Dupilumab to treat drug reaction with eosinophilia and systemic symptoms

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a relatively common and potentially life-threatening dermatologic condition. The immunopathogenesis of this disease has not yet been conclusively defined, but the literature suggests that DRESS may be a T-helper 2 (Th2) driven process. Given this ambiguity, the current standard treatment is a prolonged course of systemic corticosteroids. Objective: To determine if dupilumab, a monoclonal antibody that downregulates the Th2 axis of the immune system, is a safe and effective treatment for DRESS. Methods: A prospective case series of three patients with signs and symptoms concerning for DRESS, as determined by their respective Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) scores. Each patient received a loading dose of 600 mg of dupilumab subcutaneously followed by weekly injections of 300 mg of dupilumab, the duration of which varied on a case-by-case basis. Results: Within two weeks of initiation of dupilumab therapy, all three patients noted significant improvement in their cutaneous and systemic symptoms, while achieving or maintaining eosinophil, liver enzyme, and creatinine levels that were within normal limits. Additionally, the duration of corticosteroid use was 18 days or less for all three participants, in contrast to the current standard of at least six weeks. Notably, all three patients suffered from mild relapses following dupilumab discontinuation; however, remission was rapidly reinstated following reintroduction of the biologic therapy. There were no reported adverse events from receiving off-label dupilumab treatment. Conclusion: Dupilumab’s downregulation of the Th2 inflammation associated with DRESS translated into active and passive clinical advantages for all three of our patients. Further research regarding dupilumab’s usage and Th2 pathway modulation in DRESS may be warranted, especially given the typical use of broadly acting immunosuppressive medications for this dangerous disease.