Evaluating Baricitinib for Severe Paediatric Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with Single-Cell Sequencing

Danyang Yang,1 Xin Liu,1 Wenwen Jing,1 Xu Feng,1 Canying Lai,1 Chenyue Liu,2 Zhigang Xu,1,3 Yangang Zhang,1 Jiayi Han,1 Songmei Geng,1 Ruilian Li,1 Dan Li,4 Boyi Cheng,1 Yufei Wu,1 Zhuokun Liu,1 Jialin Lian,1 Zhenghui Wang,5 Yale Liu,1,* Xiaoli Li1,* 1Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of China; 2Department of Medical Imaging and Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 3Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 4Department of Paediatrics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of China; 5Department of Otorhinolaryngology Head and Neck Surgery, the second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yale Liu; Xiaoli Li, Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi, 710004, People’s Republic of China, Email [email protected]; [email protected]: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe type of drug reaction that has significant mortality rate. Traditional treatments, including glucocorticoids and immunosuppressants, are sometimes insufficient. We present a case of severe paediatric DRESS unresponsive to conventional therapies, in which baricitinib, guided by single-cell RNA sequencing (scRNA-seq), led to clinical improvement. Single-cell transcriptomics is a revolutionary technology that allows scientists to measure the activity of all genes in individual cells on a large scale and has emerged as a tool for personalized therapeutic targeting.Patient and Methods: A 3-year-old male with DRESS triggered by phenobarbital presented with fever, skin rash, impaired liver function, eosinophilia, and cytomegalovirus infection. After failing high-dose corticosteroids, intravenous immunoglobulin, and etanercept, baricitinib was initiated. Peripheral blood mononuclear cells and skin biopsy samples underwent scRNA-seq to identify dysregulated pathways and potential therapeutic targets.Results: Baricitinib treatment led to resolution of skin lesions, normalization of eosinophil counts and liver function, and successful tapering of corticosteroids. Single-cell RNA sequencing uncovered that clusters of CD4+ and CD8+ T cells contain JAK2.Conclusion: Our findings suggest that baricitinib, a JAK1/2 inhibitor, is a safe and effective salvage therapy for corticosteroid-refractory paediatric DRESS. scRNA-seq can guide targeted treatment decisions in DRESS.Keywords: baricitinib, drug reaction with eosinophilia and systemic symptoms syndrome, severe type, treatment, single-cell RNA sequencing analysis