Department of Dermatology, University of California Irvine, Irvine, CA, USA; Institute for Immunology and Departments of Dermatology and Biological Chemistry, University of California, Irvine, CA, USA.
Department of Dermatology, University of California Irvine, Irvine, CA, USA.
Autoimmun Rev. 2018 Oct;17(10):1002-1010. doi: 10.1016/j.autrev.2018.04.008. Epub 2018 Aug 11.
Paraneoplastic autoimmune multiorgan syndrome (PAMS) is characterized by a heterogenous group of signs and symptoms including severe desquamative stomatitis, a polymorphous cutaneous eruption, humoral immunity against plakin proteins, contribution of cell-mediated autoimmunity and commonly a progressive respiratory failure. Autoantibodies in PAMS target a wide array of antigens including plakins, cadherins, alpha-2-macroglobulin like 1 (A2ML1), BP180, plakophilin-3, and several neuromuscular antigens. Originally described as paraneoplastic pemphigus in 1990 due to some of its clinical and immunologic similarities to classic pemphigus (pemphigus vulgaris and pemphigus foliaceus), PAMS is a multiorganopathy with several distinct features from these classic forms of pemphigus. Epidemiologically, PAMS is associated with underlying neoplasia and has a differing HLA-II allele predisposition compared to classic forms of pemphigus. Clinically, lesion morphology is polymorphous, and lesion distribution fundamentally differs from that seen in classic pemphigus. PAMS has a significantly higher mortality rate and a poorer response to treatments typically effective in pemphigus. Histologically, PAMS is characterized by the presence of interface dermatitis, vacuolar changes, and dyskeratotic keratinocytes which are not seen in classic pemphigus. PAMS demonstrates not only intercellular IgG as seen in classic pemphigus, but the presence of linear basement membrane zone deposition. Antibodies against desmoglein 3 (Dsg3) map to a broader array of epitopes than in pemphigus vulgaris and there is a higher prevalence of complement binding anti-Dsg3 IgG autoantibodies in PAMS. Autoantibodies can in rare cases be absent in the more cell-mediated form of PAMS. Considering these numerable differences, we review the entity of PAMS, and provide similarities and differences to classic forms of pemphigus.
副肿瘤自身免疫性多器官综合征 (PAMS) 的特征是一组异质的体征和症状，包括严重的剥脱性口炎、多形性皮肤疹、针对桥粒蛋白的体液免疫、细胞介导的自身免疫的贡献，以及通常进行性呼吸衰竭。PAMS 中的自身抗体针对包括桥粒蛋白、钙黏蛋白、α-2-巨球蛋白样蛋白 1（A2ML1）、BP180、桥粒斑蛋白-3 和几种神经肌肉抗原在内的广泛抗原。最初于 1990 年因其某些临床和免疫学特征类似于经典天疱疮（寻常型天疱疮和落叶型天疱疮）而被描述为副肿瘤性天疱疮，PAMS 是一种多器官疾病，与这些经典形式的天疱疮有几个明显不同的特征。在流行病学上，PAMS 与潜在的肿瘤有关，与经典形式的天疱疮相比，具有不同的 HLA-II 等位基因易感性。临床上，病变形态多形性，病变分布与经典天疱疮完全不同。PAMS 的死亡率显著更高，对天疱疮通常有效的治疗反应更差。组织学上，PAMS 的特征是存在界面性皮炎、空泡化和角化不良的角质形成细胞，这些在经典天疱疮中不存在。PAMS 不仅表现为经典天疱疮所见的细胞间 IgG，还存在线性基底膜带沉积。与寻常型天疱疮相比，针对桥粒芯糖蛋白 3（Dsg3）的抗体映射到更广泛的表位，并且在 PAMS 中存在更高的补体结合抗 Dsg3 IgG 自身抗体的患病率。在更具细胞介导形式的 PAMS 中，自身抗体在罕见情况下可能不存在。考虑到这些无数的差异，我们回顾了 PAMS 的实体，并提供了与经典形式的天疱疮的相似性和差异。
