Biomarkers for itch and disease severity in atopic dermatitis

Atopic dermatitis (AD) is a common allergic disease and constitutes a huge social and economic burden for the whole country. AD usually heralds other allergic diseases, such as asthma and allergic rhinitis. The pathogenesis of AD remains to be studied but generally includes abnormal skin barrier and aberrant cutaneous immune responses. Biomarkers are important in monitoring disease severity, prognosis and treatment responses. With the investigation and robust knowledge on AD pathophysiology, more and more biomarkers are being explored. Aberrant cutaneous inflammation is associated with Th2 polarization, chemokine upregulation in Langerhans cells and keratinocytes, IgE production by B cells, and degranulation of mast cells and eosinophils, subsequently leading to changes in the levels of cell-specific biomarkers in blood or urine. Furthermore, skin barrier abnormalities, including increased transepidermal water loss and decreased skin hydration, are biomarkers for severity and itch intensity in AD. Cross-talk between skin barrier abnormalities and aberrant immune responses is evidenced by epidermal abnormalities enhancing the release of keratinocyte-derived cytokines and chemokines, including CC chemokine ligand (CCL) 17, CCL27 and thymic stromal lymphopoietin, resulting in modulation of skin immune responses. The pathophysiology of itch in AD remains unclear. The subjective nature of itch makes biomarkers to estimate its intensity crucial in AD patients. Pruritus results from the activation of small nerve endings in the skin by noxious mediators, including neuropeptides, proinflammatory cytokines and prostaglandins, all of which might serve as potential biomarkers for itch. Recently, IL-31 and gastrin-releasing peptide have been reported to be involved in the development of itch, making the estimation of itch intensity a future reality. With the enormous amount of research in immunology, skin physiology and neurology in AD, more biomarkers in AD and its itch will be found in the near future.