Cancer in Systemic Sclerosis

It has long been recognized that patients with systemic sclerosis (scleroderma) have a higher risk of cancer compared to individuals in the general population. This increased risk could be secondary to damage from the disease process itself, a consequence of the immunosuppressive and cytotoxic therapies used to treat scleroderma, common environmental exposures, or from a shared genetic predisposition to develop both cancer and autoimmunity. Alternatively, it has been hypothesized that cancer therapies may trigger the development of vascular and fibrotic complications characteristic of scleroderma. Subsets of patients, identified by distinct autoantibody responses, have paraneoplastic scleroderma due to the development of antitumor immune responses that may become cross-reactive and result in autoimmunity. Recent data demonstrate that autoantibody type and cutaneous subtype may be powerful filters to risk stratify patients for cancer and specific cancer types in scleroderma. Additionally, certain immune responses, alone or in combination, may associate with a lower risk of cancer, raising the question of whether they are cancer-protective. In this chapter, we explore these potential links between cancer and scleroderma, discuss a paraneoplastic model of scleroderma pathogenesis, and suggest implications for cancer screening and therapeutics in this patient population.