Dupilumab attenuates itch and skin inflammation in patients with atopic dermatitis (AD). However, itch-related events that are improved by dupilumab remain unclear. Therefore, the present study investigated changes in clinical scores, serum biomarkers, and the number of intraepidermal nerve fibers (IENFs) using skin biopsies and blood samples from 12 patients with moderate to severe AD before and after treatment with dupilumab. Clinical manifestations were assessed using eczema area and severity index (EASI) and visual analogue scale (VAS) scores at baseline and after 8 and 16 weeks of treatment. Serum levels of total immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), interleukin (IL)-4, IL-13, IL-22, and IL-31 were examined by electrochemiluminescence, chemiluminescent enzyme immunoassays, ProQuantum immunoassays, and enzyme-linked immunosorbent assays (ELISA) at baseline and after 8 and 16 weeks of treatment. In skin biopsies from AD patients at baseline and after 16 weeks of treatment, IENFs were examined immunohistochemically with the anti-protein gene product (PGP) 9.5 antibody. The dupilumab treatment significantly improved EASI and VAS scores and decreased serum levels of TARC, IgE, and IL-22, whereas those of IL-13 and IL-31, and the number of IENFs remained unchanged and those of IL-4 increased. VAS scores were positively correlated with serum TARC, IL-22, and IgE levels and the degree of epidermal thickening. Serum IL-31 levels were positively correlated with the number of IENFs. These results suggest that serum TARC, IL-22, and IgE levels and epidermal thickness are itch-related events associated with dupilumab treatment and that serum IL-31 levels may reflect the degree of IENF density in AD patients. Therefore, dynamic changes may be used to assess the efficacy of dupilumab treatment to treat itching and inflammation in patients with AD.

In recent years, molecular target drugs have become integral in treating malignant tumours. Multikinase inhibitors (MKIs) have been associated with serious skin disorders, including hand–foot skin reaction (HFSR), which impair patient quality of life, often disrupting activities of daily living necessitating dose reduction or discontinuation. As the pathogenic mechanisms of these skin disorders are unknown, no effective treatments have been established. Previously, by drug repurposing using an in vitro culture system, certain azole antifungal drugs (AFDs) were identified that prevented sorafenib-induced cell death of normal human epidermal keratinocytes. In this study, topical ketoconazole demonstrated clinical improvement in hyperkeratosis and pain associated with sorafenib-induced HFSR. Investigation of the mechanism using the in vitro culture system revealed sorafenib to be particularly cytotoxic among MKIs. Annexin V and TUNEL staining revealed apoptosis was mainly involved in this cytotoxicity. Antibody arrays and western blot showed increased levels of secretion of interleukin-1 receptor antagonist and macrophage migration inhibitory factor in culture supernatants. AFDs suppressed the secretion of these cytokines and reduced apoptosis in keratinocytes. This study reveals one aspect of the pathogenesis of sorafenib-induced HFSR and demonstrates that AFDs may be an effective treatment.