Eczema herpeticum in atopic dermatitis.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases leading to pruritic skin lesions. A subset of AD patients exhibits a disseminated severe HSV infection called eczema herpeticum (EH) that can cause life-threatening complications. This review gives an overview of the clinical picture, and characteristics of the patients as well as the diagnosis and therapy of EH. A special focus lies on the pathophysiological hallmarks identified so far that predispose for EH. This aspect covers genetic aberrations, immunological changes, and environmental influences displaying a complex multifactorial situation, which is not completely understood. Type 2 skewing of virus-specific T cells in ADEH+ patients has been implicated in immune profile abnormalities, along with impaired functions of dendritic cells and natural killer cells. Furthermore, aberrations in interferon pathway-related genes such as IFNG and IFNGR1 have been identified to increase the risk of EH. IL-4, IL-25, and thymic stromal lymphopoietin (TSLP) are overexpressed in EH, whereas antimicrobial peptides like human β-defensins and LL-37 are reduced. Concerning the epidermal barrier, single nucleotide polymorphisms (SNPs) in skin barrier proteins such as filaggrin were identified in ADEH+ patients. A dysbalance of the skin microbiome also contributes to EH due to an increase of Staphylococcus aureus, which provides a supporting role to the viral infection via secreted toxins such as α-toxin. The risk of EH is reduced in AD patients treated with dupilumab. Further research is needed to identify and specifically target risk factors for EH in AD patients.