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Psoriasis: HELP
Articles from St. James' University Hospital
Based on 31 articles published since 2008
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These are the 31 published articles about Psoriasis that originated from St. James' University Hospital during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. 2016

Gossec, L / Smolen, J S / Ramiro, S / de Wit, M / Cutolo, M / Dougados, M / Emery, P / Landewé, R / Oliver, S / Aletaha, D / Betteridge, N / Braun, J / Burmester, G / Cañete, J D / Damjanov, N / FitzGerald, O / Haglund, E / Helliwell, P / Kvien, T K / Lories, R / Luger, T / Maccarone, M / Marzo-Ortega, H / McGonagle, D / McInnes, I B / Olivieri, I / Pavelka, K / Schett, G / Sieper, J / van den Bosch, F / Veale, D J / Wollenhaupt, J / Zink, A / van der Heijde, D. ·Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, GRC-UPMC 08 (EEMOIS), Paris, France Department of rheumatology, AP-HP, Pitié Salpêtrière Hospital, Paris, France. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria Second Department of Medicine, Hietzing Hospital, Vienna, Austria. · Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands. · EULAR, representing People with Arthritis/Rheumatism in Europe (PARE), London, UK. · Research Laboratory and Clinical Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto, Italy. · Medicine Faculty, Paris Descartes University, Paris, France Rheumatology B Department, APHP, Cochin Hospital, Paris, France. · Leeds NIHR Musculoskeletal Biomedical Research Unit, LTHT, Leeds, UK Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. · Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands Atrium Medical Center, Heerlen, The Netherlands. · North Devon, UK. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · Rheumazentrum Ruhrgebiet, Herne and Ruhr-Universität Bochum, Herne, Germany. · Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Germany. · Arthritis Unit, Department of Rheumatology, Hospital Clínic and IDIBAPS, Barcelona, Spain. · Belgrade University School of Medicine, Belgrade, Serbia. · Department of Rheumatology, St. Vincent's University Hospital and Conway Institute, University College Dublin, Dublin, Ireland. · Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden Sweden and School of Business, Engineering and Science, Halmstad University, Halmstad, Sweden. · Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Belgium Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Department of Dermatology, University Hospital Münster, Münster, Germany. · A.DI.PSO. (Associazione per la Difesa degli Psoriasici)-PE.Pso.POF (Pan European Psoriasis Patients' Organization Forum), Rome, Italy. · Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. · Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy. · Institute and Clinic of Rheumatology Charles University Prague, Czech Republic. · Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. · Department of Rheumatology, Campus Benjamin Franklin, Charité, Berlin, Germany. · Ghent University Hospital, Ghent, Belgium. · Centre for Arthritis and Rheumatic Disease, Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland. · Schoen Klinik Hamburg, Rheumatology and Clinical Immunology, Hamburg, Germany. · Department of Rheumatology and Clinical Immunology, German Rheumatism Research Centre Berlin, Charité-University Medicine Berlin, Germany. ·Ann Rheum Dis · Pubmed #26644232.

ABSTRACT: BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

2 Review Qualifying unmet needs and improving standards of care in psoriatic arthritis. 2014

Helliwell, Philip / Coates, Laura / Chandran, Vinod / Gladman, Dafna / de Wit, Maarten / FitzGerald, Oliver / Kavanaugh, Arthur / Strand, Vibeke / Mease, Philip J / Boehncke, Wolf-Henning / Langley, Richard G / Lubrano, Ennio / Maccarone, Mara / Schulze-Koops, Hendrik / Miceli-Richard, Corinne / Queiro, Ruben. ·Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. ·Arthritis Care Res (Hoboken) · Pubmed #25047391.

ABSTRACT: -- No abstract --

3 Review MRI and ultrasonography for diagnosis and monitoring of psoriatic arthritis. 2012

Coates, Laura C / Hodgson, Richard / Conaghan, Philip G / Freeston, Jane E. ·Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK. L.C.Coates@leeds.ac.uk ·Best Pract Res Clin Rheumatol · Pubmed #23273793.

ABSTRACT: Imaging techniques such as magnetic resonance imaging (MRI) and ultrasound (US) have been increasingly used in psoriatic arthritis (PsA) providing additional clues to the pathogenesis of this peripheral, axial and dermatologic disease. This has improved our understanding of the disease and can be used to aid diagnosis and then to follow outcomes of treatment. Both imaging modalities have highlighted the differing involvement of PsA when compared with rheumatoid arthritis (RA) with a significant burden of entheseal disease, flexor tenosynovitis (occurring alone or as part of dactylitis) and other extra-capsular inflammatory changes. MRI scanning has also highlighted the link between the nail and the distal interphalangeal (DIP) joint confirming previous clinical observations. Imaging studies in psoriasis patients have discovered a high level of subclinical inflammatory change but the clinical importance of such findings has not yet been defined. The potential use of MRI and US to monitor treatment outcomes has encouraged research in this field. In MRI, the PsA MRI Score (PsAMRIS) has been developed with promising initial validation. In US, work is ongoing with the OMERACT group to define key pathologies and to develop scoring systems. A few scoring systems are available for enthesitis scoring using US which are further being developed and refined. Further improvements in technologies in both of these fields offer exciting possibilities for future research. New MRI techniques offer the chance to image previously 'dark' structures such as tendons which is key in spondyloarthritides (SpA). Sonoelastography may also improve our understanding of tendon involvement in SpA. Whole-body multi-joint MRI allows a 'snapshot' of inflammation in PsA including joints, entheses and spinal involvement. Three-dimensional US should improve reliability and comparability of US scoring reducing inter-operator variability. The latest machines offer real-time fusion imaging employing US machines with an in-built virtual navigator system linked to previous MRI acquisitions. All of these new techniques should aid our understanding of PsA and our ability to objectively measure response to therapy.

4 Review A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis. 2012

Ash, Zoe / Gaujoux-Viala, Cécile / Gossec, Laure / Hensor, Elizabeth M A / FitzGerald, Oliver / Winthrop, Kevin / van der Heijde, Désirée / Emery, Paul / Smolen, Josef S / Marzo-Ortega, Helena. ·Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. ·Ann Rheum Dis · Pubmed #21803753.

ABSTRACT: OBJECTIVES: To review the available evidence for the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and biological drug therapies for the different clinical manifestations of psoriatic arthritis (PsA) in order to provide data for the development of treatment recommendations by the European League Against Rheumatism (EULAR) taskforce. METHODS: A systematic literature review (SLR) of available treatments for PsA was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE) by two working groups formed within the EULAR taskforce. This comprised a comprehensive sample of rheumatologists, dermatologists, epidemiologists and patients. The available evidence was reviewed for NSAIDs, synthetic disease modifying antirheumatic drugs (DMARDs), local and systemic corticosteroids and biologic drugs. All articles and abstracts published between 1962 and January 2010 were reviewed and considered and a meta-analysis of data on biological therapies was performed. RESULTS: While little data are available on NSAIDs, glucocorticoids and synthetic DMARDs, the available evidence suggests an acceptable efficacy and safety profile of both NSAIDs and synthetic DMARDs (methotrexate, cyclosporine A, sulfasalazine and leflunomide) in PsA. More evidence is available (level 1B) supporting the efficacy of anti-tumour necrosis factor (anti-TNF) agents (adalimumab, etanercept, golimumab and infliximab) in treating the signs and symptoms of PsA as well as reducing radiographic progression. Registry data show no new safety concerns, although the numbers studied to date are relatively small. CONCLUSIONS: This SLR reveals some evidence to support the use of NSAIDs and synthetic DMARDs and good evidence for the efficacy of anti-TNF therapy in PsA.

5 Review The early phase of psoriatic arthritis. 2011

McGonagle, Dennis / Ash, Zoe / Dickie, Laura / McDermott, Michael / Aydin, Sibel Zehra. ·Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA, UK. D.G.McGonagle@leeds.ac.uk ·Ann Rheum Dis · Pubmed #21339224.

ABSTRACT: Evaluation of the preclinical phases of the classic autoimmune diseases including rheumatoid arthritis has been facilitated by the availability of autoantibody and genetic markers that point firmly towards the early dysregulation of the adaptive immune responses. The association of psoriatic disease with the human leucocyte antigen-Cw0602 (HLA-Cw0602) gene has likewise led to the perception that autoimmunity has a pivotal role in early psoriatic arthritis (PsA). However, this HLA-Cw0602 genetic association does not appear to hold for PsA or associated nail, scalp and intergluteal skin involvement. Of note, these three sites of psoriasis are predictive of PsA evolution. For initiation of both skin and nail disease there is a link with Koebnerisation, or site-specific trauma. Nail disease is most common in the dominant hand thumbnail, pointing towards local tissue factors as disease initiators Likewise, for PsA, there is also good evidence for a history of previous joint trauma and histological studies showing microdamage in normal entheses which are typical locations where PsA frequently occurs. Furthermore, subclinical enthesopathy including osteitis is common in subjects with psoriasis but without arthritis. Collectively, these findings indicate that the classic model of adaptive immune dysregulation does not generally hold for the early stages of PsA. The way in which knowledge pertaining to tissue-specific factors in PsA, combined with the emerging data relating to monogenic disorders and animal models, points towards perturbation in the healing response and dysregulation of innate immune responses in early PsA is discussed. The way in which this model explains the clinical disconnect between skin and joint disease and the emerging human data that support it are demonstrated.

6 Review Golimumab - a new tool in the armoury against inflammatory arthritis. 2011

Ash, Zoe / Emery, Paul. ·Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK. ·Ann Med · Pubmed #21244218.

ABSTRACT: The development of biological drugs blocking tumour necrosis factor-alpha (TNF-α) has had a dramatic impact on the treatment of inflammatory arthritis in recent years. Golimumab is a fully human monoclonal antibody which inhibits TNF-α. It is licensed for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In this review we evaluate the results of phase III studies using golimumab and explore the place of golimumab in the treatment of these diseases.

7 Review Disease measurement--enthesitis, skin, nails, spine and dactylitis. 2010

Coates, Laura C / Helliwell, Philip S. ·Academic Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK. ·Best Pract Res Clin Rheumatol · Pubmed #21035086.

ABSTRACT: Outcome measurement is a key part of study design but presents particular challenges in spondyloarthropathy. Enthesitis and dactylitis are typical features of spondyloarthropathy and validated scoring systems for both are available, although the majority of enthesitis outcome measures are validated in ankylosing spondylitis (AS) only. Assessment of axial disease is well researched in AS and composite outcome measures are routinely used. However, assessment of axial disease in predominantly peripheral arthritis, such as psoriatic arthritis, is problematic and under-researched. Extensive research in dermatology has provided multiple outcome measures for skin psoriasis. The psoriasis area and severity index (PASI) remains the most common outcome measure used, despite the fact that significant problems exist with this scale and that newer scoring methods and modifications of the PASI show better validity. Nail psoriasis is accurately measured by detailed scoring systems but these can be time-consuming.

8 Review Psoriatic arthritis: correlation between imaging and pathology. 2010

Tan, Ai Lyn / McGonagle, Dennis. ·Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds and Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, United Kingdom. a.l.tan@leeds.ac.uk ·Joint Bone Spine · Pubmed #20409741.

ABSTRACT: Psoriatic arthritis (PsA) is an archetypal type of spondyloarthritis, but may have some features of rheumatoid arthritis, namely a small joint polyarthritis pattern. Most of these features are well demonstrated on imaging, and as a result, imaging has helped us to better understand the pathophysiology of PsA. Although the unique changes of PsA such as the "pencil-in-cup" deformities and periostitis are commonly shown on conventional radiography, PsA affects all areas of joints, with enthesitis being the predominant pathology. Imaging, especially magnetic resonance imaging (MRI) and ultrasonography, has allowed us to explain the relationships between enthesitis, synovitis (or the synovio-entheseal complex) and osteitis or bone oedema in PsA. Histological studies have complemented the imaging findings, and have corroborated the MRI changes seen in the skin and nails in PsA. The advancement in imaging technology such as high-resolution "microscopy" MRI and whole-body MRI, and improved protocols such as ultrashort echo time, will further enhance our understanding of the disease mechanisms. The ability to demonstrate very early pre-clinical changes as shown by ultrasonography and bone scintigraphy may eventually provide a basis for screening for disease and will further improve the understanding of the link between skin and joint disease.

9 Review Enthesitis: an autoinflammatory lesion linking nail and joint involvement in psoriatic disease. 2009

McGonagle, D. ·NIHR, Leeds Biomedical Research Unit, Leeds Institute of Molecular Medicine (LIMM), Wellcome Trust Brenner Building, St James' University Hospital, Leeds, LS9 7TF, UK. d.g.mcgonagle@leeds.ac.uk ·J Eur Acad Dermatol Venereol · Pubmed #19686380.

ABSTRACT: The traditional model for psoriasis and psoriatic arthritis (PsA) is that autoimmunity directed against a common skin and joint autoantigen leads to chronic autoreactive T cell driven inflammation. However, recent imaging, histological and genetic studies have challenged this view, especially with respect to joint and nail disease, and provide a broader insight into the pathogenesis of PsA and associated nail involvement. Clinically unrecognized enthesitis (inflammation at tendon and ligament attachments) is commonly seen in early PsA at all sites of the disease. Specifically, enthesitis is associated with adjacent osteitis or bone and synovial inflammation. Even in normal joints, normal insertions are associated with microdamage and inflammatory change, strongly suggesting that local tissue specific, or what has been described as autoinflammatory factors, may dictate disease expression. Distal interphalangeal (DIP) joint disease in PsA is associated with diffuse inflammation that envelops the nail root and adjacent bone. In fact, the nail is intimately linked to entheses, with the extension tendon of the DIP joint sending fibres from bone that envelop the nail root in an interdigitating fashion. Furthermore, the joint collateral ligament enthesis has fibres that merge with the lateral borders of the nail. Other anchorage mechanisms include fibres that directly tether the nail plate to the underlying periosteum, which itself is closely anchored to the extension tendon. The frequent microdamage and tissue repair at normal enthesis attachment sites in healthy joints has resulted in a proposed new model of PsA pathogenesis embracing the concept of autoinflammation, whereby tissue specific factors, including microtrauma, lead to regional innate immune activation and persistent inflammation, as an alternative to primary immunopathology driven by T and B cell abnormalities. Unlike the classical autoimmune diseases, which may attack a completely normal organ, autoimmunity in psoriatic disease is likely to involve tissues where there is intrinsic dysregulation of the target tissues. These tissue specific factors related to the enthesis appear to be key to the phenotypic expression of diseases hitherto regarded as autoimmune. The pathogenesis of PsA, nail disease and to a lesser extent psoriasis therefore appear to have an autoinflammatory (innate immune driven) rather than autoimmune basis. Taken together, these findings are important for better understanding PsA, nail disease and psoriasis, and for conceptualizing the immunopathogenic basis of these diseases and further exploring the role of enthesitis in their pathophysiology.

10 Review The pathogenesis of psoriatic arthritis and associated nail disease: not autoimmune after all? 2009

McGonagle, Dennis / Benjamin, Michael / Tan, Ai Lyn. ·Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds and Chapel Allerton Hospital, Leeds, UK. d.g.mcgonagle@leeds.ac.uk ·Curr Opin Rheumatol · Pubmed #19424069.

ABSTRACT: PURPOSE OF REVIEW: Both psoriasis and psoriatic arthritis (PsA), and by implication psoriatic nail disease, have been considered as autoimmune disorders. This was based on the assumption that T-cell-directed responses against common skin and synovial antigens led to shared immunopathological mechanisms at these different sites, which was indirectly supported by the human leucocyte antigen-Cw6 disease association. This study draws on recent microanatomical and genetic studies of PsA, psoriasis and psoriatic-associated nail disease to show how the prevailing autoimmunity concepts for psoriatic disease need to be redrawn, especially in the case of joint and nail disease. RECENT FINDINGS: Recent microanatomical studies confirm that normal tendon and ligament insertion points to bone (entheses), the key territory for the inflammatory reaction associated with PsA, being subject to microdamage that strongly points to a role for microtrauma in the joints, which is reminiscent of Koebner responses in the skin. Furthermore, the nail is functionally integrated with entheses associated with the distal phalanx that provides anchorage to the skin and joint. Although type 1 psoriasis is strongly linked to the human leucocyte antigen-Cw6, recent genetic studies have suggested that both joint and nail disease do not share this association. SUMMARY: These microanatomical and genetic insights have important implications for a better understanding of PsA and nail disease and for an improved understanding of the psoriatic disease spectrum.

11 Article The Impact of Ramadan Fasting on the Reduction of PASI Score, in Moderate-To-Severe Psoriatic Patients: A Real-Life Multicenter Study. 2019

Damiani, Giovanni / Watad, Abdulla / Bridgewood, Charlie / Pigatto, Paolo Daniele Maria / Pacifico, Alessia / Malagoli, Piergiorgio / Bragazzi, Nicola Luigi / Adawi, Mohammad. ·Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20161 Milan, Italy. dr.giovanni.damiani@gmail.com. · Young Dermatologists Italian Network (YDIN), GISED, 24122 Bergamo, Italy. dr.giovanni.damiani@gmail.com. · Department of Medicine ’B’, Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel Aviv University, 5265601 Tel Aviv, Israel. watad.abdulla@gmail.com. · Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, LS7 4SA Leeds, UK. watad.abdulla@gmail.com. · Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, LS7 4SA Leeds, UK. C.D.Bridgewood@leeds.ac.uk. · Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20161 Milan, Italy. paolopigatto@valeo.it. · Clinical Dermatology Department, S. Gallicano Dermatological Institute, IRCCS, 00144 Rome, Italy. alessia.pacifico@tiscali.it. · Dermatology Unit, Azienda Ospedaliera San Donato Milanese, 20097 Milan, Italy. dermapier@gmail.com. · Postgraduate School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, Italy. robertobragazzi@gmail.com. · Padeh and Ziv Hospitals, Azrieli Faculty of Medicine, Bar-Ilan University, 5290002 Ramat Gan, Israel. adawimo1802@gmail.com. ·Nutrients · Pubmed #30691245.

ABSTRACT: Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the "Psoriasis Area and Severity Index" (PASI) score after the Ramadan fasting (mean difference = -0.89 ± 1.21,

12 Article MicroRNA-146 and cell trauma down-regulate expression of the psoriasis-associated atypical chemokine receptor ACKR2. 2018

Shams, Kave / Kurowska-Stolarska, Mariola / Schütte, Fabian / Burden, A David / McKimmie, Clive S / Graham, Gerard J. ·From the Skin Research Group, Leeds Institute of Rheumatic and Musculoskeletal Medicine, National Institute for Health Research Biomedical Research Centre and. · Department of Dermatology, Chapel Allerton Hospital, Leeds LS7 4SA, United Kingdom. · Chemokine Research Group and. · Institute of Infection, Immunity and Inflammation, 120 University Place, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom, and. · Department of Dermatology, Lauriston Building, Edinburgh EH3 9HA, Scotland, United Kingdom. · Virus Host Interaction Team, Leeds Institute of Cancer and Pathology, University of Leeds, St. James' University Hospital, Leeds LS9 7TF, United Kingdom. · Chemokine Research Group and gerard.graham@glasgow.ac.uk. ·J Biol Chem · Pubmed #29279330.

ABSTRACT: Chemokines are the principal regulators of leukocyte migration and are essential for initiation and maintenance of inflammation. Atypical chemokine receptor 2 (ACKR2) binds and scavenges proinflammatory CC-chemokines, regulates cutaneous T-cell positioning, and limits the spread of inflammation

13 Article Defining Outcome Measures for Psoriatic Arthritis: A Report from the GRAPPA-OMERACT Working Group. 2017

Ogdie, Alexis / de Wit, Maarten / Callis Duffin, Kristina / Campbell, Willemina / Chau, Jeffrey / Coates, Laura C / Eder, Lihi / Elmamoun, Musaab / FitzGerald, Oliver / Gladman, Dafna D / Goel, Niti / James, Jana / Kalyoncu, Umut / Latella, John / Lindsay, Chris / Mease, Philip J / O'Sullivan, Denis / Steinkoenig, Ingrid / Strand, Vibeke / Tillett, William / Orbai, Ana-Maria. ·From Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; University of Utah, Salt Lake City, Utah; QuintilesIMS, Denver, Colorado; Duke University School of Medicine, Durham, North Carolina; Rheumatology Research, Swedish Medical Center; University of Washington School of Medicine, Seattle, Washington; International Dermatology Outcome Measurers, West Granby, Connecticut; Cleveland Clinic, Cleveland, Ohio; Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, California; Johns Hopkins University School of Medicine; Psoriatic Arthritis Program, Johns Hopkins Arthritis Center, Baltimore, Maryland, USA; VU Medical Centre, Amsterdam, the Netherlands; University of Toronto; Krembil Research Institute; Psoriatic Disease Program, Toronto Western Hospital; Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada; Hong Kong Psoriatic Arthritis Association, Hong Kong, China; UK National Institute for Health Research (NIHR), Leeds; Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Royal United Hospital; Royal United Hospital; Pharmacy and Pharmacology, University of Bath, UK; Newman Clinical Research Professor, St. Vincent's University Hospital and University College Dublin; Our Lady's Hospice and Care Services, Dublin, Ireland; Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey. alexis.ogdie@uphs.upenn.edu. · A. Ogdie, MD, Assistant Professor of Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania; M. de Wit, PhD, Patient Research Partner, VU Medical Centre; K. Callis Duffin, MD, University of Utah; W. Campbell, BEd LLB, Patient Research Partner, Toronto Western Hospital; J. Chau, BA, MCS, Patient Research Partner, Hong Kong Psoriatic Arthritis Association; L.C. Coates, MBChB, PhD, Clinical Lecturer, NIHR, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; L. Eder, MD, PhD, Assistant Professor of Medicine, Women's College Research Institute, Women's College Hospital; M. Elmamoun, MBBS, MRCPI, Fellow, University of Toronto, Toronto Western Hospital; O. FitzGerald, MD, FRCPI, FRCP( UK), Newman Clinical Research Professor, St. Vincent's University Hospital and University College Dublin; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Senior Scientist, Krembil Research Institute, and Director, Psoriatic Disease Program, Toronto Western Hospital; N. Goel, MD, Patient Research Partner, Vice President, Advisory Services, QuintilesIMS, and Adjunct Assistant Professor, Duke University School of Medicine; J. James, Patient Research Partner, Royal United Hospital; U. Kalyoncu, MD, Assistant Professor of Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine; J. Latella, BS, MS, Patient Research Partner, and Board Member, International Dermatology Outcome Measurers; C. Lindsay, PharmD, Patient Research Partner; P.J. Mease, MD, Rheumatology Research, Swedish Medical Center, and Clinical Professor, University of Washington School of Medicine; D. O'Sullivan, BE, Patient Research Partner, Our Lady's Hospice and Care Services; I. Steinkoenig, BA, Patient Research Partner, Cleveland Clinic; V. Strand, MD, Division of Immunology/Rheumatology, Stanford University School of Medicine; W. Tillett, MBChB, PhD, Consultant Rheumatologist, Senior Lecturer, Royal United Hospital, and Pharmacy and Pharmacology, University of Bath; A.M. Orbai, MD, MHS, Assistant Professor of Medicine, Johns Hopkins University School of Medicine, and Director, Psoriatic Arthritis Program, Johns Hopkins Arthritis Center. alexis.ogdie@uphs.upenn.edu. · From Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; University of Utah, Salt Lake City, Utah; QuintilesIMS, Denver, Colorado; Duke University School of Medicine, Durham, North Carolina; Rheumatology Research, Swedish Medical Center; University of Washington School of Medicine, Seattle, Washington; International Dermatology Outcome Measurers, West Granby, Connecticut; Cleveland Clinic, Cleveland, Ohio; Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, California; Johns Hopkins University School of Medicine; Psoriatic Arthritis Program, Johns Hopkins Arthritis Center, Baltimore, Maryland, USA; VU Medical Centre, Amsterdam, the Netherlands; University of Toronto; Krembil Research Institute; Psoriatic Disease Program, Toronto Western Hospital; Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada; Hong Kong Psoriatic Arthritis Association, Hong Kong, China; UK National Institute for Health Research (NIHR), Leeds; Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Royal United Hospital; Royal United Hospital; Pharmacy and Pharmacology, University of Bath, UK; Newman Clinical Research Professor, St. Vincent's University Hospital and University College Dublin; Our Lady's Hospice and Care Services, Dublin, Ireland; Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey. · A. Ogdie, MD, Assistant Professor of Medicine and Epidemiology, Perelman School of Medicine, University of Pennsylvania; M. de Wit, PhD, Patient Research Partner, VU Medical Centre; K. Callis Duffin, MD, University of Utah; W. Campbell, BEd LLB, Patient Research Partner, Toronto Western Hospital; J. Chau, BA, MCS, Patient Research Partner, Hong Kong Psoriatic Arthritis Association; L.C. Coates, MBChB, PhD, Clinical Lecturer, NIHR, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; L. Eder, MD, PhD, Assistant Professor of Medicine, Women's College Research Institute, Women's College Hospital; M. Elmamoun, MBBS, MRCPI, Fellow, University of Toronto, Toronto Western Hospital; O. FitzGerald, MD, FRCPI, FRCP( UK), Newman Clinical Research Professor, St. Vincent's University Hospital and University College Dublin; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Senior Scientist, Krembil Research Institute, and Director, Psoriatic Disease Program, Toronto Western Hospital; N. Goel, MD, Patient Research Partner, Vice President, Advisory Services, QuintilesIMS, and Adjunct Assistant Professor, Duke University School of Medicine; J. James, Patient Research Partner, Royal United Hospital; U. Kalyoncu, MD, Assistant Professor of Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine; J. Latella, BS, MS, Patient Research Partner, and Board Member, International Dermatology Outcome Measurers; C. Lindsay, PharmD, Patient Research Partner; P.J. Mease, MD, Rheumatology Research, Swedish Medical Center, and Clinical Professor, University of Washington School of Medicine; D. O'Sullivan, BE, Patient Research Partner, Our Lady's Hospice and Care Services; I. Steinkoenig, BA, Patient Research Partner, Cleveland Clinic; V. Strand, MD, Division of Immunology/Rheumatology, Stanford University School of Medicine; W. Tillett, MBChB, PhD, Consultant Rheumatologist, Senior Lecturer, Royal United Hospital, and Pharmacy and Pharmacology, University of Bath; A.M. Orbai, MD, MHS, Assistant Professor of Medicine, Johns Hopkins University School of Medicine, and Director, Psoriatic Arthritis Program, Johns Hopkins Arthritis Center. ·J Rheumatol · Pubmed #28461531.

ABSTRACT: The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group recently published the updated 2016 psoriatic arthritis (PsA) core domain set, a set of disease features that should be measured in all clinical trials. At the GRAPPA annual meeting in July 2016, the PsA working group presented the updated PsA core domain set endorsed by 90% of participants at OMERACT in May 2016 and drafted a roadmap for the development of the PsA core outcome measurement set. In this manuscript, we review the development process of the PsA core domain set and the ongoing and proposed work streams for development of a PsA core measurement set.

14 Article Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2. 2017

Shams, Kave / Wilson, Gillian J / Singh, Mark / van den Bogaard, Ellen H / Le Brocq, Michelle L / Holmes, Susan / Schalkwijk, Joost / Burden, A David / McKimmie, Clive S / Graham, Gerard J. ·Chemokine Research Group, Institute of Infection, Immunity and Inflammation, 120 University Place, University of Glasgow, Glasgow, UK. · Department of Dermatology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands. · Glasgow Royal Infirmary, 84 Castle Street, Glasgow, UK. · Chemokine Research Group, Institute of Infection, Immunity and Inflammation, 120 University Place, University of Glasgow, Glasgow, UK; Department of Dermatology, Lauriston Building, Edinburgh, UK. · Chemokine Research Group, Institute of Infection, Immunity and Inflammation, 120 University Place, University of Glasgow, Glasgow, UK; Virus Host Interaction Team, Leeds Institute of Cancer and Pathology, University of Leeds, St James' University Hospital, Leeds, UK. Electronic address: c.s.mckimmie@leeds.ac.uk. · Chemokine Research Group, Institute of Infection, Immunity and Inflammation, 120 University Place, University of Glasgow, Glasgow, UK. Electronic address: gerard.graham@glasgow.ac.uk. ·J Invest Dermatol · Pubmed #27568525.

ABSTRACT: Elucidating the poorly defined mechanisms by which inflammatory lesions are spatially restricted in vivo is of critical importance in understanding skin disease. Chemokines are the principal regulators of leukocyte migration and are essential in the initiation and maintenance of inflammation. The membrane-bound psoriasis-associated atypical chemokine receptor 2 (ACKR2) binds, internalizes and degrades most proinflammatory CC-chemokines. Here we investigate the role of ACKR2 in limiting the spread of cutaneous psoriasiform inflammation to sites that are remote from the primary lesion. Circulating factors capable of regulating ACKR2 function at remote sites were identified and examined using a combination of clinical samples, relevant primary human cell cultures, in vitro migration assays, and the imiquimod-induced model of psoriasiform skin inflammation. Localized inflammation and IFN-γ together up-regulate ACKR2 in remote tissues, protecting them from the spread of inflammation. ACKR2 controls inflammatory T-cell chemotaxis and positioning within the skin, preventing an epidermal influx that is associated with lesion development. Our results have important implications for our understanding of how spatial restriction is imposed on the spread of inflammatory lesions and highlight systemic ACKR2 induction as a therapeutic strategy in the treatment and prevention of psoriasis and potentially a broad range of other immune-mediated diseases.

15 Article Plantar forefoot pressures in psoriatic arthritis-related dactylitis: an exploratory study. 2016

Wilkins, Richard A / Siddle, Heidi J / Redmond, Anthony C / Helliwell, Philip S. ·Section of Clinical Biomechanics and Physical Medicine, Leeds Institute of Rheumatic and Musculoskeletal Medicine, 2nd Floor, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK. r.a.wilkins@leeds.ac.uk. · Foot Health Department, Leeds Teaching Hospitals NHS Trust, Lower Ground Floor, Chancellor Wing, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK. r.a.wilkins@leeds.ac.uk. · Section of Clinical Biomechanics and Physical Medicine, Leeds Institute of Rheumatic and Musculoskeletal Medicine, 2nd Floor, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK. · Foot Health Department, Leeds Teaching Hospitals NHS Trust, Lower Ground Floor, Chancellor Wing, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK. · Rheumatology Department, Bradford Teaching Hospitals NHS foundation Trust, St Luke's Hospital, Little Horton Lane, Bradford, BD5 0NA, UK. ·Clin Rheumatol · Pubmed #27225246.

ABSTRACT: Dactylitis is a common feature of psoriatic arthritis (PsA); local physical trauma has been identified as a possible contributing factor. The aim of this study was to explore differences in forefoot plantar pressures in patients with PsA with and without dactylitis and compare to healthy controls. Thirty-six participants were recruited into three groups: group A PsA plus a history of dactylitis; group B PsA, no dactylitis; group C control participants. Forefoot plantar pressures were measured barefoot and in-shoe at the left second and fourth toes and corresponding metatarsophalangeal joints. Temporal and spatial parameters were measured and data from the foot impact scale for rheumatoid arthritis (FIS-RA), EQ5D and health assessment questionnaire (HAQ) were collected. Pressure time integral peak plantar pressure, and contact time barefoot and in-shoe were not significantly different between groups. Temporal and spatial parameters reported no significant differences between groups. ANOVA analysis and subsequent post hoc testing using Games-Howell test yielded significance in FIS-RA scores between both PsA groups versus controls, A p ≤ 0.0001 and PsA group B p < 0.0001 in the FIS-RA impairment and footwear domain, PsA group A p < 0.03 and PsA group B p ≤ 0.05 in the FIS-RA activity and participation domain compared to controls. This is the first exploratory study to investigate forefoot plantar pressures in patients with and without historical dactylitis in PsA. FIS-RA scores indicate PsA patients have significant limitations compared to controls, although a history of dactylitis does not appear to worsen patient reported outcomes.

16 Article Development of a Flare Instrument for Use in Psoriatic Disease: A Report from the 2015 GRAPPA Annual Meeting. 2016

Moverley, Anna R / Waxman, Robin / de Wit, Maarten / Parkinson, Andrew / Campbell, Willemina / Brooke, Melanie / Gossec, Laure / Helliwell, Philip S. ·From the Clinical Trials Research Unit, Leeds Institute of Molecular Medicine, University of Leeds; Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK; VU Medical Centre, Amsterdam, The Netherlands; Toronto Western Hospital, Toronto, Ontario, Canada; PsAZZ Psoriatic Arthritis Support Group, Bath, UK; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, GRC-UPMC 08 (EEMOIS); AP-HP, Pitié Salpêtrière Hospital, Department of Rheumatology, Paris, France; Bradford Hospitals UK National Health Service (NHS) Foundation Trust, Bradford, UK.A.R. Moverley, MRCP, Research Fellow, Clinical Trials Research Unit, Leeds Institute of Molecular Medicine, University of Leeds; R. Waxman, MPH, Research Coordinator, Leeds Institute of Rheumatic and Musculoskeletal Medicine; M. de Wit, PhD, Patient Research Partner, VU Medical Centre; A. Parkinson, Patient Research Partner; W. Campbell, BEd, LLB, Patient Research Partner, Toronto Western Hospital; M. Brooke, Patient Research Partner, Chair, PsAZZ Psoriatic Arthritis Support Group; L. Gossec, MD, PhD, Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, GRC-UPMC 08 (EEMOIS), AP-HP, Pitié Salpêtrière Hospital, Department of Rheumatology; P.S. Helliwell, DM, PhD, FRCP, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and Bradford Hospitals NHS Foundation Trust. ·J Rheumatol · Pubmed #27134273.

ABSTRACT: OBJECTIVE: The objective of this Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative is to develop a questionnaire to determine the presence of a flare of disease activity in psoriatic disease (PsD), for use in clinical care and research settings. METHODS: In 2014 and 2015, 2 online Delphi surveys of patients and physicians attempted to achieve consensus about items that might discriminate a flare of disease. In the first round, items were derived from previous qualitative studies with patients; in the second round, new items, suggested by both patients and physicians, were added. Survey results were discussed at the 2015 GRAPPA annual meeting, and 8 breakout groups discussed specific aspects of PsD flares. RESULTS: Survey participants were patients (n = 103 and n = 57 in rounds 1 and 2) and physicians (n = 125 and n = 81). Items for flare covered 6 domains (joints, skin, emotion, participation, fatigue, and unclassified). Patients agreed that 20 items were important (10 joints, 1 participation, 8 fatigue, 1 unclassified), and physicians agreed on 23 items (5 skin, 11 joints, 4 participation, 3 unclassified). Eight items were selected as important by both groups: 7 joint items and 1 unclassified. Patients emphasized fatigue and physicians emphasized skin and participation. Breakout groups concluded that the components of a flare instrument should be derived from patients. A flare should be defined as a change in disease state requiring intervention. CONCLUSION: The concept of flare in PsD covers articular, skin, emotional, participation, and fatigue domains. Further work is required to specify items that represent these domains.

17 Article Let's Talk about Inclusion: A Report on Patient Research Partner Involvement in the GRAPPA 2015 Annual Meeting. 2016

de Wit, Maarten / Campbell, Willemina / Coates, Laura C / Gladman, Dafna D / James, Jana / Lindsay, Chris A / MacDonald, Roland / Moverley, Anna R / Ogdie, Alexis / Orbai, Ana-Maria / O'Sullivan, Denis / Parkinson, Andrew / Steinkoenig, Ingrid / Tillett, William / Goel, Niti. ·From the VU Medical Centre, Amsterdam, The Netherlands; Krembil Research Institute of Toronto Western Hospital, and the University of Toronto, and the Psoriatic Arthritis Program, University Health Network, Toronto, Ontario, Canada; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; University of Pennsylvania, Philadelphia, Pennsylvania, USA; Johns Hopkins Division of Rheumatology, Baltimore, Maryland, USA; St. Vincent's University Hospital, Dublin, Ireland; Cleveland Clinic, Cleveland, Ohio, USA; Royal National Hospital for Rheumatic Diseases, Bath, UK; Duke University School of Medicine, Durham, North Carolina, USA.M. de Wit, PhD, Patient Research Partner, VU Medical Centre, Amsterdam, The Netherlands; W. Campbell, BEd, LLB, Patient Research Partner, Toronto Western Hospital; L.C. Coates, MBChB, PhD, UK National Institute for Health Research Clinical Lecturer, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, Senior Scientist, Krembil Research Institute, Director, Psoriatic Arthritis Program, University Health Network; J. James, Patient Research Partner; C.A. Lindsay, PharmD, Patient Research Partner; R. MacDonald, Patient Research Partner; A.R. Moverley, MB, BS, BSc, MRCP, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; A. Ogdie, University of Pennsylvania; A.M. Orbai, MD, MHS, Johns Hopkins Division of Rheumatology; D. O'Sullivan, BE, Patient Research Partner; A. Parkinson, Patient Research Partner; I. Steinkoenig, BA, Patient Research Partner; W. Tillett, BSc, MB ChB, PhD, MRCP, Royal National Hospital for Rheumatic Diseases; N. Goel, MD, Patient Research Partner, Duke University School of Medicine. ·J Rheumatol · Pubmed #27134272.

ABSTRACT: Members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) have worked since 2012 to include the patient perspective in their psoriatic arthritis (PsA) research as well as in their annual meetings. Herein, patient research partners (PRP) report the progress made in their experience at these GRAPPA meetings and discuss their perception of the challenges that remain in ensuring that patients have a voice in PsA outcome research.

18 Article Association of Toll-like receptor 4 (TLR4) with chronic plaque type psoriasis and psoriatic arthritis. 2016

Smith, Rh Ll / Hébert, H L / Massey, J / Bowes, J / Marzo-Ortega, H / Ho, P / McHugh, N J / Worthington, J / Barton, A / Griffiths, C E M / Warren, R B. ·The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, M6 8HD, UK. · Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. · NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. · The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, Manchester, UK. · Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath, UK. · NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. · The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, M6 8HD, UK. richard.warren@manchester.ac.uk. ·Arch Dermatol Res · Pubmed #26830904.

ABSTRACT: Family studies have provided overwhelming evidence for an underlying genetic component to psoriasis. Toll-like receptors (TLRs) are key transmembrane proteins in both the innate and adaptive immune responses which are known to be integral processes in psoriasis. Recent functional studies support this notion having suggested a role for TLR4 in the pathogenesis of psoriasis. Furthermore a missense polymorphism in the TLR4 gene has been associated with a number of autoimmune conditions, including Crohn diseases, making TLR4 a viable candidate gene for investigation. The aim of this study was to investigate polymorphisms across the TLR4 region with a high-density single nucleotide polymorphism (SNP) panel in a large cohort of patients with chronic plaque type psoriasis. Twenty SNPs were successfully genotyped using Sequenom iPLEX Gold platform in 2826 UK chronic plaque type psoriasis patients including subgroup data on presence of confirmed psoriatic arthritis (n = 1839) and early-onset psoriasis (n = 1466) was available. Allele frequencies for psoriasis patients were compared against imputed Wellcome Trust Case Control Consortium controls (n = 4861). Significant association was observed between a missense variant rs4986790 of TLR4 (Asp229Gly) and plaque type psoriasis (p = 2 × 10(-4)) which was also notable in those with psoriatic arthritis (p = 2 × 10(-4)) and early-onset psoriasis (p = 8 × 10(-4)). We present data suggestive of an association between a functional variant and an intronic variant of TLR4 and chronic plaque type psoriasis and psoriatic arthritis. However, validation of this association in independent cohorts will be necessary.

19 Article PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus. 2015

Bowes, John / Loehr, Sabine / Budu-Aggrey, Ashley / Uebe, Steffen / Bruce, Ian N / Feletar, Marie / Marzo-Ortega, Helena / Helliwell, Philip / Ryan, Anthony W / Kane, David / Korendowych, Eleanor / Alenius, Gerd-Marie / Giardina, Emiliano / Packham, Jonathan / McManus, Ross / FitzGerald, Oliver / Brown, Matthew A / Behrens, Frank / Burkhardt, Harald / McHugh, Neil / Huffmeier, Ulrike / Ho, Pauline / Reis, Andre / Barton, Anne. ·Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. · Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany. · Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. · Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester, UK. · Monash University, Melbourne, Victoria, Australia. · NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. · Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland. · Adelaide and Meath Hospital and Trinity College Dublin, Dublin, Ireland. · Royal National Hospital for Rheumatic Diseases and Department Pharmacy and Pharmacology, University of Bath, Bath, UK. · Department of Public Health and Clinical Medicine, Rheumatology, University Hospital, Umeå, Sweden. · Department of Biopathology, Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, University of Rome 'Tor Vergata' and Fondazione PTV 'Policlinico Tor Vergata', Rome, Italy. · Rheumatology Department, Haywood Hospital, Health Services Research Unit, Institute of Science and Technology in Medicine, Keele University. · Department of Rheumatology, St. Vincent's University Hospital, UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. · The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia. · Division of Rheumatology and Fraunhofer IME-Project-Group Translational Medicine and Pharmacology, Goethe University, Frankfurt, Germany. · Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester, UK. ·Ann Rheum Dis · Pubmed #25923216.

ABSTRACT: OBJECTIVES: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA. METHODS: A total of 15 single nucleotide polymorphisms were selected (PImmunochip <1×10(-4)) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity. RESULTS: We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49×10(-9), OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2×10(-4)). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27×10(-9)). CONCLUSIONS: For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis.

20 Article Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. 2015

Bowes, John / Budu-Aggrey, Ashley / Huffmeier, Ulrike / Uebe, Steffen / Steel, Kathryn / Hebert, Harry L / Wallace, Chris / Massey, Jonathan / Bruce, Ian N / Bluett, James / Feletar, Marie / Morgan, Ann W / Marzo-Ortega, Helena / Donohoe, Gary / Morris, Derek W / Helliwell, Philip / Ryan, Anthony W / Kane, David / Warren, Richard B / Korendowych, Eleanor / Alenius, Gerd-Marie / Giardina, Emiliano / Packham, Jonathan / McManus, Ross / FitzGerald, Oliver / McHugh, Neil / Brown, Matthew A / Ho, Pauline / Behrens, Frank / Burkhardt, Harald / Reis, Andre / Barton, Anne. ·Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK. · 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences, Manchester M13 9WU, UK. · Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen 91054, Germany. · 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, UK. · 1] JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK [2] Centre for Biostatistics, Institute of Population Health, The University of Manchester, Jean McFarlane Building, Oxford Road, Manchester M13 9PL, UK. · 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester M13 9WL, UK. · Monash University, Melbourne, Victoria 3800, Australia. · NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS7 4SA, UK. · CogGene Group, Discipline of Biochemistry and School of Psychology, National University of Ireland, Galway, Ireland. · Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland. · Adelaide and Meath Hospital and Trinity College Dublin, Dublin 24, Ireland. · The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, UK. · Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath BA1 1RL, UK. · Department of Public Health and Clinical Medicine, Rheumatology, University Hospital, Umeå 901 87, Sweden. · Department of Biopathology, Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, University of Rome 'Tor Vergata' and Fondazione PTV 'Policlinico Tor Vergata', Rome 18-00173, Italy. · Rheumatology Department, Haywood Hospital, Health Services Research Unit, Institute of Science and Technology in Medicine, Keele University, Keele ST5 5BG, UK. · Department of Rheumatology, St. Vincent's University Hospital, UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland. · The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland QLD 4102, Australia. · Division of Rheumatology and Fraunhofer IME-Project-Group Translational Medicine and Pharmacology, Goethe University, Frankfurt 60590, Germany. ·Nat Commun · Pubmed #25651891.

ABSTRACT: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8(+) memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.

21 Article Patient participation in psoriasis and psoriatic arthritis outcome research: a report from the GRAPPA 2013 Annual Meeting. 2014

de Wit, Maarten / Campbell, Willemina / FitzGerald, Oliver / Gladman, Dafna D / Helliwell, Phillip S / James, Jana / Lindsay, Chris / MacDonald, Roland / McHugh, Neil J / Mease, Philip J / Orbai, Ana-Maria / Palominos, Penélope / Parkinson, Andrew / Tillett, William / Goel, Niti. ·From the Department of Rheumatology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; University of Toronto; Toronto Western Research Institute; Psoriatic Arthritis Program, University Health Network, Toronto, Ontario, Canada; University of Leeds, Leeds, UK; Royal National Hospital for Rheumatic Diseases, UK National Health Service (NHS) Foundation Trust, Bath, UK; Swedish Medical Center, University of Washington School of Medicine, Seattle, Washington, USA; Johns Hopkins Arthritis Center, Baltimore, Maryland, USA; Rheumatology Department, Hospital de Clinicas de Porto Alegre, Brazil; Royal National Hospital for Rheumatic Diseases, Bath, UK.M. de Wit, PhD, Patient Research Partner, Amsterdam, The Netherlands; W. Campbell, BA, BEd, LLB, Patient Research Partner, Toronto, Ontario, Canada; O. FitzGerald, MD, FRCPI, FRCP(UK), Newman Clinical Research Professor, Department of Rheumatology, St. Vincent's University Hospital; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto; Senior Scientist, Toronto Western Research Institute and Director, Psoriatic Arthritis Program, University Health Network; P.S. Helliwell, DM, PhD, FRCP, Senior Lecturer in Rheumatology, University of Leeds; J. James, Patient Research Partner, Bath, UK; C. Lindsay, Patient Research Partner, Thousand Oaks, California, USA; R. MacDonald, Patient Research Partner, Toronto, Ontario, Canada; N.J. McHugh, MBChB, MD, FRCP, FRCPath, Royal National Hospital for Rheumatic Diseases, NHS Foundation Trust; P.J. Mease, MD, Director, Rheumatology Research, Swedish Medical Center, Clinical Professor, University of Washington School of Medicine; A-M. Orbai, MD, MHS, Johns Hopkins Arthritis Center; P. Palominos, MD, Rheumatology Department, Hospital de Clinicas de Porto Alegre; A. Parkinson, Patient Research Partner, Leeds, UK; W. Tillett, BSc, MBChB, MRCP, Royal National Hospital for Rheumatic Diseases; N. Goel, MD, Patient Research Partner, Durham, North Carolina, USA. ·J Rheumatol · Pubmed #24882853.

ABSTRACT: For the first time, 8 patients with psoriatic arthritis (PsA) participated as full delegates at the 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Patients were invited to provide their perspective for different sessions of the conference program. Before the conference, the patient delegates had a separate meeting to familiarize themselves with the conference program and to gain a better understanding of the vision and objectives of GRAPPA. During the conference, the patient group discussed options for increased involvement in research projects. Herein we summarize the presentations on patient participation in research, the experiences of the patient group, and plans to enhance the patient perspective in psoriasis and PsA research.

22 Article The TICOPA protocol (TIght COntrol of Psoriatic Arthritis): a randomised controlled trial to compare intensive management versus standard care in early psoriatic arthritis. 2013

Coates, Laura C / Navarro-Coy, Nuria / Brown, Sarah R / Brown, Sarah / McParland, Lucy / Collier, Howard / Skinner, Emma / Law, Jennifer / Moverley, Anna / Pavitt, Sue / Hulme, Claire / Emery, Paul / Conaghan, Philip G / Helliwell, Philip S. ·Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS7 4SA, UK. l.c.coates@leeds.ac.uk ·BMC Musculoskelet Disord · Pubmed #23517506.

ABSTRACT: BACKGROUND: Psoriatic arthritis (PsA) is estimated to occur in 10-15% of people with psoriasis and accounts for 13% of people attending early arthritis clinics. With an increasing awareness of the poor outcomes associated with PsA and the availability of new effective, but costly, treatments, there is an urgent need to research the optimal treatment for patients with PsA. The aim of the TICOPA study is to establish whether, in treatment naive early PsA patients, "tight control" intensive management with protocol driven therapies and pre-defined objective targets for treatment can improve clinical outcome compared to standard care alone. METHODS/DESIGN: TICOPA is a UK multicentre, open-label, randomised controlled, parallel group trial of 206 patients with early PsA. Patients will be randomised on a 1:1 basis to receive either standard care (12 weekly review) or intensive management (4 weekly review) for a period of 48 weeks. Patients assigned to the intensive management group will follow a strict treatment protocol whereby dose continuation/escalation is determined through the objective assessment of the minimal disease activity (MDA) criteria. Patients assigned to the standard care group will have treatment prescribed as felt appropriate by the treating clinician, with no set protocol. The primary objective of the trial is to compare intensive management with standard care in terms of the proportion of patients achieving an ACR 20 response at 48 weeks post-randomisation, in order to determine whether intensive management has superior clinical efficacy. Key secondary outcomes include ACR 50 and 70, PASI 75 and X-ray Van der Heijde score at 48 weeks post-randomisation along with cost-effectiveness at 12, 24 and 28 weeks. DISCUSSION: The TICOPA trial will provide direct evidence as to whether the use of early and intensive treatment in PsA in routine clinical care leads to an improvement in patients' disease activity and a reduction in radiological joint damage. TRIAL REGISTRATION: ISRCTN30147736, NCT01106079.

23 Article High-resolution [18F]fluoride positron emission tomography of the distal interphalangeal joint in psoriatic arthritis--a bone-enthesis-nail complex. 2013

Tan, Ai Lyn / Tanner, Steven F / Waller, Michael L / Hensor, Elizabeth M A / Burns, Alison / Jeavons, Alan P / Bury, Robert F / Emery, Paul / McGonagle, Dennis. ·Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK. ·Rheumatology (Oxford) · Pubmed #23307832.

ABSTRACT: OBJECTIVE: This study used high-resolution PET to explore the pattern of DIP joint bone metabolism to test the hypothesis that the nail was functionally integrated with the bone, based on patterns of distal phalange (DP) bone metabolism in PsA compared with OA and normal joints. METHODS: A total of 234 DIP joints were scanned in 30 subjects (10 PsA, 10 OA, 10 healthy control) with [18F]fluoride using the quad-high-density avalanche chamber nano PET scanner. The images were assessed blinded to diagnosis and symptoms for site and intensity of increased [18F]fluoride uptake. RESULTS: [18F]fluoride uptake in the DP was strong relative to the intermediate phalange in both PsA and OA. In PsA there was a trend for uptake to occur in a diffuse pattern involving the entire DP. There was also greater uptake at the enthesis, the periosteum and at the tufts of the DP of PsA compared with OA. In OA, uptake was greatest in the subchondral region adjacent to known sites of osteophytosis and erosions. Both PsA and OA joints with uptake at the subchondral or periosteal bone are likely to be more symptomatic. CONCLUSION: This exploratory study suggested diffuse increased bone metabolism involving the entire DP, periosteum and entheses, especially in PsA. The subchondral bone and periosteum at the DP have large concentrations of enthesis attachments, including attachments from the nail, supporting the concept of an integrated nail and joint apparatus leading to a wide area of abnormal bone metabolism in PsA.

24 Article GRAPPA Trainees Symposium 2011: a report from the GRAPPA 2011 annual meeting. 2012

Ash, Zoe / Ritchlin, Christopher T. ·Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. Z.Ash@leeds.ac.uk ·J Rheumatol · Pubmed #23118283.

ABSTRACT: The 2011 annual meeting in Naples, Italy, of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) began with a Trainees Symposium, which has become an important aspect of the meeting. In 2011, 25 trainees currently involved in research in psoriasis or psoriatic arthritis were invited to deliver an oral abstract or poster presentation. We present a brief overview of the oral and poster presentations, which show the diversity and focus of current research performed by members and trainees of GRAPPA.

25 Article Ten-year follow-up of SpA-related oligoarthritis involving the knee: the presence of psoriasis but not HLA-B27 or baseline MRI bone oedema predicts outcome. 2012

Bennett, Alexander N / Marzo-Ortega, Helena / Tan, Ai Lyn / Hensor, Elizabeth M A / Green, Mike / Emery, Paul / McGonagle, Dennis. ·Academic Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK. ·Rheumatology (Oxford) · Pubmed #22328564.

ABSTRACT: OBJECTIVE: Bone marrow oedema (BMO) and HLA-B27 are poor prognostic factors in axial SpA, and psoriasis is a poor prognostic factor in small-joint polyarthropathy. The aim of this study was to investigate the influence of HLA-B27, MRI BMO and psoriasis on long-term outcomes in early SpA-related knee joint oligoarthritis. METHODS: Patients with SpA-related oligoarthritis with knee involvement were recruited. Baseline assessment included ESSG criteria, RF, HLA-B27 and MRI. The degree of MRI BMO was determined on fat-suppression sequences and scored using the whole-organ magnetic resonance imaging score (WORMS) (range 0-45). Patients were treated at the discretion of their rheumatologist and followed up for 10 years. Outcome assessments included joint counts, functional and symptomatic questionnaire, CRP and radiographic assessment for OA. RESULTS: Forty-four patients were recruited [mean age 32 years (range 15-59 years), 70% male] with a mean disease duration at baseline of 9.75 months (1-48 months). Twenty-six (59%) patients (mean age 43 years, 65% male) returned for follow-up after a mean of 10 years (range 8.4-12.6 years). Ten (38%) patients had persistent clinical synovitis and 31% of knees had secondary radiographic OA. Global outcome was poor/very poor in 69% of cases. The only factor predicting outcome at 10 years was psoriasis, but neither HLA-B27 nor BMO. PsA patients had significantly worse global outcome compared with ReA (P = 0.036), and significantly worse symptomatic (P = 0.001) and functional (P = 0.001) outcome compared with other subtypes. CONCLUSION: SpA-related knee joint oligoarthritis has significant long-term clinical and radiological morbidity despite standard treatments. HLA-B27 and MRI BMO were not predictors of poor outcome as they are in axial SpA; however, the presence of psoriasis predicted significantly worse outcome.

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