细胞因子失衡，与抗肿瘤坏死因子-α治疗相关的银屑病样疹中干扰素-α产生增加。

Cytokine imbalance with increased production of interferon-alpha in psoriasiform eruptions associated with antitumour necrosis factor-alpha treatments.

机构信息

Department of Dermatology and Pediatric Dermatology, Saint André and Pellegrin Hospitals, Bordeaux University Hospitals, 33075 Bordeaux Cedex, France.

出版信息

Br J Dermatol. 2009 Nov;161(5):1081-8. doi: 10.1111/j.1365-2133.2009.09329.x. Epub 2009 Jun 5.

DOI:10.1111/j.1365-2133.2009.09329.x

PMID:19681863

Abstract

BACKGROUND

Psoriasiform eruptions occur in association with antitumour necrosis factor (TNF)-alpha treatments in autoinflammatory diseases. The major reported clinical presentation is palmoplantar pustulosis, sometimes accompanied with plaque-like psoriasis. In some reports, histological findings suggest psoriasis whereas others favour a lichenoid drug reaction. We present a case series with a comprehensive clinical, histopathological and immunohistochemical study.

OBJECTIVES

To investigate the mechanism involved in psoriasiform eruptions in patients receiving anti-TNF-alpha inhibitors.

METHODS

Between July 2004 and May 2008, 13 patients with psoriasiform eruptions arising under anti-TNF-alpha treatment were enrolled in the study. Punch biopsy specimens of lesions were processed for standard and immunohistochemical analyses using antibodies against CD3, CD4, CD8, CD20, CD1a, KP1, CXCR3, CXCL9, Tia1 and MxA, which is specifically induced by type I interferons (IFNs). Additionally, we analysed biopsies from lesional skin of patients with cutaneous discoid lupus erythematosus, lichen planus and psoriasis. Control biopsies were taken from unaffected skin.

RESULTS

All patients developed psoriasiform plaques on the body accompanied with palmoplantar keratoderma or pustulosis in three patients. Histological and immunohistochemical findings showed a psoriasiform pattern with focal lichenoid and spongiotic features. We detected strong production of the MxA protein in inflammatory cells, indicating involvement of type I IFNs, and the expression was higher than in control psoriasis samples. Expression of MxA was closely associated with the recruitment of CXCR3+ lymphocytes in the skin bearing markers of cytotoxic capacity.

CONCLUSIONS

Results support the hypothesis that psoriasiform eruptions are a new model of drug reaction characterized by an increased expression of type I IFNs induced by anti-TNF-alpha.

摘要

背景

在自身炎症性疾病中，抗肿瘤坏死因子（TNF）-α 治疗会引起银屑病样疹。主要报道的临床表现为掌跖脓疱病，有时伴有斑块状银屑病。在一些报告中，组织学发现提示为银屑病，而另一些则倾向于药物引起的苔藓样反应。我们报告了一系列病例，进行了全面的临床、组织病理学和免疫组织化学研究。

目的

研究接受抗 TNF-α 抑制剂治疗的患者发生银屑病样疹的机制。

方法

2004 年 7 月至 2008 年 5 月，我们纳入了 13 例在抗 TNF-α 治疗过程中出现银屑病样疹的患者。对皮损进行了活检，进行了标准和免疫组织化学分析，使用了针对 CD3、CD4、CD8、CD20、CD1a、KP1、CXCR3、CXCL9、Tia1 和 MxA 的抗体，MxA 是由 I 型干扰素（IFN）特异性诱导的。此外，我们还分析了皮肤盘状红斑狼疮、扁平苔藓和银屑病患者皮损的活检标本。对照活检取自未受影响的皮肤。

结果

所有患者均在身体上出现银屑病样斑块，伴有 3 例手掌足底角化过度或脓疱病。组织学和免疫组织化学表现为具有局灶性苔藓样和海绵状特征的银屑病样模式。我们检测到炎性细胞中强烈表达 MxA 蛋白，表明 I 型 IFN 参与，其表达高于对照银屑病样本。MxA 的表达与携带细胞毒性标志物的皮肤中 CXCR3+淋巴细胞的募集密切相关。