Background/Objectives: Mechanical alloknesis (m-alloknesis), the sensation of itch evoked by normally non-pruritic mechanical stimuli, is commonly observed in dry skin-associated conditions, such as xerosis, atopic dermatitis (AD), and psoriasis. Janus kinase (JAK) inhibitors are currently used to treat AD and suppress inflammation and itch. However, their specific roles in the modulation of m-alloknesis remain unclear. Therefore, in this study, we investigated the effects of various oral JAK inhibitors on m-alloknesis using a murine model of AD. Methods: An AD-like phenotype was induced in mice through the repeated topical application of an ointment containing Dermatophagoides farinae (house dust mite) extract. The mice were then orally treated with one of three JAK inhibitors: the JAK1/2 inhibitor baricitinib, the JAK1-selective inhibitor abrocitinib, or the JAK2-selective inhibitor AZ960. M-alloknesis was evaluated by quantifying scratching behavior in response to 30 controlled mechanical stimuli applied to lesional skin. Results: The JAK inhibitor treatments did not affect skin barrier integrity, dermatitis severity, or spontaneous scratching behavior. However, baricitinib and abrocitinib significantly reduced m-alloknesis scores, whereas AZ960 had no effect. Conclusions: These results suggest that JAK1 signaling plays a critical role in the induction of m-alloknesis in AD. Selective JAK1 inhibition is a promising therapeutic strategy for attenuating m-alloknesis and improving quality of life for patients with AD, independent of general skin inflammation and barrier function.

To elucidate the relationships among various itch qualities, blood biomarkers, and patient-reported outcome measures (PROMs) in atopic dermatitis (AD), we characterized 10 qualities of itch (QoIs) in adult Japanese patients with AD and examined their associations with blood biomarkers as well as objective and subjective clinical measures. The QoI was assessed by a translated 10-item questionnaire. The relationship among each QoI and blood biomarkers (including interleukin [IL]-31, thymus and activation-regulated chemokine [TARC], and lactate dehydrogenase levels; differential white blood cell counts, including eosinophil, basophil, and neutrophil relative counts; and total immunoglobulin E levels); PROMs, such as visual analog scale and patient-oriented eczema measure; and objective measures, such as eczema area and severity index, was evaluated. Patients with AD frequently suffered from a sensation similar to crawling like ant (crawling) and stinging and burning sensations. Crawling was positively correlated with serum IL-31 levels but not serum TARC level. Stinging and stabbing sensations were positively correlated with serum TARC level but not with serum IL-31 levels. Stinging, stabbing, and burning sensations were correlated with PROMs and eczema area and severity index. Our limitation is that other cytokines, such as IL-4 and IL-13, were not measured. The QoI in Japanese patients with AD could be classified into IL-31-related and TARC-related types. Our findings suggest relationships between crawling and IL-31 and between stinging and stabbing and TARC in Japanese patients with AD.