A new clinical variant of acquired reactive perforating dermatosis-like bullous pemphigoid
A new clinical variant of acquired reactive perforating dermatosis-like bullous pemphigoid
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获得性反应性穿孔性皮肤病样大疱性类天疱疮的新临床变型
DOI：
10.1111/bjd.17146
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发表时间：
2018
影响因子：
10.3
通讯作者：
Kiritsi D.
中科院分区：
文献类型：
--
作者：
Schauer F.;Kern J.S.;Virtic O.;Technau-Hafsi K.;Meiss F.;Thoma K.;Athanasiou I.;Sitaru C.;Di Zenzo G.;Izumi K.;Nishie W.;Shimizu H.;Bruckner-Tuderman L.;Kiritsi D.
亲爱的编辑：大疱性类天疱疮(BP)是一种与循环中抗BP180/XVII胶原自身抗体有关的起泡性疾病。作为前驱期的一部分，患者可能会出现湿疹皮损或红斑丘疹和瘙痒或荨麻疹样红斑，但没有任何水泡。1最近的研究描述了4例合并BP的类似获得性反应性穿孔皮肤病(ARPD)的临床特征。2、3他们最初表现为丘疹和结节，中央角化斑块，糖尿病(DM)和血液透析被认为是病因。他们后来才出现点状水泡，BP180自身抗体被发现结合在真皮-表皮交界区(DEJZ)。我们在这里描述五个以前没有报道的患者，他们的症状在临床和组织学上类似于ARPD，同时也被诊断为BP。所有患者年龄均在70岁以上，并伴有多种疾病，除患者1外，其余均为女性。他们都有高血压；患者3和4也有心房颤动，而患者1和3也有2型糖尿病并有糖尿病肾病的迹象。患者2在11年前有乳腺癌缓解期病史。我们发现IgE水平升高，血中嗜酸性粒细胞计数升高。患者1-4有突然剧烈瘙痒的病史，并有丘疹和结节，中央有角化斑块，无任何水泡(图1B)。患者5在发病前245个月出现典型的BP，伴有大的荨麻疹斑块和覆盖其被膜大部分的水泡(图1B)。在诊断出BP后，她接受了丙酸氯倍他索软膏、全身强的松龙和霉酚酸酯的局部治疗。她的治疗反应迅速，瘙痒减轻，皮损愈合。六周后，她再次出现，现在是ARPD照片，她的腿、背部和上臂上有中央角化栓子的丘疹病变(图1B)。在患者1-4的丘疹和结节的活检中，组织病理学显示，表皮呈杯状凹陷，充满坏死性碎片，真皮和表皮之间的胶原束垂直穿透，真皮中性粒细胞渗入(图1C)。这代表了反应性穿孔胶原病(RPC)的组织病理学特征。4仅在患者5的皮肤活检中，首发起水泡，发现真皮下皮肤劈裂，有致密的嗜酸性细胞浸润物和真皮水肿。所有病例均在首次发病时进行了直接免疫荧光检查。免疫球蛋白和补体C3c在DEJZ呈典型的线性沉积。间接免疫荧光显示，所有患者的水泡顶端均有免疫球蛋白沉积(图1a)。针对BP180全长形式的自身抗体的存在最近被认为与非炎症性BP表型有关，并伴有少许嗜酸性粒细胞浸润。5识别NC16A结构域的酶联免疫吸附试验在患者1、3和4中未检测到BP180自身抗体，但患者1和3有针对全长BP180的自身抗体(数据可供索取)。患者2和4也有BP230抗体。免疫球蛋白E自身抗体与BP严重程度的增加有关。我们分析了血清中抗BP180和BP230的IgE自身抗体，发现病例2和4中有低水平的BP230自身抗体，而病例5中有低水平的BP180和BP230自身抗体。为了研究自身抗体在这些患者中的致病潜力，我们使用了先前描述的体外试验(图可应要求提供)。6…的BP治疗
DEAR EDITOR, Bullous pemphigoid (BP) is a blistering disorder associated with circulating autoantibodies against BP180/collagen XVII. As part of a prodromal stage, patients might present with eczematous lesions or erythematous papules and prurigoor urticaria-like erythema without any blistering. 1 Recent studies described four patients with clinical features resembling acquired reactive perforating dermatosis (ARPD) coexisting with BP. 2, 3 They initially presented with papules and nodules with a central keratotic plaque, with diabetes mellitus (DM) and haemodialysis thought to be causative. They developed point blisters only later, and BP180 autoantibodies were found to bind at the dermoepidermal junction zone (DEJZ). We here describe five previously unreported patients whose symptoms clinically and histologically resembled ARPD with simultaneous BP diagnosis. All patients were over 70 years of age with several concomitant disorders, and all except patient 1 were female. They all had hypertension; patients 3 and 4 also had atrial fibrillation, whereas patients 1 and 3 also had type II DM with signs of diabetic nephropathy. Patient 2 had a history of breast cancer in remission, 11 years prior. We found elevated IgE levels and an elevated blood eosinophil count. Patients 1–4 presented with a history of sudden severe itch and generalized papules and nodules with a central keratotic plaque without any blisters (Fig. 1b). At presentation, patient 5 had characteristic BP with large urticarial plaques and blisters covering large parts of her integument, which had developed 245 months earlier (Fig. 1b). After the diagnosis of BP, she received topical treatment with clobetasol propionate ointment, systemic prednisolone and mycophenolate mofetil. She showed quick treatment response with reduced itch and healing of lesions. Six weeks later she presented again, now with the ARPD picture of papular lesions with central keratotic plugs on her legs, back and upper arms (Fig. 1b). In the biopsies taken from the papules and nodules in patients 1–4, the histopathology showed a cup-shaped invagination of the epidermis filled with necrotic debris and vertically penetrating collagen bundles between dermis and epidermis with a dermal neutrophilic infiltrate (Fig. 1c). This represents the histopathological hallmark of reactive perforating collagenosis (RPC). 4 Solely in the skin biopsy of patient 5, with blistering at initial presentation, subepidermal skin cleavage with dense eosinophilic infiltrate and dermal oedema was found. Direct immunofluorescence was performed in all cases at first presentation. It showed the typical linear deposition of IgG and C3c at the DEJZ. The indirect immunofluorescence showed IgG deposition on the blister roof, also in all patients (Fig. 1a). The presence of autoantibodies against the full-length form of BP180 has recently been linked to a noninflammatory BP phenotype, accompanied by scant lesional eosinophilic infiltration. 5 Enzyme-linked immunosorbent assay recognizing the NC16A domain did not detect BP180 IgG autoantibodies in patients 1, 3 and 4, but patients 1 and 3 had autoantibodies against the full-length BP180 (data available on request). Patients 2 and 4 also had BP230 antibodies. IgE autoantibodies are associated with increased BP severity. We analysed the sera for IgE autoantibodies to BP180 and BP230 and found lowlevel BP230 IgE autoantibodies in cases 2 and 4, while case 5 had low-level BP180 and BP230 IgE autoantibodies. To investigate the pathogenic potential of autoantibodies in these patients, we have used a previously described ex vivo assay (figure available on request). 6 The BP treatment …