IgG4-related disease with extensive granulomatous changes
IgG4-related disease with extensive granulomatous changes
复制标题
伴有广泛肉芽肿改变的 IgG4 相关疾病
DOI：
10.1093/rheumatology/kex154
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Terada Y
中科院分区：
文献类型：
--
作者：
Taniguchi Y;Kawano M;Zen Y;Aoyama N;Terada Y
SIR，IgG4相关疾病(IgG4-RD)是一种相对较新的疾病，典型的特征是淋巴浆细胞性炎症、条带样纤维化和闭塞性静脉炎三位一体，免疫组织化学显示IgG4阳性浆细胞和IgG4/IgG比率为40%[1]。肉芽肿的存在通常排除了对IgG4-RD的诊断[2]。在此，我们描述了一例罕见的伴有广泛肉芽肿改变的IgG4-RD。一位61岁男性患者因颌下腺增大而住进本院。他以前从未接触过结核病、卡介苗疫苗和有机溶剂。一年前，CT平扫显示主动脉根部扩张至直径53 mm，但未见右肾积水。入院前五个月，他注意到右颌下腺增大。体格检查显示右颌下腺明显增大。18F-氟代脱氧葡萄糖(FDG)-PET/CT显示右侧颌下腺、主动脉根部外侧和邻近髂总动脉的病灶摄取增加(图1AD；箭头)。增强CT显示与部分主动脉根部周围的FDG摄取相对应的肿块病变(图1E，G；箭头)。增强CT和FDG-PET/CT均未显示肺门淋巴结病变。沿着髂总动脉的摄取对应于一个肿块，导致右侧输尿管梗阻和肾积水。实验室检查结果包括血清Ig G_4(198 mg/dl)、Ig G(1963 mg/dl)和Ig E(392.1 IU/ml)升高，肝功能正常，抗SS-A/Ro、SS-B/La抗体和ANCA阴性。颌下腺活检显示广泛的炎性浸润物，富含浆细胞，偶见淋巴滤泡(图1H和I)。还观察到闭塞性静脉炎(图1J)。免疫染色显示每个高倍视野有100多个含IgG4的浆细胞(图1K)，占IgG4/IgG阳性细胞比率的40%(图1L和M)。广泛的非坏死性肉芽肿改变，CD68阳性的朗汉斯型巨细胞，也可见于星状纤维化的背景(图1N和O)。结核分支杆菌Ziehl Neelsen染色和真菌Grocott染色均为阴性。没有淋巴瘤或脉管炎的证据。此外，从颌下腺组织中分离的结核分枝杆菌培养和聚合酶链式反应均为阴性。我们诊断为IgG4-RD伴有广泛的肉芽肿改变。患者口服强的松龙0.6 mg/kg，显著降低了IgG4-RD病变的CT显着性，并降低了血清IgG4和IgG。除了许多多核巨细胞和肉芽肿外，我们的病例在临床、血清学和组织病理学上表现为典型的IgG4-RD。对CS的良好反应与肉芽肿性传染病的可能性相矛盾，如结核病或ANCA相关性脉管炎，包括肉芽肿伴多血管炎。此外，结节病的关联也是不太可能的，因为包括主动脉周围和腹膜后的不寻常的器官分布。肉芽肿和MGCS在IgG4-RD中是罕见的，它们的存在以前使这种诊断变得非常不可能[2]。然而，最近报道了一些典型的IgG4-RD合并mGCS的病例[3，4]。其中一些人有肺结核或类风湿关节炎的病史，这表明对结核病或类风湿结节的免疫反应可能与疾病的发生有关。据认为，IL-4和干扰素是…的致病因子
SIR, IgG4-related disease (IgG4-RD) is a relatively newly described condition characterized classically by the triad of lymphoplasmacytic inflammation, storiform-type fibrosis and obliterative phlebitis, with prominence of IgG4-positive plasma cells and an IgG4/IgG ratio of> 40% on immunohistochemistry [1]. The presence of granulomas generally excludes the diagnosis of IgG4-RD [2]. Herein, we describe a markedly rare case of IgG4-RD associated with extensive granulomatous changes. A 61-year-old man was admitted to our hospital with enlargement of the submandibular glands. He had never had previous exposure to tuberculosis, Bacillus Calmette Gu erin vaccination and organic solvents. One year previously, non-contrast CT had shown dilatation of the aortic root to a diameter of 53 mm, but not right hydronephrosis. Five months before admission, he had noticed enlargement of the right submandibular gland. Physical examination demonstrated a palpably enlarged right submandibular gland. 18F-Fluorodeoxyglucose (FDG)-PET/CT revealed increased uptake in the right submandibular gland, around the outside of the aortic root and in foci adjacent to the common iliac arteries (Fig. 1A D; arrow). Contrast-enhanced CT demonstrated a mass lesion corresponding to the FDG uptake partly surrounding the aortic root (Fig. 1E G; arrow). Contrast-enhanced CT and FDG-PET/CT showed no hilar lymphadenopathy. The uptake along the common iliac arteries corresponded to a mass causing right ureteral obstruction and hydronephrosis. Laboratory results included elevated serum IgG4 (198mg/dl), IgG (1963mg/dl) and IgE (392.1 IU/ml), and showed normal hepatic function tests and negative tests for anti-SS-A/Ro, SS-B/La antibodies and ANCA. Submandibular gland biopsy demonstrated an extensive inflammatory infiltrate, rich in plasma cells with occasional lymphoid follicles (Fig. 1H and I). Obliterative phlebitis was also observed (Fig. 1J). Immunostaining revealed more than 100 IgG4-bearing plasma cells per high-power field (Fig. 1K) and> 40% of IgG4/IgG-positive cell ratio (Fig. 1L and M). Extensive non-necrotizing granulomatous changes with CD68-positive Langhans-type giant cells were also noted against the background of storiform fibrosis (Fig. 1N and O). Ziehl Neelsen staining for Mycobacterium tuberculosis and Grocott staining for fungus were negative. There was no evidence of lymphoma or vasculitis. Moreover, M. tuberculosis culture and PCR from submandibular gland tissue were negative. We diagnosed IgG4-RD with extensive granulomatous changes. The patient was treated with oral prednisolone 0.6 mg/kg, which dramatically reduced the prominence of the IgG4-RD lesions on CT and also lowered the serum IgG4 and IgG. Our case illustrated clinically, serologically and histopathologically typical IgG4-RD except for many multinucleated giant cells (MGCs) and granulomas. A good response to CS contradicted the possibility of a granulomatous infectious disease, such as tuberculosis or ANCA-associated vasculitis, including granulomatosis with polyangiitis. In addition, the association of sarcoidosis was also very unlikely because of the unusual organ distribution that included the periaorta and retroperitoneum. Granulomas and MGCs are exceptional in IgG4-RD, and their presence would previously have made this diagnosis very unlikely [2]. However, some cases with typical IgG4-RD accompanied by MGCs have been recently reported [3, 4]. Some of these had a history of tuberculosis or RA, indicating that immune reactions to tuberculosis or rheumatoid nodules might be related to the disease initiation. It is thought that IL-4 and IFN …