The Itch–Scratch Cycle: A Neuroimmune Perspective

Mack, Madison R.; Kim, Brian

doi:10.1016/j.it.2018.10.001

Cited by 157 publications

(129 citation statements)

References 101 publications

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“…14,15 The expressions of key skin barrier proteins are impeded by inflammatory cytokines, which may further augment allergic sensitization and responses, impair protective innate immune responses, and trigger scratching, thereby damaging the skin and perpetuating the itch-scratch cycle. 14,[16][17][18][19] Janus kinases (JAKs) mediate type 2 and other cytokine signaling involved in the pathogenesis of AD. 20,21 In addition, JAK inhibition also occurs directly on sensory neurons 22 and may also improve skin barrier function.…”

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confidence: 99%

Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study

Kim

Sun

Papp

et al. 2020

Journal of the American Academy of Dermatology

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Background: Atopic dermatitis (AD), a chronic, highly pruritic skin disorder, impairs quality of life (QoL). Janus kinase inhibitors suppress inflammatory and pruritus-associated cytokine signaling in AD. Objective: To report the effects of ruxolitinib (RUX) cream on itch and QoL in AD. Methods: A total of 307 adult patients with an Investigator's Global Assessment (score of 2 or 3) and 3% to 20% affected body surface area were randomly assigned for 8 weeks to receive double-blind treatment with RUX (1.5% twice daily, 1.5% once daily, 0.5% once daily, or 0.15% once daily), vehicle twice daily, or triamcinolone cream (0.1% twice daily for 4 weeks then vehicle for 4 weeks). Itch was measured by using the numerical rating scale, and patient QoL was assessed with Skindex-16. Results: Improvements in itch numerical rating scale and Skindex-16 were observed with RUX cream. Overall, 42.5% of patients who applied 1.5% RUX twice daily experienced minimal clinically important difference in itch within 36 hours of treatment (vehicle, 13.6%; P \ .01); near-maximal improvement was observed by week 4. Itch reduction was associated with improved QoL burden (Pearson correlation, 0.67; P \ .001). Significant improvements in Skindex-16 overall scores were noted at week 2. Limitations: Facial AD lesions were not treated.

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confidence: 99%

Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study

Kim

Sun

Papp

et al. 2020

Journal of the American Academy of Dermatology

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“…[ ] Current theories propose that scratching results in an interplay of signals between keratinocytes, immune cells and neurons that promotes the sensation of itch. [ ] We propose that SCs may also contribute to the vicious itch‐scratch cycle. Scratching could damage epidermal nerve fibres (ie free nerve endings) leading to activation of repair SCs.…”

Section: Discussionmentioning

confidence: 99%

Schwann cells as underestimated, major players in human skin physiology and pathology

Bray

Chéret

Yosipovitch

et al. 2019

Experimental Dermatology

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Schwann cells (SCs) have long been recognized for their ability to support repair and promote axon regeneration following injury to the peripheral nervous system. In response to nerve injury, they rapidly dedifferentiate into a precursor‐like state, secrete an array of inflammatory mediators and growth factors, proliferate, undergo epithelial‐to‐mesenchymal‐like transformation to facilitate migration, phagocytose cellular debris and remodel the extracellular environment to promote regeneration of axons through the site of injury. However, even though a cutaneous role for SCs is becoming increasingly recognized, we argue in this Viewpoint essay that the likely complex functions of SCs in skin physiology and pathology beyond skin sensation and nerve repair deserve more attention and systemic research than they have received so far. For example, SCs promote wound healing, disseminate infection in leprosy, support the growth of neurofibromas/schwannomas and facilitate/accelerate the growth and invasion of melanoma. Despite representing a major dermal cell population, comparatively little is still known about the role of SCs in other dermatoses. To quintessentially illustrate the opportunities that promise to arise from a new skin research focus on SCs, we focus on two dermatoses that are not traditionally associated with SCs, that is, psoriasis and atopic dermatitis (AD), since both show distinct SC changes along with continuous nerve fibre degeneration and regeneration, and an impact of denervation on skin lesions. Specifically, we critically discuss the hypothesis that repeated activation of the SC repair programme occurs in and contributes to psoriasis and AD and delineate experimental approaches how to probe this clinically relevant hypothesis.

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“…Second, we will discuss new and emerging pathways and therapeutics across a number of chronic itch conditions. Finally, throughout the course of this review, we will introduce more recently recognized chronic itch disorders that likely share pathophysiology with well-defined allergic disorders (for more comprehensive reviews on chronic itch, see several previous reviews [5][6][7][8] ). Collectively, we highlight and underscore how a variety of chronic itch conditions, both well defined and more recently recognized, fall well within the realm of clinical allergy and immunology.…”

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confidence: 99%

Pruritus in allergy and immunology

Yang

Kim

2019

Journal of Allergy and Clinical Immunology

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Although evolutionarily conserved to expel ectoparasites and aid in the clearance of toxins and noxious environmental stimuli from the host, the type 2 immune response can become pathologic in the setting of a variety of allergic disorders. Itch can be a behavioral extension of type 2 immunity by evoking scratching and, in the setting of disease, can become chronic and thus highly pathologic as well. Classically, our understanding of itch mechanisms has centered around the canonical IgE-mast cell-histamine axis. However, therapies aimed at blocking the histaminergic itch pathway have been largely ineffective, suggesting the existence of nonhistaminergic itch pathways.Indeed, recent advances in itch biology have provided critical new insight into a variety of novel therapeutic avenues for chronic itch in the setting of a number of allergic disorders. Here we highlight how these new developments will likely inform the problem of pruritus in a variety of well-established and emerging conditions in the field of allergy. (J Allergy Clin Immunol 2019;144:353-60.)

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The Itch–Scratch Cycle: A Neuroimmune Perspective

Cited by 157 publications

References 101 publications

Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study

Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study

Schwann cells as underestimated, major players in human skin physiology and pathology

Pruritus in allergy and immunology

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