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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Koenig
Martial
M
Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Joyal
France
F
Fritzler
Marvin J
MJ
Roussin
André
A
Abrahamowicz
Michal
M
Boire
Gilles
G
Goulet
Jean-Richard
JR
Rich
Eric
E
Grodzicky
Tamara
T
Raymond
Yves
Y
Senécal
Jean-Luc
JL
D000328:Adult; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D003663:Decision Trees; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D055806:Microvessels / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011928:Raynaud Disease / Q000145:classification / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D012595:Scleroderma, Systemic / Q000145:classification / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D016036:Seroepidemiologic Studies; D055815:Young Adult
D001323:Autoantibodies