Dupilumab improved atypical fibrotic skin plaques in atopic dermatitis.
Dupilumab improved atypical fibrotic skin plaques in atopic dermatitis.
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Dupilumab 可改善特应性皮炎中的非典型纤维化皮肤斑块。
DOI：
10.1111/bjd.18359
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kabashima K.
中科院分区：
文献类型：
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作者：
Nakashima C;Ishida Y;Kaku Y;Epstein EH Jr;Otsuka A;Kabashima K.
亲爱的编辑，特应性皮炎（AD）的特征是与炎性细胞浸润相关的辅助性T细胞2型（Th 2）细胞因子占主导地位。1 Th 2细胞因子，特别是白细胞介素（IL）-13，也有助于皮肤的纤维化重塑，如在鼠AD模型中所示。2 Dupilumab是一种IL-4受体-o拮抗剂，可阻断IL-4和IL-13信号传导，并获批用于治疗中度至重度AD。3 Dupilumab可有效治疗AD症状，如湿疹和瘙痒症;然而，其对皮肤纤维化的疗效尚不清楚。我们在此报告dupilumab成功治疗了组织学上具有显著纤维化的非典型AD相关斑块。一名50岁女性，既往有儿童哮喘史，患有25年的重度AD，传统治疗无效。实验室检查显示嗜酸性粒细胞增多（占总白色血细胞计数的14 × 7%，1440个嗜酸性粒细胞mm × 3;正常70-450），血清Th 2趋化因子、胸腺和活化调节趋化因子（TARC，11 740 pg mL × 1;正常< 450）和总IgE（20 000 IU mL × 1;正常< 170）水平升高。除了AD典型的湿疹样病变外，还观察到颈部有多个红色、坚硬、光滑的斑块（图1a）。从斑块中采集的皮肤活检显示表皮不规则增厚、海绵状增生、致密炎性细胞浸润（包括嗜酸性粒细胞）和局灶性真皮纤维化（图1b）。Masson三色染色显示乳头状真皮和网状真皮中的胶原纤维明显增加（图1c）。其他引起皮肤纤维化的疾病，如系统性硬化症和硬斑病，在这种情况下没有得到临床或病理结果的支持。因此，颈部斑块被诊断为AD相关的非典型湿疹性斑块伴纤维化，可能由患者习惯性抓挠引起。该患者对常规治疗无效，如2类局部皮质类固醇、口服环孢素（2 mg kg体重）和准分子光。因此，我们决定用dupilumab（300 mg皮下注射（a）（B）（c）（d））治疗患者
DEAR EDITOR, Atopic dermatitis (AD) is characterized by a dominance of T-helper type 2 (Th2) cytokines associated with infiltration of inflammatory cells. 1 Th2 cytokines, especially interleukin (IL)-13, also contribute to fibrotic remodelling of the skin, as shown in murine AD models. 2 Dupilumab is an IL-4 receptor-o antagonist, which blocks both IL-4 and IL-13 signalling, and is approved for the treatment of moderate-tosevere AD. 3 Dupilumab is effective for treating AD symptoms such as eczema and pruritus; however, its efficacy for skin fibrosis remains unknown. We herein report that dupilumab successfully treated atypical AD-associated plaques with marked fibrosis on histology. A 50-year-old female with a past history of childhood asthma presented with a 25-year history of severe AD recalcitrant to conventional therapy. Laboratory investigations revealed eosinophilia (14Á7% of total white blood cell count, 1440 eosinophils mm À3; normal 70–450), elevated levels of serum Th2 chemokine, thymus and activation-regulated chemokine (TARC, 11 740 pg mL À1; normal< 450) and total IgE (20 000 IU mL À1; normal< 170). In addition to eczematous lesions typical of AD, multiple red, hard, smooth plaques on the neck were noted (Fig. 1a). A skin biopsy taken from the plaque showed irregular thickening of the epidermis, spongiosis, dense inflammatory cell infiltration including eosinophils and focal fibrosis in the dermis (Fig. 1b). Masson trichrome staining showed markedly increased collagen fibres in the papillary and reticular dermis (Fig. 1c). Other conditions that cause skin fibrosis, such as systemic sclerosis and morphoea, were not supported by clinical or pathological findings in this case. Therefore, the neck plaques were diagnosed as AD-associated atypical eczematous plaques with fibrosis, probably caused by habitual scratching by the patient. The patient had been refractory to conventional therapies, such as class 2 topical corticosteroids, oral ciclosporin (2 mg kg À1 body weight) and excimer light. Therefore, we decided to treat the patient with dupilumab (300 mg subcutaneous (a)(b)(c)(d)