Our first objective was to report the presenting features of systemic sclerosis (SSc) in a large cohort of French Canadian patients encompassing the full spectrum of the disease. Our second objective was to identify among these presenting features factors predictive for mortality and to compare these data with those of other series. Between 1984 and 1999, SSc was diagnosed at first presentation in 309 consecutive and unselected French Canadian patients at a single SSc center; the patients were enrolled in a prospective study and followed until September 2000. Patients were categorized into 4 subsets based on sclerodermatous skin extent: diffuse (trunk, n = 29), intermediate (proximal to metacarpophalangeal joints without trunk, n = 78), limited (sclerodactyly only, n = 152), or normal skin (n = 50) subsets. Data collection was according to a protocol encompassing 215 variables and including nailfold capillary microscopy. Standardized mortality ratios were computed using ageand gender-specific annual mortality rates in the Province of Quebec general population. Vital status was obtained from the Quebec Statistics Institute. The overall cohort female to male ratio was 6:1. Presenting features varied in frequency in each subset. Anticentromere antibodies were most common in the normal skin and limited SSc subsets (50% of patients), and less common in intermediate and diffuse subsets (34.6% and 3.4%, respectively) (p < 0.0001). The frequency of antibodies to DNA-topoisomerase I (anti-topo I) in diffuse SSc was 13.8%. By nailfold capillary microscopy, severe capillary loss was not restricted to any subset. However, the rate of onset of severe capillary loss strikingly varied among the subsets (p < 0.0001). Death occurred in 66 (21.3%) patients. SSc was the major cause of death (n = 35, 53%), followed by cancer and atherosclerosis. In the limited, intermediate, and diffuse subsets, 43.8%, 57.1%, and 100% of the deaths were SSc-related, respectively (p = 0.004). For deaths due to SSc, cumulative survival rates for these subsets were 97%, 94%, and 78% at 5 years, and 89%, 86%, and 62% at 10 years, respectively. Survival curves were significantly different (p = 0.0001). By stepwise Cox regression, independent predictors for mortality were skin involvement of the trunk, age, carbon monoxide diffusion capacity of the lungs (DLCO) ≤ 70% of predicted normal value, erythrocyte sedimentation rate ≥ 25 mm/h, and hemoglobin level ≤ 12.5 g/dL. The observed mortality increased from 2% in patients with none of these predictors to 75% in patients with all predictors. Standardized mortality ratios were 2.71, 2.76, and 6.17 in the limited, intermediate, and diffuse subsets, respectively. Further dividing of the intermediate group into skin involvement below versus above the elbow revealed no difference in the frequency of clinical manifestations, anticentromere antibodies, anti-topo I, and mortality. To our knowledge, the present study is the first report on a large French Canadian SSc cohort. The frequency of anti-topo I in diffuse SSc is the lowest reported thus far. The data provide compelling evidence in favor of a distinct intermediate SSc subset. Several factors predictive for mortality were identified at baseline. These factors are easy to determine and may provide a rationale for close medical surveillance and early therapeutic intervention in patients at high risk for mortality. Comparison with other series suggests that despite different ethnicities and geographic environments, North American and European patients with SSc share similar prognostic factors and overall prognosis. Despite improved survival, SSc continues to be associated with high excess mortality.
