title: Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis.
abstract: BACKGROUND
  Systemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status.
  
  
  OBJECTIVE
  To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc).
  
  
  METHODS
  The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed.
  
  
  RESULTS
  Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often 'other antibodies' (68.0%; p<0.0001), including anti-U1RNP, -PmScl, -Ro, -La, as well as anti-Jo-1 and -Ku antibodies. These patients developed musculoskeletal involvement earlier and more frequently (62.5%) than patients diagnosed as lcSSc (32.2%) or dcSSc (43.3%) (p<0.0001). The onset of lung fibrosis and heart involvement in SSc-overlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset.
  
  
  CONCLUSIONS
  These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement.
authors.affiliation: Department of Dermatology, Cologne University Hospital, Cologne, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Moinzadeh
authors.affiliation: Department of Dermatology, Medical University of Graz, Graz, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Aberer
authors.affiliation: Department of Rheumatology, Asklepios Clinic Altona, Hamburg, Germany.
authors.forename: Keihan
authors.initials: K
authors.lastname: Ahmadi-Simab
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Blank
authors.affiliation: Department of Rheumatology, University of Erlangen, Erlangen, Germany.
authors.forename: Joerg H W
authors.initials: JH
authors.lastname: Distler
authors.affiliation: Department of Dermatology, University of Tuebingen, Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fierlbeck
authors.affiliation: Department of Rheumatology, Clinic of Rheumatology of Aachen, Aachen, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Genth
authors.affiliation: Department of Dermatology, University-Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Guenther
authors.affiliation: Department of Dermatology, Munich University of Technology, Munich, Germany.
authors.forename: Ruediger
authors.initials: R
authors.lastname: Hein
authors.affiliation: Department of Rheumatology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Henes
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Herich
authors.affiliation: Department of Dermatology and Venereology, University of Muenster, Muenster, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Herrgott
authors.affiliation: Department of Internal Medicine and Nephrology (Centre for interdisciplinary Rheumatology), Robert-Bosch-Hospital, Stuttgart, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Koetter
authors.affiliation: Department of Dermatology, Helios Clinic Oberhausen, Oberhausen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreuter
authors.affiliation: Department of Dermatology, Cologne University Hospital, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kuhr
authors.affiliation: Department of Haemato-Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hanns-Martin
authors.initials: HM
authors.lastname: Lorenz
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kerckhoff Clinic, Bad Nauheim, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Meier
authors.affiliation: Clinical Research Unit for Rheumatology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Melchers
authors.affiliation: Clinic for Dermatology, Hamburg Alstertal, Hamburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Mensing
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kerckhoff Clinic, Bad Nauheim, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Mueller-Ladner
authors.affiliation: Department of Dermatology, Ulm University Hospital, Ulm, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Pfeiffer
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Berlin, Charité, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.affiliation: Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany.
authors.forename: Miklós
authors.initials: M
authors.lastname: Sárdy
authors.affiliation: Department of Rheumatology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmalzing
authors.affiliation: Department of Dermatology and Venereology, University of Muenster, Muenster, Germany.
authors.forename: Cord
authors.initials: C
authors.lastname: Sunderkoetter
authors.affiliation: Department of Dermatology and Venereology, Ruhr University Bochum, Bochum, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Susok
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kerckhoff Clinic, Bad Nauheim, Germany.
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Tarner
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Vaith
authors.affiliation: Department of Dermatology and Venerology, University of Berlin, Charité, Berlin, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
authors.affiliation: Department of Dermatology, University-Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Wozel
authors.affiliation: Department of Rheumatology, Johanniter-Hospital, Treuenbrietzen, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Zeidler
authors.affiliation: Department of Dermatology, Cologne University Hospital, Cologne, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hunzelmann
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D009202:Cardiomyopathies / Q000209:etiology; D003240:Connective Tissue Diseases / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000209:etiology; D045743:Scleroderma, Diffuse / Q000503:physiopathology; D045745:Scleroderma, Limited / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D013577:Syndrome
chemical_list: D001323:Autoantibodies
keywords: Autoimmune Diseases; Epidemiology; Systemic Sclerosis