Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: clinical features and possible immunopathogenesis.

Rheumatology Service, Brooke Army Medical Center, Fort Sam Houston, Texas 78234, USA. angelique.collamer@us.af.mil

Abstract

OBJECTIVE: The induction or exacerbation of psoriasis in patients treated with tumor necrosis factor (TNF) antagonists is a well-established phenomenon. The goals of this comprehensive literature analysis were to update currently available data regarding this adverse event, to identify any clinical patterns in the cohort of reported patients, and to review the possible immunopathogenesis.

METHODS: A systematic literature review was performed utilizing PubMed and Medline databases (1996 to August 2009) searching the index terms "tumor necrosis factor alpha inhibitor," "TNF," "infliximab," "etanercept," "adalimumab," combined with the terms "psoriasis," "pustular," "skin," "rash," "palmoplantar," and "paradoxical." All relevant articles were reviewed. Patients who did not appear to meet accepted classification criteria for their treated disease, who had a more probable explanation or other likely diagnosis for their skin findings or known possible triggering factor for the skin eruption, including infection, were excluded from this analysis.

RESULTS: Two hundred seven cases met inclusion criteria for review. Of these, 43% were diagnosed with rheumatoid arthritis, 26% with seronegative spondyloarthropathy, and 20% with inflammatory bowel disease. Mean patient age was 45 years and 65% were female. Fifty-nine percent were being treated with infliximab, 22% with adalimumab, and 19% with etanercept. Lesion morphology included pustular psoriasis in 56%, plaque psoriasis in 50%, and guttate lesions in 12%; 15% experienced lesions of more than 1 type. No statistically significant predisposing factors for the development of new-onset psoriasis were found. Sixty-six percent of patients were able to continue TNF antagonist therapy with psoriasis treatments. The pathogenesis appears to involve disruption of the cytokine milieu with production of unopposed interferon-α production by plasmacytoid dendritic cells in genetically predisposed individuals. Genetic polymorphisms may play a role in this paradoxical reaction to TNF blockade.

CONCLUSIONS: TNF antagonist induced psoriasis is a well-described adverse event without any known predisposing risk factors. Most patients can be managed conservatively without drug withdrawal. Registry data reporting is necessary to define the true incidence and prevalence of this condition. Genomic studies of affected patients may assist with identification of predisposed patients and elucidation of the molecular trigger of this perplexing response.

肿瘤坏死因子拮抗剂诱发银屑病皮肤损害：临床表现及其可能的免疫发病机制

Collamer AN,et al.Semin Arthritis Rheum. 2010 Dec;40(3):233-40.

目的：人们已经观察到TNF拮抗剂可诱发或加重银屑病。本文旨在更新有关此副反应的已有数据，明确已报道患者的临床表现，综述可能的免疫发病机制。

方法：以“肿瘤坏死因子α抑制剂”、“TNF”、“英夫利昔单抗”、“依那西普”、“阿达木单抗”联合“银屑病”、“脓疱”、“皮肤”、“皮疹”、“掌跖”、“反常”，在PubMed和Medline数据库（1996~2009年8月）进行检索。排除标准包括不符合所治疾病诊断标准、皮肤表现可用其他情况解释、已知皮疹的诱发因素（包括感染）。

结果：207例患者符合纳入标准，其中43%为RA、26%为血清阴性脊柱关节病、20%为炎性肠病，平均年龄45岁，女性占65%。59%使用英夫利昔单抗，22%使用阿达木单抗，19%使用依那西普。皮肤表现包括56%脓疱性银屑病，50%斑块状银屑病，12%点滴状皮损；15%有1种以上皮损类型。未发现具有统计学意义的新发银屑病倾向因素。66%患者在联合银屑病治疗的同时，能继续使用TNF拮抗剂。发病机制可能是在有遗传倾向的个体中，浆细胞样树突状细胞产生无拮抗的干扰素α，从而破坏了细胞因子环境。遗传多态性可能在其中起到一定作用。

结论：TNF拮抗剂诱发银屑病是一种众所周知的副反应，暂未发现相关危险因素。大部分患者不需撤药。登记数据报告有助于了解其发生率和患病率。受累患者的基因学研究可能有助于确定易感患者，明确其分子触发机制。