羟氯喹致眼毒性的文献分析
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摘要
目的:探讨羟氯喹致眼毒性的发生规律和特点,以期为临床安全用药提供参考。方法:检索截止2018年7月国内外文献数据库关于羟氯喹致眼毒性的临床研究文献,通过文献筛选后,对纳入的文献进行数据的提取和分析,包括患者性别、年龄、人种、原患疾病、累积剂量、给药剂量、治疗后不良反应出现时间、眼毒性类型、转归、严重程度、合并用药及眼科病史等。结果:共检索到17篇文献20例患者,其中女19例,男1例; 60岁以下患者占70%;白种人居多;原发疾病为系统性红斑狼疮10例,类风湿关节炎5例和其他疾病5例。眼毒性类型以黄斑变性、视力下降和视网膜病变居多。12例患者在治疗5年后出现药品不良反应(ADR);累积剂量低于1 000 g与超过1 000 g出现眼毒性的患者数各占一半;羟氯喹日剂量超过6. 5 mg·kg·d~(-1)的患者比例较高。20例患者中有3例症状持续无法缓解。严重不良反应患者3例(15%),其余为一般不良反应。结论:羟氯喹致眼毒性较为罕见,但可能出现严重的不可逆损害。白种人、女性、60岁以下、患有系统性红斑狼疮或类风湿关节炎、治疗时间超过5年、每日给药剂量超过6. 5 mg·kg~(-1)·d~(-1)的患者可能较易出现眼毒性,临床需格外关注,使用前和用药期间应定期行眼科检查。
Objective: To explore the general patterns and characteristics of hydroxychloroquine-induced ocular toxicity and provide a reference for clinical medication safety. Methods: Literatures of hydroxychloroquine-induced ocular toxicity were searched from domestic and foreign literature databases until July 2018. After screening,data of included literature were extracted and analyzed,including patient gender,age,race,primary disease,cumulative dose,dose,time after treatment,type of ocular toxicity,outcome,severity,combined medication and ophthalmic history. Results: A total of 17 literatures were retrieved which included 20 cases. Among them,19 cases were female and 1 was male. Patients under 60 years old accounted for 70%. Caucasian patients were the most. The primary diseases were 10 patients of systemic lupus erythematosus,5 patients of rheumatoid arthritis and the remaining 5 patients. Ocular toxicity was major with macular degeneration,decreased vision and retinopathy. 12 patients had ADR after 5 years of treatment. Numbers of ocular toxicities in patients with cumulative doses of 1 000 g whether less or more were the same. The daily dose of hydroxychloroquine administered over 6. 5 mg·kg~(-1)·d~(-1) increased risk of ocular toxicity. There were 3 patients having unabated symptoms within the total 20 cases. There were 3 patients( 15%) had severe ADR,and the remaining were general. Conclusion: Hydroxychloroquine induced ocular toxicity is rare,but may be serious irreversible damage. In clinical practice,for patients with white,female,60 years of age,suffering from systemic lupus erythematosus or rheumatoid arthritis,the treatment of more than 5 years,more than 6. 5 mg·kg~(-1)·d~(-1) may be prone to ocular toxicity,we need extra attention. Patients should be regularly examined for ophthalmia before and during hydroxychloroquine use in order to detect ocular toxicity as early as possible.
Objective: To explore the general patterns and characteristics of hydroxychloroquine-induced ocular toxicity and provide a reference for clinical medication safety. Methods: Literatures of hydroxychloroquine-induced ocular toxicity were searched from domestic and foreign literature databases until July 2018. After screening,data of included literature were extracted and analyzed,including patient gender,age,race,primary disease,cumulative dose,dose,time after treatment,type of ocular toxicity,outcome,severity,combined medication and ophthalmic history. Results: A total of 17 literatures were retrieved which included 20 cases. Among them,19 cases were female and 1 was male. Patients under 60 years old accounted for 70%. Caucasian patients were the most. The primary diseases were 10 patients of systemic lupus erythematosus,5 patients of rheumatoid arthritis and the remaining 5 patients. Ocular toxicity was major with macular degeneration,decreased vision and retinopathy. 12 patients had ADR after 5 years of treatment. Numbers of ocular toxicities in patients with cumulative doses of 1 000 g whether less or more were the same. The daily dose of hydroxychloroquine administered over 6. 5 mg·kg~(-1)·d~(-1) increased risk of ocular toxicity. There were 3 patients having unabated symptoms within the total 20 cases. There were 3 patients( 15%) had severe ADR,and the remaining were general. Conclusion: Hydroxychloroquine induced ocular toxicity is rare,but may be serious irreversible damage. In clinical practice,for patients with white,female,60 years of age,suffering from systemic lupus erythematosus or rheumatoid arthritis,the treatment of more than 5 years,more than 6. 5 mg·kg~(-1)·d~(-1) may be prone to ocular toxicity,we need extra attention. Patients should be regularly examined for ophthalmia before and during hydroxychloroquine use in order to detect ocular toxicity as early as possible.
引文
1张江林,黄烽.羟氯喹的药理作用及在风湿性疾病中的应用[J].解放军药学学报,2000,16(2):85-88
2 王文灵.硫酸羟氯喹治疗风湿病的临床效果研究[J].中国现代药物应用,2016,10(12):138-139
3 Cambioggi A. Unusual ocular lesions in a case of systemic lupus erythematosus[J]. Arch Ophthalmol,1957,57(3):451-453
4 Mavrikakis I. Sfikakis PP,Mavrikakis E. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine:a reappraisal[J]. Ophthalmology,2003,110(7):1321-1326
5 药品不良反应报告和监测管理办法[S].卫生部81号令. 2011
6 郭代红,张晓东,刘皈阳.医疗机构药物安全性监测[M].北京:人民军医出版社,2010:86-87
7 Saurabh K,Roy R,Thomas NR,et al. Multimodal imaging characteristics of hydroxychloroquine retinopathy[J]. Indian J Ophthalmol,2018,66(2):324-327
8 Hong EH,Ahn SJ,Lim HW,et al. The effect of oral acetazolamide on cystoid macular edema in hydroxychloroquineretinopathy:a case report[J]. BMC Ophthalmol,2017,17(1):124
9 Katsman D,Sanfilippo C,Sarraf D. PANRETINAL DEGENERATION ASSOCIATED WITH LONG-TERM HYDROXYCHLOROQUINE USE AND HETEROZYGOUS USH2A MUTATION[J]. Retin Cases Brief Rep,2017,11(Suppl 1):S77-S80
10 Sellam A,Massamba N,Le Hoang P,et al. Multimodal imaging of hydroxychloroquine and chloroquine retinopathy[J]. Fr Ophtalmol,2016,39(1):111-113
11 Parikh VS,Modi YS,Au A,et al. Nonleaking cystoid macular edema as a presentation of hydroxychloroquine retinal toxicity[J]. Ophthalmology,2016,123(3):664-666
12 Brandao LM,Palmowski-Wolfe AM. A possible early sign of hydroxychloroquine macular toxicity[J]. Doc Ophthalmol,2016,132(1):75-81
13 Barnes AC,Bhavsar KV,Weber ML,et al. A subtle case of hydroxychloroquine retinopathy:spectral domain optical coherence tomography findings[J]. Eye(Lond),2014,28(12):1521-1522
14 Melles RB,Marmor MF. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity[J]. Ophthalmology,2015,122(1):110-116
15 Chiang E,Jampol LM,Fawzi AA. Retinal toxicity found in a patient with systemic lupus erythematosus prior to 5 years of treatment with hydroxychloroquine[J]. Rheumatology(Oxford),2014,53(11):2001
16 Phillips BN,Chun DW. Hydroxychloroquine retinopathy after short-term therapy[J]. Retin Cases Brief Rep,2014,8(1):67-69
17 Lee WJ,Ko MK,Lee BR. Hydroxychloroquine retinopathy combined with retinal pigment epithelium detachment[J].Cutan Ocul Toxicol,2012,31(2):144-147
18 Salu P,Uvijls A,van den Brande P,et al. Normalization of generalized retinal function and progression of maculopathy after cessationof therapy in a case of severe hydroxychloroquine retinopathy with 19 years follow-up[J]. Doc Ophthalmol,2010,120(3):251-264
19 Turgut B,Turkcuoglu P,Serdar Koca S,et al. Detection of the regression on hydroxychloroquine retinopathy in optical coherence tomography[J]. Clin Rheumatol,2009,28(5):607-609
20 Rüther K,Foerster J,Berndt S,et al. Variabilitt der retinotoxischen Gesamtdosis Chloroquin/Hydroxychloroquin[J]. Der Ophthalmologe,2007,104(10):875-880
21 Gilbert ME,Savino PJ. Missing the Bull’s Eye[J]. Surv Ophthalmol,2007,52(4):440-442
22 Browning DJ. Hydroxychloroquine and chloroquine retinopathy:screening for drug toxicity[J]. Am J Ophthalmol,2002,133(5):649-656
23 Maturi RK,Folk JC,Nichols B,et al. Hydroxychloroquine retinopathy[J]. Arch Ophthalmol,1999,117(9):1262-1263
24 Fries JF,Williams CA,Ramey D. The relative toxicity of disease-modifying antirheumatic drugs[J]. Arthritis Rheum,1993,36(3):297-306
25 闫琳毅,张海艇,林玮,等.自身免疫性疾病患者长期使用羟氯喹治疗的安全性[J].中华临床免疫和变态反应杂志,2015,9(4):262-266
26 Sundelin S,Terman A. Different effects of chloroquine and hydroxychloroquine on lysosomal function in cultured retinal pigment epithelial cells[J]. APMIS,2002,110(6):481-489
27 Marmor MF,Kellner U,Lai TY,et al. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy[J]. Ophthalmol,2011,118(2):415-422
28 臧长海,曾庆馀,李小峰,等.太原地区常见风湿病流行病学研究[J].中国药物与临床,2007,7(8):597-602
29 Schraermeyer U,Peters S,Thumann G,et al. Melanin granules of retinal pigment epithelium are connected with the lysosomal degradation pathway[J]. Exp Eye Res,1999,68(2):237-245
30 Blomquist PH,Chundru RK. Screening for hydroxychlo-roquine toxicity by Texas ophthalmologists[J]. J Rheumatol,2002,29(8):1665-1670
2 王文灵.硫酸羟氯喹治疗风湿病的临床效果研究[J].中国现代药物应用,2016,10(12):138-139
3 Cambioggi A. Unusual ocular lesions in a case of systemic lupus erythematosus[J]. Arch Ophthalmol,1957,57(3):451-453
4 Mavrikakis I. Sfikakis PP,Mavrikakis E. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine:a reappraisal[J]. Ophthalmology,2003,110(7):1321-1326
5 药品不良反应报告和监测管理办法[S].卫生部81号令. 2011
6 郭代红,张晓东,刘皈阳.医疗机构药物安全性监测[M].北京:人民军医出版社,2010:86-87
7 Saurabh K,Roy R,Thomas NR,et al. Multimodal imaging characteristics of hydroxychloroquine retinopathy[J]. Indian J Ophthalmol,2018,66(2):324-327
8 Hong EH,Ahn SJ,Lim HW,et al. The effect of oral acetazolamide on cystoid macular edema in hydroxychloroquineretinopathy:a case report[J]. BMC Ophthalmol,2017,17(1):124
9 Katsman D,Sanfilippo C,Sarraf D. PANRETINAL DEGENERATION ASSOCIATED WITH LONG-TERM HYDROXYCHLOROQUINE USE AND HETEROZYGOUS USH2A MUTATION[J]. Retin Cases Brief Rep,2017,11(Suppl 1):S77-S80
10 Sellam A,Massamba N,Le Hoang P,et al. Multimodal imaging of hydroxychloroquine and chloroquine retinopathy[J]. Fr Ophtalmol,2016,39(1):111-113
11 Parikh VS,Modi YS,Au A,et al. Nonleaking cystoid macular edema as a presentation of hydroxychloroquine retinal toxicity[J]. Ophthalmology,2016,123(3):664-666
12 Brandao LM,Palmowski-Wolfe AM. A possible early sign of hydroxychloroquine macular toxicity[J]. Doc Ophthalmol,2016,132(1):75-81
13 Barnes AC,Bhavsar KV,Weber ML,et al. A subtle case of hydroxychloroquine retinopathy:spectral domain optical coherence tomography findings[J]. Eye(Lond),2014,28(12):1521-1522
14 Melles RB,Marmor MF. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity[J]. Ophthalmology,2015,122(1):110-116
15 Chiang E,Jampol LM,Fawzi AA. Retinal toxicity found in a patient with systemic lupus erythematosus prior to 5 years of treatment with hydroxychloroquine[J]. Rheumatology(Oxford),2014,53(11):2001
16 Phillips BN,Chun DW. Hydroxychloroquine retinopathy after short-term therapy[J]. Retin Cases Brief Rep,2014,8(1):67-69
17 Lee WJ,Ko MK,Lee BR. Hydroxychloroquine retinopathy combined with retinal pigment epithelium detachment[J].Cutan Ocul Toxicol,2012,31(2):144-147
18 Salu P,Uvijls A,van den Brande P,et al. Normalization of generalized retinal function and progression of maculopathy after cessationof therapy in a case of severe hydroxychloroquine retinopathy with 19 years follow-up[J]. Doc Ophthalmol,2010,120(3):251-264
19 Turgut B,Turkcuoglu P,Serdar Koca S,et al. Detection of the regression on hydroxychloroquine retinopathy in optical coherence tomography[J]. Clin Rheumatol,2009,28(5):607-609
20 Rüther K,Foerster J,Berndt S,et al. Variabilitt der retinotoxischen Gesamtdosis Chloroquin/Hydroxychloroquin[J]. Der Ophthalmologe,2007,104(10):875-880
21 Gilbert ME,Savino PJ. Missing the Bull’s Eye[J]. Surv Ophthalmol,2007,52(4):440-442
22 Browning DJ. Hydroxychloroquine and chloroquine retinopathy:screening for drug toxicity[J]. Am J Ophthalmol,2002,133(5):649-656
23 Maturi RK,Folk JC,Nichols B,et al. Hydroxychloroquine retinopathy[J]. Arch Ophthalmol,1999,117(9):1262-1263
24 Fries JF,Williams CA,Ramey D. The relative toxicity of disease-modifying antirheumatic drugs[J]. Arthritis Rheum,1993,36(3):297-306
25 闫琳毅,张海艇,林玮,等.自身免疫性疾病患者长期使用羟氯喹治疗的安全性[J].中华临床免疫和变态反应杂志,2015,9(4):262-266
26 Sundelin S,Terman A. Different effects of chloroquine and hydroxychloroquine on lysosomal function in cultured retinal pigment epithelial cells[J]. APMIS,2002,110(6):481-489
27 Marmor MF,Kellner U,Lai TY,et al. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy[J]. Ophthalmol,2011,118(2):415-422
28 臧长海,曾庆馀,李小峰,等.太原地区常见风湿病流行病学研究[J].中国药物与临床,2007,7(8):597-602
29 Schraermeyer U,Peters S,Thumann G,et al. Melanin granules of retinal pigment epithelium are connected with the lysosomal degradation pathway[J]. Exp Eye Res,1999,68(2):237-245
30 Blomquist PH,Chundru RK. Screening for hydroxychlo-roquine toxicity by Texas ophthalmologists[J]. J Rheumatol,2002,29(8):1665-1670