Presentation: Skin Thickness Progression Rate in Systemic Sclerosis with Diffuse Cutaneous Involvement: A Predictor of Outcome (2007)

2 Skin Thickness Progression Rate in Systemic Sclerosis with Diffuse Cutaneous Involvement: A Predictor of Outcome

Purpose: To examine the skin thickness progression rate, obtained by history and physical examination, as a predictor of outcome in systemic sclerosis (SSc) patients with diffuse cutaneous (dc) involvement.
Patients and Methods: We evaluated SSc patients with the following characteristics: (1) first evaluated during 1980-2004; (2) diffuse involvement at first visit; (3) duration of skin thickening less than 2 years; and (4) one and only one identified autoantibody of anti-RNA polymerase (pol) III, anti-topoisomerase (topo) I, or other. Skin thickness progression rate (STPR) was defined as the total skin thickness score (modified Rodnan method or mRSS) at first visit divided by the duration of skin thickening at the first visit. For example, if the mRSS was 24 and duration of skin thickness was 8 months, the STPR was 36/year. STPRs were divided into tertiles: rapid (>45 per year), intermediate (25-45 per year) and slow (less than 25 per year).
We first evaluated 5 year survival between STPR groups by the lifetable method. We then performed stepwise multivariate logistic regression to evaluate clinical predictors of (1) 5 year mortality and (2) development of internal organ involvement defined as scleroderma renal crisis (SRC), interstitial lung disease (ILD) or cardiac involvement within one year after onset of skin thickening. Variables evaluated included age at symptom onset, gender, race, anti-topo I, anti-RNA pol III, skin score at first visit (tertiled), and STPR group. In the model for 5 year mortality we also evaluated the association of SRC, ILD, cardiac and GI involvement.
Results: 689 patients satisfied the above criteria. 75% were female, 91% Caucasian and the mean age was 46 years at symptom onset. The 5 year cumulative survival rate for the rapid, intermediate and slow STPR subgroup were 72%, 81% and 82% respectively (p = 0.02).
Independent predictors of 5 year mortality and the associated odds ratios and confidence intervals are shown below.
Table 1: Independent Predictors of 5-year Mortality from Onset of Skin Thickening
Odds Ratio (OR)95% Confidence Interval (CI)p-value
SRC3.091.91 - 5.01< 0.0001
African American2.951.43 - 6.120.003
Cardiac Involvement2.111.33 - 3.350.001
Rapid STPR (>45)1.631.10 - 2.420.015
Age at Symptom Onset1.041.02 - 1.05< 0.0001
Anti-RNA Pol III Antibody0.440.29 - 0.66< 0.0001

The three independent significant predictors of internal organ involvement at one year were rapid skin thickness progression rate (OR 2.62; 95% CI 1.38-4.98, p=0.003), anti-topo I antibody (OR 2.04; 95% CI 1.05-3.96, p=0.035) and male gender (OR 2.03; 95% 1.05-3.93, p= 0.036).
Conclusions: Rapid STPR at first evaluation in early dcSSc patients is a predictor of both internal organ involvement at one year after onset of skin thickening and 5 year mortality. Assessment of individual risk in dcSSc patients and planning of clinical trials involving these patients should include evaluation of STPR.

 R.T. Domsic, None.