Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment
Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment
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DOI：
10.1136/gutjnl-2012-302853
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发表时间：
2014-04-01
期刊：
影响因子：
24.5
通讯作者：
Brand, Stephan
中科院分区：
文献类型：
--
作者：
Tillack, Cornelia;Ehmann, Laura Maximiliane;Brand, Stephan
背景我们分析了炎症性肠病（IBD）患者中抗肿瘤坏死因子α（TNF-α）抗体诱导的银屑病样皮肤病变的发病率、预测因子、组织学特征和特异性治疗选择。对患者进行IL 23 R和IL 12 B变体的基因分型。检查皮肤病变的浸润性Th 1和Th 17细胞。结果在434例接受抗TNF治疗的IBD患者中，21例（4.8%）发生银屑病样皮肤病变。多元logistic回归显示吸烟（p=0.007; OR 4.24，95% CI 1.55至13.60）和体重指数增加（p=0.029; OR 1.12，95% CI 1.01至1.24）是这些病变的主要预测因素。9名克罗恩病患者和严重银屑病样病变和/或抗TNF抗体诱导的脱发患者成功地用抗p40-IL-12/IL-23抗体优特克单抗治疗（应答率100%）。皮肤病变的组织学特征为IL-17 A/IL-22分泌性T辅助17（Th 17）细胞和干扰素（IFN）-γ分泌性Th 1细胞和IFN-α表达细胞浸润。需要乌司奴单抗的患者中IL-17 A表达显著强于对局部治疗有反应的患者（p=0.001）。IL 23 R基因分型提示rs 11209026（p.Arg381Gln）和rs7530511（p.Leu310Pro）在需要乌司奴单抗的患者中具有疾病修饰作用。我们确定吸烟是发展这些病变的主要危险因素。抗TNF诱导的银屑病样皮肤病变的特征在于Th 17和Th 1细胞浸润。表达IL-17 A的T细胞的数量与皮肤病变的严重程度相关。抗IL-12/IL-23抗体疗法是治疗这些病变的高效疗法。
Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor alpha (TNF-alpha) antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).Design Patients with IBD were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IL23R and IL12B variants. Skin lesions were examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-interleukin (IL)-12/IL-23 p40 antibody ustekinumab.Results Among 434 anti-TNF-treated patients with IBD, 21 (4.8%) developed psoriasiform skin lesions. Multiple logistic regression revealed smoking (p=0.007; OR 4.24, 95% CI 1.55 to 13.60) and an increased body mass index (p=0.029; OR 1.12, 95% CI 1.01 to 1.24) as main predictors for these lesions. Nine patients with Crohn's disease and with severe psoriasiform lesions and/or anti-TNF antibody-induced alopecia were successfully treated with the anti-p40-IL-12/IL-23 antibody ustekinumab (response rate 100%). Skin lesions were histologically characterised by infiltrates of IL-17A/IL-22-secreting T helper 17 (Th17) cells and interferon (IFN)-gamma-secreting Th1 cells and IFN-alpha-expressing cells. IL-17A expression was significantly stronger in patients requiring ustekinumab than in patients responding to topical therapy (p=0.001). IL23R genotyping suggests disease-modifying effects of rs11209026 (p.Arg381Gln) and rs7530511 (p.Leu310Pro) in patients requiring ustekinumab.Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL23 antibody therapy is a highly effective therapy for these lesions.