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Aktuelle Rheumatologie
DOI: 10.1055/a-2256-9610
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Update zum Sjögren-Syndrom: Diagnostik & Therapie

Update on Sjögrenʼs Syndrome: Diagnostics & Therapy
Nadine Zehrfeld 
1   Klinik für Rheumatologie und Immunologie, Medizinische Hochschule Hannover, Hannover, Germany
,
Torsten Witte
1   Klinik für Rheumatologie und Immunologie, Medizinische Hochschule Hannover, Hannover, Germany
,
Diana Ernst
1   Klinik für Rheumatologie und Immunologie, Medizinische Hochschule Hannover, Hannover, Germany
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Zusammenfassung

Mit einer Prävalenz von circa 1:100 bis 1:400 ist das Sjögren-Syndrom die häufigste Kollagenose und betrifft hauptsächlich Frauen. Bei der Erkrankung steht die Destruktion der exokrinen Drüsen im Vordergrund und führt so regelhaft zur Sicca-Symptomatik. In über 50% der Fälle kommt es auch zu extraglandulären Manifestationen. Insbesondere Fatigue und Arthralgien aber auch verschiedene systemische Organmanifestationen wie Polyneuropathien oder interstitielle Lungenerkrankungen können auftreten. PatientInnen mit bestimmten Risikofaktoren haben eine Wahrscheinlichkeit von fünf Prozent ein Lymphom zu entwickeln. Die Diagnostik orientiert sich an den aktuellen ACR/EULAR-Klassifikationskriterien, der Speicheldrüsensonographie, sowie diversen Biomarkern, insbesondere den Antikörpern gegen SSA/Ro, in Verbindung mit der klinischen Symptomatik. Es gibt bislang keine zugelassene systemische immunsuppressive Therapie. Die European League against rheumatism (EULAR) hat Therapieempfehlungen veröffentlicht, die sich an den Empfehlungen für die Therapie des Systemischen Lupus Erythematodes orientieren und je nach klinischer Ausprägung und Manifestation variieren. Verschiedene, durchaus vielversprechende Studien zu unterschiedlichen therapeutischen Ansätzen werden aktuell durchgeführt.

Abstract

With a prevalence of 1:100 to 1:400, Sjögren’s syndrome is the most common connective tissue disease, and it mainly affects women. The disease is characterised by a destruction of the exocrine glands, which usually leads to sicca symptoms. Extraglandular manifestations occur in more than 50% of cases. These include fatigue and arthralgia as well as various systemic organ manifestations such as polyneuropathy or interstitial lung disease. Patients with certain risk factors have a five per cent chance of developing lymphoma. The diagnosis is based on the current ACR/EULAR classification criteria, salivary gland sonography and various biomarkers, in particular anti-SSA/Ro antibodies, in conjunction with clinical symptoms. There is currently no approved systemic immunosuppressive therapy. The European League Against Rheumatism (EULAR) has published treatment recommendations based on the recommendations for the treatment of systemic lupus erythematosus, which vary according to clinical severity and manifestation. Several promising trials of different therapeutic approaches are currently ongoing.

Schlüsselwörter

Sjögren-Krankheit - Sicca-Symptomatik - Speicheldrüsensonographie - Biologicals - Mesenchymale Stammzelltherapie

Key words

Sjögrenʼs disease - Sonography of the salivary gland - Mesenchymal stem cell therapy - Sicca symptoms - Biologics


Publication History

Article published online:
05 March 2024

© 2024. Thieme. All rights reserved.

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  • Literatur

  • 1 Jonsson R. Henrik sjögren (1899-1986): The syndrome and his legacy. Ann Rheum Dis 2021; 80: 1108-1109 DOI: 10.1136/annrheumdis-2021-219942.
    Google Scholar
  • 2 Zehrfeld N, Benz S, Derda A. et al. Pos1458 prevalence of subclinical atherosclerosis in patients with primary sjögren’s syndrome 2023; 82: 1083.1-1083
  • 3 Zippel CL, Beider S, Kramer E. et al. Premature stroke and cardiovascular risk in primary sjögren's syndrome. Front Cardiovasc Med 2022; 9: 1048684 DOI: 10.3389/fcvm.2022.1048684.
    Google Scholar
  • 4 Bartoloni E, Baldini C, Schillaci G. et al. Cardiovascular disease risk burden in primary sjögren's syndrome: Results of a population-based multicentre cohort study. J Intern Med 2015; 278: 185-192 DOI: 10.1111/joim.12346.
    Google Scholar
  • 5 Ramos-Casals M, Font J, Garcia-Carrasco M. et al. Primary sjögren syndrome: Hematologic patterns of disease expression. Medicine (Baltimore) 2002; 81: 281-292 DOI: 10.1097/00005792-200207000-00004.
    Google Scholar
  • 6 Nocturne G, Mariette X. Advances in understanding the pathogenesis of primary sjögren's syndrome. Nat Rev Rheumatol 2013; 9: 544-556 DOI: 10.1038/nrrheum.2013.110.
    Google Scholar
  • 7 Khatri B, Tessneer KL, Rasmussen A. et al. Author correction: Genome-wide association study identifies sjögren's risk loci with functional implications in immune and glandular cells. Nat Commun 2022; 13: 6519-8 DOI: 10.1038/s41467-022-34311-8.
    Google Scholar
  • 8 Triantafyllopoulou A, Tapinos N, Moutsopoulos HM. Evidence for coxsackievirus infection in primary sjögren's syndrome. Arthritis Rheum 2004; 50: 2897-2902 DOI: 10.1002/art.20463.
    Google Scholar
  • 9 Mitsias DI, Kapsogeorgou EK, Moutsopoulos HM. The role of epithelial cells in the initiation and perpetuation of autoimmune lesions: Lessons from sjogren's syndrome (autoimmune epithelitis). Lupus. 2006; 15: 255-261 DOI: 10.1191/0961203306lu2290rr.
    Google Scholar
  • 10 Moutsopoulos HM. Sjögren's syndrome: Autoimmune epithelitis. Clin Immunol Immunopathol 1994; 72: 162-165 DOI: 10.1006/clin.1994.1123.
    Google Scholar
  • 11 Mihai A, Caruntu C, Jurcut C. et al. The spectrum of extraglandular manifestations in primary sjögren's syndrome. J Pers Med. 2023; 13: 961 DOI: 10.3390/jpm13060961.. 10.3390/jpm13060961
    Google Scholar
  • 12 McCoy SS, Woodham M, Bartels CM. et al. Symptom-based cluster analysis categorizes sjögren's disease subtypes: An international cohort study highlighting disease severity and treatment discordance. Arthritis Rheumatol 2022; 74: 1569-1579 DOI: 10.1002/art.42238.
    Google Scholar
  • 13 Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X. Primary sjogren syndrome. BMJ 2012; 344: e3821 DOI: 10.1136/bmj.e3821.
    Google Scholar
  • 14 Kramer E, Seeliger T, Skripuletz T. et al. Multimodal assessment and characterization of sicca syndrome. Front Med (Lausanne) 2021; 8: 777599 DOI: 10.3389/fmed.2021.777599.
    Google Scholar
  • 15 Seeliger T, Prenzler NK, Gingele S. et al. Neuro-sjögren: Peripheral neuropathy with limb weakness in sjögren's syndrome. Front Immunol 2019; 10: 1600 DOI: 10.3389/fimmu.2019.01600.
    Google Scholar
  • 16 Seeliger T, Kramer E, Konen FF. et al. Sjögren's syndrome with and without neurological involvement. J Neurol 2023; 270: 2987-2996 DOI: 10.1007/s00415-023-11613-5.
    Google Scholar
  • 17 Thiele T, Seeliger T, Witte T, Sander B, Skripuletz T, Ernst D. Severe polyneuropathy in primary sjögren's syndrome : Sjögren's syndrome should be considered in patients with motor neuropathy. Z Rheumatol 2020; 79: 707-709 DOI: 10.1007/s00393-020-00821-3.
    Google Scholar
  • 18 Seeliger T, Jacobsen L, Hendel M. et al. Cognitive impairment in patients with neuro-sjögren. Ann Clin Transl Neurol 2020; 7: 1352-1359 DOI: 10.1002/acn3.51123.
    Google Scholar
  • 19 Akpek EK, Mathews P, Hahn S. et al. Ocular and systemic morbidity in a longitudinal cohort of sjögren's syndrome. Ophthalmology 2015; 122: 56-61 DOI: 10.1016/j.ophtha.2014.07.026.
    Google Scholar
  • 20 Minopoulou I, Pyrgidis N, Tishukov M. et al. Sexual dysfunction in women with systemic autoimmune rheumatic disorders: A systematic review and meta-analysis. Rheumatology (Oxford) 2023; 62: 1021-1030 DOI: 10.1093/rheumatology/keac457.
    Google Scholar
  • 21 Błochowiak K. Smell and taste function and their disturbances in sjögren's syndrome. Int J Environ Res Public Health. 2022; 19: 12472 DOI: 10.3390/ijerph191912472. 10.3390/ijerph191912472.
    Google Scholar
  • 22 Paraschou V, Partalidou S, Siolos P, Papadopoulou Z, Chaitidis N. Prevalence of hearing loss in patients with sjögren syndrome: A systematic review and meta-analysis. Rheumatol Int 2023; 43: 233-244 DOI: 10.1007/s00296-022-05235-9.
    Google Scholar
  • 23 Fragkioudaki S, Mavragani CP, Moutsopoulos HM. Predicting the risk for lymphoma development in sjogren syndrome: An easy tool for clinical use. Medicine (Baltimore) 2016; 95: e3766 DOI: 10.1097/MD.0000000000003766.
    Google Scholar
  • 24 Qin B, Wang J, Yang Z. et al. Epidemiology of primary sjögren's syndrome: A systematic review and meta-analysis. Ann Rheum Dis 2015; 74: 1983-1989 DOI: 10.1136/annrheumdis-2014-205375.
    Google Scholar
  • 25 Zehrfeld N, Benz S, Seeliger T. et al. Untersuchungen zur prävalenz des primären sjögren-syndroms bei vaginaler trockenheit in der gynäkologischen vorsorgeuntersuchung. 2023 DocVK.32.
    Google Scholar
  • 26 Shiboski CH, Shiboski SC, Seror R. et al. 2016 american college of rheumatology/european league against rheumatism classification criteria for primary sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017; 69: 35-45 DOI: 10.1002/art.39859.
    Google Scholar
  • 27 Zabotti A, Zandonella Callegher S, Tullio A. et al. Salivary gland ultrasonography in sjögren's syndrome: A european multicenter reliability exercise for the HarmonicSS project. Front Med (Lausanne) 2020; 7: 581248 DOI: 10.3389/fmed.2020.581248.
    Google Scholar
  • 28 Lorenzon M, Spina E, Tulipano Di Franco F, Giovannini I, De Vita S, Zabotti A. Salivary gland ultrasound in primary sjögren's syndrome: Current and future perspectives. Open Access Rheumatol 2022; 14: 147-160 DOI: 10.2147/OARRR.S284763.
    Google Scholar
  • 29 Izzetti R, Fulvio G, Nisi M, Gennai S, Graziani F. Reliability of OMERACT scoring system in ultra-high frequency ultrasonography of minor salivary glands: Inter-rater agreement study. J Imaging. 2022; 8: 111 DOI: 10.3390/jimaging8040111.. 10.3390/jimaging8040111.
    Google Scholar
  • 30 Jousse-Joulin S, Gatineau F, Baldini C. et al. Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for primary sjögren's syndrome. J Intern Med 2020; 287: 180-188 DOI: 10.1111/joim.12992.
    Google Scholar
  • 31 Fana V, Dohn UM, Krabbe S, Terslev L. Application of the OMERACT grey-scale ultrasound scoring system for salivary glands in a single-centre cohort of patients with suspected sjögren's syndrome. RMD Open 2021; 7: e001516 DOI: 10.1136/rmdopen-001516. 10.1136/rmdopen-2020-001516.
    Google Scholar
  • 32 Cornec D, Jousse-Joulin S, Pers J. et al. Contribution of salivary gland ultrasonography to the diagnosis of sjögren's syndrome: Toward new diagnostic criteria?. Arthritis Rheum 2013; 65: 216-225 DOI: 10.1002/art.37698.
    Google Scholar
  • 33 Singh M, Teles F, Uzel NG, Papas A. Characterizing microbiota from sjögren's syndrome patients. JDR Clin Trans Res 2021; 6: 324-332 DOI: 10.1177/2380084420940623.
    Google Scholar
  • 34 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) 2014; 53: 839-844 DOI: 10.1093/rheumatology/ket427.
    Google Scholar
  • 35 Loureiro-Amigo J, Franco-Jarava C, Perurena-Prieto J, Palacio C, Martínez-Valle F, Soláns-Laqué R. Serum CXCL13, BAFF, IL-21 and IL-22 levels are related to disease activity and lymphocyte profile in primary sjögren's syndrome. Clin Exp Rheumatol 2021; 39: 131-139 DOI: 10.55563/clinexprheumatol/fp741f.
    Google Scholar
  • 36 Chatzis L, Goules AV, Stergiou IE, Voulgarelis M, Tzioufas AG, Kapsogeorgou EK. Serum, but not saliva, CXCL13 levels associate with infiltrating CXCL13+ cells in the minor salivary gland lesions and other histologic parameters in patients with sjögren's syndrome. Front Immunol 2021; 12: 705079 DOI: 10.3389/fimmu.2021.705079.
    Google Scholar
  • 37 Zampeli E, Mavrommati M, Moutsopoulos HM, Skopouli FN. Anti-Ro52 and/or anti-Ro60 immune reactivity: Autoantibody and disease associations. Clin Exp Rheumatol 2020; 38: 134-141
    Google Scholar
  • 38 Robbins A, Hentzien M, Toquet S. et al. Diagnostic utility of separate anti-Ro60 and anti-Ro52/TRIM21 antibody detection in autoimmune diseases. Front Immunol 2019; 10: 444 DOI: 10.3389/fimmu.2019.00444.
    Google Scholar
  • 39 Witte T, Engelke F, Ritter J. et al. Towards the identification of novel autoantibodies in sjögren's syndrome. Clin Exp Rheumatol 2022; 40: 2395-2397 DOI: 10.55563/clinexprheumatol/sba8k2.
    Google Scholar
  • 40 Stefanski A, Tomiak C, Pleyer U, Dietrich T, Burmester GR, Dörner T. The diagnosis and treatment of sjögren's syndrome. Dtsch Arztebl Int 2017; 114: 354-361 DOI: 10.3238/arztebl.2017.0354.
    Google Scholar
  • 41 Ramos-Casals M, Brito-Zerón P, Bombardieri S. et al. EULAR recommendations for the management of sjögren's syndrome with topical and systemic therapies. Ann Rheum Dis 2020; 79: 3-18 DOI: 10.1136/annrheumdis-2019-216114.
    Google Scholar
  • 42 Marinho A, Delgado Alves J, Fortuna J. et al. Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and sjögren's syndrome: Evidence- and practice-based guidance. Front Immunol 2023; 14: 1117699 DOI: 10.3389/fimmu.2023.1117699.
    Google Scholar
  • 43 Machado AC, Dos Santos LC, Fidelix T. et al. Effectiveness and safety of abatacept for the treatment of patients with primary sjögren's syndrome. Clin Rheumatol 2020; 39: 243-248 DOI: 10.1007/s10067-019-04724-w.
    Google Scholar
  • 44 Baer AN, Gottenberg J, St Clair EW. et al. Efficacy and safety of abatacept in active primary sjögren's syndrome: Results of a phase III, randomised, placebo-controlled trial. Ann Rheum Dis 2021; 80: 339-348 DOI: 10.1136/annrheumdis-2020-218599.
    Google Scholar
  • 45 Xu J, Wang D, Liu D. et al. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical sjögren syndrome. Blood 2012; 120: 3142-3151 DOI: 10.1182/blood-2011-11-391144.
    Google Scholar
  • 46 Liu Y, Li C, Wang S. et al. Human umbilical cord mesenchymal stem cells confer potent immunosuppressive effects in sjögren's syndrome by inducing regulatory T cells. Mod Rheumatol 2021; 31: 186-196 DOI: 10.1080/14397595.2019.1707996.
    Google Scholar
  • 47 Li F, Lu J, Shi X. et al. Effect of adipose tissue-derived stem cells therapy on clinical response in patients with primary sjogren's syndrome. Sci Rep 2023; 13: 13521-13525 DOI: 10.1038/s41598-023-40802-5.
    Google Scholar
  • 48 Jakez-Ocampo J, Atisha-Fregoso Y, Llorente L. Refractory primary sjögren syndrome successfully treated with bortezomib. J Clin Rheumatol 2015; 21: 31-32 DOI: 10.1097/RHU.0000000000000210.
    Google Scholar
  • 49 Sun R, Gu W, Ma Y, Wang J, Wu M. Relapsed/refractory acquired thrombotic thrombocytopenic purpura in a patient with sjögren syndrome: Case report and review of the literature. Medicine (Baltimore) 2018; 97: e12989 DOI: 10.1097/MD.0000000000012989.
    Google Scholar
  • 50 Walhelm T, Gunnarsson I, Heijke R. et al. Clinical experience of proteasome inhibitor bortezomib regarding efficacy and safety in severe systemic lupus erythematosus: A nationwide study. Front Immunol 2021; 12: 756941 DOI: 10.3389/fimmu.2021.756941.
    Google Scholar
  • 51 Zhang H, Liu Z, Huang L. et al. The short-term efficacy of bortezomib combined with glucocorticoids for the treatment of refractory lupus nephritis. Lupus 2017; 26: 952-958 DOI: 10.1177/0961203316686703.
    Google Scholar
  • 52 Posada J, Valadkhan S, Burge D. et al. Improvement of severe fatigue following nuclease therapy in patients with primary sjögren's syndrome: A randomized clinical trial. Arthritis Rheumatol 2021; 73: 143-150 DOI: 10.1002/art.41489.
    Google Scholar
  • 53 Chen H, Qi X, Li Y. et al. Iguratimod treatment reduces disease activity in early primary sjögren's syndrome: An open-label pilot study. Mod Rheumatol 2021; 31: 394-398 DOI: 10.1080/14397595.2020.1789335.
    Google Scholar
  • 54 Shao Q, Wang S, Jiang H, Liu L. Efficacy and safety of iguratimod on patients with primary sjögren's syndrome: A randomized, placebo-controlled clinical trial. Scand J Rheumatol 2021; 50: 143-152 DOI: 10.1080/03009742.2020.1809701.
    Google Scholar
  • 55 Bowman SJ, Fox R, Dörner T. et al. Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary sjögren's syndrome: A randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet. 2022; 399: 161-171 DOI: 10.1016/S0140-6736(21)02251-0.
    Google Scholar
  • 56 Pontarini E, Verstappen GM, Grigoriadou S, Kroese FGM, Bootsma H, Bombardieri M. Blocking T cell co-stimulation in primary sjögren's syndrome: Rationale, clinical efficacy and modulation of peripheral and salivary gland biomarkers. Clin Exp Rheumatol 2020; 38: 222-227
    Google Scholar
  • 57 Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM. Characteristics of the minor salivary gland infiltrates in sjögren's syndrome. J Autoimmun 2010; 34: 400-407 DOI: 10.1016/j.jaut.2009.10.004.
    Google Scholar
  • 58 Fisher BA, Mariette X, Papas AS. et al. Iscalimab (CFZ533) in patients with sjögren’s disease: Week 24 efficacy and safety results of a randomized, placebo-controlled, phase 2b dose-ranging study 2023; 2023 75
  • 59 Mariette X, Barone F, Baldini C. et al. A randomized, phase II study of sequential belimumab and rituximab in primary sjögren's syndrome. JCI Insight 2022; 7: e163030 DOI: 10.1172/jci.insight.163030. 10.1172/jci.insight.163030
    Google Scholar
  • 60 Retamozo S, Acar-Denizli N, Rasmussen A. et al. Systemic manifestations of primary sjögren's syndrome out of the ESSDAI classification: Prevalence and clinical relevance in a large international, multi-ethnic cohort of patients. Clin Exp Rheumatol 2019; 37: 97-106
    Google Scholar
  • 61 McCoy SS, Bartels CM, Saldanha IJ. et al. National sjögren's foundation survey: Burden of oral and systemic involvement on quality of life. J Rheumatol 2021; 48: 1029-1036 DOI: 10.3899/jrheum.200733.
    Google Scholar
  • 62 Kaur H, Alazzeh M, Thandavaram A. et al. Increased threat of thyroid diseases in patients with sjogren's syndrome: A systematic review. Cureus 2022; 14: e28062 DOI: 10.7759/cureus.28062.
    Google Scholar
  • 63 Rusthen S, Young A, Herlofson BB. et al. Oral disorders, saliva secretion, and oral health-related quality of life in patients with primary sjögren's syndrome. Eur J Oral Sci 2017; 125: 265-271 DOI: 10.1111/eos.12358.
    Google Scholar
  • 64 Kreider M, Highland K. Pulmonary involvement in sjögren syndrome. Semin Respir Crit Care Med 2014; 35: 255-264 DOI: 10.1055/s-0034-1371529.
    Google Scholar