Dr. Fritzler holds the Arthritis Society Research Chair at the University of Calgary.
Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: A twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis
Version of Record online: 26 NOV 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 12, pages 3902–3912, December 2008
How to Cite
Koenig, M., Joyal, F., Fritzler, M. J., Roussin, A., Abrahamowicz, M., Boire, G., Goulet, J.-R., Rich, É., Grodzicky, T., Raymond, Y. and Senécal, J.-L. (2008), Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: A twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis & Rheumatism, 58: 3902–3912. doi: 10.1002/art.24038
- Issue online: 26 NOV 2008
- Version of Record online: 26 NOV 2008
- Manuscript Accepted: 11 AUG 2008
- Manuscript Received: 23 JAN 2008
- The Laboratory for Research in Autoimmunity at the Centre Hospitalier de l'Université de Montréal is supported in part by Mrs. Gisèle Sarrazin-Locas and the late Mr. Fernand Locas
- Fellowship from Sclérodermie Québec
- Arthritis Society Research Chair at the University of Calgary
- Fonds de la Recherche en Santé du Québec
- Canadian Institutes of Health Research. Grant Numbers: MOP-68966, MOP-81252
- Sclérodermie Québec
To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies.
Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti–CENP-B), anti-Th/To, anti–topoisomerase I, and anti–RNA polymerase III (anti–RNAP III) autoantibodies by specific assays. Patients were studied prospectively.
Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti–CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti–RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc.
In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.