Wendling Daniel, Balblanc Jean-Charles, Briançon Daniel, Brousse Alain, Lohse Anne, Deprez Philippe, Humbert Philippe, Aubin François
Rheumatology Department, CHU Jean Minjoz, Minjoz Teaching Hospital, Franche-Comté University, Boulevard Fleming, 25030 Besançon Cedex, France.
Joint Bone Spine. 2008 May;75(3):315-8. doi: 10.1016/j.jbspin.2007.06.011. Epub 2008 Feb 11.
The widespread use of TNFalpha antagonists in recent years has led to the recognition of paradoxical adverse effects, defined as the onset or exacerbation of disorders that are usually improved by TNFalpha antagonists. Cutaneous psoriasis is an example, of which several cases have been reported.
To identify cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy and to look for potential predictive factors.
We retrospectively reviewed cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy. For each case we recorded the following data: age, sex, underlying disease, nature of the TNFalpha antagonist, effectiveness in improving the underlying disease, history of psoriasis in the patient or family, time to psoriasis development, type of psoriasis (confirmed by an experienced dermatologist), concomitant treatments, whether the TNFalpha antagonist was stopped or continued, and the outcome of the psoriasis. These data were compared to those in the literature.
We identified 12 patients, six men and six women, with a mean age of 45.5 years. The TNFalpha antagonist was adalimumab in four patients, etanercept in six patients, and infliximab in two patients. The underlying disease was ankylosing spondylitis in six cases, rheumatoid arthritis in four, and psoriatic arthritis in two. Mean time from treatment initiation to psoriasis was 4.1 months (range, 1-15 months). A previous history of psoriasis in the patient was noted in six cases, including four of the six patients taking etanercept. TNFalpha antagonist therapy was effective on the underlying disease in 11 of the 12 patients. The drug was discontinued in five patients, of whom four experienced resolution of their psoriasis. In the remaining seven patients, the drug was continued and the skin lesions remained unchanged. Most of the patients had psoriasis vulgaris (plaque psoriasis); palmoplantar pustulosis was a feature in five patients.
Over 40 cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy have been reported in the literature. The prevalence of this adverse effect has been estimated at 1.5-5% of patients taking TNFalpha antagonists. The findings from our case series are consistent with data in the literature. Psoriasis is a class effect that has been reported with all the currently available TNFalpha antagonists. The skin lesions develop within the first few months of therapy. Patients with a wide range of underlying diseases can be affected. Palmoplantar pustulosis is a common feature. A previous history of psoriasis seems more common in patients who experience psoriasis onset or exacerbation during etanercept therapy (four of six patients in our study and 55% in the literature); thus, previous psoriasis may be a risk factor for psoriasis exacerbation during etanercept therapy.
近年来肿瘤坏死因子α拮抗剂的广泛使用已导致认识到矛盾的不良反应，即通常由肿瘤坏死因子α拮抗剂改善的疾病的发作或恶化。皮肤银屑病就是一个例子，已有数例相关报道。
识别肿瘤坏死因子α拮抗剂治疗期间银屑病发作或恶化的病例，并寻找潜在的预测因素。
我们回顾性分析了肿瘤坏死因子α拮抗剂治疗期间银屑病发作或恶化的病例。对于每个病例，我们记录了以下数据：年龄、性别、基础疾病、肿瘤坏死因子α拮抗剂的性质、改善基础疾病的有效性、患者或家族的银屑病病史、银屑病发生的时间、银屑病类型（由经验丰富的皮肤科医生确诊）、联合治疗、肿瘤坏死因子α拮抗剂是否停用或继续使用以及银屑病的转归。将这些数据与文献中的数据进行比较。
我们识别出12例患者，6名男性和6名女性，平均年龄45.5岁。4例患者使用阿达木单抗，6例使用依那西普，2例使用英夫利昔单抗。基础疾病为强直性脊柱炎6例，类风湿关节炎4例，银屑病关节炎2例。从开始治疗到发生银屑病的平均时间为4.1个月（范围1 - 15个月）。6例患者有银屑病既往史，其中6例使用依那西普的患者中有4例。12例患者中有11例肿瘤坏死因子α拮抗剂治疗对基础疾病有效。5例患者停用了该药物，其中4例银屑病消退。其余7例患者继续使用该药物，皮肤病变无变化。大多数患者为寻常型银屑病（斑块状银屑病）；5例患者有掌跖脓疱病。
文献中已报道40多例肿瘤坏死因子α拮抗剂治疗期间银屑病发作或恶化的病例。据估计，这种不良反应在使用肿瘤坏死因子α拮抗剂的患者中的发生率为1.5% - 5%。我们病例系列的结果与文献数据一致。银屑病是一种类效应，所有目前可用的肿瘤坏死因子α拮抗剂均有报道。皮肤病变在治疗的最初几个月内出现。多种基础疾病的患者均可受累。掌跖脓疱病是常见特征。既往有银屑病病史在依那西普治疗期间发生银屑病发作或恶化的患者中似乎更常见（我们研究中的6例患者中有4例，文献中为55%）；因此，既往银屑病可能是依那西普治疗期间银屑病恶化的一个危险因素。
