Abstract

Itch or pruritus is the hallmark of atopic dermatitis and is defined as an unpleasant sensation that evokes the desire to scratch. It is also believed that itch is a signal of danger from various environmental factors or physiological abnormalities. Because histamine is a well-known substance inducing itch, H1-antihistamines are the most frequently used drugs to treat pruritus. However, H1-antihistamines are not fully effective against intractable itch in patients with atopic dermatitis. Given that intractable itch is a clinical problem that markedly decreases quality of life, its treatment in atopic dermatitis is of high importance. Histamine-independent itch may be elicited by various pruritogens, including proteases, cytokines, neuropeptides, lipids, and opioids, and their cognate receptors, such as protease-activated receptors, cytokine receptors, Mas-related G protein-coupled receptors, opioid receptors, and transient receptor potential channels. In addition, cutaneous hyperinnervation is partly involved in itch sensitization in the periphery. It is believed that dry skin is a key feature of intractable itch in atopic dermatitis. Treatment of the underlying conditions that cause itch is necessary to improve the quality of life of patients with atopic dermatitis. This review describes current insights into the pathophysiology of itch and its treatment in atopic dermatitis.

Highlights

  • Patients with atopic dermatitis (AD) suffer from recurrent dermatitis and intractable itch

  • Since severe pruritus leads to disturbances in patient sleep and work that markedly decrease quality of life, H1 -antihistamine-resistant itch is a clinical problem in AD

  • The terms used for retrieval were “dry skin”, “intractable itch”, “itch”, “pruritus”, “keratinocyte”, “sensory nerve fiber” etc. combined with “atopic dermatitis” as keywords

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Summary

Introduction

Patients with atopic dermatitis (AD) suffer from recurrent dermatitis and intractable itch. In addition to the social stigmatization due to visible skin lesions, severe pruritus can disrupt sleep in patients with AD, which can lead to psychosocial comorbidities, including depression, anxiety, and suicidal ideations [2]. The pathogenesis of AD has not been fully elucidated, it is influenced in a complicated manner by genetic factors, immune dysfunction, physical conditions, Biomedicines 2021, 9, 229. H1 -antihistamines, even at high doses, are not fully effective against intractable itch in patients with AD [7]. Since severe pruritus leads to disturbances in patient sleep and work that markedly decrease quality of life, H1 -antihistamine-resistant itch is a clinical problem in AD. Understanding the pathogenesis of itch and its treatment is important. This review highlights recent knowledge regarding the mechanisms of itch in AD and itch treatment

Methods
Transduction of Itch
Histamine
Proteases
Cytokines
Neuropeptides
Lipids
Opioids
Cutaneous Nerve Fibers
Skin Dryness
Dysregulation of the Expression of Antimicrobial Peptides
Conclusions
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