Study On Clinical Prognosis And Biomarker Of Systemic Sclerosis In China

Background & objectivesSystemic sclerosis is an autoimmune disease of uncertain etiology. Many countries worldwide have carried out systemic sclerosis (SSc) clinical cohort studies and have obtained the clinical characteristics and prognostic analysis of their SSc population. Both clinical course and survival can be affected by the impact of race in SSc. But there is no large-scaled clinical cohort based on Chinese SSc patients. Lung involvement has become the major cause of death in SSc. The insidious onset and highly heterogeneous of clinical course have set up a challenge for early and accurate diagnosis of systemic sclerosis associated interstitial lung disease (SSc-ILD). A number of researches related to risk factors of interstitial lung disease (ILD) have been reported. However, there are few small-scaled retrospective studies in China. Serum KL-6 has been gradually applied into practice for its role in the ILD diagnosis and assessment. Few studies involve the predictive effect of KL-6.The aim of the study is to accomplish the clinical and prognostic analysis and explore SSc-ILD related risk factors of Chinese SSc PUMCH single-centered cohort. We try to describe the natural course of SSc-ILD and risk factors related to new-onset of ILD. And we hope to find out KL-6’s predictive effect of new-onset and deterioration of lung involvement.MethodsThis research is based on Chinese Rheumatism Data Center (CRDC). Patients diagnosed with SSc and eligible for this research were followed up. Demographic, clinical, and outcome date were gathered for statistical analysis. Mann-Whitney and χ2 tests were used to identify differences among groups; Kaplan-Meier analysis was used to estimate survival, and Cox proportional hazards regression analysis was used to identify factors associated with mortality.; Multiple logistic regression analysis was used to identify factors for ILD and the develop of ILD. Both baseline and serum before and after 2-years follow-up were collected for the measurement of serum KL-6 levels.ResultsA total of 448 patients were included, of whom 56.7% were lcSSc. Women predominated in the entire cohort. Mean age at diagnosis was 40 years. The prevalence of ILD and pulmonary arterial hypertension (PAH) was 85.5% and 21.6% respectively. Valvular disease, left ventricular diastolic dysfunction and pericardial effusion were common in cardiac involvement. LVEF decrease and scleroderma renal crisis (SRC) were rare. Over 2167 patient-years,23 of 40 deaths were attributable to SSc. Median survival time was 53 months. Survival rates from disease onset were 97.3%,94.3%,90.8% and 87.5% at 1,3,5 and 10 years, respectively, with poorer survival in patients with PAH. Independent prognostic factors for mortality were PAH (HR 7.7,95%CI 3.2,19.1) and pericardial effusion (HR 7.0,95%CI 2.4,20.2). Positive ATA (OR 3.18, p=0.000), gastroesophageal reflux (OR1.83, p=0.047) and elevated ESR (OR 2.31, p=0.017) were independent risk factors for ILD. It took 6.3 to 8.5 years from disease onset to new onset of ILD in our cohort. It seemed that the course of ILD was more evident in the early stage of SSc, especially within 6 years after diagnosis. Positive ACA (HR 0.119,95%CI 0.026,0.540, p=0.006) was independent protect factor for new-onset of ILD. Our research verified the diagnostic value of KL-6 in SSc-ILD. We proved that patients with elevated serum KL-6 level at baseline were prone to develop ILD during follow-up. Among SSc-ILD patients with mild lung injury, elevated KL-6 had some predictive value for lung progression 2 years later.ConclusionsTen-year survival is 87.5% in Chinese SSc patients. PAH at baseline and pericardial effusion are the main risk factors for mortality. PAH is the major cause of death.6.3 to 8.5 years is needed for the emergence of SSc-ILD from disease onset in our cohort. ILD may rapidly progress within 6 years from disease diagnosis. Positive ACA is the independent protect factor for new-onset of ILD. We have also proved the value of KL-6 in predicting the development and progression of ILD.