Susceptibility to herpes simplex virus in atopic dermatitis

• Applicant: Privatdozent Dr. Stephan Traidl
• Subject Area: Clinical Immunology and Allergology ; Dermatology
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504117717

• Final Report Year: 2025

Final Report Abstract

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, characterized by eczema, intense itching, and impaired skin barrier function. Many patients also suffer from bacterial and viral skin infections. Particularly concerning is infection with herpes simplex virus (HSV), which can lead to a severe disease course in AD patients, known as eczema herpeticum (EH). The aim of this project was to better understand why some individuals are especially susceptible to HSV infections. To address this question, we applied modern investigative methods, including immune cell analyses from blood samples, skin biopsies, and data from the nationwide TREATgermany registry. In an analysis of nearly 900 patients, more than 20% reported at least one episode of EH, and over 50% of those had recurrent infections. This suggests an underlying predisposition to EH in a specific subgroup of patients. An increased risk was associated with allergic diseases and asthma. In a second part of the project, we investigated how treatment with the monoclonal antibody dupilumab affects the immune response to HSV. The results indicate that antiviral immune responses are enhanced under treatment, which may reduce the risk of recurrent EH episodes. In addition, transcriptomic analyses of skin biopsies from TREATgermany patients were performed. Among patients with a history of EH, we observed specific alterations in the JAK signaling pathway in lesional skin. These findings are currently being further explored using spatial transcriptomics, which allow for high-resolution mapping of gene expression in tissue sections. The insights gained from this project contribute to a better understanding of the risk of severe viral infections in atopic dermatitis and may support more personalized treatment strategies in the future.

Publications

• 046 Influence of dupilumab on HSV-specific immune response in atopic dermatitis. Journal of Investigative Dermatology, 142(12), S188.
  Traidl, S.; Harries, L.; Kienlin, P.; Begemann, G.; Roesner, L. & Werfel, T.
  
• Dupilumab strengthens herpes simplex virus type 1–specific immune responses in atopic dermatitis. Journal of Allergy and Clinical Immunology, 152(6), 1460-1469.e5.
  Traidl, Stephan; Harries, Leonard; Kienlin, Petra; Begemann, Gabriele; Roesner, Lennart M. & Werfel, Thomas
  
• High recurrence rate of eczema herpeticum in moderate/severe atopic dermatitis –TREATgermany registry analysis. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 21(12), 1490-1498.
  Traidl, Stephan; Heinrich, Luise; Siegels, Doreen; Rösner, Lennart; Haufe, Eva; Harder, Inken; Abraham, Susanne; Ertner, Konstantin; Kleinheinz, Andreas; Schäkel, Knut; Wollenberg, Andreas; Effendy, Isaak; Quist, Sven; Asmussen, Andrea; Wildberger, Julia; Weisshaar, Elke; Wiemers, Franka; Brücher, Jens‐Joachim; Weidinger, Stephan ... & Werfel, Thomas
  
• Influence of dupilumab on HSV-specific immune response in atopic dermatitis. Vortrag. ISDS 2023
  Traidl S., Harries L., Kienlin P., Begemann G., Roesner L.M. & Werfel T.
  
• Algorithms in Allergy: Diagnosis and Treatment of Atopic Dermatitis Complicated by Eczema Herpeticum. Allergy, 80(8), 2417-2420.
  Traidl, Stephan; Heratizadeh, Annice & Werfel, Thomas