Mechanisms and Treatments of Dry Skin-Induced itch

Itch sensation is provoked by the binding of itch inducing substances (pruritogens) to their cognate receptors (pruriceptors) on peripheral sensory afferents. Because histamine is a well-known pruritogen, antihistamines are the class of agents used most frequently to treat itch. However, antihistamines are not fully effective in some dermatological and systemic diseases characterized by dry skin, suggesting that dry skin is an important feature of antihistamine-resistant itch. Recent studies have described various pruritogens and pruriceptors involved in a patient with dry skin, such as xerosis, and a mouse model of dry skin-induced itch, involving continuous treatment with acetone, diethyl ether, and water (AEW). In comparison with single acetone treatment, continuous AEW treatment showed increased induction of scratching behavior, with the latter depending on the number of treatments. The finding, that increased scratching behavior required repetitive AEW treatment, indicated that dry skin-induced itch was not only caused by skin barrier disruption. This mouse model additionally shows abnormal itch sensations, including alloknesis (itch induced by non-itchy stimuli) and hyperknesis (enhanced itch induced by itchy stimuli), which may result from neural sensitization (i.e., lowering of neural thresholds for their stimuli). Dry skin-induced itch may be caused not only by the concentrations of pruritogens and pruriceptors or by the distributions of nerve fibers but by functional changes in neurons. To date, there is no universally accepted therapy for dry skin-induced itch. Moisturizers improve barrier function and help alleviate pruritus. Following a decline in skin barrier function, varying conditions in dry skin may be causes of neural sensitization and itch-scratch-itch cycle. Treatment may therefore require prevention and rapid disruption of the vicious itch-scratch-itch cycle.