Amber Vanhaecke1,2, Maurizio Cutolo3, Oliver Distler4, Valeria Riccieri5, Yannick Allanore6, Christopher P Denton7, Eric Hachulla8,9,10, Francesca Ingegnoli11, Ellen Deschepper12, Jérôme Avouac6, Suzana Jordan4, David Launay8,9,10, Karin Melsens1,2, Carmen Pizzorni3, Alberto Sulli3, Massimiliano Vasile5, Ariane L Herrick13,14, Vanessa Smith1,2,15. 1. Department of Internal Medicine, Ghent University, Ghent, Belgium. 2. Department of Rheumatology, Ghent University Hospital, Ghent, Belgium. 3. Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, IRCCS San Martino Polyclinic Hospital, Genoa, Italy. 4. Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 5. Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. 6. Service de Rheumatology, Université de Paris, Höpital Cochin, AP-HP CUP, Paris, France. 7. Department of Rheumatology, University College London, Royal Free Hospital, London, UK. 8. Institute for Translational Research in Inflammation (INFINITE), Université de Lille, Lille, France. 9. INSERM, Lille, France. 10. Service de Médecine Interne et Immunologie Clinique, Centre de référence des maladies autoimmunes systémiques rares du Nord et Nord-Ouest de France (CeRAINO), CHU Lille, Lille, France. 11. Division of Clinical Rheumatology, ASST Pini-CTO, Milano, Italy; Dept of Clinical Sciences & Community Health, Università degli Studi di Milano, Milano, Italy. 12. Biostatistics Unit, Department of Public Health and Primary Care, Ghent University, Ghent, Belgium. 13. Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester, UK. 14. NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. 15. Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Centre (IRC), Ghent, Belgium.
Abstract
OBJECTIVES: Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary Raynaud's phenomenon due to systemic sclerosis (SSc). However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time. METHODS: Follow-up data from 334 SSc patients (265 women; 18 LSSc/203 LcSSc/113 DcSSc) registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardised definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed. RESULTS: 257/334 (76.9%) patients developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less frequent novel overall severe organ involvement/progression (OR = 0.77, p < 0.001) and novel peripheral vascular involvement (OR = 0.79, p = 0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, p = 0.029); and a "severe" (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, p = 0.002) and skin progression (OR = 1.70, p = 0.049). CONCLUSIONS: Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardised way, we were underpowered to detect associations with infrequent severe organ involvement/progression.
OBJECTIVES: Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary Raynaud's phenomenon due to systemic sclerosis (SSc). However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time. METHODS: Follow-up data from 334 SSc patients (265 women; 18 LSSc/203 LcSSc/113 DcSSc) registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardised definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed. RESULTS: 257/334 (76.9%) patients developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less frequent novel overall severe organ involvement/progression (OR = 0.77, p < 0.001) and novel peripheral vascular involvement (OR = 0.79, p = 0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, p = 0.029); and a "severe" (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, p = 0.002) and skin progression (OR = 1.70, p = 0.049). CONCLUSIONS: Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardised way, we were underpowered to detect associations with infrequent severe organ involvement/progression.
Keywords:
EULAR Study Group on Microcirculation in Rheumatic Diseases; EUSTAR; Systemic sclerosis; disease progression; microcirculation; nailfold videocapillaroscopy; organ involvement