Clinical Pharmacology Department, Institute of Biology, CHU Nantes, France.
Clin Exp Rheumatol. 2012 Sep-Oct;30(5):700-6. Epub 2012 Oct 17.
Tumour necrosis factor (TNF) alpha inhibitors (infliximab, etanercept, adalimumab) revolutionised the treatment of autoimmune diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD) and plaque psoriasis. During these treatments, cutaneous adverse effects may occur like eczema, lupus, alopecia areata or psoriasis, which represents a paradoxical adverse effect. The aim of this study was to collect and to analyse characteristics and outcomes of psoriasis induced by anti-TNF alpha treatments.
A search in the French Pharmacovigilance Database was performed between January 2002 and September 2009 using the following terms 'infliximab', 'etanercept', 'adalimumab' combined with the term 'psoriasis'. A literature review was performed utilising PubMed Database and Google scholar using permutations of the following terms 'infliximab', 'etanercept', 'adalimumab', 'tumour necrosis factor-α inhibitor' combined with 'psoriasis', 'palmoplantar pustular psoriasis', palmoplantar pustulosis'. Certolizumab pegol and golimumab were approved only recently and so were not included in the search.
We found 57 cases in the French Pharmacovigilance Database and 184 cases in the literature. It appeared that the eruptions are most often pustular lesions and occur mainly on palms and/or soles (33.3% in the French Pharmacovigilance Database and 42.9% in the literature), while palmoplantar pustular psoriasis represents only 1.7% of the psoriatic patients. The three anti-TNF-alpha are involved in the psoriasis induction. Half the cases appeared with infliximab. The patients affected by this adverse effect are mostly women aged between 40-50 years old. The time of onset of psoriasis is highly variable. Those patients treated for their psoriasis with TNF-alpha inhibitor developed a psoriasis induced by the treatment with a different localisation and a different morphology from the initial psoriasis while other patients had a recurrence of this side effect with two different TNF-alpha antagonists, then the psoriasis developed with the 2nd anti-TNF alpha is of the same type as the psoriasis developed with the first molecule.
This suggests that psoriasis occurring during anti-TNF alpha therapy are de novo psoriasis and not an aggravation of a pre-existing psoriasis. To this day several hypotheses have been proposed to explain the mechanism of action. The occurrence of this adverse effect may call into question the continuation of the treatment which is nevertheless effective.
肿瘤坏死因子（TNF）α抑制剂（英夫利昔单抗、依那西普、阿达木单抗）彻底改变了类风湿关节炎（RA）、强直性脊柱炎（AS）、克罗恩病（CD）和斑块状银屑病等自身免疫性疾病的治疗方法。在这些治疗过程中，可能会出现皮肤不良反应，如湿疹、狼疮、斑秃或银屑病，这代表一种矛盾的不良反应。本研究的目的是收集并分析抗 TNF-α 治疗引起的银屑病的特征和结局。
在 2002 年 1 月至 2009 年 9 月期间，使用以下术语“英夫利昔单抗”、“依那西普”、“阿达木单抗”并结合“银屑病”在法国药物警戒数据库中进行搜索。利用 PubMed 数据库和 Google Scholar 进行文献综述，使用以下术语的排列组合：“英夫利昔单抗”、“依那西普”、“阿达木单抗”、“肿瘤坏死因子-α抑制剂”并结合“银屑病”、“掌跖脓疱性银屑病”、掌跖脓疱病。由于 Certolizumab pegol 和 golimumab 最近才获得批准，因此未包含在搜索范围内。
我们在法国药物警戒数据库中发现了 57 例病例，在文献中发现了 184 例病例。结果表明，这些皮疹最常见的是脓疱性病变，主要发生在手掌和/或脚底（法国药物警戒数据库中为 33.3%，文献中为 42.9%），而掌跖脓疱性银屑病仅占银屑病患者的 1.7%。三种抗 TNF-α 均参与了银屑病的诱导。一半的病例与英夫利昔单抗有关。受这种不良反应影响的患者主要是 40-50 岁的女性。银屑病的发病时间差异很大。那些因银屑病接受 TNF-α 抑制剂治疗的患者出现了一种与初始银屑病不同部位和形态的银屑病，而其他患者在使用两种不同的 TNF-α 拮抗剂后出现了这种不良反应的复发，然后用第二种抗 TNF-α 治疗出现的银屑病与用第一种分子治疗出现的银屑病类型相同。
这表明抗 TNF-α 治疗过程中发生的银屑病是新发银屑病，而不是原有银屑病的恶化。到目前为止，已经提出了几种假说来解释其作用机制。这种不良反应的发生可能会引起对治疗的质疑，但治疗仍然有效。
