Okune Mari, Okiyama Naoko, Fukuzono Maki, Sasaki Katsuhito, Nomura Toshifumi
Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Dermatology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.
J Dermatol. 2022 May;49(5):556-559. doi: 10.1111/1346-8138.16322. Epub 2022 Feb 27.
Dupilumab, a monoclonal antibody that specifically inhibits signal transductions by interleukin (IL)-4 and IL-13, has been used to treat T-helper (Th)2-type allergic disorders, including atopic dermatitis and asthma. We report a 21-year-old female patient with atopic dermatitis who developed systemic lupus erythematosus (SLE) unexpectedly after dupilumab treatment. Her skin lesions partially improved after dupilumab treatment; however, a part of her skin lesions on the face, nape, and upper extremities were refractory even after a 15-month period of dupilumab treatment. These dupilumab-refractory skin lesions were histopathologically diagnosed as cutaneous lupus erythematosus, moreover, subsequent phenomenons, diffuse alopecia, joint pain, lymphopaenia, hypocomplementemia, and positivities for anti-nuclear, anti-double-stranded DNA, anti-U1 ribonucleoprotein, anti-Smith, and anti-Sjögren's syndrome-related antigen A antibodies made a diagnosis of SLE. Our retrospective investigations on her serum samples indicted that these abnormalities of laboratory examinations had not appeared at the initiation of dupilumab treatment. Our case at least indicated that dupilumab was not effective in treating SLE. Moreover, inhibition of Th2-type immune responses by dupilumab may accelerate the pathogenesis of Th1-related inflammatory disorders, including SLE, as observed in our case. Our case also presented another possibility that dupilumab has no effect on the progression of underlying SLE. Because a significant relationship exists between atopic dermatitis/asthma and the risk of SLE, the utility of dupilumab should be carefully considered for each case.
度普利尤单抗是一种特异性抑制白细胞介素（IL）-4和IL-13信号转导的单克隆抗体，已被用于治疗2型辅助性T细胞（Th2）介导的过敏性疾病，包括特应性皮炎和哮喘。我们报告了一名21岁的特应性皮炎女性患者，在接受度普利尤单抗治疗后意外发生了系统性红斑狼疮（SLE）。度普利尤单抗治疗后她的皮肤病变部分改善；然而，即使在接受度普利尤单抗治疗15个月后，她面部、颈部和上肢的部分皮肤病变仍难以治愈。这些对度普利尤单抗耐药的皮肤病变经组织病理学诊断为皮肤红斑狼疮，此外，随后出现的弥漫性脱发、关节疼痛、淋巴细胞减少、补体血症降低以及抗核抗体、抗双链DNA抗体、抗U1核糖核蛋白抗体、抗史密斯抗体和抗干燥综合征相关抗原A抗体阳性，最终确诊为SLE。我们对她血清样本的回顾性研究表明，这些实验室检查异常在度普利尤单抗治疗开始时并未出现。我们的病例至少表明度普利尤单抗对治疗SLE无效。此外，如我们病例中所观察到的，度普利尤单抗对Th2型免疫反应的抑制可能会加速包括SLE在内的Th1相关炎症性疾病的发病机制。我们的病例还提出了另一种可能性，即度普利尤单抗对潜在SLE的进展没有影响。由于特应性皮炎/哮喘与SLE风险之间存在显著关联，对于每个病例都应仔细考虑度普利尤单抗的适用性。
