9 research outputs found

    Pruritic bluish-black subcutaneous papules on the chest

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    Microarray analysis of port wine stains before and after pulsed dye laser treatment.

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    Background and objectivesNeither the pathogenesis of port wine stain (PWS) birthmarks nor tissue effects of pulsed dye laser (PDL) treatment of these lesions is fully understood. There are few published reports utilizing gene expression analysis in human PWS skin. We aim to compare gene expression in PWS before and after PDL, using DNA microarrays that represent most, if not all, human genes to obtain comprehensive molecular profiles of PWS lesions and PDL-associated tissue effects.Materials and methodsFive human subjects had PDL treatment of their PWS. One week later, three biopsies were taken from each subject: normal skin (N); untreated PWS (PWS); PWS post-PDL (PWS + PDL). Samples included two lower extremity lesions, two facial lesions, and one facial nodule. High-quality total RNA isolated from skin biopsies was processed and applied to Affymetrix Human gene 1.0ST microarrays for gene expression analysis. We performed a 16 pair-wise comparison identifying either up- or down-regulated genes between N versus PWS and PWS versus PWS + PDL for four of the donor samples. The PWS nodule (nPWS) was analyzed separately.ResultsThere was significant variation in gene expression profiles between individuals. By doing pair-wise comparisons between samples taken from the same donor, we were able to identify genes that may participate in the formation of PWS lesions and PDL tissue effects. Genes associated with immune, epidermal, and lipid metabolism were up-regulated in PWS skin. The nPWS exhibited more profound differences in gene expression than the rest of the samples, with significant differential expression of genes associated with angiogenesis, tumorigenesis, and inflammation.ConclusionIn summary, gene expression profiles from N, PWS, and PWS + PDL demonstrated significant variation within samples from the same donor and between donors. By doing pair-wise comparisons between samples taken from the same donor and comparing these results between donors, we were able to identify genes that may participate in formation of PWS and PDL effects. Our preliminary results indicate changes in gene expression of angiogenesis-related genes, suggesting that dysregulation of angiogenic signals and/or components may contribute to PWS pathology

    Immunohistochemistry of angiogenesis mediators before and after pulsed dye laser treatment of angiomas.

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    Tissue effects of vascular lesion laser treatment are incompletely understood. Injury caused by pulsed dye laser (PDL) treatment may result in altered expression of mediators associated with angiogenesis.Eight human subjects had one angioma treated with PDL (7 mm, 1.5 millisecond pulse duration, 9 J/cm(2), cryogen spray cooling of 30 millisecond with a 30 millisecond delay). One week later, three biopsies were taken: normal skin, untreated angioma, angioma post-PDL. Tissue was frozen and sections processed for immunohistochemistry staining of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase 9 (MMP-9), and angiopoietin 2 (ANG-2). Images were graded in a blinded fashion by a board certified dermatopathologist.There were no clear trends in VEGF expression in the epidermis, dermis, or endothelial cells. As compared to normal skin, angiomas demonstrated the following: bFGF was decreased in the epidermis; MMP-9 was decreased or unchanged in the epidermis and increased in the endothelial cells; ANG-2 was increased in the endothelial cells. When comparing normal skin to angiomas + PDL, bFGF was decreased in the epidermis and increased in the dermis; MMP-9 was decreased or unchanged in the epidermis; ANG-2 was again increased in the endothelial cells. Comparison of staining in angioma to angioma + PDL samples revealed increased dermal bFGF expression.Alterations in angiogenesis mediators were noted after PDL. Angiogenesis mediator changes associated with PDL treatment differed from those previously reported for incisional biopsies. This pilot study can guide future work on laser-induced alterations in vascular lesions and such information may ultimately be used to optimize treatment outcomes

    Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis.

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    BACKGROUND Prurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis. METHODS In this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≄4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≄2 points). There were five key secondary end points. RESULTS A total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%). CONCLUSIONS Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.)
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