Biomarkers of disease severity in morbilliform drug eruption identified by skin tape strip proteomics

Summary: Abstract Body: Morbilliform drug eruptions (MDE) account for ~90% of cutaneous drug reactions and up to 2% of all systemic drug exposures. While most MDE cases are mild and largely skin-limited, others quickly progress to erythroderma or portend underlying systemic involvement, such as with drug reaction with eosinophilia and systemic symptoms (DRESS). Identifying reproducible MDE-associated biomarkers and differentiating severe, higher-risk cases are of critical importance. Skin tape stripping is gaining recognition as a simple non-invasive method for identifying and tracking disease biomarkers. Tape strips from lesional skin of 12 MDE cases, including 6 with DRESS and 5 with erythroderma, and matched sites of 13 healthy controls (HC) were analyzed with a multiplex proximity extension immunoassay of 368 proteins relevant to inflammation. Differentially expressed proteins (DEPs) were assessed comparing all MDE vs HC, DRESS vs HC, DRESS vs non-DRESS, and erythrodermic vs non-erythrodermic cases. A total of 126 DEPs were upregulated in MDE skin compared with HC (p<0.05, FDR<0.05) including those involved in Th2 responses and IL-10 and MAPK signaling. Many DEPs have been previously validated in hypersensitivity drug reactions. When comparing DRESS vs HC, 203 DEPs were upregulated in DRESS (p<0.05, FDR<0.05) including strong IL-4 and IL-18 signaling and cell death receptor signaling (e.g. FAS). When comparing DRESS vs non-DRESS, 121 proteins trended higher (p<0.05, FDR>0.05) in DRESS, including those involved in IL-4, IL-5 and IL-12 signaling, NFkB signaling, and response to wounding. When comparing erythrodermic vs non-erythrodermic skin, 168 proteins were upregulated in erythrodermic skin (p<0.05, FDR<0.05). DEPs spanned pathways of IL-17 signaling, NFkB signaling, programmed cell death, and VEGF signaling. In conclusion, skin tape strips were able to identify biomarkers that may prove useful in diagnosing and predicting disease severity in MDE and guiding management for these patients. Zachary Thomas¹, Yae Lee Kye¹, William Nguyen¹, Sammer Marzouk¹, Yoo Jung Kim¹, Madison Ernst¹, Spencer Evans¹, Kurt Lu¹, Cuong Nguyen¹, Alan Zhou¹ 1. Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States. Translational Studies: Cell and Molecular Biology