Systemic Manifestations of Primary Sjögren Syndrome out of the ESSDAI Classification: Prevalence and Clinical Relevance in a Large International, Multi-ethnic Cohort of Patients

Soledad Retamozo¹, Nihan Acar-Denizli ², Astrid Rasmussen ³, Ildiko Fanny Horváth ⁴, Chiara Baldini ⁵, Roberta Priori ⁶, Pulukool Sandhya ⁷, Gabriela Hernandez-Molina ⁸, Berkan Armagan ⁹, SONJA PRAPROTNIK ¹⁰, Marika Kvarnstrom ¹¹, Roberto Gerli ¹², Agata Sebastian ¹³, Roser Solans-Laqué ¹⁴, Maureen Rischmueller ¹⁵, Sandra G. Pasoto ¹⁶, Valeria Valim ¹⁷, Gunnel Nordmark ¹⁸, Aike Kruize ¹⁹, Takashi Nakamura ²⁰, Benedikt Hofauer ²¹, Roberto Giacomelli ²², Virginia Fernandes Moça Trevisani ²³, Valérie Devauchelle Pensec ²⁴, Fabiola Atzeni ²⁵, Tamer A Gheita ²⁶, Sandra Consani-Fernández ²⁷, Antonia Szántó ²⁸, Kathy Sivils ³, Angelina Gattamelata ²⁹, Debashish Danda ⁷, Levent Kilic ³⁰, Elena Bartoloni ¹², Stefano Bombardieri ³¹, Jorge Sánchez-Guerrero ³², Marie Wahren-Herlenius ¹¹, Xavier Mariette ³³, Manuel Ramos-Casals ³⁴ and Pilar Brito-Zerón ³⁵, ¹Instituto De Investigaciones En Ciencias De La Salud, Univ. Nacional de Córdoba, Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina., Cordoba, Argentina, ²Department of Statistics, Faculty of Science and Letters, Mimar Sinan Fine Arts University, Istanbul, Turkey., Istanbul, Turkey, ³Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Oklahoma, OK, ⁴Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Debrecen, Hungary, ⁵Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, Pisa, Italy, ⁶Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy, Roma, Italy, ⁷Department of Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, India., Vellore, India, ⁸Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, ⁹Department of Internal Medicine, Hacettepe University, Faculty of Medicine, Ankara, Turkey., Ankara, Turkey, ¹⁰Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia., LJUBLJANA, Slovenia, ¹¹Department of Medicine, Solna, Division of Experimental Rheumatology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden., Stockholm, Sweden, ¹²Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy, Perugia, Italy, ¹³Department of Rheumatology and Internal Medicine, Wroclaw Medical Hospital, Wroclaw, Poland, Wroclaw, Poland, ¹⁴Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain., Barcelona, Catalonia, Spain, ¹⁵Department of Rheumatology, The Queen Elizabeth Hospital and University of Adelaide, South Australia, Australia, ¹⁶Rheumatology Division, Hospital das Clinicas, Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo, Brazil., Sao Paulo, Brazil, ¹⁷Department of Medicine, Federal University of Espírito Santo, Vitória, Brazil., Vitória, Brazil, ¹⁸Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden., Uppsala, Sweden, ¹⁹Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands, Utrecht, Netherlands, ²⁰Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Nagasaki, Japan, ²¹Otorhinolaryngology, Head and Neck Surgery, Technical University Munich, Munich, Germany., Munich, Germany, ²²Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy, L'Aquila, Italy, ²³Department of Evidence-Based Medicine, Brazilian Cochrane Centre, Federal University of São Paulo, Sao Paulo, Brazil, Sao Paulo, Brazil, ²⁴University Hospital of Brest, Brest, France, ²⁵Rheumatology Unit, University of Messina, Messina, Italy., Messina, Italy, ²⁶Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt., Cairo, Egypt, ²⁷Internal Medicine, Hospital Maciel, Montevideo, Uruguay. Universidad de la República (UdelaR) , Montevideo, Uruguay., Montevideo, Uruguay, ²⁸Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, Debrecen, Hungary, ²⁹Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Rome, Italy, Rome, Italy, ³⁰Hacettepe University, Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Ankara, Turkey, ³¹Rheumatology Unit, University of Pisa, Pisa, Italy, Pisa, Italy, ³²Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. México City, Mexico, Mexico, Mexico, ³³Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France, ³⁴Department of Autoimmune Diseases, ICMiD. Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX. Department of Medicine, University of Barcelona, Hospital Clínic, Barcelona, Spain., Barcelona, Spain, ³⁵Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic. Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona, Spain., Barcelona, Spain

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: essdai and Systemic manifestations, Sjogren's syndrome

Session Information

Date: Monday, November 11, 2019

Title: Sjögrenʼs Syndrome – Basic & Clinical Science Poster II

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: To analyse the frequency and characterize the systemic presentation of primary Sjögren syndrome (SjS) out of the ESSDAI classification in a large international, multi-ethnic cohort of patients.

Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry based on worldwide data-sharing and cooperative merging of pre-existing clinical SjS databases from leading centres in clinical research in SjS from the five continents. A list of 26 organ-by-organ systemic features not currently included in the ESSDAI classification was defined according to previous studies; these features were retrospectively recorded.

Results: Information about non-ESSDAI features was available in 6331 patients (5,917 female, mean age at diagnosis 52 years, mainly White (86.3%). A total of 1641 (26%) of 6331 patients presented at least one of the out of ESSDAI systemic features listed in Annex 1; among them, there were 359 (22%) patients who presented two or more of these features. The most frequent organs involved included cardiovascular in 1079 (17%) patients, digestive in 390 (6.2%), pulmonary in 145 (2.3%), neurological in 110 (1.7%), ocular in 97 (1.5%), ENT in 80 (1.3%), cutaneous in 55 (0.9%) and urological features in 43 (0.7%) patients (Figure). Cardiovascular manifestations were the most frequent organ-specific group of non-ESSDAI features reported in our patients (17% of the total cohort), with Raynaud phenomenon being reported in 15%. Patients with systemic disease due to non-ESSDAI features had a lower frequency of dry mouth (90.7% vs 94.1%, p< 0.001) and positive minor salivary gland biopsy (86.7% vs 89%, p=0.033), a higher frequency of anti-Ro/SSA (74.7% vs 68.7%, p< 0.001), anti-La/SSB antibodies (44.5% vs 40.4%, p=0.004), ANA (82.7% vs 79.5%, p=0.006), low C3 levels (17.4% vs 9.7%, p< 0.001), low C4 levels (14.4% vs 9.6%, p< 0.001), and positive serum cryoglobulins (8.6% vs 5.5%, p=0.001). Systemic activity measured by the ESSDAI, clinESSDAI and DAS was higher in patients with systemic disease out of the ESSDAI in comparison with those without these features (p< 0.001 for all comparisons).

Conclusion: More than a quarter of patients with primary SjS may have systemic manifestations not currently included in the ESSDAI classification, with a wide variety of cardiovascular, digestive, pulmonary, neurological, ocular, ENT, cutaneous and urological features that increase the scope of the systemic phenotype of the disease. However, the individual frequency of each of these non-ESSDAI features was very low, except for Raynaud phenomenon. The results of this study, together with the already-published evidence supporting a pivotal role of systemic disease in primary SjS, are pointing out the need of a future re-evaluation about how we are defining, classifying and diagnosing primary SjS.

Disclosure: S. Retamozo, None; N. Acar-Denizli, None; A. Rasmussen, None; I. Horváth, None; C. Baldini, None; R. Priori, None; P. Sandhya, None; G. Hernandez-Molina, None; B. Armagan, None; S. PRAPROTNIK, None; M. Kvarnstrom, None; R. Gerli, None; A. Sebastian, None; R. Solans-Laqué, None; M. Rischmueller, AbbVie, 5, Bristol-Myers Squibb, 5, Celgene, 5, GlaxoSmithKline, 5, Hospira, 5, Janssen, 5, MSD, 5, Novartis, 5, Pfizer, 5, Roche, 5, Sanofi, 5, UCB, 5; S. Pasoto, Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP #2015/03756-4), 2; V. Valim, None; G. Nordmark, None; A. Kruize, None; T. Nakamura, None; B. Hofauer, None; R. Giacomelli, None; V. Fernandes Moça Trevisani, None; V. Devauchelle Pensec, Bristol_myers Squibb, 2, CHUGAI, 2, Chugai Pharma France, 8, Roche, 2; F. Atzeni, None; T. Gheita, None; S. Consani-Fernández, None; A. Szántó, None; K. Sivils, None; A. Gattamelata, None; D. Danda, None; L. Kilic, None; E. Bartoloni, None; S. Bombardieri, None; J. Sánchez-Guerrero, None; M. Wahren-Herlenius, None; X. Mariette, Biogen, 2, Bristol-Myers Squibb, 5, GlaxoSmithKline, 5, Janssen, 5, LFB Pharmaceuticals, 5, OSE Immunotherapeutics, 2, Pfizer, 2, 5, UCB Pharma, 5, 8; M. Ramos-Casals, None; P. Brito-Zerón, None.

To cite this abstract in AMA style:

Retamozo S, Acar-Denizli N, Rasmussen A, Horváth I, Baldini C, Priori R, Sandhya P, Hernandez-Molina G, Armagan B, PRAPROTNIK S, Kvarnstrom M, Gerli R, Sebastian A, Solans-Laqué R, Rischmueller M, Pasoto S, Valim V, Nordmark G, Kruize A, Nakamura T, Hofauer B, Giacomelli R, Fernandes Moça Trevisani V, Devauchelle Pensec V, Atzeni F, Gheita T, Consani-Fernández S, Szántó A, Sivils K, Gattamelata A, Danda D, Kilic L, Bartoloni E, Bombardieri S, Sánchez-Guerrero J, Wahren-Herlenius M, Mariette X, Ramos-Casals M, Brito-Zerón P. Systemic Manifestations of Primary Sjögren Syndrome out of the ESSDAI Classification: Prevalence and Clinical Relevance in a Large International, Multi-ethnic Cohort of Patients [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/systemic-manifestations-of-primary-sjogren-syndrome-out-of-the-essdai-classification-prevalence-and-clinical-relevance-in-a-large-international-multi-ethnic-cohort-of-patients/. Accessed .

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