发生于特瑞普利单抗长期治疗后的大疱性类天疱疮二例

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例1女,63岁,全身皮疹2个月伴瘙痒,表现为红斑基础上水疱大疱。2年前因直肠肛管恶性黑素瘤行肠周淋巴结清扫术,静脉注射特瑞普利单抗预防性治疗1年,停药后2周出现全身皮疹。上肢红斑处皮损直接免疫荧光示,IgG沿基底膜带沉积;血清盐裂间接免疫荧光,IgG沿表皮侧线状沉积。血清酶联免疫吸附试验示,BP180 > 200 U/ml。诊断:大疱性类天疱疮,PD-1抑制剂引起?予口服米诺环素200 mg/d,醋酸泼尼松龙20 mg/d,配合全身外用卤米松乳膏,半个月后水疱结痂,红斑变暗。例2女,全身水疱伴痒3月余,皮疹表现为浮肿性红斑基础上紧张性水疱、大疱、血疱,伴结痂。患者有3年阴道恶性黑素瘤史,为阴道黑素瘤术后Ⅳ期,局部复发,右髂血管淋巴结转移。静脉注射特瑞普利单抗治疗2年后出现全身皮疹。红斑处直接免疫荧光,IgG弱阳性,沿基底膜带线状沉积;血清盐裂间接免疫荧光,IgG沿表皮侧线状沉积。血清BP180 > 200 U/ml。诊断:大疱性类天疱疮,PD-1抑制剂引起?予口服多西环素200 mg/d、醋酸泼尼松龙40 mg/d,2周后水疱完全结痂,红斑变暗。“,”Case 1, a 63-year-old female patient presented with blisters and bullae arising in erythema all over the body with itching for 2 months. Two years ago, the patient underwent peri-intestinal lymph node dissection for the treatment of malignant melanoma of the rectum and anal canal, and received intravenous injection of toripalimab for preventive treatment for 1 year, and generalized skin lesions occurred 2 weeks after drug withdrawal. Direct immunofluorescence testing of erythema on the upper extremities showed that immunoglobulin G (IgG) was deposited along the basement membrane zone; salt-split indirect immunofluorescence testing of a serum sample showed liner deposition of IgG in the epidermis. Enzyme-linked immunosorbent assay (ELISA) revealed that the serum level of anti-BP180 antibodies was over 200 U/ml. The patient was diagnosed with bullous pemphigoid, but it was doubtful whether the disease was caused by PD-1 inhibitor toripalimab or not. Then, the patient received oral minocycline at a dose of 200 mg/d and prednisolone acetate at a dose of 20 mg/d, and topically applied halometasone cream all over the body. After half-a-month treatment, the blisters crusted over and the erythema darkened in color. Case 2, a 36-year-old female patient presented with generalized blisters and itching for more than 3 months. The skin lesions manifested as tense blisters, bullae, bloody bullae and crusts on the edematous erythema. The patient had a 3-year history of vaginal malignant melanoma, which was stage Ⅳ postoperative melanoma with local recurrence and lymph node metastasis nearby the right iliac vessels. After 2-year treatment with intravenous injection of toripalimab, generalized skin lesions occurred all over the body. Direct immunofluorescence testing of the erythema showed weakly positive staining for IgG, and linear deposition of IgG along the basement membrane zone; salt-split indirect immunofluorescence testing of a serum sample showed liner deposition of IgG in the epidermis. ELISA revealed that the serum level of anti-BP180 antibodies was over 200 U/ml. The case 2 was diagnosed with bullous pemphigoid, but it was also doubtful whether the disease was caused by PD-1 inhibitor toripalimab or not. Then, the case 2 was treated with oral doxycycline at a dose of 200 mg/d and oral prednisolone acetate at a dose of 40 mg/d. After 2-week treatment, the blisters completely crusted over and erythema darkened in color.
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