Inflammatory cytokines and peripheral mediators in the pathophysiology of pruritus in cutaneous T‐cell lymphoma

Abstract

Cutaneous T-cell lymphoma (CTCL) includes a diverse group of neoplasms, including mycosis fungoides and Sézary syndrome. One of the earliest and most common symptoms of CTCL is pruritus, which affects up to 88% of patients. The severity of pruritus can range from mild to very debilitating, producing tremendous discomfort and a significant decrease in quality of life. Patients with advanced disease, in particular, may experience a more chronic, intractable pruritus. However, the underlying mechanism of pruritus in CTCL remains unknown. Conventional antipruritic agents, such as antihistamines, gamma-aminobutyric acid analogs and antidepressants, are only partially effective in relieving symptoms, suggesting a more complex, unique pathophysiology. In this review, we summarize the current research on cytokines and peripheral mediators implicated in pruritus in CTCL.

Pruritus as a Distinctive Feature of Type 2 Inflammation

“…SS clinically is characterized by diffuse erythroderma, lymphadenopathy, and peripheral blood involvement, and is typically refractory to multiple treatments [103]. Patients affected by extensive MF and particularly those with SS might complain about a persistent and devastating itch, causing a profound reduction in the quality of life [105]. MF and SS are Th2-type diseases, frequently accompanied by eosinophilia and high serum levels of IgE.…”

Cellular Interactions and Inflammation in the Pathogenesis of Cutaneous T-Cell Lymphoma

“…Using an organotypic skin model of CTCL, Thode et al (2015) provided evidence that the malignant T cells secrete factors which affect the behavior of keratinocytes leading to increased proliferation, disorganized stratification and decreased resistance to mechanical stress. The malignant T cells have also been shown to produce IL-31, which together with IL-4, IL-5 and IL-13, is believed to stimulate the sensation of pruritus in CTCL patients (Ohmatsu et al, 2012;Singer et al, 2013;Cedeno-Laurent et al, 2015;Nattkemper et al, 2016;Lewis et al, 2018). At such, the malignant T cells may facilitate mechanical disruption of the skin integrity indirectly by producing factors that elicit scratching.…”

Itching as a systemic disease

“…Patients with advanced-stage CTCL have more severe itch than those with early-stage disease. 39 IL-31 is a putative pruritogen in patients with CTCL. Serum levels of IL-31 are greater in patients with CTCL compared with those in healthy control subjects.…”