Department of Dermatology, Aarhus University Hospital, DK-8000, Aarhus C, Aarhus, Denmark.
Br J Dermatol. 2015 Feb;172(2):345-53. doi: 10.1111/bjd.13236. Epub 2014 Dec 10.
The application of Aldara(®) cream containing 5% imiquimod stimulates Toll-like receptor 7/8 on plasmacytoid dendritic cells, thereby producing a potent immunomodulatory effect. This has been reported to trigger psoriasis.
To establish a human model of Aldara-induced psoriasis-like skin inflammation in patients with psoriasis.
Nonlesional psoriatic skin of 13 patients was treated with Aldara for 2 or 7 days. The skin was evaluated clinically and histologically on days 2, 4 and 7. Cytokine expression in Aldara-treated, lesional and nonlesional psoriatic skin was compared using reverse-transcription quantitative polymerase chain reaction.
Nine of the 10 patients receiving application of Aldara under occlusion for 2 days developed redness, induration and scaling. Histological analysis revealed focal parakeratosis, acanthosis and perivascular mononuclear infiltration. On days 4 and 7 both clinical and histological signs of inflammation subsided. Two of the three patients treated with Aldara for 7 days developed erosions leading to psoriasis on day 21. Cytokine markers of activation of the innate immune system [interferon-α, interferon regulatory factor-7 and interleukin (IL)-1β] were equally expressed in lesional and Aldara-treated skin (n = 6). IL-6 and tumour necrosis factor-α were preferentially expressed in Aldara-treated skin. Adaptive immune system activation occurred only partially: IL-23p19 and IL-22 were similarly overexpressed in Aldara-treated and lesional psoriatic skin, but IL-17A and IL-12p40 were significantly underexpressed in Aldara-treated skin compared with lesional psoriatic skin. IL-10 was significantly overexpressed in Aldara-treated skin.
We were able to induce psoriasis-like skin inflammation although typical psoriasis did not develop, possibly due to incomplete adaptive immune system recruitment and the powerful stimulation of IL-10 counter-regulation.
使用含有 5%咪喹莫特的 Aldara（®）乳膏刺激浆细胞样树突状细胞上的 Toll 样受体 7/8，从而产生有效的免疫调节作用。据报道，这会引发银屑病。
在银屑病患者中建立 Aldara 诱导的银屑病样皮肤炎症的人体模型。
13 例银屑病非皮损皮肤连续 2 或 7 天外用 Aldara 治疗。第 2、4 和 7 天评估皮肤的临床表现和组织学变化。使用逆转录定量聚合酶链反应比较 Aldara 治疗、皮损和非皮损银屑病皮肤中的细胞因子表达。
10 例接受 Aldara 封闭治疗 2 天的患者中，9 例出现发红、硬结和鳞屑。组织学分析显示局灶性角化过度、棘层肥厚和血管周围单核细胞浸润。第 4 和 7 天，炎症的临床和组织学征象均消退。3 例接受 Aldara 治疗 7 天的患者中，有 2 例出现糜烂，导致第 21 天出现银屑病。固有免疫激活的细胞因子标志物[干扰素-α、干扰素调节因子-7 和白细胞介素（IL）-1β]在皮损和 Aldara 治疗皮肤中表达相等（n=6）。IL-6 和肿瘤坏死因子-α在 Aldara 治疗皮肤中优先表达。适应性免疫系统激活仅部分发生：IL-23p19 和 IL-22 在 Aldara 治疗和皮损银屑病皮肤中过度表达，但与皮损银屑病皮肤相比，IL-17A 和 IL-12p40 在 Aldara 治疗皮肤中表达明显减少。IL-10 在 Aldara 治疗皮肤中显著过表达。
尽管未出现典型银屑病，但我们能够诱导出银屑病样皮肤炎症，这可能是由于适应性免疫系统募集不完全和强大的 IL-10 反向调节刺激所致。
