IgG4-related dacryoadenitis

A 44-year-old female presented with bilateral eyelid swelling and painless, palpable mass over the lacrimal gland area for more than 1 year. A bilateral enlarged lacrimal gland with mild contrast enhancement was noted on computed tomography. Biopsy of the lacrimal gland showed lymphoplasmacytic infiltrate with focal hyaline and sclerotic change, and immunohistochemical staining revealed numerous IgG4-positive plasma cells, which was characteristic of IgG4 dacryoadentitis. Serum IgG and IgG4 levels were within normal range. The patient was treated with surgical excision instead of systemic steroid owing to poor tolerance. No tumor recurrence or systemic involvement was noted during the follow-up period. Our case highlights the importance of IgG4 dacryoadenitis in differentiating bilateral lacrimal gland inflammatory conditions. A normal serum IgG4 level does not rule out the diagnosis and surgical excision may be an alternative for those who are considered ineligible for corticosteroid treatment.     

以眼球运动障碍为首要表现的IgG4相关疾病的临床特征

目的 总结以眼球运动障碍为首要表现的IgG4相关疾病(IgG4-RD)的临床特征。设计 回顾性病例系列。研究对象 2020年12月至2021年12月北京同仁医院以眼球运动障碍为首要表现的IgG4-RD患者8例。方法 回顾患者的病历资料,包括眼位、眼球运动障碍方向、血清IgG4水平、眼眶磁共振成像(MRI)眼外肌表现、病理检查结果 、治疗方案等。主要指标 临床表现、眼眶MRI及病理结果 。结果 8例(100%)患者均表现为眼球运动障碍,其中外展受限87.5%、上转受限75.0%、下转受限37.5%、内收受限37.5%;视力下降5例(62.5%),头痛/眼痛3例(37.5%)。眼眶MRI显示局限性眼上肌群和外直肌增粗伴强化2例(25.0%),局限性眼上肌群和外直肌受压2例(25.0%),弥漫性眼外肌群增粗伴强化3例(37.5%),眼外肌正常但颅脑MRI示脑膜增厚伴强化1例(12.5%)。患者均合并神经系统外部位受累,表现为泪腺增大5例(62.5%)、鼻窦黏膜增生肥厚4例(50.0%)、淋巴结反应性增生4例(50.0%)。眼眶肿物、鼻窦黏膜、胸腺组织病理中均可见大量IgG4阳性浆细胞,伴组织...     

IgG4-related ophthalmic disease

IgG4-related disease is a fibro-inflammatory condition with tendency to form tumors with inflammatory infiltrate with IgG4 rich plasma cells and elevation of IgG4 level in serum, which may affect virtually every organ and tissue in the organism. IgG4-related ophthalmic disease may present as dacryoadenitis, myositis, other orbital tissues, hypophysitis or pachymeningitis causing cranial neuropathies. The diagnosis of IgG4-related disease is based on a typical clinical scenario, supportive laboratory data, expected radiological characteristics and distinct histopathological and immunohistochemical features. Corticosteroid followed by the use of long-term immunosuppressive therapy is the most commonly attempted treatment.     

Clinical features and outcomes of IgG4-related idiopathic orbital inflammatory disease: from a large southern China-based cohort

PurposeTo investigate the clinical features and treatment outcomes of IgG4-related ophthalmic disease (IgG4-ROD) among idiopathic orbital inflammatory disease (IOID) patients.MethodsThe medical records of 165 biopsy-proven IOID patients were retrospectively reviewed. Biopsy specimens were immunostained to detect IgG4 and IgG, and data regarding the clinicopathologic features, treatment outcomes, and recurrence were analyzed.ResultsAmong the 165 IOID patients enrolled, 100 (60.6%) were histopathologically IgG4-positive. The IgG4-positive patients had a lower rate of painful swelling or mass (17.0% versus 33.8%, p = 0.013), a longer symptom duration (p = 0.070), and a lower proportion of eyelid hyperemia (39.0% versus 58.5%, p = 0.014) than the IgG4-negative patients. Increased Ki-67 expression (15.02 ± 6.86%, p < 0.001) was observed in the IgG4-positive patients with characteristic pathological manifestations (more lymphocyte infiltration, nodular plasma cell infiltration, and follicular hyperplasia). IgG4-positive group had a higher recurrence rate in the subgroup of patients treated with surgery plus oral glucocorticoids (p = 0.046), and combined radiotherapy group has a higher cumulative proportion with recurrence (p = 0.011).ConclusionOver 60% of biopsy-proven IOID were classified as IgG4-ROD with a stronger proliferation potential. Additional radiotherapy after surgical debulking with oral corticosteroids still has a higher relapse rate, and more effective treatments are needed to prevent recurrence.Subject terms: Autoimmune diseases, Lacrimal apparatus diseases, Autoimmune diseases, Lacrimal apparatus diseases     

IgG4相关性疾病眼部病变的临床及影像学特征分析

目的 探讨IgG4相关性疾病眼部病变的临床及影像学特征。设计 回顾性病例系列。研究对象 25例在2010年10月-2014年5月期间首诊于眼科并经实验室和（或）活组织检查证实的IgG4相关性疾病患者。方法 回顾性分析25例患者眼部病变的临床及影像学表现。主要指标 临床表现,眼眶MRI,生长抑素受体SPECT/CT显像（SRS）。结果 25例患者双眼睑肿胀、眼球突出为主要临床表现,其中23例为双眼受累,22例患者有≥2个器官受累,眼外受累器官多见于鼻部（19例）和涎腺（13例）。眼眶MRI主要表现为弥漫性泪腺增大（22例）、眼外肌增粗（14例）、眶周软组织浸润（10例）等。SRS显示治疗前眼眶摄取示踪剂显著增高（UR=1.87±0.43）;经免疫抑制治疗后活动期眼眶示踪剂摄取减少（UR=1.51±0.24）。结论 IgG4相关性疾病的眼部病变具有较典型的临床特征,泪腺弥漫性增大为眼眶MRI最常见表现,SRS能客观反映受累眼眶的免疫活动程度,对临床疗效评价有较好的价值。 （眼科,2015, 24： 309-312）       

IgG4相关性眼病研究进展

IgG4相关性眼病是一种与IgG4密切相关的慢性系统性疾病,是以血清IgG4水平升高及IgG4阳性浆细胞浸润泪腺、眼外肌、眶下神经等眼部附属器为特征,而且经常是全身系统性病变的首发症状.糖皮质激素对该病治疗有效.本文就近年来IgG4相关性眼病的病因发病机制,临床表现,诊断及治疗方面的最新进展进行综述.     

IgG4相关性眼病研究进展

IgG4相关性疾病是一种近几年才被认识的疾病,病因尚不明确。以同时或逐步出现的一种或多种组织和器官中大量IgG4阳性淋巴浆细胞浸润、席纹状纤维化、闭塞性静脉炎为特征,可伴有血清IgG4水平升高。当累及眼部时称为IgG4相关性眼病。任何眼附属器均可受累,多见于泪腺、眼眶脂肪、眶下神经、眼外肌和眼睑。本文将对近年来IgG4相关性眼病的流行病学特点、病理特点、临床表现、影像特点、诊断和治疗方面的最新进展作一综述。     

Orbital Inflammation in IgG4-related Sclerosing Disease

IgG4-related sclerosing disease is a recently described systemic inflammatory disease that should be considered when evaluating patients with nonspecific orbital inflammation (pseudotumor). Orbital biopsy is necessary to establish a diagnosis and demonstrates lymphoplasmacytic infiltration, fibrosis, obliterative phlebitis of medium and small veins, and variable degrees of eosinophilia. We report the clinical and histopathological findings of 2 patients who developed chronic orbital inflammation as a manifestation of IgG4-related sclerosing disease. The 2 cases illustrate the widely varying clinical characteristics of this elusive disease.     

Co-existing ligneous conjunctivitis and IgG4-related disease

Herein, we elucidate that ligneous conjunctivitis (LC) was proved as an IgG4-related disease (IgG4-RD) by a series of pathologic studies from primary and recurrent episodes of an LC patient. LC was diagnosed based on clinical presentation and pathological appearance; furthermore, combined with serological examination and immunohistochemical study, the case also conformed to the diagnosis of IgG4-RD. The IgG4-RD, broadly discussed in recent times, is an idiopathic disease entity with tissue fibrosis possibly involving multiple organs. To the best of our knowledge, IgG4-RD has never been reported with LC. By reporting the clinical course and literature review, we should pay attention to the association between these two diseases.Key words: IgG4, IgG4-related disease, ligneous conjunctivitisLigneous conjunctivitis (LC) is a rare form of chronic conjunctivitis characterized by a fibrinous pseudomembrane on the conjunctiva and the development of firm fibrin-rich, woody pseudomembranous lesions mainly on the tarsal conjunctivae.[1] Similar lesions may also involve extra-ocular mucosa such as the gingiva, ear, upper and lower respiratory tracts, renal collecting system, or female genital tract.[1]The IgG4-related disease (IgG4-RD) is an idiopathic disease entity with tissue fibrosis possibly involving multiple organs. It is characterized by elevated serum IgG4 concentrations and tissue infiltration by IgG4-positive plasma cells, accompanied by tissue fibrosis and sclerosis.[2] IgG4-RD has been broadly discussed in recent times, with a rapidly increasing understanding of the disease and its causes.In this case report, we show that LC may be an IgG4-RD based on the ocular pathological findings, clinical presentation, and serological tests.     

Orbital inflammation in IgG4-related sclerosing disease

IgG4-related sclerosing disease is a recently described systemic inflammatory disease that should be considered when evaluating patients with nonspecific orbital inflammation (pseudotumor). Orbital biopsy is necessary to establish a diagnosis and demonstrates lymphoplasmacytic infiltration, fibrosis, obliterative phlebitis of medium and small veins, and variable degrees of eosinophilia. We report the clinical and histopathological findings of 2 patients who developed chronic orbital inflammation as a manifestation of IgG4-related sclerosing disease. The 2 cases illustrate the widely varying clinical characteristics of this elusive disease.     

IgG4相关性眼眶病一例

患者,男,62岁,因“左眼肿胀不适1年余”于2016年5月23日入院。1年前患者自觉左眼肿胀不适,伴有轻微眼球突出,无眼红、眼痛,无视物模糊及复视,无流涕、涕血,无发热等全身症状。之后症状逐渐加重,未诊治。既往无相关眼部病史,有高血压、糖尿病史5年,冠心病史1年,发现肝功能异常1年,曾于内科行保肝治疗。眼科专科检查：双眼裸眼视力均为0 LogMAR;眼压：右眼15 mmHg（1 mmHg=0.133 kPa）,左眼16 mmHg;左眼眶周肿胀轻,眶周未扪及明显肿物,指测眶压T+1,左眼球外上移位,较对侧眼突出约2 mm,左眼向内下运动轻度受限,其余方向无明显受限;左眼球结膜无充血水肿,角膜透明,其余前节及眼底检查未见明显异常。眼眶CT检查结果示：左眼眶内下方软组织影,大小约32 mm×17 mm,近椭圆形,边界欠清,与内直肌和下直肌粘连,下直肌增粗,左侧筛窦软组织影,眼球大小形态未见明显异常（见图1）。肺部CT平扫示：双肺气肿,左肺片絮状影,考虑炎症,右肺上叶、中叶条索状影。生化检查：总胆红素21.10 µmol/l,直接胆红素4.40 µmol/l,血糖7.01 mmol/l。C-反应蛋白正常。甲状腺功能检查示促甲状腺激素、游离甲状腺素、抗甲状腺球蛋白抗体均正常。 患者于2016年5月25日在全身麻醉下经鼻内镜筛窦纸板径路行左侧眶内肿瘤切除及鼻内镜下左侧筛窦开窗术,术中可见肿瘤源于眼眶软组织,向鼻下方突出压迫筛窦,紫红色,质软,较韧,有包膜,与内直肌及周边组织粘连明显,给予钝性分离,完整摘除肿瘤,并给予压迫止血,肿物大小约33 mm×15 mm×10 mm（见图2）。术后组织病理学检查显示病变组织为纤维结缔组织慢性炎症,纤维组织增多,小血管增生,病变组织内见大量淋巴细胞、浆细胞、嗜酸性粒细胞浸润,可见淋巴滤泡（见图3）。免疫组织化学检查显示IgG阳性（见图4）,IgG4+/IgG+＞40%,IgG4+细胞50~60个每高倍视野。诊断为IgG4相关性眼眶病（IgG4-related orbital disease,IgG4-ROD）。术后视力、眼压均正常,于术后第7天出院,出院后继续给予口服糖皮质激素40 mg每日晨起顿服,每2周减10 mg,维持量5 mg,逐渐停药,治疗3个月,定期复诊观察4个月,肿物未复发,未见其他相关自身免疫性疾病的发生。 讨论：IgG4相关性疾病（IgG4-related disease,IgG4-RD）是一种以大量IgG4淋巴细胞浸润为特征的全身免疫系统性疾病[1]。IgG4-ROD是指累及眼眶组织的IgG4相关性疾病,其具有一系列独特的病理生理改变,主要表现为眼附属器组织有IgG4阳性浆细胞浸润,同时伴有血清IgG4升高[2,3]。 IgG4-RD病因尚不明确,多见于中老年男性,其发病率为0.28‰~1.08‰[4]。可累及全身任何器官,最常见的是胰腺[5,6],眼眶组织为其第6位常累及的部位,发生率3.6%~12.5%[1,7-9]。IgG4-ROD常表现为单侧或双侧长期无痛性眼眶肿胀、眼球突出,无明显视力损害,可累及眼眶、泪腺、眼外肌、球后软组织、眶下神经等多个组织,其中泪腺受累最为多见,一般不累及结膜,其病理学特征主要表现为：弥漫性淋巴细胞、浆细胞浸润,组织纤维化,淋巴滤泡增生,有时可见嗜酸性粒细胞,免疫组织化学显示IgG4阳性浆细胞[10-13]。 IgG4-RD的诊断标准尚未完全统一,目前应用较为广泛的是2011年日本的诊断标准[14]：①单一或多脏器弥漫性或局部肿大、肿块形成、结节、肥厚的表现;②血清IgG4水平升高＞1.35 g/L;③组织病理学检查：有明显淋巴细胞、浆细胞浸润及纤维化;IgG4+浆细胞浸润,IgG4+/IgG+ 40%以上,且IgG4+细胞超过10个每高倍视野。但在IgG4-RD的患者中只有60%~70%的患者血清IgG4水平升高[15],因此,不能完全依赖血清IgG4水平来排除IgG4-RD[16]。 IgG4-ROD需注意与以下几种疾病相鉴别：①眼眶淋巴瘤：黏膜相关淋巴样组织淋巴瘤（Lymphoma of mucosa-associated lymphoid tissue,MALT）为结外边缘区B细胞淋巴瘤的一种,是最常见的眼眶淋巴瘤,临床表现无特异性,主要表现为眼睑肿胀、眼球突出等,可扪及无痛性肿块,累及结膜可见局部鱼肉样肿块[17]。与眼眶MALT淋巴瘤相比,IgG4-ROD的病理学检查缺乏如下特征：淋巴上皮病变、似单核样B细胞的淋巴样细胞、弥漫成片的CD20+ B细胞,轻链的限制性,异常的免疫表型和克隆性免疫球蛋白基因重排[18]。②炎性假瘤：组织学特征为中等量淋巴细胞及浆细胞平均分散在病变组织中,伴明显的梭形细胞（肌纤维母细胞及梭形组织细胞）,通常无静脉炎,免疫组织化学染色梭形细胞呈actin阳性或CD68阳性,IgG4阳性浆细胞不增加[19]。③干燥综合征：中老年女性多见,以干燥性角结膜炎、口干症、涎腺或泪腺的间歇性肿胀为特征,出现抗SS-A和抗SS-B自身抗体,血清IgG4不升高,类固醇治疗效果不佳[20,21]。 IgG4-ROD尚无统一的治疗方案,主要经验还是源于IgG4-RD的治疗,以糖皮质激素作为一线治疗方案[22],对于激素治疗无效或复发性患者,利妥昔单抗具有一定疗效[23]。其他辅助治疗方案还包括放射治疗、手术减压治疗[22]。 本病例为单眼眼眶发病,组织病理学检查显示病变组织为纤维结缔组织慢性炎症,纤维组织增多,小血管增生,病变组织内见大量淋巴细胞、浆细胞、嗜酸性粒细胞浸润,符合IgG4-ROD表现。免疫组织化学检查显示,IgG4+细胞40~60个每高倍视野,IgG4+/IgG+＞40%,符合IgG4相关疾病的诊断标准,可以确诊为IgG4-ROD。该病例累及眼眶肌肉及脂肪组织,未累及泪腺,无干眼等症状,尚无全身不适症状,治疗方式采用经鼻内窥镜微创手术摘除病变组织及联合糖皮质激素治疗,效果显著,创伤较小,且直接有效地清除局部病变,解除组织压迫。该治疗方案与Glass和Freitag[22]的治疗方案相吻合。 患者随访4个月未见肿瘤复发及其他全身症状,考虑可能为单纯性累及眼眶的IgG4相关疾病,术后4周外院检查血清IgG4水平为1.29 g/L,但尚不能排除全身其他器官受累的可能。即使是单纯性累及眼眶的IgG4相关疾病,也不能排除随着病程的延长全身其他脏器受累的可能,因此需半年复查1次,并密切随访,有全身症状应考虑IgG4相关疾病累及。 由于IgG4-RD是最近几年来新发现的疾病,相应的临床治疗经验较少,容易漏诊和误诊。笔者报告1例发生于眼眶组织的IgG4相关性疾病,并进行文献复习,以提高对该疾病的认识。     

A clinicopathological study on IgG4-related ophthalmic disease

AIM: To investigate clinicopathological features of immunoglobulin G4-related ophthalmic disease (IgG4-ROD), and analyze the recurrence rates following systemic corticosteroid administration. METHODS: We retrospectively searched clinical features, laboratory and histological findings based on the medical records of 21 patients with IgG4-ROD. All the patients examined in this study underwent surgical resection in the ocular adnexal lesions and underwent histological evaluation. This study further investigated clinical and histopathological features of 15 patients who received systemic corticosteroid after the resection. RESULTS: The mean age of the patients consisting of 7 males (33%) and 14 females (67%) was 61y. Fourteen patients were diagnosed as definitive, and 2 and 5 patients were probable and possible IgG4-ROD, respectively. Eyelid swelling was an initial symptom in 11 patients (52%) who did not show systemic involvements at a diagnosis. Fifteen patients received systemic corticosteroid administration, and all showed remission of inflammation. Among them, 10 patients did not recur, whereas 5 patients (33%) recurred during tapering. There were no significant difference between patients with or without recurrence in clinicopathological features. CONCLUSION: In this study, female patients are more predominant in IgG4-ROD. While inflammation recurs in one-third of patients, this study do not identify factors associated with recurrence after systemic corticosteroid administration.