ABSTRACT
Introduction: Few reports of severe cutaneous adverse reactions following COVID-19 vaccines exist and causes remain to be elucidated. We describe a case of DRESS syndrome (drug rash with eosinophilia and systemic symptoms). Case report: A 52-year-old woman presented with a generalized rash occuring 1 day after vaccination with the Moderna vaccine. The patient met clinical criteria defining a probable DRESS syndrome. Investigations included a lymphocyte transformation test to the excipient trometamol showing increased proliferation. A consecutive vaccination with Janssen® COVID-19 vaccine led to a recurring rash of lesser severity. Discussion: This case shows the development of DRESS following administration of the Moderna mRNA vaccine. The course of symptoms with recurrence of a rash after the consecutive vaccination with the vector based Janssen® vaccine suggests a common elicitor of the adverse reaction. COVID-19 vaccine induced adverse events may be caused by molecular mimicry with human proteins due to structural similarities with SARS-CoV-2 sequences. Conclusions: Careful allergological work-up reveals some causes of hypersensitivity to COVID-19 vaccines, with sensitization to trometamol possibly playing a role in this case. The spike glycoprotein is suspected as a main driver of adverse skin reactions. Bringing light to the underlying mechanisms of cutaneous reactions to SARS-CoV- 2 vaccine is necessary for prevention and treatment.
ABSTRACT
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.
ABSTRACT
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.