Systemic sclerosis

Abstract

True comorbidity is the independent occurrence of more than one disease in a patient. In a disease like systemic sclerosis (SSc) which involves almost all organs, it is problematic to define comorbidity. A good example is SSc and primary Sjögren's disease. Figures as high as 80% comorbidity have been published, but in the majority it may be caused by fibrosis and not inflammation and thus should be interpreted as manifestation of SSc. The real comorbidity figure may be around 14%. A further illustration is the frequent uncertainty regarding the cause of death at a time when less than 10% of patients even in trials of novel therapy undergo postmortem examination. This review examines associations with malignancy, autoimmune overlap conditions, liver disease, cardiovascular disease, myasthenia gravis, depression, and osteoporosis. Malignancy occurs either concomitant with onset or years after the onset of SSc. This is related to the kind of SSc-associated autoantibodies. A rare single gene mutation links some anti-RNA polymerase III positive SSc patients' malignancy to a mutation in the POLR3 region, indicating a pathogenic correlation. Several vascular features affecting endothelial function in SSc contribute to an increased prevalence of cardiovascular disease and contribute to comorbidity with vascular disease. Impaired quality of life could be a reasonable explanation for increased prevalence of depression and risk of suicide.