Atopic dermatitis (AD), one of the most common chronic inflammatory skin diseases, causes pruritic skin lesions. A subset of AD patients can be present with disseminated severe herpes simplex virus (HSV) infection called eczema herpeticum (EH), which can lead to life-threatening complications. It is induced by specific barrier dysfunctions and immunological aberrations like a type 2 skewing of virus-specific T cells and a malfunction of the interferon (IFN)-pathway.

Type 2 skewing of virus-specific T cells in AD patients with a history of eczema herpeticum (ADEH⁺) patients has been involved in immune profile abnormalities, including impaired functions of dendritic cells and natural killer cells. Furthermore, aberrations in interferon pathway-related genes like IFNG and IFNGR1 also increase the risk of EH. Interleukin (IL)-4, IL-25 and thymic stromal lymphopoietin (TSLP) remain overexpressed in EH, while antimicrobial peptides like human β-defensins and LL-37 are reduced. Regarding the epidermal barrier, single nucleotide polymorphisms (SNPs) in skin barrier proteins like filaggrin are present in ADEH+ patients. An imbalance of the skin microbiome also donates to EH because of an increase of Staphylococcus aureus, which delivers a supporting role to the viral infection via secreted toxins such as α-toxin.

A thorough understanding of the contributing genetic factors will help to identify AD patients at risk of developing EH. New therapeutic approaches like dupilumab or other anti-type 2 inflammation drugs may symbolize a specific prevention measure, especially in patients with recurrent EH episodes.

Further research is required to determine and specifically target risk factors for EH in AD patients.

Source: Traidl S, Roesner L, Zeitvogel J, et al. Eczema herpeticum in atopic dermatitis. Allergy. 2021;76(10):3017-27.