BackgroundChronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus.Methods and FindingsTwenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/−1.7) before treatment to 4.9 VAS points (SD +/−3.2) (p<0.001, CI 1.913–5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients.ConclusionsThe high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial.

No abstract

The PBI for pruritus is a feasible, reliable and valid instrument that is highly accepted in daily routine for recording patient-reported benefit.

Melanoma accounts for ∼ 79% of skin cancer-related deaths, and the receptor activator of NF-κB (RANK)-receptor activator of NF-κB ligand (RANKL) pathway has been shown to be involved in the migration and metastasis of epithelial tumor cells. In this study, we demonstrate that RANK was significantly increased in peripheral circulating melanoma cells, primary melanomas, and metastases from stage IV melanoma patients compared with tumor cells from stage I melanoma patients. However, upregulated RANK expression was not found in stage IV melanoma patients with bone metastases compared with stage IV melanoma patients without bone metastases, providing a possible explanation for the clinical observation that melanoma cells do not preferentially metastasize to bone tissue. Strikingly, RANK-expressing melanoma cells from peripheral blood, primary tumors, or metastases of stage IV patients coexpressed ATP-binding cassette (ABC) B5 and CD133, both markers characteristic of melanoma-initiating cells, suggesting a tumor stem cell-like phenotype. In support of this hypothesis, RANK-expressing melanoma cells showed a reduced Ki67 proliferation index compared with RANK(-) melanoma cells from the same patient and are able to induce tumor growth in immunodeficient mice. Together, our data demonstrate that RANK expression is increased in metastatic melanoma and highly upregulated on melanoma-initiating cells, suggesting that RANK might be involved in the development and maintenance of melanoma-initiating cells and possibly in metastatic spreading.

Background: In the treatment of atopic dermatitis, pimecrolimus has high antipruritic effects. Objective: To investigate the efficacy of 1% pimecrolimus cream in comparison to 1% hydrocortisone cream in non-atopic prurigo nodularis (PN). Methods: A randomized, controlled, double-blind study with intraindividual randomization was done in 30 patients (17 females, 13 males; mean age 58.5 years) with PN. Results: Pruritus intensity decreased significantly (p < 0.001) on both treated sides as early as after 10 days of treatment; scratch lesions improved (p < 0.001). Quality of life as assessed by the Dermatology Life Quality Index improved significantly. However, a significant advantage of pimecrolimus over hydrocortisone was not found. Conclusion: The results suggest that the non-steroid pimecrolimus is an effective alternative for PN treatment.