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Background: Atopic dermatitis (AD) is a highly prevalent inflammatory skin disorder characterized by episodic exacerbations and remissions. Why the clinically healthy skin of AD patients becomes rapidly inflamed and very pruritic is poorly understood., Objective: To investigate cowhage- and histamine-induced itch and skin expression levels of their target receptors in lesional and non-lesional skin of AD, compared to the skin of patients with psoriasis, chronic spontaneous urticaria (CSU) and healthy subjects., Methods: Patients with AD, psoriasis and chronic spontaneous urticaria (CSU) as well as healthy control subjects (HC) (n = 20 each) were assessed for differences in itch parameters, neurogenic flare reaction and local blood flow responses to skin provocations with cowhage and histamine. Skin biopsies from 10 AD, 10 psoriasis,11 CSU and 12 HC were obtained to assess expression of protease-activated receptors 2 and 4 (PAR-2, PAR-4), histamine H1 and H4 receptors (H1R, H4R), and mast cells., Results: Provocation of non-lesional skin of AD patients with cowhage resulted in prolonged itch (p = 0.020), which was not observed in psoriasis and CSU. Significantly prolonged and more intense cowhage- and histamine-induced itch (for duration, peak and overall intensity) was also observed in lesional AD skin. Diminished neurogenic flare reaction and blood flow after histamine provocation were shown in AD and psoriasis patients. Non-lesional AD skin along with lesional AD and psoriasis skin showed an increased expression of PAR-2 and PAR-4, H1R and H4R. Mast cell number was higher in lesional AD and psoriasis skin (p = 0.006 and p = 0.006, respectively)., Conclusion: The non-lesional skin of AD patients markedly differs from healthy skin in cowhage-induced itch responses and the expression of receptors for proteases and histamine. Proactive therapeutic interventions that downregulate these receptors may prevent episodic exacerbation in AD., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Cryosurgery is a common destructive treatment method for intraepidermal carcinoma (IEC) above the knee. Curettage alone is a simple, non-aggressive and inexpensive treatment method commonly used on benign skin lesions. However, only one study has assessed curettage for treatment of IEC., Objective: We aimed to (1) compare the effectiveness of cryosurgery (standard method) to curettage (experimental method) for treatment of IEC in regard to overall clearance rates at 1-year follow-up, and (2) investigate whether wound healing times differed between the treatment groups., Methods: In this randomized and controlled, non-inferiority trial, adult patients with one or more IEC with a diameter of 5-20 mm, located above the knee and suitable for destructive treatment were recruited from Sahlgrenska University Hospital (Gothenburg, Sweden). Lesions were randomized to treatment with either cryosurgery or curettage. Wound healing was assessed by a nurse after 4-6 weeks and through self-report forms. Overall clearance was assessed by a dermatologist after 1 year., Results: In total, 183 lesions in 147 patients were included, with 93 lesions randomized to cryosurgery and 90 to curettage. Eighty-eight (94.6%) of the lesions in the cryosurgery group and 71 (78.9%) in the curettage group showed an overall clearance at the 1-year follow-up visit (p = 0.002). The non-inferiority analysis was inconclusive. Curettage resulted in both shorter self-reported wound healing times (mean time 3.1 vs. 4.8 weeks, p < 0.001) and a larger proportion of healed wounds after 4-6 weeks (p < 0.001)., Conclusions: Cryosurgery and curettage both result in high clearance rates for treatment of IEC, but cryosurgery is significantly more effective. On the other hand, curettage may result in shorter wound healing times., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Pruritus is prevalent in psoriasis but still many features of pruritus, its response to therapy and its burden in psoriasis remain to be better characterized., Objective: To investigate characteristics and burden of pruritus in an international cohort of patients with psoriasis., Methods: This cross-sectional study included a total of 634 patients and 246 controls from Germany, Poland and Russia. Physicians examined and interviewed participants, recording clinical characteristics, such as severity, therapy and localization of psoriatic lesions. Participants filled out self-reported questionnaires including questions on pruritus severity and impact, characteristics, and response to therapy, and quality of life (QoL). Localization patterns of pruritus and skin lesions were visualized using body heat maps., Results: Most patients (82%) experienced pruritus throughout their disease, and 75% had current pruritus. The majority of patients (64%) perceived pure pruritus, and those who reported additional painful and/or burning sensations (36%) reported overall stronger pruritus. The scalp was the most frequently reported localization of pruritus, even in the absence of skin lesions. Body surface area (BSA) of pruritus was not linked to pruritus intensity, but to BSA of psoriatic lesions (rho = 0.278; P < 0.001). One third of patients (31%) reported impaired sex-life, and 4% had suicidal ideations due to pruritus. In up to one third of patients, psoriasis therapies had little or no effect on pruritus. The only therapeutic option offered to some of these patients were antihistamines, which appeared to be effective in most cases., Conclusion: Pruritus is highly prevalent in psoriasis and is linked to a significant burden. Current psoriasis therapies are frequently insufficient to control pruritus. Managing psoriasis should include the assessment and control of itch. Efficient antipruritic therapies should be developed and be made available for patients with psoriasis., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background and Objective: Pruritus is a major symptom of many inflammatory diseases and impacts greatly the quality of life in patients. We aimed to specify the characteristics of experimentally induced pruritus in normal skin and in experimentally induced inflammatory dermatitis in healthy volunteers., Methods: Skin inflammation was induced by the repeated application of sodium lauryl sulphate (SLS 2%) on the volar forearms of 30 healthy volunteers. Inflammatory dermatitis intensity was assessed using the eczema score adapted from Frosch and Kligman. Non-histaminergic pruritus was induced by cowhage spicules rubbed on the volar forearms and recorded for 30 min on a 10-cm visual analogue scale (VAS) in both non-inflamed and inflamed skin., Results: Induction of inflammatory dermatitis by SLS resulted in a mild inflammatory dermatitis with an inflammation score of 2.3 ± 0.1 within 7 days of treatment. Cowhage-induced pruritus was of markedly higher intensity (P < 0.001), and all but two individuals had higher maximum pruritus intensity in inflamed skin as compared to non-inflamed skin, whereas the kinetics of the pruritus response were similar. The quality of cowhage-induced pruritus was significantly different with more 'burning' and 'painful sensations' in inflamed skin (P < 0.01). Maximum pruritus intensity in inflamed skin strongly correlated with maximum pruritus intensity in non-inflamed skin (r = 0.51, P = 0.004). Skin hydration, skin barrier integrity and dermatitis severity did not correlate with pruritus intensity., Conclusion: Taken together, pruritus in inflamed skin is perceived as more intense, painful and burning. This may explain, in part, why pruritus is a major driver of quality-of-life impairment in patients with chronic inflammatory skin conditions such as atopic dermatitis., (© 2019 European Academy of Dermatology and Venereology.)

Background: In skin diseases and experimental models of pruritus, pure itch is accompanied by additional sensations that are poorly characterized., Objectives: This study compared the sensory qualities evoked by different models of experimentally induced pruritus including skin prick testing (SPT) with histamine or capsaicin and application of cowhage spicules. SPT as a method of capsaicin application was validated for this purpose., Methods: Two pilot experiments were performed in eight healthy volunteers. First, a concentration of 8% capsaicin was identified as evoking a reproducible itch using SPT. Further, a list of the seven most frequently reported sensations was chosen after SPT with 10 mg/mL histamine, 8% capsaicin and application of 40-45 cowhage spicules. Finally, 31 subjects were challenged with the same itch-inducers. Wheal and flare were measured at 10, 20, 40, 60 and 90 min, itch intensity every minute for 30 min, and the overall evaluation of sensory descriptors were recorded on a 100-mm visual analogue scale once itching had subsided., Results: Skin prick testing with histamine and capsaicin resulted in flare reactions, which were 23% smaller for capsaicin (P < 0.001). Histamine, capsaicin and cowhage-induced pruritus, the duration of which was shorter for cowhage than for histamine (13.5 ± 1.4 vs. 8.8 ± 1.2 min, P = 0.005). Different mediators induced sensations of different intensities. Capsaicin produced less itch and physical urge to scratch than histamine (P = 0.001) and cowhage (P < 0.001). However, both capsaicin and cowhage induced more burning than histamine (P = 0.002 and P = 0.04, respectively). Provocation with cowhage caused more intense sensations of pricking than histamine (P = 0.033)., Conclusion: This study shows that provocation with histamine, capsaicin and cowhage results in itch responses that are different in their duration, the profile of accompanying sensations, and the flare that comes with the itch., (© 2019 European Academy of Dermatology and Venereology.)