Atopic dermatitis, a skin disorder caused by skin dryness and barrier dysfunction, causes skin inflammation and chronic itch (or pruritus). A lowering of the itch threshold may trigger its pathogenesis due to dry skin. This lowering of the itch threshold may be partially due to increased intraepidermal nerve fibers and sensitization of sensory nerves by interleukin (IL)-33 produced and secreted by keratinocytes. Mechanical stimuli, such as rubbing of clothing and chemical stimuli from itch mediators can easily itch this type of skin.

In patients with atopic dermatitis, as the itch initiates, it further increases by scratching, and the associated scratching breaks down the skin barrier. When the skin barrier gets disrupted, external substances, such as allergens derived from house dust mites, can enter the epidermis, triggering type 2 inflammatory responses. As a result, Th2 cells secrete type 2 cytokines IL-4, IL-13 and IL-31, and they act on sensory nerve fibers causing further itch sensitization. These sequences of events occur simultaneously in patients with atopic dermatitis, causing a vicious itch-scratch cycle. When this vicious cycle becomes a negative spiral, it leads to a disease burden. Thus, controlling itch is a prime requisite for treating atopic dermatitis. 

Cytokines remain central to peripheral itch sensitization; thus, adding opioids as modulators might tune itch intensity. Additionally, the diversity of itch mediators and the types of sensory nerves that receive them might alter the quality of itch sensation in atopic dermatitis. In the future, researchers might uncover these issues and provide evidence-based medicine to overcome the itchiness of atopic dermatitis.

Source: Tominaga M, Takamori K. Peripheral itch sensitization in atopic dermatitis. Allergol Int. 2022;71(3):265-77.