Diffuse biphasic cutaneous amyloidosis in an HCV‐seropositive patient: another extrahepatic manifestation of HCV infection?
Diffuse biphasic cutaneous amyloidosis in an HCV‐seropositive patient: another extrahepatic manifestation of HCV infection?
复制标题
HCV 血清阳性患者的弥漫性双相皮肤淀粉样变性：HCV 感染的另一种肝外表现？
DOI：
10.1111/j.1742-1241.2005.00542.x
复制
发表时间：
2005
影响因子：
2.6
通讯作者：
A. Tuncel
中科院分区：
文献类型：
--
作者：
Z. Erbagci;S. Erkilic;A. Tuncel
淀粉样变性是一大类蛋白质错误折叠疾病，其中纤维状蛋白质淀粉样蛋白沉积在细胞外组织和器官中。原发性皮肤淀粉样变性（PCA）分为黄斑、丘疹（苔藓样）和结节性淀粉样变性。黄斑和苔藓样病变共存称为双相淀粉样变性（BA）。弥漫性BA非常罕见，主要在东南亚报道（1）。HCV感染与多种肝外表现相关，包括自身免疫性甲状腺炎、淋巴细胞性涎腺炎、膜增生性肾小球肾炎、混合性冷球蛋白血症、白细胞破碎性血管炎、扁平苔藓和迟发性皮肤卟啉症（2）。迄今为止，尚未报告与PCA相关的HCV病例。我们提出了一个白人的情况下，广泛的BA与慢性非活动性丙型肝炎谁对IFN-α反应良好。一位75岁男性，有10年的进行性色素沉着病史，随后出现瘙痒和逐渐发展的大量坚硬丘疹。检查发现广泛的灰褐色色素沉着过度，口腔粘膜、手掌和脚掌除外，大量角化过度性丘疹主要位于四肢、背部、腹部、腰骶部和臀肌的伸肌面。两种类型的病变累及下肢最严重，但膝关节幸免于难。在胫骨前部苔藓样丘疹中有色素脱失的萎缩区（图1）。除先天性脊柱后凸外，其余检查结果均正常。黄斑和丘疹病变的组织学检查显示角化过度、颗粒增多、不规则棘皮症、色素失禁、浅表血管周围淋巴细胞浸润和扩张的真皮乳头中结晶紫和刚果红染色的球形均匀嗜酸性沉积物。在属于丘疹的标本中变化更明显。免疫组化显示，淀粉样蛋白沉积物与单克隆抗角蛋白抗体如AE 1识别低分子角蛋白肽K10，14，15，16和19反应。包括生化特征、ESR、尿液分析、凝血试验、血清PTH、T3、T4、TSH、补体和免疫球蛋白水平的分析显示正常结果。血清蛋白电泳显示无单克隆峰。血清学检查抗-HCV、HCV-RNA阳性，HBsAg、抗-HBs、抗-HBc IgM、HIV-1、HIV-2抗体、类风湿因子、抗核抗体、抗平滑肌抗体、抗甲状腺抗体、抗肝抗体、抗肾抗体、抗DNA抗体阴性。进一步的调查显示，12年前因交通事故输血的历史。用原位杂交技术在病变皮肤切片中不能检测到HCV复制。考虑到患者的年龄，未计划针对非活动性HCV感染的特异性治疗。患者最初接受口服抗组胺药、局部皮质类固醇治疗，并在胫骨上进行闭塞性覆盖，但无有益效果。每周三次的系统UVB治疗3个月也没有改善。随后患者暂时失访。后来我们再次见到他，得知他在一家私人诊所接受了300万单位的IFN-α，每周三次，持续6个月。有趣的是，这种治疗产生了显着的消退色素沉着斑和他的瘙痒沿着与HCV的血清转换，而丘疹病变通常持续。背部皮肤的对照活检显示没有淀粉样蛋白沉积。PCA的发病机制尚未完全了解。慢性皮肤刺激，导致过度变性角蛋白产生，随后转化为淀粉样沉积物，已被认为是一个病因因素（3）。这些类型的淀粉样变性中的淀粉样沉积物被认为是源自凋亡的基底角质形成细胞的变性角蛋白，因为它们含有巯基并与角蛋白抗体结合。最近的免疫组织化学研究显示，角蛋白抗原决定簇与角蛋白抗体的淀粉样沉积物呈阳性染色（4）。多种因素可能导致角质形成细胞变性，导致淀粉样蛋白形成，包括反复局部机械创伤。Gecit 1. No：1/5，27090加济安泰普，Turkey传真：8990 342 3601617电子邮件：zerbagci@yahoo.com
The amyloidoses are a large group of protein-misfolding diseases in which a fibrillar protein amyloid is deposited in extracellular tissues and organs. Primary cutaneous amyloidosis (PCA) is classified as macular, papular (lichenoid) and nodular amyloidosis. Coexistence of macular and lichenoid lesions is termed as biphasic amyloidosis (BA). Diffuse BA is very rare and mostly reported from Southeast Asia (1). HCV infection is associated with various extrahepatic manifestations including autoimmune thyroiditis, lymphocytic sialadenitis, membranoproliferative glomerulonephritis, mixed cryoglobulinemia, leukocytoclastic vasculitis, lichen planus and porphyria cutanea tarda (2). No case of HCV in association with PCA has been reported up to date. We present a Caucasian case of widespread BA in association with chronic inactive hepatitis C who responded well to IFN-a. A 75-year-old man presented with a 10-year history of progressive hyperpigmentation, followed by itching and gradual development of numerous firm papules. Examination revealed extensive grey-brown hyperpigmentation sparing oral mucosa, palms and soles and numerous hyperkeratotic papules located mainly on the extensor aspects of extremities, back, abdomen, lumbosacral regions and glutea. The lower extremities were most severely involved by two types of lesions, but the knees were spared. There were depigmented atrophic areas among the lichenoid papules on the anterior aspects of the shins (Figure 1). Remaining findings were normal except congenital kyphoscoliosis. Histological examinations of macular and papular lesions revealed hyperkeratosis, hypergranulosis, irregular acanthosis, pigment incontinence, superficial perivascular lymphocytic infiltrate and globular homogeneous eosinophilic deposits stained with crystal violet and Congo red in the expanded dermal papillae. Changes were more pronounced in the specimen belonging to a papule. Immunohistochemistry revealed that amyloid deposits reacted with monoclonal antikeratin antibodies like AE1 recognising low molecular keratin peptides K10, 14, 15, 16 and 19. Analyses including biochemical profile, ESR, urine analysis, coagulation tests, serum PTH, T3, T4, TSH, complement and immunoglobulin levels showed normal results. No monoclonal spike was demonstrated by serum protein electrophoresis. Serological investigations revealed that anti-HCV and HCV-RNA were positive, whereas HBsAg, anti-HBs, anti-HBc IgM, HIV-1, HIV-2 antibodies, rheumatoid factor, cryoglobulins, and antinuclear, antismooth muscle, antithyroid, anti-liver, anti-kidney and anti-DNA antibodies were negative. Further interview revealed a history of blood transfusion because of a traffic accident 12 years ago. HCV replication could not be detected in lesional skin sections by in situ hybridisation technique. Considering the age of the patient, no specific therapy for inactive HCV infection was planned. The patient was initially treated with oral antihistamines, topical corticosteroids with occlusive covering on the shins without beneficial effects. Systemic UVB therapy thrice weekly for 3 months also yielded no improvement. The patient was then temporarily lost to follow-up. We later saw him again and learned that he had received 3 million units of IFN-a thrice weekly for 6 months in a private clinic. Interestingly, this therapy yielded a significant regression in hyperpigmented macules and his pruritus along with seroconversion of HCV while papular lesions generally persisted. A control biopsy from the back skin showed no amyloid deposits. The pathogenesis of PCA is not well understood. Chronic cutaneous irritation, causing excessive degenerate keratin production with subsequent conversion into amyloid deposits, has been proposed to be an aetiologic factor (3). Amyloid deposits in these types of amyloidosis are thought to be derived from degenerate keratins of apoptotic basal keratinocytes, as they contain sulfhydryl groups and bind to keratin antibodies. Recent immunohistochemical studies showed keratin epitopes with a positive staining of amyloid deposits with antibodies to keratin (4). Various factors may be responsible for keratinocyte degeneration leading to amyloid formation later, including repeated localised mechanical traumas Correspondence to: Dr Zülal Erbagci, Gazimuhtarpasa Bulvari. Gecit 1. No: 1/5, 27090 Gaziantep, Turkey Fax: þ 90 342 3601617 Email: zerbagci@yahoo.com