Das Sjögren-Syndrom

Zusammenfassung

Das Sjögren-Syndrom ist eine chronische Autoimmunerkrankung mit Beteiligung der Tränen- und Speicheldrüsen. Durch lymphozytäre Infiltration und sekundäre Destruktion des exokrinen Drüsengewebes kommt es zur Sicca-Symptomatik. Es handelt sich um eine der 3 häufigsten Autoimmunerkrankungen mit einer Prävalenz von 0,03–2,1%, abhängig von Alters- und Populationsgruppen sowie der angewandten Diagnostik-Kriterien, und betrifft deutlich häufiger Frauen (ca. 10:1) [1] [2] [3]. Neben der charakteristischen Sicca-Symptomatik leiden viele Patienten unter systemischen Manifestationen wie z. B. Arthralgien, seltener Hautvaskulitis, interstitieller Lungenerkrankung oder Nierenbeteiligung.

Nicht-steroidale Antirheumatika, Kortikosteroide und Immunsuppressiva werden zur Therapie dieser Komplikationen angewandt während die Sicca-Symptomatik meist lokal-symptomatisch behandelt wird. Das Risiko der Entwicklung eines malignen Lymphoms ist beim Sjögren-Syndrom erhöht. Ein Großteil der Patienten leidet außerdem unter einer ausgeprägten Abgeschlagenheit (Fatigue) [4], die das subjektiv schwerwiegendste Symptom darstellen kann. Die Prävalenz von depressiven Störungen ist ebenfalls erhöht [5]. Auch wenn neue therapeutische Angriffspunkte und B-Zell-gerichtete Therapien, die sich derzeit in klinischer Testung befinden, auf eine Verbesserung der Behandlungsmöglichkeiten hoffen lassen, bleibt die Heterogenität des Krankheitsbildes und der Symptome eine Herausforderung in Klinik und Forschung.

Abstract

Sjögren’s syndrome is a chronic autoimmune disease involving both lacrimal and salivary glands. Lymphocytic infiltration and secondary destruction of the exocrine gland tissue leads to sicca symptoms. It is one of the 3 most common autoimmune diseases with a prevalence of 0.03–2.1%, depending on age and population groups as well as the diagnostic criteria used, and mostly affects women (ca. 10:1) [1] [2] [3].

Apart from the characteristic sicca symptoms many patients also suffer from systemic manifestations such as arthralgia or, less frequently, skin vasculitis, interstitial lung disease or kidney involvement. Sicca symptoms are usually treated locally whereas non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immunosuppressants are used for complications.

Sjögren’s syndrome is associated with an increased risk of developing a malignant lymphoma. In addition, most patients suffer from severe fatigue [4], which may be the most severe subjective symptom. The prevalence of depressive disorders is increased as well [5].

Even though promising new therapeutic approaches and B-cell-targeted therapies are currently under clinical investigation, the heterogeneity of the disease and its symptoms continues to be challenging for researchers and physicians alike.

Schlüsselwörter

Sjögren-Syndrom - Diagnostik - Therapie

Key words

Sjögren’s syndrome - diagnostics - therapy

• Literatur

• 1 Patel R, Shahane A. The epidemiology of Sjögren’s syndrome. Clin Epidemiol 2014; 6: 247-255
• 2 Baldini C, Talarico R, Tzioufas AG. et al. Classification criteria for Sjogren’s syndrome: A critical review. J Autoimmun 2012; 39: 9-14
• 3 Ramos-Casals M, Brito-Zerón P, Kostov B. et al. Google-driven search for big data in autoimmune geoepidemiology: Analysis of 394,827 patients with systemic autoimmune diseases. Autoimmun Rev 2015; 14: 670-679
• 4 Tensing EK, Solovieva SA, Tervahartiala T. et al. Fatigue and health profile in sicca syndrome of Sjögren’s and non-Sjögren’s syndrome origin. Clin Exp Rheumatol 2001; 19: 313-316
• 5 Harboe E, Tjensvoll AB, Maroni S. et al. Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjögren syndrome: A comparative population-based study. Ann Rheum Dis 2009; 68: 1541-1546
• 6 Mikulicz Jv. Über eine eigenartige symmetrische Erkrankung der Tränen- und Mundspeicheldrüsen. In: Beitr Chir Fortsch Gewidmet Theodor Billroth. Stuttgart: Enke; 1892: 610-630
• 7 Sjögren H. ZUR KENNTNIS DER KERATOCONJUNCTIVITIS SICCA II. Acta Ophthalmologica 1935; 13: 1-39
• 8 Fox RI. Sjögren’s syndrome. Lancet 2005; 366: 321-331
• 9 Manoussakis MN, Georgopoulou C, Zintzaras E. et al. Sjögren’s syndrome associated with systemic lupus erythematosus: Clinical and laboratory profiles and comparison with primary Sjögren’s syndrome. Arthritis Rheum 2004; 50: 882-891
• 10 Tzioufas AG, Kapsogeorgou EK, Moutsopoulos HM. Pathogenesis of Sjögren’s syndrome: What we know and what we should learn. J Autoimmun 2012; 39: 4-8
• 11 Baer AHJ, Hochberg MC, Silman AJ. et al. Rheumatology. (Sixth Edition). 6^th. Aufl Mosby, an imprint of Elsevier Ltd.; 2015
• 12 Hatron PY, Tillie-Leblond I, Launay D. et al. Pulmonary manifestations of Sjögren’s syndrome. Presse Med 2011; 40: e49-e64
• 13 Seror R, Bowman SJ, Brito-Zeron P. et al. EULAR Sjögren’s syndrome disease activity index (ESSDAI): A user guide. RMD Open 2015; 1: e000022
• 14 Ramos-Casals M, Brito-Zerón P, Seror R. et al. Characterization of systemic disease in primary Sjögren’s syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements. Rheumatology (Oxford) 2015; 54: 2230-2238
• 15 Soto-Cardenas MJ, Perez-De-Lis M, Bove A. et al. Bronchiectasis in primary Sjögren’s syndrome: Prevalence and clinical significance. Clin Exp Rheumatol 2010; 28: 647-653
• 16 Brucato A. Prevention of congenital heart block in children of SSA-positive mothers. Rheumatology (Oxford) 2008; 47 (Suppl. 03) iii35-iii37
• 17 Kyriakidis NC, Kapsogeorgou EK, Tzioufas AG. A comprehensive review of autoantibodies in primary Sjögren’s syndrome: clinical phenotypes and regulatory mechanisms. J Autoimmun 2014; 51: 67-74
• 18 Mégevand P, Chizzolini C, Chofflon M. et al. Cerebrospinal fluid anti-SSA autoantibodies in primary Sjogren’s syndrome with central nervous system involvement. Eur Neurol 2007; 57: 166-171
• 19 Vitali C, Del Papa N. Pain in primary Sjögren’s syndrome. Best Pract Res Clin Rheumatol 2015; 29: 63-70
• 20 Usmani ZA, Hlavac M, Rischmueller M. et al. Sleep disordered breathing in patients with primary Sjögren’s syndrome: A group controlled study. Sleep Med 2012; 13: 1066-1070
• 21 Atzeni F, Cazzola M, Benucci M. et al. Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol 2011; 25: 165-171
• 22 Ostuni P, Botsios C, Sfriso P. et al. Prevalence and clinical features of fibromyalgia in systemic lupus erythematosus, systemic sclerosis and Sjögren’s syndrome. Minerva Med 2002; 93: 203-209
• 23 Segal B, Thomas W, Rogers T. et al. Prevalence, severity, and predictors of fatigue in subjects with primary Sjögren’s syndrome. Arthritis Rheum 2008; 59: 1780-1787
• 24 Westhoff G, Dörner T, Zink A. Fatigue and depression predict physician visits and work disability in women with primary Sjögren’s syndrome: Results from a cohort study. Rheumatology (Oxford) 2012; 51: 262-269
• 25 Liang Y, Yang Z, Qin B. et al. Primary Sjogren’s syndrome and malignancy risk: A systematic review and meta-analysis. Ann Rheum Dis 2014; 73: 1151-1156
• 26 Nocturne G, Mariette X. Sjögren Syndrome-associated lymphomas: An update on pathogenesis and management. Br J Haematol 2015; 168: 317-327
• 27 Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: A meta-analysis. Arch Intern Med 2005; 165: 2337-2344
• 28 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
• 29 Gottenberg JE, Aucouturier F, Goetz J. et al. Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogren’s syndrome. Ann Rheum Dis 2007; 66: 23-27
• 30 Makula E, Pokorny G, Kiss M. et al. The place of magnetic resonance and ultrasonographic examinations of the parotid gland in the diagnosis and follow-up of primary Sjögren’s syndrome. Rheumatology (Oxford) 2000; 39: 97-104
• 31 Cornec D, Jousse-Joulin S, Pers JO. et al. Contribution of salivary gland ultrasonography to the diagnosis of Sjögren’s syndrome: Toward new diagnostic criteria?. Arthritis Rheum 2013; 65: 216-225
• 32 Jousse-Joulin S, Milic V, Jonsson MV. et al. Is salivary gland ultrasonography a useful tool in Sjögren’s syndrome? A systematic review. Rheumatology (Oxford) 2016; 55: 789-800
• 33 García-Carrasco M, Ramos-Casals M, Rosas J. et al. Primary Sjögren syndrome: Clinical and immunologic disease patterns in a cohort of 400 patients. Medicine (Baltimore) 2002; 81: 270-280
• 34 Gottenberg JE, Seror R, Miceli-Richard C. et al. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjögren’s syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS One 2013; 8: e59868
• 35 Pertovaara M, Pukkala E, Laippala P. et al. A longitudinal cohort study of Finnish patients with primary Sjögren’s syndrome: Clinical, immunological, and epidemiological aspects. Ann Rheum Dis 2001; 60: 467-472
• 36 Fisher BA, Brown RM, Bowman SJ. et al. A review of salivary gland histopathology in primary Sjögren’s syndrome with a focus on its potential as a clinical trials biomarker. Ann Rheum Dis 2015; 74: 1645-1650
• 37 Cornec D, Jamin C, Pers JO. Sjögren’s syndrome: Where do we stand, and where shall we go?. J Autoimmun 2014; 51: 109-114
• 38 Vitali C, Bombardieri S, Jonsson R. et al. Classification criteria for Sjögren’s syndrome: A revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002; 61: 554-558
• 39 Malladi AS, Sack KE, Shiboski SC. et al. Primary Sjögren’s syndrome as a systemic disease: A study of participants enrolled in an international Sjögren’s syndrome registry. Arthritis Care Res (Hoboken) 2012; 64: 911-918
• 40 Shiboski SC, Shiboski CH, Criswell L. et al. American College of Rheumatology classification criteria for Sjögren’s syndrome: A data-driven, expert consensus approach in the Sjögren’s International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012; 64: 475-487
• 41 Seror R, Ravaud P, Bowman SJ. et al. EULAR Sjogren’s syndrome disease activity index: Development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis 2010; 69: 1103-1109
• 42 Seror R, Ravaud P, Mariette X. et al. EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI): Development of a consensus patient index for primary Sjogren’s syndrome. Ann Rheum Dis 2011; 70: 968-972
• 43 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
• 44 Liu Y, Hirayama M, Cui X. et al. Effectiveness of Autologous Serum Eye Drops Combined With Punctal Plugs for the Treatment of Sjögren Syndrome-Related Dry Eye. Cornea 2015; 34: 1214-1220
• 45 Ciurtin C, Ostas A, Cojocaru VM. et al. Advances in the treatment of ocular dryness associated with Sjögrenʼs syndrome. Semin Arthritis Rheum 2015; 45: 321-327
• 46 Ramos-Casals M, Tzioufas AG, Stone JH. et al. Treatment of primary Sjögren syndrome: A systematic review. JAMA 2010; 304: 452-460
• 47 Gottenberg JE, Ravaud P, Puéchal X. et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: The JOQUER randomized clinical trial. JAMA 2014; 312: 249-258
• 48 Winzer M, Aringer M. Use of methotrexate in patients with systemic lupus erythematosus and primary Sjögren’s syndrome. Clin Exp Rheumatol 2010; 28: S156-S159
• 49 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
• 50 Brown S, Navarro Coy N, Pitzalis C. et al. The TRACTISS protocol: A randomised double blind placebo controlled clinical trial of anti-B-cell therapy in patients with primary Sjögren’s Syndrome. BMC Musculoskelet Disord 2014; 15: 21
• 51 St Clair EW, Levesque MC, Prak ET. et al. Rituximab therapy for primary Sjögren’s syndrome: An open-label clinical trial and mechanistic analysis. Arthritis Rheum 2013; 65: 1097-1106
• 52 De Vita S, Quartuccio L, Seror R. et al. Efficacy and safety of belimumab given for 12 months in primary Sjögren’s syndrome: The BELISS open-label phase II study. Rheumatology (Oxford) 2015; 54: 2249-2256
• 53 Tsuboi H, Matsumoto I, Hagiwara S. et al. Effectiveness of abatacept for patients with Sjögren’s syndrome associated with rheumatoid arthritis. An open label, multicenter, one-year, prospective study: ROSE (Rheumatoid Arthritis with Orencia Trial toward Sjögren’s syndrome Endocrinopathy) trial. Mod Rheumatol 2016; 1-9
• 54 Whitcher JP, Shiboski CH, Shiboski SC. et al. A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjögren’s Syndrome International Registry. Am J Ophthalmol 2010; 149: 405-415
• 55 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
• 56 Gheitasi H, Kostov B, Solans R. et al. How are we treating our systemic patients with primary Sjögren syndrome? Analysis of 1120 patients. Int Immunopharmacol 2015; 27: 194-199
• 57 Sène D, Ghillani-Dalbin P, Amoura Z. et al. Rituximab may form a complex with IgMkappa mixed cryoglobulin and induce severe systemic reactions in patients with hepatitis C virus-induced vasculitis. Arthritis Rheum 2009; 60: 3848-3855
• 58 Kollert F, Balcarek K, Müller-Schmah C. et al. Spuriously low IgG levels in lupus-associated mixed cryoglobulinaemia type II complicated by iatrogenic immunoglobulin-induced immune complex vasculitis. Clin Exp Rheumatol 2012; 30: 982-983