Systemic Sjögrens: More Than a Sicca Disease

Therefore, the need for a consensus on a homogeneous diagnostic and therapeutic approach to systemic involvement in pSS is clear. The EULAR-SS Task Force Group is now working on the development of EULAR-SS recommendations for the characterization and treatment of organ-specific extraglandular involvement in pSS on the basis of a systematic review of the current scientific evidence. This systematic review revealed a low level of evidence in studies of systemic SS, especially with respect to the diagnostic approach. The body of evidence relied predominantly on information retrieved from individual cases, and the main sources of bias were the heterogeneous definitions of organ involvement—or even the lack of definition in some studies—and the heterogeneous diagnostic approach used in studies to investigate each organ involvement.

A greater understanding of the pathogenesis of systemic immune-mediated damage, along with active international collaborations to develop standardized guidelines, is critical.

Pilar Brito-Zerón, MD, PhD, and Manuel Ramos-Casals, MD, PhD, both work for the Laboratory of Autoimmune Diseases Josep Font, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain.

Members of the EULAR-SS Task Force Steering Group are: Manuel Ramos-Casals, Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain; Pilar Brito-Zerón, Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain; Raphaèle Seror, Assistance Publique–Hopitaux de Paris, Hôpital Bicêtre, Department of Rheumatology, INSERM U802, Le Kremlin Bicêtre, France; Université Paris-Sud 11; INSERM U1012, Le Kremlin Bicêtre, France, and Center of Clinical Epidemiology, Hôpital Hôtel Dieu, Paris, France; INSERM U738, Université Paris-René Descartes, Paris, France; Hendrika Bootsma, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Simon J. Bowman, Rheumatology Department, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK; Thomas Dörner, Rheumatology Department, Charité, University Hospital, Berlin, Germany; Jacques-Eric Gottenberg, Department of Rheumatology, Strasbourg University Hospital, Université de Strasbourg, EA 4438, Strasbourg, France; Xavier Mariette, Assistance Publique–Hopitaux de Paris, Hôpital Bicêtre, Department of Rheumatology, INSERM U802, Le Kremlin Bicêtre, France; Université Paris-Sud 11; INSERM U1012, Le Kremlin Bicêtre, France; Elke Theander, Department of Rheumatology, Malmö University Hospital, Lund University, Sweden; Stefano Bombardieri, Rheumatology Unit, University of Pisa, Pisa, Italy; Salvatore de Vita, Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital Santa Maria della Misericordia, 133100 Udine, Italy; Thomas Mandl, Department of Rheumatology, Malmö University Hospital, Lund University, Lund, Sweden; Wan-Fai Ng, Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; Aike Kruize, Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; Athanasios Tzioufas, Department of Pathophysiology, School of Medicine, University of Athens, Greece; and Claudio Vitali, “Villamarina” Hospital, Department of Internal Medicine and section of Rheumatology, Piombino, Italy, on behalf of the EULAR Sjögren Syndrome Task Force.

Disclosure

Dr. Brito-Zerón is supported by the Josep Font Research Fellow Award, Hospital Clinic, Barcelona, Spain.

References

1. Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X. Primary Sjögren syndrome. BMJ. 2012;344:e3821.
2. Helmick CG, Felson DT, Lawrence RC, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008 Jan;58(1):15–25.
3. Brito-Zerón P, Ramos-Casals M. Advances in the understanding and treatment of systemic complications in Sjögren syndrome. Curr Opin Rheumatol. 2014 Jul 19;[Epub ahead of print]. PubMed PMID: 25050925.
4. Ramos-Casals M, Brito-Zerón P, Solans R, et al; SS Study Group; Autoimmune Diseases Study Group (GEAS) of the Spanish Society of Internal Medicine (SEMI). Systemic involvement in primary Sjogren’s syndrome evaluated by the EULAR-SS disease activity index: Analysis of 921 Spanish patients (GEAS-SS Registry). Rheumatology (Oxford). 2014;53:321–331.
5. Baldini C, Pepe P, Quartuccio L, et al. Primary Sjogren’s syndrome as a multi-organ disease: Impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology (Oxford). 2013 Dec 24;[Epub ahead of print]. PubMed PMID: 24369420.
6. Seror R, Gottenberg JE, Devauchelle-Pensec V, et al. European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index and European League Against Rheumatism Sjögren’s Syndrome Patient-Reported Index: A complete picture of primary Sjögren’s syndrome patients. Arthritis Care Res (Hoboken). 2013;65:1358–1364.
7. Seror R, Theander E, Brun JG, et al; on behalf of the EULAR Sjögren’s Task Force. Validation of EULAR primary Sjogren’s syndrome disease activity (ESSDAI) and patient indexes (ESSPRI). Ann Rheum Dis. 2014 Mar 11;[Epub ahead of print] PubMed PMID: 24442883.
8. Brito Zeron P, Retamozo S, Solans R, et al. The degree of activity measured with the EULAR-SS disease activity index (ESSDAI) strongly correlated with death in patients with primary Sjogren syndrome. Ann Rheum Dis. 2014;73(Suppl2).
9. Brito-Zerón P, Ramos-Casals M, Bove A, et al. Predicting adverse outcomes in primary Sjogren’s syndrome: identification of prognostic factors. Rheumatology (Oxford). 2007 Aug;46(8):1359–1362.
10. Goules AV, Tatouli IP, Moutsopoulos HM, Tzioufas AG. Clinically significant renal involvement in primary Sjögren’s syndrome: Clinical presentation and outcome. Arthritis Rheum. 2013;65:2945–2953.
11. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012 Feb 9;366(6):539–551.
12. Brito-Zerón P, Ramos-Casals M, Stone JH. The clinical spectrum of IgG4-related disease. Autoimmun Rev. 2014 (in press).
13. Ramos-Casals M, Tzioufas AG, Stone JH, et al. Treatment of primary Sjögren syndrome: A systematic review. JAMA. 2010;304:452–460.
14. Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, et al. Topical and systemic medications for the treatment of primary Sjögren’s syndrome. Nat Rev Rheumatol. 2012;8:399–411.
15. Gottenberg JE, Cinquetti G, Larroche C, et al; Club Rhumatismes et Inflammations and the French Society of Rheumatology. Efficacy of rituximab in systemic manifestations of primary Sjogren’s syndrome: Results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis. 2013;72:1026–1031.
16. Carubbi F, Cipriani P, Marrelli A, et al. Efficacy and safety of rituximab treatment in early primary Sjögren’s syndrome: A prospective, multi-center, follow-up study. Arthritis Res Ther. 2013;15:R172.
17. St Clair EW, Levesque MC, Prak ET, et al; Autoimmunity Centers of Excellence. Rituximab therapy for primary Sjögren’s syndrome: An open-label clinical trial and mechanistic analysis. Arthritis Rheum. 2013;65:1097–1106.
18. Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Treatment of primary Sjögren syndrome with rituximab: A randomized trial. Ann Intern Med. 2014 Feb 18;160(4). doi: 10.7326/M13-1085.
19. Mariette X, Seror R, Quartuccio L, et al. Efficacy and safety of belimumab in primary Sjogren’s syndrome: Results of the BELISS open-label phase II study. Ann Rheum Dis. 2013 Dec 17;[Epub ahead of print]. PubMed PMID: 24347569.