眶内注射复方倍他米松治疗IgG4相关性眼病的效果观察

doi:10.3969/j.issn.1674-8115.2023.02.011

摘要/Abstract

摘要：

目的·探讨眶内注射复方倍他米松治疗IgG4相关性眼病（IgG4-related ophthalmic disease，IgG4-ROD）的效果。方法·纳入2016年9月—2021年8月在上海交通大学医学院附属瑞金医院眼科接受复方倍他米松眶内注射治疗的IgG4-ROD患者。纳入的患者符合2019年美国风湿病学会/欧洲抗风湿病联盟制定的IgG4相关性疾病（IgG4-related disease，IgG4-RD）分类标准，且均有泪腺受累。眶内给药方案为每周患侧眼眶注射0.5 mL复方倍他米松（含丙酸倍他米松5 mg/mL，倍他米松磷酸钠2 mg/mL），连续6周；然后每月注射1次，连续3个月。眶内注射于眼眶颞上方贴近骨壁处缓慢进针，当进入病变的泪腺及其周围眼眶浅层组织中时，开始缓慢注射药液。对于合并有眼外肌、视神经受累的患者，增加球旁注射。治疗前后，根据临床表现、血清IgG4水平、影像学表现等计算IgG4-RD反应指数（IgG4-RD responder index，IgG4-RD RI），根据IgG4-RD RI判定有无复发。如复发则进行维持治疗，维持治疗为每月注射1次，连续6个月，而后根据医师的判断，改为每2个月1次。结果·根据治疗前后的IgG4-RD RI，初始治疗后所有患者均获得完全缓解，病例1、2、3和4的缓解期分别为4、4、6和5个月，在缓解期后均有复发；虽然有复发，但是每月或每2个月1次的维持治疗可以有效控制症状。病例1、3和4的随访时间分别为50、45和27个月，在维持治疗下均维持缓解状态。由于总的糖皮质激素用量较低，患者在治疗过程中未发生明显的全身和局部不良反应，也未发生严重的注射相关不良反应。病例2拒绝维持治疗，停药后泪腺恢复到原来的大小，但在47个月的随访中没有进一步加重。结论·眶内注射复方倍他米松可能是一种有效的缓解IgG4-ROD的选择，但是患者需要重复注射。

关键词: IgG4相关性眼病, 倍他米松, 眶内注射, 治疗反应

Abstract:

Objective ·To investigate the effect of intraorbital injection of compound betamethasone on IgG4-related ophthalmic disease (IgG4-ROD). Methods ·Patients with IgG4-ROD who received intraorbital injection of compound betamethasone in the Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2016 to August 2021 were included. The enrolled patients met the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease (IgG4-RD) and all had lacrimal gland involvement. The intraorbital administration regimen was 0.5 mL compound betamethasone (containing betamethasone propionate 5 mg/mL, and betamethasone sodium phosphate 2 mg/mL) into the affected orbit once a week for 6 weeks, and then once a month for 3 months. The drug was injected into the lacrimal gland and its surrounding superficial orbital tissue. For patients with extraocular muscle and optic nerve involvement, periocular injection was added. Before and after treatment, the IgG4-RD responder index (IgG4-RD RI) was recorded according to the clinical manifestations, serum IgG4 level and imaging findings. If recurrence was determined according to the IgG4-RD RI, maintenance treatment was adopted. Maintenance treatment regimen was once a month for 6 months, and then changed to bimonthly according to the doctor's judgment. Results ·According to the IgG4-RD RI before and after treatment, all patients achieved complete remission after initial treatment with remission periods of 4, 4, 6, and 5 months in case 1, 2, 3 and 4, respectively, but relapse occurred. Despite recurrence, case 1, 3, and 4 remained in remission with maintenance therapy in the follow-up of 50, 45, and 27 months, respectively. Due to the low total dosage of glucocorticoid, no obvious systemic and local side effects occurred during treatment. Also no serious injection-related side effects occurred. Case 2 refused maintenance therapy and the lacrimal gland returned to its original size after discontinuation, but did not aggravate further in the 47 months follow-up. Conclusion ·Intraorbital injection of compound betamethasone may be a useful treatment option for IgG4-ROD. However, patients require repeat injections due to relapse.

Key words: IgG4-related ophthalmic disease (IgG4-ROD), betamethasone, intraorbital injection, treatment response

中图分类号:

R777.5

刘小红, 王亚娜, 焦秦, 程瑜. 眶内注射复方倍他米松治疗IgG4相关性眼病的效果观察[J]. 上海交通大学学报（医学版）, 2023, 43(2): 215-221.

LIU Xiaohong, WANG Yanuo, JIAO Qin, CHENG Yu. Observation on the therapeutic effect of intraorbital injection of compound betamethasone on the treatment of IgG4-related ophthalmic disease[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 215-221.

图/表 5

参考文献 17

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Item	Case 1	Case 2	Case 3	Case 4
Gender	Male	Male	Female	Male
Age/year	76	71	44	58
Brief history of illness	Progressive exophthalmos for 1 year, suspected of thyroid-associated ophthalmopathy	Swelling of the left upper eyelid for 5 months, slowly worsened	Bilateral upper eyelids swelling for 1 year, slowly worsened	Bilateral upper eyelids swelling for half a year （mainly the right）, slowly worsened
Sites of orbital involvement	Bilateral lacrimal glands, some extraocular muscles, optic nerve	Bilateral lacrimal glands （mainly the left）	Bilateral lacrimal glands	Bilateral lacrimal glands （mainly the right）
Extraocular sites of involvement	Suspected submandibular gland lesions （resected in other hospital）	Submandibular gland enlargement, tonsillitis	Submandibular lymph nodes enlargement, pharyngitis	Sinusitis, left parotid gland lesion （partial resection）
Pathology	No	No	No	IgG4-RD confirmed by another hospital
Corrected visual acuity^① （R/L）	0.6/0.4	0.9/0.8	1.2/1.2	1.0/1.0
NCT （R/L）/ mmHg	20.1/23.4	17.6/18.2	13.3/16.4	15.2/14.8
Conjunctiva	Hyperaemia （＋＋）, chemosis （＋）	Hyperaemia （-）	Hyperaemia （-）	Hyperaemia （-）
Anterior segment	Punctate epithelial erosions in the left, bilateral mild nuclear sclerosis	Bilateral mild nuclear sclerosis	（-）	（-）
Optic disc	Swelling	（-）	（-）	（-）
Macula	（-）	（-）	（-）	（-）
Exophthalmus （R/L）/mm	21/23	15/16	18/18	17/15
Serum IgG4/（g·L^-1）^②	24.10	28.90	4.10	14.40
Serum IgG/（g·L^-1）^③	29.00	18.10	12.20	26.70
IgG4-RD RI	10	6	6	6

Item	Case 1	Case 2	Case 3	Case 4
Gender	Male	Male	Female	Male
Age/year	76	71	44	58
Brief history of illness	Progressive exophthalmos for 1 year, suspected of thyroid-associated ophthalmopathy	Swelling of the left upper eyelid for 5 months, slowly worsened	Bilateral upper eyelids swelling for 1 year, slowly worsened	Bilateral upper eyelids swelling for half a year （mainly the right）, slowly worsened
Sites of orbital involvement	Bilateral lacrimal glands, some extraocular muscles, optic nerve	Bilateral lacrimal glands （mainly the left）	Bilateral lacrimal glands	Bilateral lacrimal glands （mainly the right）
Extraocular sites of involvement	Suspected submandibular gland lesions （resected in other hospital）	Submandibular gland enlargement, tonsillitis	Submandibular lymph nodes enlargement, pharyngitis	Sinusitis, left parotid gland lesion （partial resection）
Pathology	No	No	No	IgG4-RD confirmed by another hospital
Corrected visual acuity^① （R/L）	0.6/0.4	0.9/0.8	1.2/1.2	1.0/1.0
NCT （R/L）/ mmHg	20.1/23.4	17.6/18.2	13.3/16.4	15.2/14.8
Conjunctiva	Hyperaemia （＋＋）, chemosis （＋）	Hyperaemia （-）	Hyperaemia （-）	Hyperaemia （-）
Anterior segment	Punctate epithelial erosions in the left, bilateral mild nuclear sclerosis	Bilateral mild nuclear sclerosis	（-）	（-）
Optic disc	Swelling	（-）	（-）	（-）
Macula	（-）	（-）	（-）	（-）
Exophthalmus （R/L）/mm	21/23	15/16	18/18	17/15
Serum IgG4/（g·L^-1）^②	24.10	28.90	4.10	14.40
Serum IgG/（g·L^-1）^③	29.00	18.10	12.20	26.70
IgG4-RD RI	10	6	6	6

Item	Case 1	Case 2	Case 3	Case 4
Corrected visual acuity^① (R/L)	0.7/0.6	0.9/0.8	1.2/1.2	1.0/1.0
NCT (R/L)/mmHg	13.6/12.5	17.6/18.2	14.3/15.4	16.2/14.8
Conjunctiva	Hyperaemia (-), chemosis (-)	Hyperaemia (-)	Hyperaemia (-)	Hyperaemia (-)
Anterior segment	Bilateral mild nuclear sclerosis	Bilateral mild nuclear sclerosis	(-)	(-)
Optic disc	No swelling	(-)	(-)	(-)
Macula	(-)	(-)	(-)	(-)
Exophthalmus (R/L)/mm	14/14	15/14	16/16	15/15

Item	Case 1	Case 2	Case 3	Case 4
Corrected visual acuity^① (R/L)	0.7/0.6	0.9/0.8	1.2/1.2	1.0/1.0
NCT (R/L)/mmHg	13.6/12.5	17.6/18.2	14.3/15.4	16.2/14.8
Conjunctiva	Hyperaemia (-), chemosis (-)	Hyperaemia (-)	Hyperaemia (-)	Hyperaemia (-)
Anterior segment	Bilateral mild nuclear sclerosis	Bilateral mild nuclear sclerosis	(-)	(-)
Optic disc	No swelling	(-)	(-)	(-)
Macula	(-)	(-)	(-)	(-)
Exophthalmus (R/L)/mm	14/14	15/14	16/16	15/15

Item	Case 1	Case 2	Case 3	Case 4
1 month after treatment
Serum IgG4/(g·L^-1)	5.8	8.3	2.5	11.0
IgG4-RD RI	4	3	3	3
3 months after treatment
Serum IgG4/(g·L^-1)	3.8	9.8	1.3	3.7
IgG4-RD RI	2	2	2	3
6 months after treatment
Serum IgG4/(g·L^-1)	8.4	11.9	2.1	4.5
IgG4-RD RI	3	3	3	3
Duration of remission/month	4	4	6	5
The last follow up
Serum IgG4/(g·L^-1)	4.2	42.9	1.1	6.0
IgG4-RD RI	2	3	2	2