Case of toxic epidermal necrolysis successfully treated with repeated i.v. immunoglobulin
Case of toxic epidermal necrolysis successfully treated with repeated i.v. immunoglobulin
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DOI：
10.1111/1346-8138.15356
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发表时间：
2020-04
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影响因子：
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通讯作者：
K. Tomii;T. Deguchi;T. Katsumi;Takeo Suzuki;A. Fujimoto;H. Miida;R. Abe
中科院分区：
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作者：
K. Tomii;T. Deguchi;T. Katsumi;Takeo Suzuki;A. Fujimoto;H. Miida;R. Abe
尊敬的编辑，中毒性表皮坏死松解症（TEN）是一种罕见的、危及生命的、主要由药物引起的皮肤粘膜反应，其特征是广泛的皮肤脱离。皮质类固醇和血浆置换已用于治疗TEN。静脉注射免疫球蛋白（IVIg）是目前的治疗选择;然而，结果一直相互矛盾。在这里，我们报告了一个案例，TEN成功地治疗反复IVIg联合皮质类固醇。一名67岁男性患者，皮肤和上唇出现弥漫性红斑和多发性糜烂（图1a）。红斑上的Nikolsky征阳性，表皮脱落超过体表面积的30%。患者在发病前1天接受了巴氨西林进行牙科治疗。常规实验室检查显示C反应蛋白（5.47 mg/dL）、血尿素氮（37 mg/dL）和肌酐（1.15 mg/dL）升高。支原体抗原阴性。单纯疱疹病毒抗体显示以前的感染模式。皮肤活检显示表皮下水疱伴全层表皮坏死（图1b）。根据这些结果，患者被诊断为TEN。尽管停用巴氨西林并给予类固醇脉冲治疗（甲基强的松龙1000 mg/天，连续3天），但皮肤病变加重。在入院第4天开始IVIg（400 mg/kg/天，连续5天），联合60 mg/天泼尼松龙。皮肤病变未改善;入院第9天，患者出现38.0°C发热伴菌血症。进行了广谱静脉注射抗生素和额外的IVIg。入院第10天，发热迅速消退，皮肤病变开始改善。泼尼松龙逐渐减少，在入院第38天上皮再生几乎完成（图1c）。药物诱导的淋巴细胞刺激试验（DLST）对巴氨西林呈阴性。未进行斑贴试验。我们使用重复IVIg，总剂量为4 g/kg，并联合皮质类固醇。尽管仅IVIg治疗TEN的疗效仍存在争议，但一项荟萃分析报告称，高剂量IVIg（总剂量>2 g/kg）联合皮质类固醇可缩短TEN的恢复时间。在这种情况下，最初的IVIg联合皮质类固醇是无效的;然而，重复IVIg导致了有利的结果，没有观察到不良事件。药物史表明，巴氨西林是TEN的原因;然而，DLST对巴氨西林呈阴性。因此，未明确确定TEN的原因（例如药物或细菌）。感染，如支原体或疱疹病毒，是TEN的一个众所周知的原因，感染相关的TEN也需要免疫抑制治疗。在本病例中，难以判断重复高剂量IVIg或抗生素给药是否改善了TEN的临床症状，因为在额外的IVIg和抗生素联合治疗后，表皮脱落的体表面积开始改善。此外，严重感染后循环中的IG水平急剧下降。我们的病人出现菌血症，可能受益于额外的IVIg。总之，重复IVIg治疗应被视为（a）
Dear Editor, Toxic epidermal necrolysis (TEN) is a rare, life-threatening, mostly drug-induced mucocutaneous reaction characterized by extensive skin detachment. Corticosteroids and plasma exchange have been used for the treatment of TEN. i.v. immunoglobulin (IVIg) is a current treatment option; however, the results have been conflicting. Here, we report a case of TEN successfully treated with repeated IVIg combined with corticosteroids. A 67-year-old man presented with diffuse erythema and multiple erosions on the skin and upper lip (Fig. 1a). Nikolsky’s sign was positive on the erythema, and epidermal detachment was more than 30% of the body surface area. The patient had received bacampicillin for dental treatment 1 day before the onset. Routine laboratory tests showed elevated C-reactive protein (5.47 mg/dL), blood urea nitrogen (37 mg/dL) and creatinine (1.15 mg/dL). Mycoplasma antigen was negative. Antibodies to herpes simplex virus showed a previous infection pattern. A skin biopsy indicated subepidermal blister with full-thickness epidermal necrosis (Fig. 1b). Based on these findings, the patient was diagnosed with TEN. Although bacampicillin was discontinued and steroid pulse therapy (methylprednisolone 1000 mg/day for 3 consecutive days) was administrated, the skin lesion exacerbated. IVIg (400 mg/kg per day for 5 consecutive days) was initiated on day 4 of admission combined with 60 mg/day prednisolone. The skin lesions did not improve; on day 9 of admission, the patient showed a fever of 38.0°C associated with bacteremia. Broad-spectrum i.v. antibiotics with additional IVIg was performed. The fever rapidly subsided and the skin lesions started to improve on day 10 of admission. Prednisolone was tapered and re-epithelization was nearly complete on day 38 of admission (Fig. 1c). Drug-induced lymphocyte stimulation tests (DLST) were negative for bacampicillin. Patch tests were not performed. We used repeated IVIg at a total dose of 4 g/kg combined with corticosteroid. While the efficacy of IVIg-only treatment for TEN is still controversial, a meta-analysis has reported that high-dose IVIg (total dose, >2 g/kg) combined with corticosteroid could reduce the recovery time for TEN. In this case, the initial IVIg combined with corticosteroid was not effective; however, repeated IVIg resulted in a favorable outcome, and no adverse event was observed. The drug history suggested that bacampicillin was the cause of TEN; however, DLST was negative for bacampicillin. Therefore, the cause of TEN (e.g. drug or bacteria) was not clearly determined. Infection, such as from Mycoplasma or herpesvirus, is a well-known cause of TEN, and infection-related TEN also requires immunosuppressive therapy. In the present case, it was difficult to judge whether a repeated high dose of IVIg or administration of antibiotics improved the clinical symptoms of TEN because the body surface area of epidermal detachment started to improve after additional combined IVIg and antibiotic therapy. Furthermore, circulating Ig levels after severe infection are dramatically diminished. Our patient presented with bacteremia and might have benefitted from additional IVIg. In conclusion, repeated IVIg therapy should be considered as a (a)