Overlap-Syndrome

Zusammenfassung

Einige Patienten weisen Krankheitsmanifestationen verschiedener Autoimmunerkrankungen auf, ohne dass eine definierte Erkrankung vorliegt. Auch Patienten, welche genügend Kriterien für eine bestimmte Diagnose erfüllen, können „überlappend“ Befunde anderer Autoimmunerkrankungen haben. Diese können als „Overlap-Syndrome“ im weiteren Sinne verstanden werden. Bei eindeutigem Nachweis antinukleärer Antikörper (ANA) und/oder bestimmter ENA-Ak und weiteren klinischen Hinweisen für eine Kollagenose (meist zuerst ein Raynaud-Phänomen), kann man von einer undifferenzierten Kollagenose (UCTD) sprechen. Wenn bestimmte klinische und hiermit assoziierte immunserologisch typische Konstellationen vorliegen, kann man von „Overlap-Syndromen“ im engeren Sinne sprechen. Hierfür sind die Mischkollagenose vom Typ der „mixed connective tissue disease“ (MCTD, Sharp-Syndrom) mit Anteilen eines Lupus, einer Systemsklerose und einer Dermatomyositis und das Lupus-Sjögren-Überlappungssyndrom die Hauptvertreter. Beide sind – neben ANA – durch typische Auto-Antikörper (gegen u1-RNP bzw. SS-A) gekennzeichnet. Die Diagnose, Ausbreitungsdiagnostik und Therapie dieser Overlap-Syndrome richtet sich nach den vorherrschenden Organmanifestationen und entspricht dann dem Vorgehen bei den jeweiligen Einzelerkrankungen.

Abstract

Some patients have manifestations of various autoimmune diseases without a defined diagnosis. Patients who meet the criteria for a particular illness may also have “overlapping” findings of other autoimmunopathies. This can be regarded as an “overlap syndrome” in a broader sense. If antinuclear antibodies (ANA) and/or certain anti-ENA antibodies have been detected with certainty, and other clinical symptoms of a connective tissue disease are present as well (with Raynaud’s phenomenon mostly being the first such symptom), this may be called ‘undifferentiated connective tissue disease’ (UCTD). If certain clinical and typical immunoserological findings are present, one can speak of overlap syndromes in a strict sense. The main representatives are the ‘mixed connective tissue disease’ (MCTD, Sharp’s syndrome), which includes features of lupus, systemic sclerosis and dermatomyositis, as well as the ‘Lupus-Sjögren’s overlap syndrome’. In addition to ANA, both types are characterised by typical autoantibodies (against U1-RNP or SS-A). Diagnosis, staging and treatment of these overlap syndromes depend on the prevailing organ manifestations and follow the procedures used in the respective individual diseases.

Schlüsselwörter

Mischkollagenose - Overlap-Syndrome - Sharp-Syndrom - Lupus-Sjögren-Überlappungssyndrom

Key words

mixed connective tissue disease - overlap syndromes - lupus-sjögren’s overlap syndrome - sharp’s syndrome

• Literatur

• 1 LeRoy EC, Maricq HR, Kahaleh MB. Undifferentiated connective tissue syndromes. Arthritis Rheum 1980; 23: 341-343
• 2 Cervera R, Khamashta MA, Hughes GR. ‘Overlap’ syndromes. Ann Rheum Dis 1990; 49: 947-948 Review. PubMed PMID: 2256747; PubMed Central PMCID: PMC1004273
• 3 Mosca M, Tani C, Vagnani S et al. The diagnosis and classification of undifferentiated connective tissue diseases. J Autoimmun 2014; 48-49: 50-52 Epub 2014 Feb 8. Review. PubMed PMID: 24518855
• 4 Tani C, Carli L, Vagnani S et al. The diagnosis and classification of mixed connective tissue disease. J Autoimmun 2014; 48-49: 46-49 Epub 2014 Jan 22. Review. PubMed PMID: 24461387
• 5 Sharp GC, Irvin WS, Tan EM et al. Mixed connective tissue disease – an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 1972; 52: 148-159 PubMed PMID: 4621694
• 6 Habets WJ, de Rooij DJ, Salden MH et al. Antibodies against distinct nuclear matrix proteins are characteristic for mixed connective tissue disease. Clin Exp Immunol 1983; 54: 265-276 PubMed PMID: 6352106; PubMed Central PMCID: PMC1536194
• 7 Payet J, Goulvestre C, Bialé L et al. Anticyclic citrullinated peptide antibodies in rheumatoid and nonrheumatoid rheumatic disorders: experience with 1162 patients. J Rheumatol 2014; 41: 2395-2402 Epub 2014 Oct 1. Erratum in: J Rheumatol 2015 Mar; 42(3): 558. PubMed PMID: 25274898
• 8 Ortega-Hernandez OD, Shoenfeld Y. Mixed connective tissue disease: an overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol 2012; 26: 61-72 Review. PubMed PMID: 22424193
• 9 Richter J, Klein-Weigel P, Acar H et al. Kapillarmikroskopische Befunde bei Lupus erythematodes – Einflüsse der klinischen Manifestationen und des Geschlechts. Zeitschrift für Rheumatologie 2012; Band 71 (Supplement 2) S21
• 10 Gunnarsson R, Molberg O, Gilboe IM et al. PAHNOR1 Study Group. The prevalence and incidence of mixed connective tissue disease: a national multicentre survey of Norwegian patients. Ann Rheum Dis 2011; 70: 1047-1051 Epub 2011 Mar 11. PubMed PMID: 21398332
• 11 Benett RM. Clinical manifestations of mixed connective tissue disease. In: Ramirez Curtis M. (Ed.) UpToDate. Waltham: MA; Topic 7546 Version 12.0, accessed on August 09 2015
• 12 Dalakas MC. Inflammatory muscle diseases. N Engl J Med 2015; 372: 1734-1747 Review. PubMed PMID: 25923553
• 13 Gunnarsson R, Aaløkken TM, Molberg Ø et al. Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study. Ann Rheum Dis 2012; 71: 1966-1972 Epub 2012 May 1. PubMed PMID: 22550317
• 14 Gunnarsson R, Andreassen AK, Molberg Ø et al. Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature. Rheumatology (Oxford) 2013; 52: 1208-1213 Epub 2013 Feb 12. Review. PubMed PMID: 23407386
• 15 Vegh J, Szodoray P, Kappelmayer J et al. Clinical and immunoserological characteristics of mixed connective tissue disease associated with pulmonary arterial hypertension. Scand J Immunol 2006; 64: 69-76 PubMed PMID: 16784493
• 16 Mattioli M, Reichlin M. Heterogeneity of RNA protein antigens reactive with sera of patients with SLE. – Description of a cytoplasmic nonribosomal antigen. Arthritis Rheum 1974; 17: 421-429
• 17 Alspaugh MA, Tan EM. Antibodies to cellualar antigens in Sjögren’s Syndrome. J Clin Invest 1975; 55: 1067-1073
• 18 Trueb RM, Borelli S, Schmid-Grendelmeier P et al. Sjögren-Lupus erythematodes-Überlappungssyndrom. Hautarzt 1995; 46: 467-471
• 19 Provost TT, Watson R, Simmons-O’Brien E. Anti-Ro (SS-A) antibody positive Sjögren’s/lupus erythematosus overlap syndrome. Lupus 1997; 6: 105-111
• 20 Hernández-Molina G, Zamora-Legoff T, Romero-Díaz J et al. Predicting Sjögren’s syndrome in patients with recent-onset SLE. Rheumatology (Oxford). 2013; 52: 1438-1442 Epub 2013 Apr 16. PubMed PMID: 23594470
• 21 Lockshin MD, Levine AB, Erkan D. Patients with overlap autoimmune disease differ from those with ‘pure’ disease. Lupus Sci Med. 2015 2. e000084 eCollection 2015. PubMed PMID: 25973214; PubMed Central PMCID: PMC4422903
• 22 Cozzani E, Drosera M, Gasparini G et al. Serology of Lupus Erythematosus: Correlation between Immunopathological Features and Clinical Aspects. Autoimmune Dis 2014; 2014: 321359 Epub 2014 Feb 6. Review. PubMed PMID: 24649358; PubMed Central PMCID: PMC3932647
• 23 Eliasson H, Sonesson SE, Sharland G et al. Fetal Working Group of the European Association of Pediatric Cardiology. Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients. Circulation 2011; 124: 1919-1926 Epub 2011 Oct 10. PMID: 2198628
• 24 Sontheimer RD, Thomas JR, Gilliam JN. Subacute cutaneous lupus erythematosus. Arch Dermatol 1979; 115: 1409-1415
• 25 McCauliffe DP. Cutaneous diseases in adults associated with anti-Ro/SS-A autoantibody production. Lupus 1997; 6: 158-166
• 26 Senecal JL, Chartier S, Rothfield N. Hypergammaglobulinemic purpura in systemic autoimmune rheumatic diseases: predictive value of anti-Ro(SSA) and anti-La(SSB) antibodies and treatment with indomethacin and hydroxychloroquine. J Rheumatol 1995; 22: 868-875
• 27 Cervera R, Khamashta MA, Font J et al. Clinical and immunological patterns of disease expression in a cohort of 1 000 patients. Medcine 1993; 72: 113-124
• 28 Bernatsky S, Ramsey-Goldman R, Labrecque J et al. Cancer risk in systemic lupus: an updated international multi-centre cohort study. J Autoimmun 2013; 42: 130-135 Epub 2013 Feb 12. PubMed PMID: 23410586
• 29 Kim P, Grossman JM. Treatment of mixed connective tissue disease. Rheum Dis Clin North Am 2005; 31: 549-565 viii. Review. PubMed PMID: 16084325
• 30 Benett RM. Prognosis and treatment of mixed connective tissue disease. In: Ramirez Curtis M. (Ed.). UpToDate. Waltham: MA; Topic 7555 Version 8.0, accessed on August 15 2015
• 31 Mavragani CP, Moutsopoulos NM, Moutsopoulos HM. The management of Sjögren’s syndrome. Nat Clin Pract Rheumatol 2006; 2: 252-261 Review. PubMed PMID:16932698
• 32 Wallace DJ. Antimalarial drugs in the treatment of rheumatic disease. In: Ramirez Curtis M. (Ed.) UpToDate. Waltham: MA; Topic 7964 Version 20.0, accessed on August 16 2015
• 33 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 PubMed PMID: 25027140
• 34 Jonsson MV, Skarstein K, Jonsson R et al. Serological implications of germinal center-like structures in primary Sjögren’s syndrome. J Rheumatol 2007; 34: 2044-2049 Epub 2007 Sep 1. PubMed PMID: 17787040
• 35 Baer AN. Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren’s syndrome. In: Ramirez Curtis M. (Ed.) UpToDate. Waltham: MA; (Topic 14923 Version 8.0, accessed on August 16 2015
• 36 Tashkin DP, Elashoff R, Clements PJ et al. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med 2007; 176: 1026-1034 Epub 2007 Aug 23. PubMed PMID: 17717203; PubMed Central PMCID: PMC2078679
• 37 Varga J. Prognosis and treatment of interstitial lung disease in systemic sclerosis (scleroderma). In: Ramirez Curtis M. (Ed.) UpToDate. Waltham: MA; Topic 4375 Version 8.0, accessed on August 16 2015
• 38 Dellaripa PF, Miller ML. Interstitial lung disease in dermatomyositis and polymyositis: Treatment. In: Ramirez Curtis M. (Ed.) UpToDate. Waltham: MA; Topic 4357 Version 15.0, accessed on August 16 2015
• 39 Richeldi L, du Bois RM, Raghu G et al. INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014; 370: 2071-2082 Epub 2014 May 18. PubMed PMID: 24836310