Itch

Chronic itch is a socioeconomic burden with limited management options. Non-histaminergic itch, involved in problematic pathological itch conditions, is transmitted by a subgroup of polymodal C-fibers. Cowhage is traditionally used for studying experimentally induced non-histaminergic itch in humans, but encounter some limitations. The present study therefore aims to design a new human, experimental model of non-histaminergic itch based on the application of bovine adrenal medulla (BAM)8-22, an endogenous peptide that activates MrgprX1 receptor. 22 healthy subjects were recruited. Different concentrations (0.5, 1, and 2 mg/ml) of BAM8-22 solution and vehicle, applied by a single skin prick test (SPT), were tested in the first session. In the second session, the BAM8-22 solution (1 mg/ml) was applied by different number of SPTs (1, 5, and 25) and by heat-inactivated cowhage spicules coated with BAM8-22. Provoked itch and pain intensities were monitored for 9 minutes followed by the measurement of superficial blood perfusion (SBP), mechanical and thermal sensitivity. BAM8-22 induced itch at the concentration of 1 mg/ml, 2 mg/ml (p<0.05), and with the significantly highest intensity when applied through BAM8-22 spicules (p<0.001). No concomitant pain sensation nor increased SBP were observed. SBP increased only in the 25 SPTs area probably due to micro-trauma from the multiple skin penetrations. Mechanical and thermal sensitivities were not affected by any of the applications. BAM8-22 applied through heat-inactivated spicules was the most efficient method to induce itch (without pain nor changes in SBP, mechanical and thermal sensitivity) suggesting BAM8-22 as a novel non-histaminergic, human, experimental itch model.

The objective of this article is to review abrocitinib, an oral Janus kinase (JAK) 1 inhibitor, for the treatment of patients with moderate-to-severe atopic dermatitis (AD).

Chronic pruritus is one of the most common conditions in dermatology as well as a common manifestation in many systemic diseases. Since the etiology of chronic pruritus remains somewhat unknown, hence, conventional medications may not always show a good therapeutic response. This finding has led both investigators and patients to use herbal and complementary remedies for its treatment. The aim of this study was to review clinical trials in which herbal and complementary medicine was used in the control and treatment of chronic pruritus.

Dupilumab has demonstrated a great reduction on chronic pruritus that is the hallmark of atopic dermatitis (AD). Underscoring relevant pathogenesis similarities emerging from AD, chronic idiopathic pruritus (CIP) and chronic prurigo (CP), several authors suggested the beneficial role of dupilumab in these conditions. The evidence on this subject is limited with no precise data available. In this study, we carried out a systematic literature review in order to evaluate the efficacy of dupilumab on both pruritus and skin manifestations in the two largest retrospective cohorts of patients with CP and CIP and tried to identify potential response predictors. Electronic searches were conducted on 4 databases. Our primary outcome was the improvement in pruritus measured by a reduction in patient's reported numerical rating scale of itch (NRSI) by > 4. Secondary outcomes included: proportion of patients with complete response at the end of treatment, reduction in the number of lesions by the Investigator Global Assessment (IGA), improvement in numerical rating scale of sleep (NRSS), improvement in quality of life measured by the Dermatology Life Quality Index (DLQI), time until patient perceived any improvement (Time-First) and time until patient reported absence of pruritus (Time-Final). Descriptive statistics were calculated for each demographic and clinical variable. Univariate logistic regression analyses were conducted to explore association between response to dupilumab and potential predictive factors. We included 25 articles in the analysis, counting a total of 153 patients. Based on CP patients' cohort (n=132), the mean NRSI at baseline was 8.79 ±0.86 and the NRSI final was 2.32 ±1.27. The mean time to first improvement was 5.18 ±3.13 weeks, while the time to complete improvement of pruritus (Time-final) was 13.6 ±12.0 weeks. Ninety patients out of 109 (83%) noticed improvement in pruritus before 4 weeks of dupilumab therapy. At the end of treatment, 18 patients out of 126 (14%) had a complete remission of pruritus and 110 patients out of 123 (89%) had a reduction of NRSI > 4. The reduction in NRSI was significantly greater in patients improving before 4 weeks of treatment (6.57 ±1.71) compared to patients improving in more than 4 weeks (5.49 ±1.39, p<0.001). Patients with history of AD and those who have been previously treated with cyclosporine or methotrexate had a significantly lower reduction in NRSI (e.g. 6.05 ±1.34 vs 7.08 ±1.90 p<0.01 for non-associated AD patients). Based on CIP patient's cohort (n=21), the mean NRSI at baseline was 8.33 ±0.80 and the NRSI final was 0.95 ±0.59. The mean time to first improvement was 2 ±0 weeks, while the time to complete improvement (Time-final) was 14.6 ±10 weeks. At the end of treatment, 3 patients out of 21 (14%) had a complete remission of pruritus and 100% of patients had a reduction of NRSI > 4. No serious treatment-emergent adverse events were reported. The most common adverse event was mild conjunctivitis (13 cases). We highlight the importance of one early sign of improvement as predictor of the future response to dupilumab: the improvement before 4 weeks of treatment that leads significantly to a greater final reduction in NRSI. Furthermore, patients with the presence or history of atopy appear to be less responsive to dupilumab than non-atopic patients and develop more side effects, in particular conjunctivitis.

While the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch.

The ability to sense the environment is essential to survival and is the primary purpose of the somatosensory nervous system. However, despite its highly conserved nature, the sensation of itch has been historically overlooked, and its importance in medicine underappreciated. Herein, we highlight how fundamental discoveries, coupled to rapid successes of new therapeutics, have placed itch biology at the forefront of a translational revolution in the field of somatosensation and beyond.