Vasilyev V I, Safonova T N, Socol E V, Probatova N A, Kokosadze N V, Pavlovskaya A I, Kovrigina A M, Radenska-Lopovok S G, Gorodetsky V R, Rodionova E B, Palshina S G, Aleksandrova E N, Shornikova N S, Gaiduk I V
V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia.
Research Institute of Eye Diseases, Moscow, Russia.
Ter Arkh. 2018 May 11;90(5):61-71. doi: 10.26442/terarkh201890561-71.
To provide demographic, clinical, laboratory, ultrasound, radiological, morphological/ immunomorphological phenotype of IgG4-related ophthalmic diseases, which allowsmaking a differential diagnosis with granulomatous, autoimmune, inflammatory, endocrine and hematologic diseases affecting the eye and orbits.
From 2004 to 2016 108 (78.2%) of the 138 patients were diagnosed with non-tumoral lesions of eye and orbits. In 48 patients (35%) at admission and 5 patients in the follow were diagnosed IgG4-related ophthalmic disease. In the analysis of 82 (f-44, m-38) patients with IgG4-related disease, localization of lesions in orbit observed in 53 (f-36, m-17) and it was the most frequent involvement in patients with IgG4-related disease (64.5%). Only 7 patients had isolated IgG4-related ophthalmic disease, whereas 46 patients (87%) had involvement of 2-7 locations, as a manifestation of IgG4-related systemic disease.During the examination, the average age of patients with IgG4-related ophthalmic disease was 47.5 years (19-73 years). Median time to diagnosis was 52.8 months before 2004 and 36 months 2004-2016.
We noted the predominance of females in the ratio 2: 1 inthe group of patients with IgG4-related ophthalmic disease. Edema of the eyelids, nasal congestion (55-60%), tumor-like formations of the upper eyelids and increased lacrimation prevailed at the onset of the disease, whereas such functional impairment like limited mobility and pain in eyeballs, exophthalmos, ptosis and diplopia appeared later at 15-38% with a loss visual acuity in one case. Bilateral lesion (86%), mainly affecting the lacrimal glands (93.5%), infiltration of the ex- traocular muscles (83.5%) and retrobulbar tissue with a thickening of the optic nerve in one third of patients were the main localizations IgG4-related ophthalmic disease. Clinical symptoms were accompanied by the appearance of moderate inflammatory activity (38%), in- creased levels IgG (44%), IgG4(88%) and IgE (61%). Indicators of autoimmune disorders observed in 6-22% of patients, most often in pa- tients with simultaneous involvement of the salivary glands. Significant lymphoplasmacytic infiltration (94%) with a ratio of plasma cells (IgG4/IgG) secreting IgG4> 40% (90%) with fibrosis formation (94%) and follicle formation (71%) with a moderate amount of eosinophils (34%) were the major morphological / immunomorphological manifestations of IgG4-related ophthalmic disease. Signs of vasculitis and obliterative phlebitis were found in a small amount of patients.
Determination of elevated levels of IgG-4 / IgE in patients with edema, pseudotumor of the eyelid, sinusitis and increase of the palpebral lobe of the lacrimal gland suggests the presence of IgG4-related ophthalmic disease. Minimally invasive incisional biopsy of lacrimal glands and salivary glands followed by morphological / immunomorphological research is needed for the correct diagnosis. Diagnostic orbitotomy in ophthalmic hospitals in such cases is inexpedient, since it leads to the development of dry eye. Massive lymphoplasmacytic infiltration with IgG4 / IgG ratio more than 40%, advanced fibrosis in biopsiesof the orbits tissue or salivary glands when combined lesions are required for the making the diagnosis of IgG4-related ophthalmic disease.
提供IgG4相关性眼病的人口统计学、临床、实验室、超声、放射学、形态学/免疫形态学表型，以便与影响眼和眼眶的肉芽肿性、自身免疫性、炎症性、内分泌性和血液性疾病进行鉴别诊断。
2004年至2016年，138例患者中有108例（78.2%）被诊断为眼和眼眶的非肿瘤性病变。入院时48例患者（35%）及随访中的5例患者被诊断为IgG4相关性眼病。在对82例（女44例，男38例）IgG4相关性疾病患者的分析中，53例（女36例，男17例）病变定位于眼眶，这是IgG4相关性疾病患者中最常见的受累部位（64.5%）。仅7例患者患有孤立性IgG4相关性眼病，而46例患者（87%）有2 - 7个部位受累，作为IgG4相关性全身疾病的表现。检查期间，IgG4相关性眼病患者的平均年龄为47.5岁（19 - 73岁）。2004年前诊断的中位时间为52.8个月，2004 - 2016年为36个月。
我们注意到IgG4相关性眼病患者组中女性占优势，比例为2:1。疾病发作时，眼睑水肿、鼻塞（55 - 60%）、上睑肿瘤样形成和泪液分泌增加较为常见，而眼球活动受限、疼痛、眼球突出、上睑下垂和复视等功能障碍较晚出现，发生率为15 - 38%，其中1例患者视力丧失。双侧病变（86%），主要累及泪腺（93.5%）、眼外肌浸润（83.5%）和球后组织，三分之一患者伴有视神经增粗，是IgG4相关性眼病的主要定位。临床症状伴有中度炎症活动（38%）、IgG水平升高（44%）、IgG4（88%）和IgE（61%）。6 - 22%的患者观察到自身免疫紊乱指标，最常见于同时累及唾液腺的患者。显著的淋巴浆细胞浸润（94%），分泌IgG4的浆细胞（IgG4/IgG）比例>40%（90%），伴有纤维化形成（94%）和滤泡形成（71%），有中等数量的嗜酸性粒细胞（34%），是IgG4相关性眼病的主要形态学/免疫形态学表现。少量患者发现血管炎和闭塞性静脉炎迹象。
对于出现水肿、眼睑假瘤、鼻窦炎及泪腺睑叶增大的患者，检测到IgG - 4 / IgE水平升高提示存在IgG4相关性眼病。为明确诊断，需要对泪腺和唾液腺进行微创切开活检，随后进行形态学/免疫形态学研究。在眼科医院进行诊断性眼眶切开术在这种情况下是不合适的，因为它会导致干眼症。当合并病变时，眼眶组织或唾液腺活检中大量淋巴浆细胞浸润且IgG4 / IgG比例超过40%、纤维化进展是诊断IgG4相关性眼病所必需的。
