类风湿关节炎合并角膜溃疡的临床特点和相关因素分析

doi:10.19723/j.issn.1671-167X.2021.06.004

摘要/Abstract

摘要：

目的:探讨类风湿关节炎(rheumatoid arthritis,RA)合并角膜溃疡(ulcerative keratitis,UK)的临床特点、相关因素及临床转归。方法:选取2003年1月至2021年5月于北京大学人民医院住院的RA患者4 773例,筛选出合并UK的患者16例(UK组),通过倾向性评分匹配(propensity score matching,PSM), 选取无UK的对照组患者72例。对PSM后的两组患者的临床及实验室资料进行统计和分析。结果:RA合并UK表现为单纯边缘性UK 8例、边缘性UK伴穿孔5例、边缘性UK伴葡萄膜炎2例、中央性UK伴穿孔1例。UK组肿胀关节数显著高于对照组[6.0(2.5,23.0) vs. 3.0(1.0, 9.8),Z=-2.047,P=0.041],UK组继发干燥综合征(Sjögren syndrome,SS)的比例(37.5% vs. 6.9%, χ²=11.175,P=0.004)及间质性肺炎(interstitial lung disease,ILD,37.5% vs. 8.3%, χ²=9.456,P=0.008)的比例显著高于对照组,柳氮磺吡啶(12.5% vs. 48.6%, χ²=7.006,P=0.008)、来氟米特(31.3% vs. 63.9%, χ²=5.723,P=0.017)及金制剂(6.3% vs. 33.8%, χ²=4.841,P=0.032)的使用率显著低于对照组。回归分析显示肿胀关节数(OR=1.148)、继发SS(OR=79.118)、合并ILD(OR=6.596)及柳氮磺吡啶的使用(OR=0.037)与RA合并UK的发生存在独立相关性(P<0.05)。结论:UK为RA的少见并发症,多为边缘性UK。肿胀关节数、继发SS、合并ILD及柳氮磺吡啶的使用与RA合并UK发生存在独立相关性。

关键词: 类风湿关节炎, 角膜溃疡, 相关因素

Abstract:

Objective: To investigate the clinical characteristics, risk factors and prognosis of ulcerative keratitis (UK) in patients with rheumatoid arthritis (RA). Methods: Sixteen patients with UK (the UK group) were screened among 4 773 RA patients hospitalized at Peking University People’s Hospital from January 2003 to May 2021, and 72 patients with RA without UK in the control group were selected by propensity score matching (PSM). The clinical features, laboratory data and medications between the two groups were collected and analyzed. Results: The average age of the patients with RA was 60 years at the time of the complication of UK. UK appeared on average in the 16th year of RA, with the majority of UK occurring in the 7th year of RA and beyond (14 cases), however, a minority of UK was the first symptom of RA (1 case). UK associated with RA manifested as simple marginal UK in 8 cases, marginal UK with perforation in 5 cases, marginal UK with uveitis in 2 cases and central UK with perforation in 1 case. The number of swollen joints was significantly higher in the UK group than in the control group [6.0(2.5,23.0) vs. 3.0(1.0, 9.8), Z=-2.047, P=0.041], and the proportion of secondary Sjögren syndrome (SS,37.5% vs. 6.9%, χ²=11.175, P=0.004) and interstitial lung disease (ILD, 37.5% vs. 8.3%, χ ²=9.456, P=0.008) were significantly higher in the RA patients with UK than the patients without UK. The uses of sulfasalazine (12.5% vs. 48.6%, χ ²=7.006, P=0.008), leflunomide (31.3% vs. 63.9%, χ ²=5.723, P=0.017) and gold salt(6.3% vs. 33.8%, χ ²=4.841, P=0.032)were significantly lower in the UK group than in the control group. However, there was no statistically significant comparison between the two groups for the 28-joint disease activity score-erythrocyte sedimentation rate (5.3±1.8 vs. 5.1±1.6, t=0.309, P=0.761). Logistic analysis showed the number of swollen joints (OR=1.148), secondary SS (OR=79.118), complicated with ILD (OR=6.596) and the use of sulfasalazine (OR=0.037) were independent relevant factors (P<0.05) for UK in RA patients. Conclusion: The number of swollen joints, secondary SS, complicated with ILD and the use of sulfasalazine are independent relevant factors for UK in patients with RA.

Key words: Rheumatoid arthritis, Ulcerative keratitis, Relevant factor

中图分类号:

R593.22

罗靓,霍文岗,张钦,李春. 类风湿关节炎合并角膜溃疡的临床特点和相关因素分析[J]. 北京大学学报（医学版）, 2021, 53(6): 1032-1036.

LUO Liang,HUO Wen-gang,ZHANG Qin,LI Chun. Clinical characteristics and risk factors of rheumatoid arthritis with ulcerative keratitis[J]. Journal of Peking University (Health Sciences), 2021, 53(6): 1032-1036.

图/表 5

图1

图2

表1

表2

表3

参考文献 23

[1]	Jayaraj K, Alvin G, Charles S, et al. Correlation of ocular manifestations with the duration and activity of disease in patients with rheumatoid arthritis[J]. Int J Med Sci, 2017, 6(1):34-37.
[2]	Hamideh F, Prete P. Ophthalmologic manifestations of rheumatic diseases[J]. Semin Arthritis Rheum, 2001, 30(4):217-241.
[3]	Foster CS, Forstot SL, Wilson LA. Mortality rate in rheumatoid arthritis patients developing necrotizing scleritis or peripheral ulcerative keratitis: effects of systemic immune suppression[J]. Ophthalmology, 1984, 91(10):1253-1263. pmid: 6514289
[4]	Zandavalli F, Castro G, Mazzucco M, et. al. Infliximab is effective in difficult-to-control peripheral ulcerative keratitis. A report of three cases[J]. Rev Bras Reumatol, 2015, 55(3):310-312. doi: 10.1016/j.rbr.2014.05.006 pmid: 25440698
[5]	Aletaha D, Neogi T, Silman J, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology / European League Against Rheumatism Collaborative Initiative[J]. Arthritis Rheum, 2010, 62(9):2569-2581. doi: 10.1002/art.27584
[6]	Yoshida M, Hariya T, Yokokura S, et al. Concomitant herpes simplex keratitis and autoimmune-associated ulcerative keratitis in rheumatoid arthritis patients[J]. Am J Ophthalmol Case Rep, 2020, 18:100648.
[7]	Artifoni M, Rothschild R, Brézin A, et al. Ocular inflammatory diseases associated with rheumatoid arthritis[J]. Nat Rev Rheumatol, 2014, 10(2):108-116. doi: 10.1038/nrrheum.2013.185 pmid: 24323074
[8]	Watanabe R, Ishii T, Yoshida M, et al. Ulcerative keratitis in patients with rheumatoid arthritis in the modern biologic era: a series of eight cases and literature review[J]. Int J Rheum Dis, 2017, 20(2):225-230. doi: 10.1111/1756-185X.12688 pmid: 26179634
[9]	Harrold R, Shan Y, Rebello S, et al. Prevalence of Sjögren’s syndrome associated with rheumatoid arthritis in the USA: an observational study from the Corrona registry[J]. Clin Rheumatol, 2020, 39(6):1899-1905. doi: 10.1007/s10067-020-05004-8 pmid: 32130579
[10]	Singh S, Das V, Basu S. Ocular involvement in Sjögren syndrome: risk factors for severe visual impairment and vision-threatening corneal complications[J]. Am J Ophthalmol, 2021, 225:11-17. doi: 10.1016/j.ajo.2020.12.019
[11]	Maseda D, Bonami R, Crofford L. Regulation of B lymphocytes and plasma cells by innate immune mechanisms and stromal cells in rheumatoid arthritis[J]. Expert Rev Clin Immunol, 2014, 10(6):747-762. doi: 10.1586/1744666X.2014.907744
[12]	Galor A, Thorne J. Scleritis and peripheral ulcerative keratitis[J]. Rheum Dis Clin North Am, 2007, 33(4):835-854. doi: 10.1016/j.rdc.2007.08.002
[13]	Wang F, Misra L, Patel V. In vivo confocal microscopy of the human cornea in the assessment of peripheral neuropathy and systemic diseases[J]. Biomed Res Int, 2015, 2015:951081.
[14]	Sainz M, Foster S, Jabbur S, et al. Ocular characteristics and disease associations in scleritis-associated peripheral keratopathy[J]. Arch Ophthalmol, 2002, 120(1):15-19. doi: 10.1001/archopht.120.1.15
[15]	Knox NE, Tole DM, Georgoudis P, et al. Peripheral ulcerative keratitis and corneal melt: a 10-year single center review with historical comparison[J]. Cornea, 2014, 33(1):27-31. doi: 10.1097/ICO.0000000000000008
[16]	祝磊, 王丽娅, 张俊杰, 等. 0.05%他克莫司滴眼液治疗难治性免疫相关角膜溃疡的疗效及安全性研究[J]. 中华实验眼科杂志, 2015, 33(9):823-827.
[17]	杨纪忠, 李冰. 类风湿关节炎相关性边缘角膜溃疡临床分析[J]. 山西医药杂志, 2009, 38(8):748-749.
[18]	Bonnet I, Rousseau A, Duraffour P, et al. Efficacy and safety of rituximab in peripheral ulcerative keratitis associated with rheumatoid arthritis[J]. RMD Open, 2021, 7(1):e001472. doi: 10.1136/rmdopen-2020-001472
[19]	Lucia D, Lara S, Vanesa R, et al. Biologic therapy in severe and refractory peripheral ulcerative keratitis (PUK). Multicenter study of 34 patients[J]. Semin Arthritis Rheum, 2020, 50(4):608-615. doi: 10.1016/j.semarthrit.2020.03.023
[20]	Puéchal X, Gottenberg E, Berthelot M, et al. Rituximab therapy for systemic vasculitis associated with rheumatoid arthritis: results from the autoimmunity and rituximab registry[J]. Arthritis Care Res, 2012, 64(3):331-339. doi: 10.1002/acr.20689
[21]	Peter K, Dirk B, Susann A, et al. Rapid healing of peripheral ulcerative keratitis in rheumatoid arthritis with prednisone, methotrexate and adalimumab combination therapy[J]. Rheumatology (Oxford), 2017, 56(7):1094. doi: 10.1093/rheumatology/kex007
[22]	Messmer M, Foster S. Vasculitic peripheral ulcerative keratitis[J]. Surv Ophthalmol, 1999, 43(5):379-396. pmid: 10340557
[23]	Messmer M, Foster S. Destructive corneal and scleral disease associated with rheumatoid arthritis: medical and surgical management[J]. Cornea, 1995, 14(4):408-417. pmid: 7671613

相关文章 15

[1]	高超,陈立红,王莉,姚鸿,黄晓玮,贾语博,刘田. 类风湿关节炎合并纤维肌痛简易分类标准的临床验证[J]. 北京大学学报（医学版）, 2022, 54(2): 278-282.
[2]	张璐,胡小红,陈澄,蔡月明,王庆文,赵金霞. 类风湿关节炎初治患者颈椎失稳情况及临床特征[J]. 北京大学学报（医学版）, 2021, 53(6): 1049-1054.
[3]	钟华,徐丽玲,白明欣,苏茵. 类风湿关节炎患者趋化因子CXCL9和CXCL10在骨侵蚀中的作用[J]. 北京大学学报（医学版）, 2021, 53(6): 1026-1031.
[4]	娄雪,廖莉,李兴珺,王楠,刘爽,崔若玫,徐健. 类风湿关节炎患者外周血TWEAK基因启动子区甲基化状态及其表达[J]. 北京大学学报（医学版）, 2021, 53(6): 1020-1025.
[5]	曹迪,王燕,王柳青,孙晓麟,黄妃,孟洋,任丽丽,张学武. 血浆Dickkopf-1在类风湿关节炎患者中的表达及其与外周血T细胞亚群的相关性[J]. 北京大学学报（医学版）, 2021, 53(2): 255-260.
[6]	赵凯,常志芳,王志华,庞春艳,王永福. 基因沉默肽基精氨酸脱亚胺酶4的表达对胶原诱导关节炎小鼠肺间质病变的影响[J]. 北京大学学报（医学版）, 2021, 53(2): 235-239.
[7]	钟剑球,曾沛英,王庆文. 类风湿关节炎合并淋巴水肿2例及文献回顾[J]. 北京大学学报（医学版）, 2020, 52(6): 1157-1161.
[8]	唐果,龙丽,韩雅欣,彭清,刘佳君,尚华. 类风湿关节炎合并结核感染的临床特点及相关因素[J]. 北京大学学报（医学版）, 2020, 52(6): 1029-1033.
[9]	张警丰,叶修玲,段萌,周小利,姚中强,赵金霞. 抗核抗体阳性类风湿关节炎的临床和实验室检查特点[J]. 北京大学学报（医学版）, 2020, 52(6): 1023-1028.
[10]	张璐,胡小红,王庆文,蔡月明,赵金霞,刘湘源. 类风湿关节炎合并颈椎失稳的人群分布及临床特征[J]. 北京大学学报（医学版）, 2020, 52(6): 1034-1039.
[11]	陈家丽,金月波,王一帆,张晓盈,李静,姚海红,何菁,李春. 老年发病类风湿关节炎的临床特征及其心血管疾病危险因素分析:一项大样本横断面临床研究[J]. 北京大学学报（医学版）, 2020, 52(6): 1040-1047.
[12]	彭嘉婧,刘田. 类风湿关节炎合并色素沉着绒毛结节性滑膜炎1例及文献回顾[J]. 北京大学学报（医学版）, 2020, 52(6): 1135-1139.
[13]	罗采南,李正芳,武丽君,陈海娟,杨春梅,徐文晖,刘小玲,唐薇,乔平,热娜·白合提亚. 类风湿关节炎不同分类标准的多中心临床比较[J]. 北京大学学报（医学版）, 2020, 52(5): 897-901.
[14]	竺红,赵丽娟,周艳,陈瑶. 抗氨基甲酰化蛋白抗体在类风湿关节炎合并肺间质病变早期诊断中的价值[J]. 北京大学学报（医学版）, 2019, 51(6): 1003-1007.
[15]	车新艳,吴士良,陈宇珂,黄燕波,杨洋. 女性医务人员尿失禁及其对生活质量影响的现况调查[J]. 北京大学学报（医学版）, 2019, 51(4): 706-710.

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed

Items	UK group (n=16)	Control group (n=72)	Z/t/χ²	P
ESR/(mm/H), $\overline{x}$±s	57.4±38.3	50.3±30.7	0.839	0.404
CRP/(mg/L), M (P₂₅, P₇₅)	15.8 (5.4, 42.3)	11.2 (3.2, 38.6)	-0.155	0.877
Anti-CCP/(U/mL), M (P₂₅, P₇₅)	303.0 (97.5, 650.0)	100.0 (33.3, 300.0)	-0.879	0.379
RF/(IU/mL), M (P₂₅, P₇₅)	222.0 (144.2, 266.4)	125.5 (18.5, 293.8)	-1.862	0.063
TJCs, M (P₂₅, P₇₅)	7.0 (1.0, 16.5)	7.0 (2.0, 15.8)	-0.836	0.836
DJCs, M (P₂₅, P₇₅)	1.5 (0, 10.0)	0 (0, 4.0)	-1.899	0.058
SJCs, M (P₂₅, P₇₅)	6.0 (2.5, 23.0)	3.0 (1.0, 9.8)	-2.047	0.041
Secondary SS, n (%)	6 (37.5)	5 (6.9)	11.175	0.004
DAS28-ESR score, $\overline{x}$±s	5.3±1.8	5.1±1.6	0.309	0.761
Complicated with ILD, n (%)	6 (37.5)	6 (8.3)	9.456	0.008
Rheumatoid nodules, n (%)	3 (18.8)	3 (4.2)	4.382	0.122

Parameters	UK group (n=16)	Control group (n=72)	χ²	P
HCQ/%	25.0	59.7	1.304	0.392
MTX/%	37.5	56.9	0.166	0.784
SASP/%	12.5	48.6	7.006	0.008
GS/%	6.3	33.8	4.841	0.032
LEF/%	31.3	63.9	5.723	0.017
GC/%	31.3	54.2	1.135	0.404
Biologics/%	6.3	81.9	1.364	0.450
Untreated/%	43.8	25.0	2.263	0.218

Parameters	B	Wald	P	OR	95%CI
SJCs	0.138	5.875	0.015	1.148	1.027-1.284
Secondary SS	4.371	8.333	0.004	79.118	4.068-1 538.736
ILD	1.886	4.230	0.040	6.596	1.093-39.813
SASP	-3.288	4.494	0.034	0.037	0.002-0.780
LEF	-1.696	2.485	0.115	0.183	0.022-1.511
GS	-1.219	0.567	0.623	0.451	0.012-7.042