Nakamura M, Toyoda M, Morohashi M
Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Br J Dermatol. 2003 Oct;149(4):718-30. doi: 10.1046/j.1365-2133.2003.05586.x.
Although some patients with psoriasis vulgaris also complain of severe pruritus, the data available regarding pruritus in psoriasis are sparse.
To clarify the mechanism and mediators involved in the pruritus of psoriasis vulgaris, we compared itch-associated factors in lesional skin from psoriatic patients vs. skin without pruritus quantitatively using a panel of histological and immunohistological parameters.
Biopsied specimens were obtained from 38 patients with psoriasis vulgaris who were divided into two groups according to the presence or absence of pruritus.
When compared with psoriatic patients devoid of pruritus, lesional skin from patients with pruritus showed the following characteristic features: (i) a rich innervation both in the epidermis and in the papillary dermis; (ii) an increase in neuropeptide substance P-containing nerve fibres in perivascular areas; (iii) decreased expression of neutral endopeptidase in the epidermal basal layer as well as in the endothelia of blood vessels; (iv) many mast cells showing degranulating processes in the papillary dermis; (v) a strong immunoreactivity for nerve growth factor (NGF) throughout the entire epidermis and an increased NGF content in lesional skin homogenates; (vi) an increase in the expression of high-affinity receptors for NGF (Trk A) in basal keratinocytes and in dermal nerves; (vii) an increased population of interleukin-2-immunoreactive lymphocytes; and (viii) a strong expression of E-selectin on vascular endothelial cells. A significant correlation was observed between the severity of pruritus and protein gene product 9.5-immunoreactive intraepidermal nerve fibres, NGF-immunoreactive keratinocytes, expression of Trk A in the epidermis and the density of immunoreactive vessels for E-selectin. These findings indicate that possible pruritogenic mediators in psoriatic lesional skin are neurogenic factors including innervation, neuropeptide substance P, neuropeptide-degrading enzymes and NGF, activated mast cells, one or more cytokines and endothelial-leucocyte adhesion molecules.
These data document for the first time itch-related local markers in psoriasis, and suggest complex and multifactorial mechanisms of pruritus in the disease. These results provide the groundwork for further studies to evaluate the efficacy of antipruritic treatment for psoriatic patients.
尽管一些寻常型银屑病患者也抱怨有严重瘙痒,但关于银屑病瘙痒的现有数据很少。
为阐明寻常型银屑病瘙痒的机制及介质,我们使用一系列组织学和免疫组织学参数,对银屑病患者皮损处皮肤与无瘙痒皮肤中与瘙痒相关的因素进行了定量比较。
从38例寻常型银屑病患者获取活检标本,根据有无瘙痒将患者分为两组。
与无瘙痒的银屑病患者相比,有瘙痒患者的皮损处皮肤呈现以下特征:(i)表皮和乳头真皮内神经支配丰富;(ii)血管周围含神经肽P物质的神经纤维增加;(iii)表皮基底层及血管内皮中中性内肽酶表达降低;(iv)乳头真皮中有许多显示脱颗粒过程的肥大细胞;(v)整个表皮对神经生长因子(NGF)有强免疫反应性,且皮损处皮肤匀浆中NGF含量增加;(vi)基底角质形成细胞和真皮神经中NGF高亲和力受体(Trk A)表达增加;(vii)白细胞介素-2免疫反应性淋巴细胞数量增加;(viii)血管内皮细胞上E-选择素强表达。瘙痒严重程度与蛋白基因产物9.5免疫反应性表皮内神经纤维、NGF免疫反应性角质形成细胞、表皮中Trk A表达及E-选择素免疫反应性血管密度之间存在显著相关性。这些发现表明,银屑病皮损处皮肤中可能的致痒介质为神经源性因子,包括神经支配、神经肽P物质、神经肽降解酶和NGF、活化的肥大细胞、一种或多种细胞因子以及内皮-白细胞黏附分子。
这些数据首次记录了银屑病中与瘙痒相关的局部标志物,并提示该病瘙痒机制复杂且涉及多因素。这些结果为进一步研究评估抗瘙痒治疗对银屑病患者的疗效奠定了基础。