady’s Hospital for Sick Children, Crumlin and in Temple Street University Hospital, Dublin before sub-specialising in Paediatric Rheumatology. She undertook her paediatric rheumatology training at Great Ormond Street Hospital in London and went on to complete a Barbara Ansell Fellowship in Paediatric Rheumatology in the Royal Hospital for Sick Children, Glasgow. She was appointed as Ireland’s first Paediatric Rheumatologist in 2004, and is based at Our Lady’s Children’s Hospital Crumlin and St Vincent’s University Hospital, Dublin since July 2006.

Chairpersons

Michael G Molloy is former Consultant Physician/Rheumatologist at Cork University Hospital and University College Cork. He is Course Director of the Master of Sport and Exercise Medicine (MMedSc) degree at Cork University Medical School. He is also Chief Medical Officer of the International Rugby Board and former Medical Advisor to the I.R.F.U. He is inaugural Dean of the Faculty of Sport and Exercise Medicine. He qualified at University College Galway, and did his postgraduate training at The London Hospital, Whitechapel, and Kings College Hospital, Denmark Hill.

In 1979 he returned to Ireland to take up a post as Consultant/Physician Rheumatologist at Cork University Hospital. He is a Fellow of the Royal College of Physicians of Ireland and the Royal College of Physicians of London and a Member of the American College of Rheumatology, the Irish and British Societies of Rheumatology and Society of Irish American Rheumatologists and is a past President of the latter two.

His research interests include the genetics of rheumatoid arthritis and osteoporosis. As Chief Medical Officer of the International Rugby Board, he is involved with collaborative research with all the major sporting federations worldwide. This involves research in concussion, sudden cardiac death and catastrophic injuries in sport and is involved in many injury prevention programmes.

Prof Michael Molloy Consultant Rheumatologist Cork University Hospital, Ireland

Prof Molloy will co-chair Session 3 and will lead the panel discusion at the end of Session 3

Dr David Kane, Consultant RheumatologistAMNCH, Tallaght, Dublin, Ireland

Dr Kane will co-chair Session 2

David Kane attended medical school at Trinity College, Dublin, Ireland and was conferred MB BCh BAO BA in 1991. He has trained in rheumatology with Prof Barry Bresnihan and Prof Oliver FitzGerald at St Vincent’s University Hospital, Dublin, Ireland and with Prof Roger Sturrock, Prof Iain McInnes and Dr Peter Balint at Glasgow Royal Infirmary, Glasgow, United Kingdom. He was appointed as Senior Lecturer in Rheumatology at the University of Newcastle in 2003 where he worked with Prof John Isaacs and Prof Tim Cawston. In 2005 he was appointed as Consultant Rheumatologist at the Adelaide and Meath Hospital and as Clinical Senior Lecturer at Trinity College Dublin, Ireland. His special interests are musculoskeletal ultrasound, inflammatory arthritis, education in rheumatology and bone health. He is a member of the European Working Party on Musculoskeletal Ultrasound and the OMERACT special interest group on musculoskeletal ultrasound which have established international training guidelines and diagnostic standards. He organised the British Society for Rheumatology Introductory Musculoskeletal Ultrasound course in Glasgow in 2002 and in Newcastle in 2005, he is a regular tutor on the BSR and EULAR Musculoskeletal ultrasound course and he was the convenor of the BSR Special Interest Group on Musculoskeletal Ultrasound. He has over 100 publications and has authored several book chapters on musculoskeletal ultrasound with invited lectures in the past few years from national rheumatology societies in New Zealand, UAE, Spain, France, Belgium, Mexico and the United Kingdom.

Session 1

9:45 – 10:15

T-cell modulation in RA

Prof Vivianne Malmstrom, Karolinksa Institute, Sweden

Vivianne Malmström is a cellular immunologist, and her research group is devoted to studying adaptive immunity in patients with inflammatory rheumatic disease.

She defended her thesis on T cell tolerance in murine arthritis in 1997 under the supervision of Professor Rikard Holmdahl and then went on to the University of Oxford as a Post-doctoral Fellow in the laboratory of Professor Fiona Powrie at the John Radcliffe Hospital. Here she studied murine colitis and the importance of different T cell subsets e.g. regulatory T cells.

In 2000 she moved to Stockholm and joined the constellation around Professor Lars Klareskog at the Center for Molecular Medicine, and at this point she switched from experimental models of inflammatory disease to translational research based on patient samples from the rheumatology clinic. During the last 10 years she has focused her work on understanding the contribution of T and B cell subsets to local inflammation and disease perpetuation, e.g. the first description of human regulatory T cells from a site of inflammation. Another longstanding interest is the so called CD28null T cells, a proinflammatory subset first described by Weyand and Goronzy. A third and more recent focus is the specificity of the citrulline response in RA where current efforts are focused on tracking both T and B cells and dissecting their functional contributions to the chronic inflammation.

Biographical Sketch

T cells have long been associated with RA based on the HLA shared epitope hypothesis. Still, their importance has been debated due to the scarcity of demonstrated T cell

autoreactivity in RA. I will present an updated view on T cells in RA, and discuss mechanisms of action whereby T cells are modulated by biological therapy.

Overview of Presentation

Chairpersons

Dr Alexander Fraser Consultant Rheumatologist,Mid-Western Regional Hospital, Limerick, Ireland

Dr Fraser will co-chair Session 3

Alexander Fraser is Consultant Rheumatologist, General Physician and Honorary Senior Lecturer Mid-Western Regional Hospitals, Dooradoyle, Limerick. He graduated in medicine from Trinity College Dublin in 1991. He began practicing Rheumatology in 1996 and the following year was appointed Specialist Registrar in Rheumatology at the Yorkshire Deanery. Training with Professor Emery’s group in Leeds he developed a research interest in clinical, immunological and therapeutic aspects of Rheumatoid Arthritis, Psoriatic Arthritis and the Seronegative Spondyloarthropathies. He was appointed Consultant Rheumatologist and Honorary Senior Lecturer at the Leeds Teaching Hospitals NHS Trust, working at The Leeds General Infirmary and St James University Hospital, in October 2001 and working closely with Professor Paul Emery and Professor Doug Veale he has published in the area of Angiogenesis, Vascularity and Inflammation in early and established arthritis and Biomarkers of cartilage turnover.

Dr Fraser took up his current appointment as Consultant Rheumatologist, General Physician and Honorary Senior Lecturer in the Mid-Western Region in August 2006.

11:15 – 11:45

Progressive multifocal leukoencephalopathy: relevance to the rheumatologist

Dr Eamonn Molloy, St Vincent’s University Hospital, Dublin, Ireland

Eamonn Molloy graduated from University College Dublin in 1997. Post-graduate training in Rheumatology was in Dublin, Ireland and Cleveland Clinic, Cleveland, Ohio, USA. In April 2008, he was appointed to the Consultant Staff at the Cleveland Clinic, jointly at the Center for Vasculitis Care and Research and the Center for Clinical Immunology. He joined the Department of Rheumatology at St Vincent’s University Hospital, Dublin in February 2010. Subspecialty interests include vasculitis, biologic therapies in rheumatic diseases and crystal-induced arthritis.

Session 2

Biographical Sketch

Progressive multifocal leukoencephalopathy (PML) is a rare infectious complication observed in patients with compromised immune systems from various causes. Advances in the understanding of PML have led to recognition that it may mimic neuroinflammatory diseases, including neuropsychiatric lupus and cerebral vasculitis. Several cases of PML have recently been reported in association with synthetic and biologic immunosuppressive agents used by

rheumatologists. These reports have served to heighten awareness and concern regarding this devastating infectious complication. In addition, data is emerging regarding a possible susceptibility to PML among patients with SLE, not solely referable to iatrogenic immunosuppression. This presentation will discuss these issues, with particular emphasis on the relevance to physicians treating patients with rheumatic disorders.

Overview of Presentation

Dr Ruperto will discuss the management of children with juvenile idiopathic arthritis.

Overview of Presentation

Biographical Sketch

Nicolino Ruperto was awarded a Degree in Medicine Magnum Cum Laudae from the University of Pavia, Italy, in 1990. He subsequently achieved a specialisation in Paediatrics in 1994, and a Masters in Public Health from Harvard School of Public Health, USA, in 1997.

Dr Ruperto began his professional career with a Paediatric Fellowship at Clinica Pediatrica, University of Pavia, Italy (1990–1994) and a Paediatric Rheumatology Research Fellowship at the Children’s Hospital Medical Center, Cincinnati, Ohio (1995–1996). Following his Masters in Public Health at the Harvard School of Public Health in Boston, MA (USA), Dr Ruperto took the position of Medical Director (Dirigente Medico) at the Department of Medical Informatics, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Policlinico S. Matteo, University of Pavia, Italy (1996–2001). Since 2001 he has held the position of Medical Director (Dirigente Medico) at the Paediatric clinic - Rheumatology IRCCS G Gaslini Children’s Hospital, Genova, Italy (2002). Paediatric clinic - Rheumatology IRCCS G Gaslini Children’s Hospital has been award the recognition of EULAR Centre of Excellence in Rheumatology 2008-2013.

He was among the founders (1997) of the Paediatric Rheumatology International Trials Organisation (PRINTO), where he holds the position of Senior Scientist since the foundation. Dr Ruperto has been granted several research grants, and was awarded the 2005 Gerolamo Gaslini Prize for Excellence in Research from the Gerolamo Gaslini Foundation.

Dr Ruperto’s research interests include paediatric rheumatology, clinical trials and outcomes assessment. He was active in the multinational consensus efforts leading to the development and validation of the core set of response variables, and preliminary definition of improvement for use in juvenile idiopathic arthritis, juvenile dermatomyositis and juvenile systemic lupus erythematosus. He is the Co-Principal Investigator and Project Manager for the five PRINTO grants from the European Union and is the Principal Investigator for several clinical trials (both for profit and not for profit).

Dr Ruperto has also published more than 150 peer-reviewed papers.

10:15 – 10:45

Management of children with juvenile idiopathic arthritisDr Nicolino Ruperto, Istituto Giannina Gaslini, Italy

Session 1

13:30 – 14:00

The new world of autoinflammatory diseasesDr Richard Siegel, NIH/National Institute of Arthritis, Musculoskeletal & Skin Diseases, USA

Richard Siegel obtained his Ph.D. in Immunology and M.D. from the University of Pennsylvania School of Medicine. He trained in Internal Medicine and Rheumatology at Hospital of the University of Pennsylvania, and then moved to the NIH to do postdoctoral training 1996, where he worked in Michael Lenardo’s laboratory in NIAID studying the molecular basis of autoimmunity in the Autoimmune Lymphoproliferative Syndrome (ALPS). In 2001, Dr Siegel moved to the National Institute of Arthritis, Musculoskeletal Diseases and Skin (NIAMS) at the NIH as an Investigator, where he also attends on the Rheumatology service at the NIH Clinical Center. He is presently Senior Investigator and Acting Chief of the Autoimmunity Branch in NIAMS, where he directs the Immunoregulation Section. The lab seeks to understand how alterations in regulatory signaling pathways in immune cells lead to abnormal immune responses, chronic inflammation, and autoimmune diseases, focusing principally on TNF-family cytokines. For the past five years, he has collaborated with Dan Kastner’s group to investigate the pathogenesis of the TNF-receptor associated periodic fever syndrome (TRAPS). He was elected to the Americal Society of Clinical Investigation in 2007 and also directs the NIH MD/PhD partnership training programme. More about the his research can be found at www.niams.nih.gov.

Biographical Sketch

In the past decade, there has been a revolution in our understanding of immune responses, with the discovery of receptors and signalling pathways underlying the ability of the innate immune system to sense pathogen and tissue-derived molecules. Rheumatological diseases can now be reclassified on this basis by placing them on a spectrum between autoimmune, which are driven by autoreactive T cells and/or autoantibodies, and autoinflammatory, in which inflammation and tissue damage occurs without evidence of abnormal adaptive immune cell activation or involvement of autoantigen-specific T cells. A number of Mendelian disorders have been discovered

in which key components of innate immune sensing and signal transduction are mutated in ways that hyperactivate the innate immune system. Some of the same molecules that are mutated in these rare syndromes, are crtitical in the pathogenesis of common common rheumatological conditions, such as NLRP3 in gout and TNF-receptor 1 in rheumatoid arthritis. Using mutations in TNF-receptor 1 associated with the autoinflammatory syndrome TRAPS as an example, what we have learned about pathogenesis and treatment of autoinflammatory diseases and the implications for our understanding of more common rheumatic conditions will be discussed.

Overview of Presentation

Session 3Session 2

Biographical Sketch

Walter Grassi gained his MD at the University of Ancona, Italy in 1979. Since 1997, he is Professor of Rheumatology and Director of the Postgraduate School in Rheumatology at the Università Politecnica delle Marche, and Chief of the Rheumatology Clinic at the Jesi Medical Center, Ancona, Italy.

His main interests include musculoskeletal imaging, ultrasonography, chronic arthritis, microcirculation, and nailfold capillary microscopy.

His current research interests focus on the role of sonography in early diagnosis and therapy monitoring of rheumatoid arthritis and seronegative spondyloarthropathies. He has authored over 200 publications including original articles and chapters in various textbooks of Rheumatology and Internal Medicine, has delivered over 200 invited lectures at international meetings, and is a peer reviewer for the leading international journals. He is also a member of the editorial boards of Annals of the Rheumatic Diseases, Clinical and Experimental Rheumatology, Clinical Rheumatology, and Reumatismo.

11:45 – 12:15

Revealing the picture beneath: how novel imaging techniques have changed our approach to RAProf Walter Grassi, Università Politecnica delle Marche, Italy

Prof Grassi will discuss how novel imaging techniques have changed our approach to RA.

Overview of Presentation

14:00 – 14:30

DXA in 2010: Diagnostic test or fracture risk predictorDr John Carey, Merlin Park University Hospital, Galway, Ireland

Biographical Sketch

John Carey is a Consultant Physician in Rheumatology and Medicine at Galway University Hospitals, and Clinical lecturer in Medicine, National University of Ireland, Galway. Dr Carey graduated from University College Dublin Medical School (MBBChBAO), and Case Western Reserve University, Cleveland, Ohio USA (MS). He completed his clinical training in medicine and rheumatology at St Vincent’s Hospital Dublin, Ireland, Boston University Medical Centre, Massachusetts, USA and The Cleveland Clinic, Cleveland, Ohio, USA. Dr Carey’s publications include book chapters, research and review papers on osteoporosis, osteoarthritis, imaging in musculoskeletal diseases and vasculitis. His current research projects observational studies of osteoporosis and diagnostic testing.

Osteoporosis is endemic in developed countries. Although many fractures are preventable most patients at risk are not evaluated and remain untreated. Bone mineral density (BMD) accounts for approximately 70% of bone strength, which can be measured by a variety of methods. Diagnostic criteria for osteoporosis using central dual-energy X-ray absorptiometry (DXA) were first proposed in 1994 and were hailed as a ‘Gold Standard’.

More recently DXA has been incorporated into fracture prediction tools. Similar to all diagnostic tests and clinical prediction tools such criteria have strengths and limitations. In his talk Dr Carey will discuss these issues as they related to DXA. His talk will focus on issues including sensitivity, specificity, positive and negative predictive value, risk assessment tools including accuracy, reliability and internal and external validity.

Overview of Presentation

Session 3 Notes

Notes

Royal College of Physicians of Ireland No.6 Kildare Street, Dublin 2Website: www.numbersix.ie

This meeting is supported by an unrestricted educational grant provided by BriStOl-MyerS SquiBB

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