Mechanisms and Management of Itch in Dry Skin

Abstract

Itch is an unpleasant sensation that may disturb quality of life, and for which the pathomechanism and appropriate treatments are unclear. Chronic itch, which lasts more than 6 weeks, often accompanies pathological dry skin-based conditions, such as xerosis, atopic dermatitis, liver and kidney diseases. A decline in skin barrier function is thought to be the primary cause of itch induced by dry skin. Many kinds of mediators, receptors, and channels are involved in itch signalling among the skin nervous system, skin cells, and central nervous system. Several therapeutic options for itching have thus been developed, such as phototherapy, phospholipids, antioxidants, and emollients. Chronic itch is a burdensome clinical problem that often accompanies pathological dry skin-based conditions, such as atopic dermatitis, and systemic disorders, such as kidney diseases, with an unclear pathomechanism and treatments. One of the basic mouse models to investigate mechanisms of itch associated with dry skin is a mixture of acetone and ether followed by water. Animal studies using the acetone and ether followed by water model have revealed that many mediators and receptors, e.g. mas-related G protein-coupled receptor family, transient receptor potential, and chemokines, are responsible for itch and its hypersensitivity, supporting the hypothesis that dry skin-induced itch is a histamine-independent pathway. New insights have been acquired into the interplay between neurones and non-neuronal cells in the initiation, modulation, and sensitization of itch. Several thera peutic options for itching have thus been developed. This review summarizes the updated pathogenesis and therapeutic strategies for itch in dry skin conditions.

Molecular and Cellular Mechanisms of Itch in Psoriasis

“…Unmyelinated C-fibers mainly transmit the itch signal and more slowly than myelinated Aδ-fibers. Unmyelinated C-fibers are further subdivided into peptidergic and non-peptidergic fibers [27][28][29]. The former comprise neuropeptides, such as substance P (SP) and/or calcitonin gene-related peptide (CGRP), whereas the latter express the purinergic receptor P2X3 and isolectin B4 [29].…”

Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus

“…Along with these morphological changes, dry skin induces pruritus, a sensation that evokes a desire to scratch. Although several theories have been suggested ( 1 ), it remains difficult to fully understand the precise mechanisms by which dry skin conditions evoke pruritus. In this study, we therefore aimed to elucidate the cutaneous neuroimmune interactions between dry skin conditions and pruritus.…”

Adipokines as Biomarkers of Atopic Dermatitis in Adults

“…Dysfunction of the skin barrier, both in lesional and non-lesional skin, plays a fundamental role in the pathogenesis of AD. Keratinocytes in the barrier-disrupted skin accelerate the type 2 immune response by producing alarmins, like thymic stromal lymphopoietin, IL-25, and IL-33 [11,17]. The thymus activation-regulated chemokine is a frequently considered biomarker of AD.…”