Calcinosis is associated with digital ischaemia in systemic sclerosis-a longitudinal study.
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).


CONCLUSIONS
Ischaemia may play a role in the development of calcinosis in SSc.
Department of Medicine, McGill University mbaron@rhu.jgh.mcgill.ca.|Division of Rheumatology Jewish General Hospital, Montréal.
Murray
M
Baron
Deparment of Medicine, University of Western Ontario, London.
Janet
J
Pope
Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba.
David
D
Robinson
Department of Medicine, University of Alberta, Edmonton, Alberta.
Niall
N
Jones
Department of Medicine, McMaster University, Hamilton, Ontario.|Division of Rheumatology, St Joseph's Healthcare Hamilton, Hamilton, Ontario.
Nader
N
Khalidi
Division of Rheumatology, The Moncton Hospital, Moncton, New Brunswick.
Peter
P
Docherty
Faculty of Medicine, University of Calgary, Calgary, Alberta.
Elzbieta
E
Kaminska
Department of Medicine, Université de Sherbooke, Sherbrooke, Quebec.
Ariel
A
Masetto
Division of Rheumatology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia.
Evelyn
E
Sutton
Division of Rheumatology, Hôpital Maisonneuve-Rosemont.
Jean-Pierre
JP
Mathieu
Division of Rheumatology, Hôpital Maisonneuve-Rosemont.
Sophie
S
Ligier
Department of Rheumatology, Hôpital Notre-Dame, Montreal, Quebec.
Tamara
T
Grodzicky
Faculty of Medicine, University of Calgary, Calgary, Alberta.
Sharon
S
LeClercq
Medicine, Southlake Regional Health Centre, Newmarket.
Carter
C
Thorne
Department of Medicine, McGill University.|Division of Rheumatology Jewish General Hospital, Montréal.
Geneviève
G
Gyger
Division of Rheumatology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario.
Douglas
D
Smith
Faculty of Medicine, Université Laval, Quebec, Canada.
Paul R
PR
Fortin
Department of Medicine, McMaster University, Hamilton, Ontario.|Division of Rheumatology, St Joseph's Healthcare Hamilton, Hamilton, Ontario.
Maggie
M
Larché
Faculty of Medicine, University of Calgary, Calgary, Alberta.
Maysan
M
Abu-Hakima
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Tatiana S
TS
Rodriguez-Reyna
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Antonio R
AR
Cabral-Castaneda
Faculty of Medicine, University of Calgary, Calgary, Alberta.
Marvin J
MJ
Fritzler
Jewish General Hospital, Lady Davis Institute, Montréal, Quebec, Canada.
Mianbo
M
Wang
Department of Medicine, McGill University.|Division of Rheumatology Jewish General Hospital, Montréal.|Jewish General Hospital, Lady Davis Institute, Montréal, Quebec, Canada.
Marie
M
Hudson
D002114:Calcinosis / Q000209:etiology* / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D005260:Female; D005385:Fingers / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000150:complications*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012042:Registries; D012595:Scleroderma, Systemic / Q000150:complications*; D013997:Time Factors
D002121:Calcium Channel Blockers
autoantibodies; calcinosis; calcium channel blockers; capillaroscopy; ischaemia; multivariate analysis; scleroderma; smoking; systemic