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Recommendation
Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome
  1. Benjamin A Fisher1,2,
  2. Roland Jonsson3,4,
  3. Troy Daniels5,
  4. Michele Bombardieri6,
  5. Rachel M Brown7,
  6. Peter Morgan8,
  7. Stefano Bombardieri9,
  8. Wan-Fai Ng10,
  9. Athanasios G Tzioufas11,
  10. Claudio Vitali12,
  11. Pepe Shirlaw13,
  12. Erlin Haacke14,
  13. Sebastian Costa15,
  14. Hendrika Bootsma16,
  15. Valerie Devauchelle-Pensec17,
  16. Timothy R Radstake18,
  17. Xavier Mariette19,
  18. Andrea Richards20,
  19. Rebecca Stack1,
  20. Simon J Bowman1,2,
  21. Francesca Barone1
  22. on behalf of the Sjögren's histopathology workshop group (appendix) from ESSENTIAL (EULAR Sjögren's syndrome study group)
    1. 1 Rheumatology Research Group and Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), University of Birmingham, Birmingham, UK
    2. 2 Department of Rheumatology, University Hospitals Birmingham NHS Trust, Birmingham, UK
    3. 3 Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
    4. 4 Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
    5. 5 Department of Orofacial Sciences, University of California San Francisco, San Francisco California, USA
    6. 6 Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK
    7. 7 Department of Pathology, University Hospitals Birmingham NHS Trust, Birmingham, UK
    8. 8 Department of Pathology, King's College London, London, UK
    9. 9 Rheumatology Unit, University of Pisa, Pisa, Italy
    10. 10 Musculoskeletal Research Group and NIHR Biomedical Research Centre in Ageing and Chronic Diseases, Newcastle University, Newcastle, UK
    11. 11 Department of Pathophysiology, University of Athens, Athens, Greece
    12. 12 Section of Rheumatology, Casa di Cura di Lecco, Lecco, Italy
    13. 13 Department of Oral Medicine, King's College London, London, UK
    14. 14 Department of Pathology, University of Groningen, Groningen, The Netherlands
    15. 15 Department of Pathology, Brest University Hospital, Brest, France
    16. 16 Department of Rheumatology and Clinical Immunology, University of Groningen, Groningen, The Netherlands
    17. 17 Rheumatology Department, Cavale Blanche Hospital and Brest Occidentale University, ER129, Brest, France
    18. 18 Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
    19. 19 Rheumatology Department, Université Paris-Sud, Assistance Publique—Hôpitaux de Paris, INSERM U1184, Le Kremlin-Bicêtre, France
    20. 20 Department of Oral Medicine, Dental Hospital, Birmingham, UK
    1. Correspondence to Dr Benjamin Fisher, Rheumatology Research Group, Centre for Translational Inflammation Research, Queen Elizabeth Hospital Birmingham, Birmingham B15 2WB, UK; b.fisher{at}bham.ac.uk

    Abstract

    Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0–10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus.

    • Sjøgren's Syndrome
    • Autoimmunity
    • Outcomes research

    This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

    https://doi.org/10.1136/annrheumdis-2016-210448

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      Footnotes

      • Handling editor Tore K Kvien

      • Collaborators  Appendix: Additional Participants of the Histopathology Workshop Group: Rui PP de Albuquerque, Department of Oral Medicine, Birmingham Dental Hospital and School of Dentistry, University of Birmingham, UK. Rigel Allen, Oral Medicine, University of Manchester, Manchester, UK. Elisa Astorri, Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK. Chiara Baldini, Rheumatology Unit, University of Pisa, Pisa, Italy. Rajdeep Bhabra, patient partner. Pilar Brito-Zerón, Department of Autoimmune Diseases, University of Barcelona, Barcelona, Spain. Preetha Chengot, Department of Histopathology, St. James's University Hospital, Leeds, UK. Stefano Fedele, UCL Eastman Dental Institute London, University College London and National Institute for Health Research UCLH Biomedical Research Centre, London, UK. Aike A Kruize, Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands. Roald Omdal, Clinical Immunology Unit, Stavanger University Hospital, Stavanger, Norway. Kingsley Osayi, Department of Pathology, Basildon and Thurrock University Hospital, Basildon, UK. Stephen Porter, UCL Eastman Dental Institute London, University College London, London, UK. John Potts, Department of Oral Medicine, School of Dentistry, University of Cardiff, Cardiff, UK. Ana Poveda-Gallego, Department of Oral Medicine, Dental Hospital, Birmingham, UK. Elizabeth Price, Great Western Hospitals NHS Foundation Trust, Swindon, UK. Roberta Priori, Rheumatology Unit, Sapienza University of Rome, Rome Italy. Manuel Ramos-Casals, Department of Autoimmune Diseases, University of Barcelona, Barcelona, Spain. Soledad Retamozo, Department of Autoimmune Diseases, University of Barcelona, Barcelona, Spain. Krishna Suchak, Department of Pathology, Institute of Dentistry, Queen Mary University of London, London, UK. Nurhan Sutcliffe, Department of Rheumatology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Zahra Syed, Department of Oral Medicine, Leeds Dental Institute, Leeds, UK. Anwar R Tappuni, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Elke Theander, Department of Rheumatology, Skåne University Hospital, Lund University, Malmö, Sweden. Marie Wahren-Herlenius, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. Asterios Triantafyllou, Oral and Maxillofacial Pathology, School of Dentistry, University of Liverpool, Liverpool, UK. Arjan Vissink, Department of Oral and Maxillofacial Surgery, University of Groningen, Groningen, The Netherlands. Salvatore de Vita, Department of Medical and Biological Sciences, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, Udine, Italy. Christina Yap, Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.

      • Contributors All authors have contributed to the development of the recommendations and the Delphi process, and have contributed to and approved the final manuscript.

      • Funding The workshop was funded by the Translational Research Partnership in Joint and related Inflammatory Disease, established by the National Institute for Health Research Office for Clinical Research Infrastructure to facilitate early phase translational research and clinical trials, on a collaborative basis between industry, academia and the National Health Service in the UK. FB has a senior fellowship from Arthritis Research UK (21236). The Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence was part-funded by Arthritis Research UK (20298); this Centre is a collaboration between the Universities of Glasgow, Newcastle and Birmingham. The funders did not influence the content of these recommendations.

      • Competing interests SJB has received honoraria/consultancy fees in the field of Sjögren's syndrome in 2015–2016 for AstraZeneca, Celgene, Glenmark, Eli Lilly, Novartis, Ono and UCB Pharmaceuticals. Roche provided rituximab for the TRACTISS study. BAF has received honoraria/consultancy fees from Novartis, Roche and Medimmune. FB has received honoraria/consultancy fees from Roche, GlaxoSmithKline, Glenmark and Medimmune, and research funding from UCB. Other authors have declared no competing interests.

      • Provenance and peer review Not commissioned; externally peer reviewed.

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