Divalproex sodium: A potential therapy for scleroderma digital ulcers.

ER: extended release HDACi: Histone deacetylase inhibitor TSA: trichostatin A TGF-b: Transforming growth factor beta INTRODUCTION Scleroderma is an autoimmune connective tissue disease that involves the skin and internal organs for which there are few reliably effective treatments. The cutaneous manifestations of scleroderma include fibrosis and sclerodactyly, calcinosis cutis, digital ulcers, pigmentary changes, and mat telangiectasias. Three major pathways are thought to be important in the pathogenesis of scleroderma: autoimmunity and inflammation, microvascular alteration, and fibrosis. Although immunosuppression (eg, methotrexate) and vasodilatory therapy (eg, nifedipine) are commonly used to address the inflammatory and microvascular components, respectively, therapy directed at tissue fibrosis has remained elusive. Histone deacetylase inhibitors (HDACi) may have antifibrogenic effects in the skin and other organs via mediation of transforming growth factor beta (TGF-b). Divalproex sodium has known activity as an HDACi. We report the therapeutic outcome of a patient treated with the HDACi, divalproex sodium.