TNF-α blockade for carbamazepine-induced drug reaction with eosinophilia and systemic symptoms.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially fatal adverse drug reaction featuring widespread eruption, fever, and multi-organ involvement. Carbamazepine is a leading causative agent in Asian populations. While systemic corticosteroids remain first-line therapy, a subset of patients exhibits corticosteroid-refractory or corticosteroid-dependent disease. Elevated tumor necrosis factor-alpha (TNF-α) levels during the acute phase provide a rationale for TNF-α blockade as an adjunctive treatment, yet clinical experience with TNF-α blockade in DRESS remains limited. Objective: To explore the potential effectiveness and safety of TNF-α inhibitors as an adjunctive treatment for DRESS. Methods: We retrospectively reviewed three consecutive inpatients diagnosed with carbamazepine-induced DRESS (RegiSCAR scores 5-9) at our dermatology department between September 2025 and March 2026. All received subcutaneous etanercept biosimilar, with individualized dosing. A systematic literature search was also performed to summarize previously published cases of DRESS treated with TNF-α inhibitors. Results: In our cohort, the three patients represented distinct phenotypes, and all had responded inadequately or transiently to corticosteroids alone. The addition of etanercept biosimilar was associated with clinical stabilization, progressive cutaneous improvement, and improvement in hepatic enzymes. Hospital stays ranged from 16 to 20 days with no etanercept-related adverse events. The literature review identified 8 previously reported DRESS cases treated with TNF-α inhibitors, the majority of which demonstrated a therapeutic response. Conclusion: Combined with previously published cases and our single-center experience, these findings support the potential benefit and an acceptable short-term safety profile of TNF-α inhibitors in this limited DRESS cohort.