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.     

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。     

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.     

A prevalence study of IgG4-related ophthalmic disease in Japan

Purpose

Immunoglobulin (Ig)G4-related ophthalmic disease belongs to a category of ocular adnexal lymphoproliferative disorders, the most frequent group of orbital tumors and simulating lesions. The aim of this study was to elucidate the number of IgG4-related diseases of orbital lymphoproliferative disorders and correlate ages and sex of such patients from 18 centers in Japan.

Methods

One thousand and fourteen patients with orbital lymphoproliferative disorders were enrolled in this study. All had pathologically diagnosed lymphoproliferative disorders with surgical samples of ocular adnexal tissue. Patients with conjunctival lesions and intraocular lymphoma were excluded.

Results

Of the 1,014 cases of orbital lymphoproliferative disorders 404 (39.8 %) had extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, 156 (15.4 %) had other malignant lymphomas, 191 (18.8 %) had non-IgG4 orbital inflammation, 219 (21.6 %) had IgG4-related orbital inflammation, and 44 (4.3 %) had IgG4-positive MALT lymphoma. Median age of the IgG4-related orbital inflammation group was 62 years, which is significantly lower than that of the MALT lymphoma group (median 66 years) and higher than the non-IgG4 orbital inflammation group (median 57 years). The male/female ratio was 105/114 in the IgG4-related orbital inflammation group.

Conclusions

Nearly a quarter of orbital lymphoproliferative disorders in Japan are related to IgG4.     

Pathological findings of infraorbital nerve enlargement in IgG4-related ophthalmic disease

Purpose

We report a case of bilateral infraorbital nerve enlargement (IONE) associated with immunoglobulin (Ig)G4-related ophthalmic disease and describe the associated histopathologic findings.

Case

An otherwise healthy 59-year-old man presented with bilateral exophthalmos and right visual disturbance. Orbital magnetic resonance imaging showed bilateral IONE and a soft tissue mass in the right orbit. Excisional biopsy in the left infraorbital canal was performed. Histopathologic assessment revealed IgG4-related disease involving the epineurium of the infraorbital nerve. The patient received systemic steroid therapy, to which he responded well.

Conclusion

IONE in IgG4-related ophthalmic disease is due to IgG4-related disease involving the epineurium.     

IgG4相关性眼病的诊疗研究进展

免疫球蛋白G4(IgG4)相关性疾病(IgG4-RD)是近年来受关注度较高的一类慢性、系统性疾病。IgG4-RD可累及全身各个组织,主要表现为累及器官的肿胀及占位改变,当病变侵犯至眼部周围时称为IgG4相关性眼病(IgG4-ROD),主要侵犯泪腺、眼眶脂肪、眶下神经、眼外肌和眼睑等。目前,针对IgG4-ROD的主要治疗方式有药物治疗、手术、放射治疗等。随着近年对该病认识的不断提升,治疗有效率不断提高,本文就IgG4-ROD的流行病学特点、临床表现、影像特点、诊断和治疗的最新进展进行综述。     

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...     

首诊于眼科的IgG4相关疾病初步研究

目的 对一组首诊于眼科的IgG4相关疾病患者进行总结分析.方法 回顾性病例分析.选取2011年1月～2021年4月解放军总医院第一医学中心神经眼科住院治疗的9例IgG4相关眼病(IgG4-ROD)纳入分析.总结患者临床表现、实验室检查、眼眶磁共振成像(MRI)、病理学检查和治疗情况.结果 9例患者,男性6例、女性3例,...     

基质蛋白Fibulin-5在眼眶IgG4相关性疾病中的表达

目的　探讨基质蛋白Ｆｉｂｕｌｉｎ-５与眼眶ＩｇＧ４相关性疾病（ＩｇＧ４-ｒｅｌａｔｅｄｏｃｕｌａｒｄｉｓ-ｅａｓｅ,ＩｇＧ４-ＲＯＤ）纤维化、炎症、硬化的关系。方法　收集２０例（２０眼）眼眶开放性粉碎性骨折清创术中采集的正常泪腺组织标本作为对照组,２０例（２０眼）眼眶ＩｇＧ４-ＲＯＤ患者的泪腺肿物作为ＩｇＧ４-ＲＯＤ组,采用免疫组织化学染色结合图像分析法对基质蛋白Ｆｉｂｕｌｉｎ-５进行半定量分析,采用实时荧光定量ＰＣＲ和Ｗｅｓｔｅｒｎ-ｂｌｏｔｔｉｎｇ法检测Ｆｉｂｕｌｉｎ-５ｍＲＮＡ及蛋白的相对表达量。结果　ＩｇＧ４-ＲＯＤ组中Ｆｉｂｕｌｉｎ-５ｍＲＮＡ的表达水平为３．６９±１．７２,显著高于对照组（１．６９±０．４５）,两组比较差异有统计学意义（Ｐ＜０．０５）。Ｆｉｂｕｌｉｎ-５蛋白与Ｆｉｂ-ｕｌｉｎ-５ｍＲＮＡ表达变化趋势较为一致。ＩｇＧ４-ＲＯＤ组中Ｆｉｂｕｌｉｎ-５蛋白的表达水平为０．５５±０．１２,对照组中Ｆｉｂｕｌｉｎ-５蛋白表达水平为０．１９±０．１１,两组比较差异有统计学意义（Ｐ＜０．０１）。免疫组织化学结果显示,ＩｇＧ４-ＲＯＤ组中泪腺细胞排列不规则,染色为黄色、棕黄色的纤维化细胞排列紊乱,对照组中泪腺腺管规则,细胞规则排列,核染蓝色。ＩｇＧ４-ＲＯＤ组Ｆｉｂｕｌｉｎ-５蛋白的阳性表达显著高于对照组。结论　ＩｇＧ４-ＲＯＤ组中Ｆｉｂｕｌｉｎ-５ｍＲＮＡ和蛋白表达较对照组显著升高,Ｆｉｂｕｌｉｎ-５可能促进眼眶ＩｇＧ４-ＲＯＤ的纤维化及硬化。     

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）       

Clinical features of IgG4-related dacryoadenitis

Background

To elucidate the clinical characteristics of IgG4-related dacryoadenitis.

Methods

Clinical features, laboratory findings, radiological findings, associated diseases, treatment, and prognosis were prospectively examined in 12 patients (seven men, five women; mean age, 60.9?±?15.1 years) with IgG4-related dacryoadenitis.

Results

In addition to eyelid swelling, other ophthalmologic symptoms were observed in seven patients, including diplopia (n?=?4), ptosis (n?=?2), visual field disturbance (n?=?2), eye pain (n?=?2), decrease of visual acuity (n?=?2), eye-movement disturbance (n?=?1), dry eye (n?=?1), corneal ulcer (n?=?1), and epiphora (n?=?1). Swelling of the lacrimal glands was bilateral in half of the patients. Other IgG4-related diseases were present in nine patients, including sialadenitis (n?=?5), autoimmune pancreatitis (n?=?4), retroperitoneal fibrosis (n?=?2), and lymphadenopathy (n?=?8). Serum IgG4 levels were significantly higher in patients with other IgG4-related disease (1070?±?813 mg/dl) than in those without (197?±?59 mg/dl, p?=?0.017). Allergic histories and elevated serum IgE levels were each detected in six patients. Eight patients showed inflammatory extension beyond the lacrimal gland, such as thickened rectus muscle (n?=?6), inflammation of the optic nerve (n?=?2), and retrobulbar inflammation (n?=?3). Steroid therapy was effective in seven patients, but dacryoadenitis relapsed in two patients with markedly higher serum IgG4 levels and autoimmune pancreatitis.

Conclusions

IgG4-related dacryoadenitis showed various ophthalmologic symptoms due to extensive inflammation beyond the lacrimal gland, frequent association with other IgG4-related disease or allergic phenomena, and steroid responsiveness.     

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.     

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.     

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.