Patients with diffuse cutaneous systemic sclerosis (SSc) who experience progressive skin fibrosis may be at an increased risk for worsening lung function and all-cause mortality, according to research.
SSc is associated with major morbidity and mortality due to visceral organ complications, according to the study authors, including interstitial lung fibrosis, pulmonary arterial hypertension, scleroderma renal crisis, and cardiac and gastrointestinal involvement. Early identification of high-risk patients could help reduce the odds of irreversible organ damage.
Prior research found that patients with early diffuse cutaneous SSc whose skin did not improve over two years had greater mortality rates compared to those with skin improvement—regardless of their baseline modified Rodnan skin score (mRSS)—but the association between two-year skin improvement and internal organ damage was not as clear. Therefore, the present study aimed to quantify the relationship between one-year skin fibrosis progression and visceral organ disease progression and mortality.
Using the European Scleroderma Trials and Research (EUSTAR) database, researchers gathered data on patients with diffuse cutaneous SSc, baseline mRSS ≥7, valid mRSS at 12±3 months after baseline, and ≥1 annual follow-up visit. Patients with mRSS increase >5 and ≥25% from baseline to 12±3 months were considered to have progressive skin fibrosis. Primary outcomes included pulmonary, cardiovascular, and renal progression, as well as all-cause death.
Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research EUSTAR cohort.: To determine whether progressive skin… https://t.co/PCzMWtIMAB
— Dermatology News (@Dermatology_bio) March 11, 2019
Skin Progression Patients Experience Worsening FVC
A total of 1,021 patients were included in final analysis. Mean age was 52.0±13.7 years, and about three-quarters of patients were female. Mean disease duration was 7.7±7.5 years, and patients were followed for a median 3.4 years. Among the 1,021 total patients, 78 (7.6%) displayed skin fibrosis progression at one-year follow-up.
“Survival analyses indicated that skin progressors had a significantly higher probability of [forced vital capacity (FVC)] decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors,” the researchers observed. “These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09).”
The study was limited by several missing values and patients lost to follow-up. The researchers could also not determine specific death causes for all participating centers. There was also a large amount of new pulmonary hypertension cases during follow-up. And because the study was observational in design, the study authors could not evaluate how treatment affected outcomes.
“In conclusion, progressive skin fibrosis is associated with decline in lung function and worse survival in [diffuse cutaneous SSc] during follow-up,” the study authors wrote. “The evidence-based findings obtained from the large prospective EUSTAR cohort allow [optimization] of cohort enrichment in future clinical trials aimed at skin and lung fibrosis, and also help clinicians to identify patients at risk of lung progression in clinical practice.”