Pathogenesis and Therapeutics of Interstitial Lung Disease in Systemic Sclerosis

Interstitial lung disease is a common manifestation in systemic sclerosis and is considered as one of the two main causes of death among these patients. Although the pathogenesis of interstitial lung disease related to systemic sclerosis (SSc-ILD) is very complex and not yet fully understood, diverse mechanisms such as vascular injury, altered immunological response and inflammatory activation have been proposed. Vascular injury is considered as the earliest event in the pathogenesis of this disease and has been associated with an excessive formation of alveolar capillaries, circulating endothelial cells, and increased expression of endothelin-1. Different cells like myofibroblasts, fibroblasts, endothelial cells and T lymphocytes are involved in the inflammatory activation. Meanwhile, lymphocyte activation, release of several cytokines and autoantibody production play an important role in the immunological response. To date, the treatment of SSc-ILD is not totally defined, as studies have shown mixed results. Given the high progression of the disease, it is difficult to enroll patients for clinical trials. Therefore, there is lack of evidence to guide therapeutic approaches. Throughout this paper, we present evidence supporting that the combination of glucocorticoids and cyclophosphamide is considered the best regimen for patients with SSc-ILD. In addition, we present data regarding the use of azathioprine, mycophenolate, anti-fibrosing agents, bosentan, rituximab, and imatinib mesylate as alternative therapies. Finally, for patients who are unresponsive to pharmacologic interventions, we present data regarding the efficacy of high-dose immunosuppression with autologous transplantation of hematopoietic stem cells, and lung transplantation.