Subclinical inflammation precedes atopic dermatitis relapses

Atopic dermatitis (AD), a widespread inflammatory skin disease, is characterized by disease recurrence, even after successful treatment. Past clinical research has mainly focused on understanding the active disease state as opposed to what drives and triggers AD relapses in the first place. To elucidate the unknown molecular mechanisms behind AD relapses. An observational clinical study with patients in remission was conducted, comparing biopsies from skin that would relapse within the next weeks with skin that stayed in remission using single-cell-RNA sequencing and immunohistochemistry analyses. Signs of subclinical inflammation were present in the clinically healthy appearing pre-relapse state. On the one hand, we detected molecular signals reminiscent of active AD, such as epidermal barrier dysregulation, chemokine signaling, increased vascular permeability and first signs of T cell activity and infiltration. On the other hand, we also observed signals for processes specific to the pre-relapse state, including epidermal growth factor receptor (EGFR) signaling and macrophage phagocytosis. Taken together, this work uncovers novel aspects of AD development, and putatively paves the way for new therapeutic approaches that are specifically designed to prevent AD recurrence.