Although researchers continue working to understand the pathophysiology of systemic sclerosis (SSc), evidence suggests SSc is mediated by vasculopathy, immunologic dysregulation and fibrosis. Given this evidence, it comes as no surprise studies have documented that 5–8% of SSc patients develop severe gastrointestinal (GI) disease. Moreover, independent associations appear to exist between severe GI disease, higher skin scores and telangiectasia. Reinforcing the association is the fact complications from GI dysmotility may be associated with anti-cardiolipin antibody (ACA) positivity.
These observations led Nicolas Richard, MD, a rheumatology fellow at Hopital Maisonneuve-Rosemont, Montreal, Canada, and colleagues to examine the incidence, predictors and outcomes associated with severe GI disease in a large inception SSc cohort. They found many patients with early SSc experience severe GI disease and the GI disease was associated with significant morbidity and increased mortality. The results of their research were published online in Rheumatology.1
The study cohort comprised 556 patients (Canadians and Australians) with SSc who had a disease duration of less than two years. The investigators followed these patients for a mean of 4.3±3.0 years and used physician reports, as opposed to objective verification, to document the presence of severe GI disease. The researchers found almost 10% of subjects developed severe GI disease at two years and more than 15% of subjects developed severe GI disease by the fourth year.
Patients with severe GI disease had markers of muscle inflammation, skin fibrosis and vasculopathy. Inflammatory arthritis and fecal incontinence was also associated with severe GI disease. In addition to the high incidence of severe GI disease, 58.3% of patients developed malabsorption, 19.4% developed hyperalimentation and 27.8% developed pseudo-obstruction during follow up.
Over the course of the study, 19.4% of subjects with severe GI disease and 14.5% of patients without severe GI disease died. When the investigators adjusted for age and sex, they found severe GI disease was associated with a greater than two-fold increase in the risk of death. When the investigators examined the health-related quality of life of the 311 Canadian patients who completed 1,132 visits with Medical Outcomes Study Short Form-36 (SF-36) data, they found severe GI disease was associated with a worse health-related quality of life.
“Our results not only show an increased risk of mortality, but also an association with significant impairment in [health-related quality of life],” write the authors in their discussion. “Other studies have also shown an influence of GI involvement on health-related quality of life in SSc, and our study confirms these findings for subjects with severe GI involvement using a generic measure of health status. Using robust methodology accounting for bias due to missing data, we were able to assess the independent relationship between the presence of severe GI disease and both physical and mental health status impairment.”
The authors concluded their paper by calling for more research to understand, prevent and mitigate severe GI disease in SSc.
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
- Richard N, Hudson M, Wang M, et al. Severe gastrointestinal disease in very early systemic sclerosis is associated with early mortality. Rheumatology (Oxford). 2018 Dec 4. [Epub ahead of print]