Abstract
Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients’ quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.
Highlights
Pruritus is defined as an unpleasant sensation that provokes the desire to scratch
Pruritus is a common symptom of numerous inflammatory skin diseases, and it can be severe enough to interfere with sleeping and daily activities, and impact markedly on patients’
Chronic pruritus (CP) is a common symptom of a heterogeneous spectrum of cutaneous inflammatory skin diseases, which were recently re-classified according to their immune response pattern, based on specific cellular and cytokine signatures [4]
Summary
Pruritus is defined as an unpleasant sensation that provokes the desire to scratch. Pruritus is a common symptom of numerous inflammatory skin diseases, and it can be severe enough to interfere with sleeping and daily activities, and impact markedly on patients’. CP is a common symptom of a heterogeneous spectrum of cutaneous inflammatory skin diseases, which were recently re-classified according to their immune response pattern, based on specific cellular and cytokine signatures [4]. Group 2 ILC (ILC2) are the main actors of type-2 immunity, producing large amounts of Th2-cytokines in response to environmental stimuli [6]. We discuss the prominent role of type 2 immune responses and Th2 cytokines in the pathophysiology of chronic pruritic skin diseases. Emerging clinical and experimental evidence points to an involvement of type 2 immune responses and cytokines in other chronic itch diseases. The skin disorders most frequently associated with CP are those characterized by type 2 inflammation or immune response, and are reviewed here, underlining the therapeutic implications
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