Murray Baron1,2, Janet Pope3, David Robinson4, Niall Jones5, Nader Khalidi6,7, Peter Docherty8, Elzbieta Kaminska9, Ariel Masetto10, Evelyn Sutton11, Jean-Pierre Mathieu12, Sophie Ligier12, Tamara Grodzicky13, Sharon LeClercq9, Carter Thorne14, Geneviève Gyger15,2, Douglas Smith16, Paul R Fortin17, Maggie Larché6,7, Maysan Abu-Hakima9, Tatiana S Rodriguez-Reyna18, Antonio R Cabral-Castaneda18, Marvin J Fritzler9, Mianbo Wang19, Marie Hudson15,2,19. 1. Department of Medicine, McGill University mbaron@rhu.jgh.mcgill.ca. 2. Division of Rheumatology Jewish General Hospital, Montréal. 3. Deparment of Medicine, University of Western Ontario, London. 4. Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba. 5. Department of Medicine, University of Alberta, Edmonton, Alberta. 6. Department of Medicine, McMaster University, Hamilton, Ontario. 7. Division of Rheumatology, St Joseph's Healthcare Hamilton, Hamilton, Ontario. 8. Division of Rheumatology, The Moncton Hospital, Moncton, New Brunswick. 9. Faculty of Medicine, University of Calgary, Calgary, Alberta. 10. Department of Medicine, Université de Sherbooke, Sherbrooke, Quebec. 11. Division of Rheumatology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia. 12. Division of Rheumatology, Hôpital Maisonneuve-Rosemont. 13. Department of Rheumatology, Hôpital Notre-Dame, Montreal, Quebec. 14. Medicine, Southlake Regional Health Centre, Newmarket. 15. Department of Medicine, McGill University. 16. Division of Rheumatology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario. 17. Faculty of Medicine, Université Laval, Quebec, Canada. 18. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. 19. Jewish General Hospital, Lady Davis Institute, Montréal, Quebec, Canada.
Abstract
OBJECTIVE: To determine if ischaemia is a causal factor in the development of calcinosis in SSc. METHODS: Patients with SSc were assessed yearly. Physicians reported the presence of calcinosis, digital ischaemia (digital ulcers, digital necrosis/gangrene, loss of digital pulp on any digits and/or auto- or surgical digital amputation) and nailfold capillary dropout assessed using a dermatoscope. The number of digits with digital ischaemia was used as an assessment of the severity of digital ischaemia. SSc specific antibodies were detected with a line immunoassay. Multiple logistic regression and Cox proportional hazards models were generated to determine associations between calcinosis, digital ischaemia and capillary dropout. RESULTS: One thousand three hundred and five patients were included in this study, of whom 300 (23.0%) had calcinosis at study entry. In a cross-sectional multivariate analysis, at baseline, calcinosis was associated with digital ischaemia (odds ratio (OR) = 2.37, 95% CI: 1.66, 3.39), severity of ischaemia (OR = 1.12, 95% CI: 1.06, 1.18), capillary dropout (OR = 1.41, 95% CI: 1.05, 1.89), ACAs (OR = 1.68, 95% CI: 1.17, 2.43) and anti-RNA polymerase III antibodies (OR = 1.77, 95% CI: 1.08, 2.89). Current use of calcium channel blockers was inversely associated with the presence of calcinosis (OR = 0.70, 95% CI: 0.52, 0.96). Of the 805 patients with no calcinosis at study entry and at least one follow-up visit, 215 (26.7%) developed calcinosis during follow-up. Significant baseline predictors of the development of calcinosis in follow-up were digital ischaemia (hazard ratio (HR) = 1.82, 95% CI: 1.30, 2.54), capillary dropout (HR = 1.46, 95% CI: 1.08, 1.99), dcSSc (HR = 1.57, 95% CI: 1.11, 2.21), ACA (HR = 2.18, 95% CI: 1.50, 3.17) and anti-RNA polymerase III antibodies (HR = 2.58, 95% CI: 1.65, 4.04). CONCLUSION: Ischaemia may play a role in the development of calcinosis in SSc.
OBJECTIVE: To determine if ischaemia is a causal factor in the development of calcinosis in SSc. METHODS:Patients with SSc were assessed yearly. Physicians reported the presence of calcinosis, digital ischaemia (digital ulcers, digital necrosis/gangrene, loss of digital pulp on any digits and/or auto- or surgical digital amputation) and nailfold capillary dropout assessed using a dermatoscope. The number of digits with digital ischaemia was used as an assessment of the severity of digital ischaemia. SSc specific antibodies were detected with a line immunoassay. Multiple logistic regression and Cox proportional hazards models were generated to determine associations between calcinosis, digital ischaemia and capillary dropout. RESULTS: One thousand three hundred and five patients were included in this study, of whom 300 (23.0%) had calcinosis at study entry. In a cross-sectional multivariate analysis, at baseline, calcinosis was associated with digital ischaemia (odds ratio (OR) = 2.37, 95% CI: 1.66, 3.39), severity of ischaemia (OR = 1.12, 95% CI: 1.06, 1.18), capillary dropout (OR = 1.41, 95% CI: 1.05, 1.89), ACAs (OR = 1.68, 95% CI: 1.17, 2.43) and anti-RNA polymerase III antibodies (OR = 1.77, 95% CI: 1.08, 2.89). Current use of calcium channel blockers was inversely associated with the presence of calcinosis (OR = 0.70, 95% CI: 0.52, 0.96). Of the 805 patients with no calcinosis at study entry and at least one follow-up visit, 215 (26.7%) developed calcinosis during follow-up. Significant baseline predictors of the development of calcinosis in follow-up were digital ischaemia (hazard ratio (HR) = 1.82, 95% CI: 1.30, 2.54), capillary dropout (HR = 1.46, 95% CI: 1.08, 1.99), dcSSc (HR = 1.57, 95% CI: 1.11, 2.21), ACA (HR = 2.18, 95% CI: 1.50, 3.17) and anti-RNA polymerase III antibodies (HR = 2.58, 95% CI: 1.65, 4.04). CONCLUSION:Ischaemia may play a role in the development of calcinosis in SSc.
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