成人眼眶黄色肉芽肿病的临床研究进展

成人眼眶黄色肉芽肿病是一种较罕见的眼眶和眼附属器疾病,属于非朗格汉斯组织细胞增多病(Ⅱ型),分为四个亚型:成人起病的黄色肉芽肿、坏死性黄色肉芽肿、Erdheim-Chester病和成人起病的眶周黄色肉芽肿合并哮喘型.该病的诊断依靠临床表现和病理特征.治疗多为经验性,根据临床分型和表现的不同选择合适的治疗策略,主要为糖皮质激素、免疫抑制剂和手术治疗等.本文就该病的发病机制、临床分型、诊断和治疗的研究进展进行综述,以期为该病的临床诊治提供参考.     

曲安奈德在眼眶疾病中的应用

球后注射或病变内注射曲安奈德治疗甲状腺相关眼病、婴儿型血管瘤和黄色肉芽肿等眼眶疾病疗效好，局部并发症少，可以避免系统应用糖皮质激素和细胞毒制剂及其他免疫抑制剂引起的毒副作用。[眼科新进展2007；27（3）：233-234，238]     

眼眶嗜酸性肉芽肿的临床诊治分析

目的 探讨眼眶嗜酸性肉芽肿的临床特点及诊治情况,进一步提高对眼眶嗜酸性肉芽肿的认识.方法 回顾分析中山大学中山眼科中心2005年5月至2009年8月收治的7例(7眼)眼眶嗜酸性肉芽肿,对其临床资料进行整理、分析.结果 7例中,男4例,女3例;右眼4例,左眼3例.3～9岁6例,10岁以上1例.临床主要表现为上睑或颞侧眶周局部软组织肿胀,发红,可伴眼部疼痛、眼球突出、上睑下垂、局部皮肤麻木感等.眼眶CT显示为眼眶颞上前眶低密度肿物,相邻骨质破环.B超均为中低光团,内回声强弱不均,边界不清.术前定性诊断困难,手术活检或部分切除病变后,激素或小剂量放疗效果好.结论 眼眶嗜酸性肉芽肿多发生于10岁以内小儿,单眼发病,临床主要表现为上睑或颞侧眶周局部软组织肿胀,可伴疼痛,CT显示外上前眶骨质破坏,术前定性诊断困难,手术部分切除后激素治疗效果好.     

成年人的角巩膜缘青少年黄色肉芽肿病

青少年黄色肉芽肿病(JXG)是皮肤的肉芽肿性疾病，很少发生在成人，仅报道过在极少数病例中发生在角巩膜缘上。我们描述了1例在角巩膜缘不寻常的肿物伴皮疹，组织学诊断为JXG。这里讨论这种罕见病的临床特征和处理：     

矩形推进皮瓣在幼年性黄色肉芽肿手术中的应用

幼年性黄色肉芽肿也称青少年黄色肉芽肿,以前称痣黄内皮瘤或先天性黄色瘤复合体,是一种良性组织细胞增多所引起的皮肤,眼部和眼眶病变.其发病机制不明,可能与自身免疫疾病有关.临床上婴幼儿患此疾病者少见.2009年8月我院经手术治疗病理证实的1例左眼睑幼年性黄色肉芽肿,报告如下.     

眼部Wegener肉芽肿12例临床分析

目的:研究韦格纳肉芽肿病(wegener granulomatosis,WG)的眼部表现、实验室检查、病理及影像学特点,提高眼科医师对本病的认识。方法:分析44例WG病例,入选其中有眼部表现的12例患者,回顾性研究其眼部临床表现、实验室指标、病理结果以及影像学特点。结果:发病平均年龄39岁。从发病到确诊的平均时间为11mo。眼部的任何一个部位都可能受累,包括眼球、附属器及视路。其中眼前节及眼眶最常累及。83%患者AN-CA结果阳性。病理表现有实质组织坏死、肉芽肿、多核巨细胞、微脓肿和血管炎等。CT、MRI是目前辅助诊断WG的有效方法。结论:WG是一种致死性疾病,早期诊断和治疗至关重要,对于以眼科首诊和仅有眼部表现的可疑病例,眼科医生要注意鉴别。     

额面部美容填充治疗致眼睑肉芽肿样肿物的临床特征分析

目的探讨行额面部美容填充治疗后眼睑肉芽肿样肿物患者的临床特征。设计回顾性病例系列。研究对象2019-2020年北京同仁医院眼科门诊因面部填充治疗致眼睑肉芽肿样肿物患者16例22眼。方法回顾患者的症状、体征、影像学检查以及病情转归。主要指标临床表现、眼眶及头颅CT、MRI表现以及治疗情况。结果16例患者均为女性,平均年龄(36.43±5.65)岁。3例(18.7%)仅进行了面部玻尿酸或肉毒素填充注射;13例(81.3%)曾行面部自体脂肪填充治疗,其中1例同时行前额肉毒素注射,4例在面部自体脂肪填充治疗后曾行双眼重睑术。从手术到出现肿物的时间间隔6~72个月,平均(19.50±19.70)个月。6例(37.5%)表现双侧眼睑肿物,10例(62.5%)为单侧眼睑肿物。2例(12.5%)眼睑肿胀;13例(81.2%)肿物位于上睑,2例(12.5%)位于下睑,1例(6.3%)上下睑均出现。所有患者均在无意间发现眼睑多发皮下肿物,有一定活动性、界清、质硬、局部无红肿和压痛。MRI显示,12例(75.0%)14眼肿物在T1WI表现为长或等信号,12例(75.0%)17眼肿物在T2WI上表现为长信号;增强后不均匀强化。16例均保守观察,随访半年肿物大小无明显变化。结论面部美容填充治疗可导致眼睑肉芽肿样肿物,其特征为眼睑皮下一个或多个无痛性、界清的肿物。结合患者的面部填充治疗史、临床表现和影像学特征可确定诊断。     

原发性眼睑肿瘤291例临床病理分析

目的:了解原发性眼睑肿瘤的组织病理学特征及发病率。方法:收集第三军医大学附属西南眼科医院2003-01/2009-12门诊及住院治疗的291例原发性眼睑肿瘤患者的临床病理资料进行回顾性分析。结果:良性眼睑肿瘤172例(59.1%),其构成位于前10位的依次为:乳头状瘤、色素痣、炎性肉芽肿、皮样囊肿或表皮样囊肿、淀粉样变性、疣、血管瘤、黄色瘤、浆细胞肉芽肿、毛发上皮瘤。恶性眼睑肿瘤119例(40.9%),其构成位于前5位的肿瘤依次为:基底细胞癌、鳞状细胞癌(含梭形细胞癌)、皮脂腺癌、恶性淋巴瘤、恶性黑色素瘤。对眼睑三大恶性肿瘤的临床流行病学资料进行了总结分析,讨论了眼睑肿瘤切除术后的眼睑修复方法。结论:眼睑肿瘤临床病理分类繁多,对病变进行临床病理分析有助于正确的诊断及治疗。     

眼部Wegener肉芽肿17例临床分析

目的 分析累及眼部的Wegener肉芽肿（Wegener's granulomatosis, WG）患者的临床资料, 提高对本病的认识。设计 回顾性病例系列。研究对象 2000年1月至2014年6月武警总医院眼眶病研究所收治的病理诊断为WG的患者17例。方法 回顾性分析患者的病历资料。记录分析眼部及全身临床表现、实验室检查、影像学特征及预后。主要指标 眼部及全身临床表现、实验室检查、影像学特征及预后。结果 17例患者中,女性7例。发病年龄17~65岁,平均（38.4±13.2）岁。眼部多个部位均可能受累, 包括眼球、泪腺、眼外肌、视神经及眶周软组织等。8例患者行抗中性粒细胞胞浆抗体（ANCA）检查,7例胞浆型ANCA（c-ANCA）阳性,其中1例c-ANCA和核周型ANCA（p-ANCA）均阳性。所有患者均行眶部占位病变切除手术,术后病理学检查,主要病理改变为坏死性肉芽肿和/或血管炎。经糖皮质激素或联合应用免疫抑制剂或联合应用局部放疗效果较好（8/11）,随访期间2例患者术后复发,仍给予上述治疗达到临床缓解。2例患者死于肾功能衰竭,1例患者死于呼吸衰竭。结论 WG是一种累及多系统的致死性疾病,可以累及眼的任何部位,ANCA检查有助于明确诊断,但仍需病理检查明确诊断。应用糖皮质激素、免疫抑制剂以及局部放疗可取得较好效果。     

眼眶嗜酸性肉芽肿3例

眼眶嗜酸性肉芽肿是少见的眼眶肿瘤，主要见于儿童，与眼眶血管瘤，眶蜂窝织炎，眼眶血肿和炎性假瘤相鉴别，因可伴有全身其他部位的病变，故应引起临床医生的重视。现将我院2002年收治的3例嗜酸性肉芽肿患者报告如下。     

Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review

BACKGROUND/AIMS: Adult xanthogranulomatous disease involving the ocular tissues is rare and poorly understood. Adult onset xanthogranuloma (AOX), adult onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD) are the four syndromes within this disorder, which is diagnosed by characteristic histopathology. Experience with eight cases prompted a multi-institutional effort to study the histopathology, immunohistochemistry, clinical findings, and systemic associations in this disorder. METHODS: 22 cases, including histopathological slides, were compiled. Published reports were identified by an English language Medline search (1966-2005) and review of reference citations. Each case in this series and the literature was classified as one of four syndromes and then analysed for age onset, sex, skin xanthoma, orbital location, immune dysfunction, internal organ and bone lesions, treatment, and outcome. The histopathology in each of these cases was reviewed by two pathologists. Immunhistochemical stains (CD3, CD4, CD8, L26) were performed in 14 cases where unstained slides were available. RESULTS: 137 cases were compiled. There was no sex or age difference between syndromes. AOX, AAPOX, NBX affect the anterior orbit, ECD tends to be diffuse and intraconal. Skin lesions are found in all the syndromes. Immune dysfunction was noted in all cases of AAPOX and NBX; 11% of NBX and all ECD patients had internal organ disease. Treatment included surgery, corticosteroids, other chemotherapeutic agents, radiotherapy, and combinations of these. No AOX or AAPOX deaths occurred; 66% of ECD patients died. All 22 cases had xanthoma cells; most had Touton giant cells. Lymphocytes were present in all cases and occurred as aggregates (mostly in AAPOX) or diffuse populations mixed with fibroblasts (mostly in ECD). Immunohistochemistry revealed the majority of these to be CD8+. Necrosis was most marked in NBX. CONCLUSION: Adult xanthogranuloma of the orbit is rare, making prospective evaluation or meta-analysis impossible. The best treatment is unknown but seems to be with multiagent chemotherapy guided by histopathological, immunohistochemical, and systemic findings.     

TIMP-1 Mediates Inflammatory and Immune Response to IL-6 in Adult Orbital Xanthogranulomatous Disease

Abstract

Purpose: To explore the pathogenesis that TIMP-1 mediated in adult orbital xanthogranulomatous disease (AOXGD), a rare type of non-Langerhans histiocytosis that damages the appearance and quality of life of patients

Methods: We reviewed 22 patients diagnosed with AOXGD based on clinical manifestations and histological analysis, and then investigated the expression of TIMP-1 and IL-6 with q-PCR and IHC in AOXGD tissues and the possible mechanism involved in the induction of TIMP-1 by IL-6.

Results: IL-6 and TIMP-1 were significantly increased in AOXGD tissues. IL-6 promoted TIMP-1 production by M1 macrophages by stimulating the phosphorylation of JAK2 and STAT3. Moreover, IL-17 and IFN-γ, the classical markers of Th1 and Th17 cells, were increased in AOXGD.

Conclusion: These data implied that the IL6~JAK2/STAT3-TIMP-1 signalling pathway is activated in AOXGD and that adaptive Th1 and Th17 responses are involved in the development of AOXGD.     

Erdheim-Chester disease: a comprehensive review from the ophthalmologic perspective

Erdheim–Chester disease (ECD) is a rare clonal histiocytic neoplasm with less than 1200 documented cases to date. The disease is life-threatening and difficult to recognize, although increasing awareness as well as the integration of clinical, imaging, pathology information, and genetic studies have led to a recent exponential increase in new reported cases. ECD affects multiple organs and systems, including skeletal, neurologic, and cardiovascular. Pulmonary, retroperitoneal, and cutaneous lesions have also been reported in various combinations. Until the discovery that more than half of ECD patients harbor the BRAF-V600E mutation or other mutations in the mitogen-activated protein kinase (MAPK) and RAS pathways, Interferon-a was the first-line treatment. Nowadays BRAF and MEK-inhibitors targeted therapies are the mainstay of treatment. Ophthalmologic involvement occurs in 25% ?30% of ECD cases, usually in the form of orbital involvement presenting with exophthalmos and ophthalmoplegia. Other ophthalmologic manifestations include palpebral xanthelasmas, anterior uveitis and vitritis, optic disk edema, choroidal infiltration, recurrent serous retinal detachment, retinal drusen–like deposits and retinal pigment epithelial changes. ECD patients can also present with ocular symptoms as a result of adverse effects of the treatment regimens. In some cases with smoldering or protean symptoms, the emergence of eye manifestations triggered the diagnosis. Ophthalmologists have to be aware of the disease, recognize the constellation of ECD symptoms, and contribute to the diagnosis, treatment, and follow-up of ECD patients.     

Orbital liposarcoma: a retrospective, single-center study of thirteen patients

AIM: To explore the clinical and pathological characteristics of thirteen patients with orbital liposarcoma. METHODS: The clinical history data of thirteen patients diagnosed as orbital liposarcoma at Beijing Tongren Hospital, from 2006 to 2021 were collected and analyzed. The data includes age, gender, affected orbital side, course of disease, status of disease (primary or recurrent), clinical manifestations, preoperative visual acuity, operative treatment, the relations between liposarcoma and surrounding tissue, longest diameter of liposarcoma, histological subtype, immunohistochemical indicators, follow-up treatment and prognosis. RESULTS: The initial symptoms are diverse. Proptosis is the most frequent chief complaint and the others included vision loss, epiphora, diplopia, and eyelid palpable mass. Results of imaging examination [computed tomography (CT) or magnetic resonance imaging (MRI)] showed orbital mass. In terms of treatment, 10 patients received tumor resection, and the mean longest diameter of the tumor was 3.39±1.36 cm. The other 3 patients had optic nerve invaded, so they received orbital exenteration. Pathological examination results confirmed the diagnose of liposarcoma for 13 patients. Six patients displayed as myxoid type, and three patients in each type of dedifferentiated and well-differentiated type. One patient was verified as pleomorphic, which was a rare type of liposarcoma. All of the patients showed Vimentin positive, and most showed CD34 and S-100 positive. Besides, four patients showed smooth muscle actin positive. All thirteen patients were alive. CONCLUSION: Orbital liposarcoma is a rare disease and it has no specific clinical manifestation. The diagnosis of liposarcoma should be considered when proptosis and orbital mass occurred in orbit. It is recommended to perform pathological examination to achieve early detection and early treatment.     

Azathioprine and prednisone combination treatment for adult periocular and orbital xanthogranulomatous disease

Purpose: To report the authors’ experience with azathioprine and prednisone combination for adult periocular and orbital xanthogranulomatous disease. Methods: We identified 13 adults with histology‐proven periocular or orbital xanthogranuloma in two tertiary referral orbital centres from 1984 to 2008. Patient records were reviewed and data collected on orbital localization, immune dysfunction, applied treatment and outcome. Results: Five patients with periocular or orbital xanthogranulomatous disease were fully treated with prednisone and azathioprine combination, which resulted in stabilization in two and regression in three. Two other patients had to discontinue azathioprine because of side‐effects. Of the non‐fully treated prednisone/azathioprine patients, four out of eight progressed. Conclusion: In adult periocular and orbital xanthogranuloma, combined treatment with prednisone and azathioprine yields adequate immunosuppression, often for a prolonged period of time.     

Juvenile xanthogranuloma of the corneoscleral limbus

PURPOSE: To report an 11-year-old Chinese girl with juvenile xanthogranuloma of the limbus, occurring in isolation without dermatologic involvement, and to discuss the clinical and histologic features, pathogenesis, and treatment of juvenile xanthogranuloma. METHODS: Case report and review of medical literature. RESULTS: A total excision and biopsy of the limbal lesion with lamellar graft was performed. Histologic examination showed a xanthogranuloma. At 12-month follow-up, there was no recurrence of tumor. CONCLUSION: The diagnosis of juvenile xanthogranuloma may be straightforward in cases that have concomitant cutaneous manifestations. However, in isolated ocular forms, histopathological examination is necessary. Unlike the more common iris lesions that are preferably treated nonsurgically, limbal lesions require surgical excision.     

Adult orbital xanthogranuloma with associated adult-onset asthma

: The authors report a case of adult orbital xanthogranuloma with associated adult-onset asthma in a 44-year-old man. Adult orbital xanthogranuloma was diagnosed on the basis of the clinical findings of bilateral, indurated, yellow eyelid lesions in a patient presenting with adult-onset asthma. Incisional biopsy of the eyelid lesions demonstrated a diffuse histiocytic infiltrate of the orbit and Touton giant cells without evidence of necrobiosis. Systemic evaluation failed to show evidence of bone lesions or paraproteinemia. When patients present with atypical indurated yellow eyelid lesions, a biopsy should be considered. If Touton giant cells are present, a systemic evaluation should be undertaken to rule out both Erdheim-Chester disease and necrobiotic xanthogranuloma. If no systemic findings are present, other than the possibility of adult-onset asthma, the rare entity of adult orbital xanthogranuloma should be considered.     

Erdheim-Chester disease: A case report

Background Erdheim-Chester disease (ECD) is a rare histiocytosis, histologically characterized by xanthogranulomatous inflammation. It may affect the bones, heart, lung, liver, kidneys, retroperitoneum, brain, and, rarely, the orbit. In the majority of patients, orbital infiltration is bilateral.Case A 61-year-old man presented with bilateral exophthalmos and progressive loss of visual function caused by chorioretinal folds and papillary swelling due to retrobulbar pseudotumor. The computed tomogram of the abdomen showed retroperitoneal thickening, leading to the interpretation of multifocal fibrosclerosis. This was further substantiated by an orbital biopsy revealing chronic fibrosing inflammation. Retrobulbar radiotherapy (20 Gy) and long-term systemic corticosteroid treatment followed. Although the retroperitoneal involvement decreased, no significant effect on orbital involvement was achieved. A second review of the orbital biopsy revealed foamy cell infiltration and the presence of a sclerotic process. Immunohistochemical examination demonstrated positive CD 68 stains, whereas S-100 and CD 1a were negative, thus confirming ECD. The histologic finding was comparable to a biopsy of the retroperitoneum. Endonasal decompression was performed but visual acuity (VA) decreased to 20/250 in the right eye and on finger counting in the left eye. The patient continues to be under therapy with prednisolone 20 mg/day and methotrexate 25 mg/ week.Conclusions The clinical orbital manifestation of ECD occurs in two different forms: one presenting as a mild impairment of visual function, while the second, clinical form, observed in our patient, is characterized by a progressive loss of VA despite therapeutic efforts such as immunosuppressive systemic therapy, radiation, and surgery. The described case illustrates that clinical findings in multifocal fibrosclerosis overlap with those observed in ECD.     

Orbital Necrobiotic Xanthogranuloma Associated With Systemic IgG4 Disease

Purpose: The authors describe 2 cases of orbital xanthogranulomatous disease associated with an increase in IgG4-positive plasma cells, and also examine IgG4 in other types of orbital inflammation.

Methods: Immunohistochemistry for total IgG and IgG4 was performed in 18 cases of orbital inflammation, including chronic dacryoadenitis (n?=?10), necrobiotic xanthogranuloma (n?=?2), xanthogranuloma (n?=?1), idiopathic orbital inflammation/pseudotumor (n?=?4), and fungal infection (n?=?1).

Results: One patient presenting with necrobiotic xanthogranuloma had signs of systemic IgG4 disease. His orbital lesion showed an elevated number of IgG4 positive plasma cells (55%). An orbital xanthogranulomatous lesion in a second patient lacking systemic symptoms also contained a high percentage of IgG4-positive plasma cells (80%). Only 1 case of chronic dacryoadenitis contained prominent IgG4-positive plasma cells (mean 17/hpf).

Conclusions: IgG4-positive plasma cells are relatively rare in nonsclerosing orbital inflammatory lesions. However, systemic disease IgG4 can be associated with necrobiotic xanthogranuloma of the orbit.