Anhalt G J, Kim S C, Stanley J R, Korman N J, Jabs D A, Kory M, Izumi H, Ratrie H, Mutasim D, Ariss-Abdo L
Department of Dermatology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
N Engl J Med. 1990 Dec 20;323(25):1729-35. doi: 10.1056/NEJM199012203232503.
We describe five patients with underlying neoplasms in whom painful mucosal ulcerations and polymorphous skin lesions developed, usually with progression to blistering eruptions on the trunk and extremities. Histologic examination showed vacuolization of epidermal basal cells, keratinocyte necrosis, and acantholysis. Immunofluorescence testing revealed atypical pemphigus-like autoantibodies in perilesional epithelium and serum from all five patients. We studied the antigenic specificities of the autoantibodies by indirect immunofluorescence and immunoprecipitation, using extracts of 14C-labeled human keratinocytes. IgG purified from the serum of one patient was passively transferred to four neonatal mice to test for pathogenicity.
Immunofluorescence testing showed that the autoantibodies bound to the surface of tissues containing desmosomes, including complex and simple epithelia, and myocardium. An identical and unique complex of four polypeptides with molecular weights of 250, 230, 210, and 190 was immunoprecipitated by all serum samples. The 250-kd polypeptide comigrated with desmoplakin I (a protein found in the desmosomes of all epithelia), and the 230-kd antigen comigrated with the antigen of bullous pemphigoid. Cutaneous blisters, a positive Nikolsky's sign, and epidermal and esophageal acantholysis developed in all mice into which the autoantibody was injected. Electron microscopy showed epidermal acantholysis similar to lesions of experimentally induced pemphigus vulgaris.
These five patients with cancer had a novel acantholytic mucocutaneous disease characterized by autoantibodies that were pathogenic after passive transfer. The autoantibodies from these patients reacted with an antigen complex composed of desmoplakin I and the 230-kd antigen of bullous pemphigoid and two as yet unidentified epithelial antigens. We suggest the term "paraneoplastic pemphigus" for this disease.
我们描述了5例患有潜在肿瘤的患者，他们出现了疼痛性黏膜溃疡和多形性皮肤损害，通常进展为躯干和四肢的水疱性皮疹。组织学检查显示表皮基底细胞空泡化、角质形成细胞坏死和棘层松解。免疫荧光检测显示，所有5例患者的病损周围上皮和血清中均存在非典型类天疱疮样自身抗体。我们使用14C标记的人角质形成细胞提取物，通过间接免疫荧光和免疫沉淀研究了自身抗体的抗原特异性。从1例患者血清中纯化的IgG被动转移至4只新生小鼠以检测其致病性。
免疫荧光检测显示，自身抗体与含有桥粒的组织表面结合，包括复层和单层上皮以及心肌。所有血清样本均免疫沉淀出一种由分子量为250、230、210和190的4种多肽组成的相同且独特的复合物。250kd多肽与桥粒斑蛋白I（一种存在于所有上皮桥粒中的蛋白质）迁移率相同，230kd抗原与大疱性类天疱疮抗原迁移率相同。注射自身抗体的所有小鼠均出现皮肤水疱、尼氏征阳性以及表皮和食管棘层松解。电子显微镜显示表皮棘层松解类似于实验性寻常型天疱疮的病变。
这5例癌症患者患有一种新型棘层松解性黏膜皮肤疾病，其特征为自身抗体在被动转移后具有致病性。这些患者的自身抗体与一种由桥粒斑蛋白I、大疱性类天疱疮的230kd抗原以及另外两种尚未鉴定的上皮抗原组成的抗原复合物发生反应。我们建议将这种疾病命名为“副肿瘤性天疱疮”。
