抗肿瘤坏死因子-α诱导的皮肤病变与克罗恩病患者所选细胞因子之间的相关性

Correlations between skin lesions induced by anti-tumor necrosis factor-α and selected cytokines in Crohn's disease patients.

作者信息

Włodarczyk Marcin, Sobolewska Aleksandra, Wójcik Bartosz, Loga Karolina, Fichna Jakub, Wiśniewska-Jarosińska Maria

机构信息

Marcin Włodarczyk, Aleksandra Sobolewska, Bartosz Wójcik, Karolina Loga, Maria Wiśniewska-Jarosińska, Department of Gastroenterology, Medical University of Lodz, 90-647 Lodz, Poland.

出版信息

World J Gastroenterol. 2014 Jun 14;20(22):7019-26. doi: 10.3748/wjg.v20.i22.7019.

DOI:10.3748/wjg.v20.i22.7019

PMID:24944497

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4051946/

Abstract

AIM

To investigate the correlation between the appearance of skin lesions and concentration of interleukin (IL)-17A, IL-23 and interferon-γ (IFN-γ) in Crohn's disease (CD) patients during anti-tumor necrosis factor-α (TNF-α) therapy

METHODS

A prospective study included 30 adult patients with CD of Caucasian origin (19 men and 11 women; mean age ± SD 32.0 ± 8.6 years) during biological therapy with anti-TNF-α antibodies from January 2012 to March 2013. Eighteen patients were treated with infliximab, seven with adalimumab and five with certolizumab. Inclusion criteria were exacerbation of the underlying disease, Crohn's Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies. Patients with a history of psoriasis, atopic dermatitis and other autoimmune skin lesions were excluded from the study. The control group consisted of 12 healthy subjects. A diagnostic survey was carried out, blood tests and careful skin examination were performed, and the serum levels of IL-17, IL-23 and IFN-γ were measured using an enzyme-linked immunosorbent assays technique. Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by anti-TNF-α therapy.

RESULTS

Skin manifestations occurred in 18 of CD patients during the anti-TNF-α therapy (60%), in the average time of 10.16 ± 3.42 mo following the beginning of the 52-wk treatment cycle. Skin lesions observed in CD patients during biological therapy included psoriasiform lesions (44.4%), and eczema forms lesions (22.2%). In CD patients with drug induced skin lesions significantly higher levels of hemoglobin (13.3 ± 1.5 g/dL vs 10.8 ± 1.9 g/dL, P = 0.018) and hematocrit (39.9% ± 4.5% vs 34.3% ± 5.4%, P = 0.01), as well as a significantly lower level of platelets (268 ± 62 × 10(3)/μL vs 408 ± 239 × 10(3)/μL, P = 0.046) was observed compared with CD patients without skin manifestations. The concentrations of IL-17A and IL-23 in CD patients with skin lesions developed under anti-TNF-α therapy were significantly higher compared to those in patients without lesions (IL-17A: 39.01 ± 7.03 pg/mL vs 25.71 ± 4.90 pg/mL, P = 0.00004; IL-23: 408.78 ± 94.13 pg/mL vs 312.15 ± 76.24 pg/mL, P = 0.00556).

CONCLUSION

Skin lesions in CD patients during biological therapy may result from significantly increased concentrations of IL-17A and IL-23, which are strongly associated with TNF-α/Th1 immune pathways.

摘要

目的

探讨抗肿瘤坏死因子-α（TNF-α）治疗期间克罗恩病（CD）患者皮肤病变的出现与白细胞介素（IL）-17A、IL-23和干扰素-γ（IFN-γ）浓度之间的相关性。

方法

一项前瞻性研究纳入了2012年1月至2013年3月期间接受抗TNF-α抗体生物治疗的30例成年白种人CD患者（19例男性和11例女性；平均年龄±标准差32.0±8.6岁）。18例患者接受英夫利昔单抗治疗，7例接受阿达木单抗治疗，5例接受赛妥珠单抗治疗。纳入标准为基础疾病加重、克罗恩病活动指数超过300以及先前使用的非生物治疗无效。有银屑病、特应性皮炎和其他自身免疫性皮肤病变病史的患者被排除在研究之外。对照组由12名健康受试者组成。进行了诊断性调查，进行了血液检查和仔细的皮肤检查，并使用酶联免疫吸附测定技术测量了IL-17、IL-23和IFN-γ的血清水平。在生物治疗过程中出现的、此前没有类似特征皮肤病变的患者所发生的皮肤病被判定为抗TNF-α治疗诱导的皮肤病变。

结果

18例CD患者在抗TNF-α治疗期间出现皮肤表现（60%），平均出现在52周治疗周期开始后的10.16±3.42个月。CD患者在生物治疗期间观察到的皮肤病变包括银屑病样病变（44.4%）和湿疹样病变（22.2%）。与无皮肤表现的CD患者相比，有药物诱导皮肤病变的CD患者血红蛋白水平显著更高（13.3±1.5 g/dL对10.8±1.9 g/dL，P = 0.018）、血细胞比容显著更高（39.9%±4.5%对34.3%±5.4%，P = 0.01），以及血小板水平显著更低（268±62×10³/μL对408±239×10³/μL，P = 0.046）。与无病变的患者相比，抗TNF-α治疗期间出现皮肤病变的CD患者中IL-?17A和IL-23的浓度显著更高（IL-17A：39.01±7.03 pg/mL对25.71±4.90 pg/mL，P = 0.00004；IL-23：408.78±94.13 pg/mL对312.15±76.24 pg/mL，P = 0.00556）。