Dermatomyositis (DM) is a systemic autoimmune disease with characteristic skin findings such as violaceous patches on the eyelids (heliotrope sign), on the interphalangeal joints (Gottron's papules), on the knees and elbows (Gottron's sign), and prominent nailfold telangiectasias. These skin findings are often painful and disfiguring and cause significant impairment in quality of life for patients (Goreshi et al., 2011; Robinson et al., 2015). Current treatment options for DM include corticosteroids, methotrexate, and immunomodulators such as mycophenolate mofetil and rituximab. Therapy options for cutaneous DM have been classically guided by case series, retrospective reviews, and open trials (Femia et al., 2013), and there remains a need for more effective and safer therapeutics to treat recalcitrant cutaneous disease in DM.

Sirota et al. previously developed an integrative computational method to guide drug repositioning using genome-wide molecular data in Connectivity Map (Dudley et al., 2011; Lamb et al., 2006; Sirota et al., 2011). This approach has been applied successfully to identify potential therapeutics for lung cancer and inflammatory bowel disease and has been recognized in a case study for psoriasis (Qu et al., 2014), but it has yet to be studied in other dermatologic conditions. Here, we applied our systematic integrative approach comparing microarray data from 38 DM skin biopsies to molecular data from over 1,600 US Food and Drug Administration (FDA)-approved drugs and identified alpha-adrenergic agonists as potential therapeutic agents for cutaneous DM (Figure 1A). A pilot trial of alpha-adrenergic agonists revealed marked efficacy in three patients with cutaneous DM.