Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (6): 1032-1036. doi: 10.19723/j.issn.1671-167X.2021.06.004

Previous Articles     Next Articles

Clinical characteristics and risk factors of rheumatoid arthritis with ulcerative keratitis

LUO Liang1,2,HUO Wen-gang3,ZHANG Qin4,(),LI Chun1,()   

  1. 1. Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing 100044, China
    2. Department of Rehabilitation, Chongqing Rehabilitation Hospital of Integrated Traditional and Western, Chongqing 400013, China
    3. Department of Rheumatology and Immunology, Hebei Yiling Hospital, Shijiazhuang 050091, China
    4. Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China
  • Received:2021-08-16 Online:2021-12-18 Published:2021-12-13
  • Contact: Qin ZHANG,Chun LI E-mail:tonimck@sina.com;13811190098@163.com
  • Supported by:
    Beijing Natural Science Foundation(7192211)

RICH HTML

  

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

CLC Number: 

  • R593.22

Figure 1

Two types of ocular manifestations of ulcerative keratitis A, marginally ulcerative keratitis; B, central ulcerative keratitis with perforation."

Figure 2

Ocular manifestations of ulcerative keratitis after treatments. A, marginally ulcerative keratitis after 2 weeks of topical application of glucocorticoid; B, central ulcerative keratitis after 10 months with multi-layer amniotic membrane repair."

Table 1

Clinical manifestations and laboratory parameters between the two groups"

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

Table 2

The Medications between the two groups"

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

Table 3

Binary Logistic analysis results of risk factors related to RA with UK"

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
[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
[1] Hui WEI, Jingfeng ZHANG, Zhongqiang YAO, Jinxia ZHAO. Clinical characteristics and relevant factors of rheumatoid arthritis patients with anemia of chronic disease [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 307-312.
[2] Tao WU, Jianzi LIN, Yafeng ZHU, Jianda MA, Peiwen JIA, Lijuan YANG, jie PAN, Yaowei ZOU, Ying YANG, Ye LU, Lie DAI. Serum inter-alpha-trypsin inhibitor heavy chain H3 is identified as a potential biomarker for myopenia in patients with rheumatoid arthritis using proteomic profiling [J]. Journal of Peking University (Health Sciences), 2025, 57(6): 1024-1031.
[3] Yan DING, Lifang WANG, Chaoran LI, Zhemin LU, Lianjie SHI. Rheumatoid arthritis combined with IgG4-related disease successfully treated with rituximab: A case report [J]. Journal of Peking University (Health Sciences), 2025, 57(6): 1203-1207.
[4] Ju YANG, Jing XU, Juhua DAI, Lianjie SHI. Expression of lumican protein in serum of patients with rheumatoid arthritis and its correlation with disease and immune activities [J]. Journal of Peking University (Health Sciences), 2025, 57(5): 911-918.
[5] Lianghua FENG, Lirong HONG, Yujia CHEN, Xueming CAI. Role and mechanism of ubiquitin-specific protease 35 in ferroptosis of rheumatoid arthritis-fibroblast like synoviocytes [J]. Journal of Peking University (Health Sciences), 2025, 57(5): 919-925.
[6] Peiwen JIA, Ying YANG, Yaowei ZOU, Zhiming OUYANG, Jianzi LIN, Jianda MA, Kuimin YANG, Lie DAI. Clinical characteristics of overlapping syndromes of low muscle mass in patients with rheumatoid arthritis and their impact on physical function [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 1009-1016.
[7] Doudou MA, Zhemin LU, Qian GUO, Sha ZHU, Jin GU, Yan DING, Lianjie SHI. Successful treatment of rheumatoid arthritis complicated with myasthenia gravis with low-dose rituximab: A case report [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 1110-1114.
[8] Rui YAN, Dan KE, Yan ZHANG, Li LI, Huanran SU, Wei CHEN, Mingxia SUN, Xiaomin LIU, Liang LUO. Diagnostic significance of serum chemokine CXCL-10 and Krebs von den lungen-6 level in patients with rheumatoid arthritis associated interstitial lung disease [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 956-962.
[9] Liang ZHAO, Chenglong SHI, Ke MA, Jing ZHAO, Xiao WANG, Xiaoyan XING, Wanxing MO, Yirui LIAN, Chao GAO, Yuhui LI. Immunological characteristics of patients with anti-synthetase syndrome overlap with rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 972-979.
[10] Yijun HAN, Xiaoli CHEN, Changhong LI, Jinxia ZHAO. Application status of methotrexate in patients with rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 994-1000.
[11] Dongwu LIU, Jie CHEN, Mingli GAO, Jing YU. Rheumatoid arthritis with Castleman-like histopathology in lymph nodes: A case report [J]. Journal of Peking University (Health Sciences), 2024, 56(5): 928-931.
[12] Huina HUANG,Jing ZHAO,Xiangge ZHAO,Ziran BAI,Xia LI,Guan WANG. Regulatory effect of lactate on peripheral blood CD4+ T cell subsets in patients with rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(3): 519-525.
[13] Xiaofei TANG,Yonghong LI,Qiuling DING,Zhuo SUN,Yang ZHANG,Yumei WANG,Meiyi TIAN,Jian LIU. Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2024, 56(2): 279-283.
[14] Xue ZOU,Xiao-juan BAI,Li-qing ZHANG. Effectiveness of tofacitinib combined with iguratimod in the treatment of difficult-to-treat moderate-to-severe rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1013-1021.
[15] Qi WU,Yue-ming CAI,Juan HE,Wen-di HUANG,Qing-wen WANG. Correlation between dyslipidemia and rheumatoid arthritis associated interstitial lung disease [J]. Journal of Peking University (Health Sciences), 2023, 55(6): 982-992.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!