Ritlecitinib, a JAK3/TEC family kinase inhibitor, stabilizes active lesions and repigments stable lesions in vitiligo.

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

Histological Skin Changes After Treatment with 675 nm Laser.

Objective: To evaluate the histological effects of a new 675-nm laser device on the skin. Background: Innovative technologies based on physical principles have been proposed in recent years to improve the treatment of aging skin. Laser technology is currently being studied for its potential in skin care treatments. A new 675-nm laser device is being used for the treatment of hyperpigmentation, scars, and various types of wrinkles. Methods: A 42-year-old man underwent a 675-nm RedTouch® laser session for the treatment of aging signs on the neck. Two 2.5-mm biopsies were taken from the treated area and the adjacent area untreated with the laser, 45 days after the procedure. Comparison of the immunohistochemistry findings and assessment of the collagen and elastin fibers were performed by a board-certified dermatopathologist. Results: Skin biopsies revealed histological changes that comprised proliferation of new collagen fibers in the treated area, when compared to that in the untreated areas. Conclusions: Histological analysis suggests that the 675-nm laser has a potential role in stimulating collagen remodeling, with a significant increase in thin and new collagen fibers.

High-dimensional analysis defines multicytokine T-cell subsets and supports a role for IL-21 in atopic dermatitis.

BACKGROUND: Flow cytometry is a well-accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad-scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients' comprehensive profiling, critical for leveraging new targeted treatments, is not available. IL-21 may be involved in inflammatory skin diseases but its role in AD is not well established. METHODS: We studied T-cell polarization in the blood of 20 moderate-to-severe AD and 15 controls. Using CyTOF and an unsupervised analysis, we measured the frequencies and mean metal intensities of activated polar CD4+ /CD8+ T-cell subsets. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to analyze skin samples. RESULTS: Examining 24 surface, intracellular markers, and transcription factors, we identified six CD4+ and five CD8+ T-cell metaclusters. A CD4+ skin-homing IL-13+ monocytokine and a novel IL-13+ IL-21+ multicytokine metaclusters were increased in AD vs. controls (p < .01). While IL-13 signature characterized both clusters, levels were significantly higher in the IL-21+ group. Both clusters correlated with AD severity (r = 0.49, p = .029). Manual gating corroborated these results and identified additional multicytokine subsets in AD. Immunohistochemistry and immunofluorescence, validated by mRNA expression, displayed significantly increasedIL-21 counts and colocalization with IL-13/IL-4R in AD skin. CONCLUSION: A multicytokine signature characterizes moderate-to-severe AD, possibly explaining partial therapeutic responses to one cytokine targeting, particularly in severe patients. Prominent IL-21 signature in blood and skin hints for a potential pathogenic role of IL-21 in AD.

Spider bites of medical significance in the Mediterranean area: misdiagnosis, clinical features and management.

Despite the disrepute spiders have had for centuries, their bite is a rare occurrence. In the Mediterranean area, only two of the numerous known species are considered of medical significance: Latrodectus tredecimguttatus and Loxosceles rufescens. Spider bites have no pathognomonic signs or symptoms, therefore most diagnoses are presumptive; a spider bite can only be diagnosed when a spider (seen at the time of the bite) is collected and identified by an expert, since most physicians and patients are unable to recognize a certain spider species or distinguish spiders from other arthropods. Skin lesions of uncertain etiology are too often attributed to spider bites. In most cases, these are actually skin and soft-tissue infections, allergic reactions, dermatoses etc. Misdiagnosing a wound as a spider bite can lead to delays in appropriate care, cause adverse or even fatal outcomes and have medical-legal implications. Concerningly, misinformation on spider bites also affects the medical literature and it appears there is lack of awareness on current therapeutic indications for verified bites.

Spider bites of medical significance in the Mediterranean area: misdiagnosis, clinical features and management

Despite the disrepute spiders have had for centuries, their bite is a rare occurrence. In the Mediterranean area, only two of the numerous known species are considered of medical significance: Latrodectus tredecimguttatus and Loxosceles rufescens. Spider bites have no pathognomonic signs or symptoms, therefore most diagnoses are presumptive; a spider bite can only be diagnosed when a spider (seen at the time of the bite) is collected and identified by an expert, since most physicians and patients are unable to recognize a certain spider species or distinguish spiders from other arthropods. Skin lesions of uncertain etiology are too often attributed to spider bites. In most cases, these are actually skin and soft-tissue infections, allergic reactions, dermatoses etc. Misdiagnosing a wound as a spider bite can lead to delays in appropriate care, cause adverse or even fatal outcomes and have medical-legal implications. Concerningly, misinformation on spider bites also affects the medical literature and it appears there is lack of awareness on current therapeutic indications for verified bites.(AU)