Benralizumab for corticosteroid-refractory DRESS in two COVID-19 patients

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare severe drug hypersensitivity reaction. Treatment of DRESS currently consists of systemic corticosteroids. Here, we report benralizumab (Fasenra®) as a treatment for corticosteroid-refractory DRESS occurring in two severely ill COVID-19 patients. Both patients received high-dose intravenous corticosteroids for 4-6 days, but cutaneous symptoms, eosinophilia and signs of related organ damage were deteriorating. Based on its successful use in PDGFRA-independent hypereosinophilia, we decided to treat our patients with benralizumab. The patients showed clinical improvement and a rapid substantial drop in eosinophils. Targeted high-throughput serum proteomics prior vs. after treatment revealed a significant reduction mostly in eosinophil- and T cell response-related proteins (a.e. IL-5, CD8, TNF and PD-L1), thus pointing towards an impact of benralizumab on the (drug-directed) T cell response in DRESS.

Systemic hyperinflammation as a driver of maculopapular drug exanthema in severely ill COVID-19 patients?

Coronavirus disease 2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions Here, we utilize imaging mass cytometry (IMC) to characterize the cutaneous immune response in maculopapular drug rashes (MDR), including those associated with COVID-19 infection (COVID MDR). For comparison skin from healthy controls and patients with drug rash with eosinophilia and systemic symptoms (DRESS) was analyzed. Results demonstrated that COVID MDR are characterized by a more prominent infiltration of cytotoxic CD8+ T cells and highly activated, phenotypically shifted monocyte/macrophage (Mo/Mac) clusters in comparison to MDR and DRESS. RNA sequencing transcriptome of the affected skin also demonstrated a more robust cytotoxic response in lesional COVID MDR skin Serum proteomic profiling of COVID MDR patients revealed up-regulation of various inflammatory mediators (IL-4, IL-5, IL-8, IL-18, IL-6, TNF and IFN-γ), eosinophil and Mo/Mac -attracting chemokines MCP-2, MCP- 3, MCP-4 and CCL11. Analyses of cytokine networks demonstrated a relatively milder cytokine storm in DRESS compared to COVID MDR while MDR did not exhibit such features. Our results suggest that a massive systemic cytokine storm promotes activation of Mo/Mac and cytotoxic CD8+ T cells, which impacts MDR development in severely ill COVID-19 patients.