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1 원저 ISSN 일산병원학술지 2018;17(2):70-74 국민건강보험일산병원류마티스내과 1, 안과 2, 연구분석팀 박진수 1, 박종운 2, 임현선 3, 이찬희 Clinical Characteristics of Patients Visiting Rheumatology Clinics Jin Su Park 1, Jong Woon Park 2, Hyunsun Lim 3, Chan Hee Lee 1 Department of 1 Rheumatology, Department of 2 Ophthalmology, 3 Research and Analysis Team, National Health Insurance Service Ilsan Hospital, Goyang, Korea 1 3 Background: The purpose of this study was to evaluate clinical characteristics of uveitis patients visiting a rheumatology clinic (RC). Method: New uveitis patients visiting an RC from January 2012 to December 2016 in National Health Insurance Service Ilsan hospital were included. We collected information on age, clinical characteristics of uveitis, clinical characteristics of rheumatologic manifestations, laboratory findings including human leukocyte antigen (HLA)-B27, HLA-B51, and presence of rheumatologic disease. Result: Among 38 uveitis patients visiting the RC, 22 were new uveitis patients. The male to female ratio was 1:1, age at visiting the RC was 42.8 years, and age at diagnosis of uveitis was 42.6 years. Seventeen patients (81.0%) visited the RC for evaluation of RHD at the time of the their diagnosis of uveitis. Six patients (27.3%) were diagnosed with RHD along with uveitis, 10 patients (45.5%) were HLA-B27 positive, and four patients (20.0%) were HLA-B51 positive. No significant difference in sex, onset age of uveitis, site of uveitis, oral ulcer, and back pain were noted between HLA-B27 positive and negative-patients. However, RHD incidence was higher in HLA-B27 positive patients (50.0%) than in HLA-B27 negative patients (8.3%, p=0.06). Incidence of HLA-B27 positive patients was higher in patients with RHD (83.3%) than in patients without RHD (31.3%, p=0.06). Conclusion: Among HLA-B27 positive uveitis patients, 50% have RHD. Also among uveitis patients with RHD, 83% of them are HLA-B27 positive. For HLA-B27 positive patients with uveitis, careful evaluation for an association with RHD is recommended. Key Words:, Rheumatologic disease, HLA-B27 서론 류마티스내과에서진료중인자가면역질환은침범하는장기와 발병기전에따라다양한임상증상을나타낼수있다. 질병의특 성상전신을침범할수있으며, 안과질환과동반되는경우도드 물지않다. 그중가장대표적인질환은베체트병으로, 50% 이상 책임저자 : 이찬희 경기도고양시일산동구일산로 100 국민건강보험일산병원류마티스내과전화: (031) , 팩스: chanhee@nhimc.or.kr * 본연구는국민건강보험일산병원의연구비지원으로이루어졌음 (NHIMC 2017CR025). 의환자에서눈을침범하는것으로알려져있으며, 가장흔한병 변은포도막염으로, 실명을초래할수도있다. 1,2 강직성척추염을 포함한혈청음성척추관절염도포도막염이발생할수있으며, 강 직성척추염의척추증상보다먼저발현되는경우도있다. 3-6 이 외에도소아기특발성관절염이나, 혈관염, 감염, 약제등에서도 포도막염이발생할수있다. 2,7,8 이러한이유로안과에서는포도 막염이새로이진단된환자에게자가면역질환에대한평가를위 해류마티스내과진료를받아보도록권유하고있으며, 류마티스 내과에서도환자가안구증상을호소하는경우안과진료를받아 보도록권유하고있다. 9 1,022 명의포도막염환자를대상으로한 Llorenc 의연구에 의하면, 25% 에서전신면역질환이동반되었고, 그중베체트병이 5%, HLA-B27 연관전방포도막염이 5%, 강직성척추염이 5% 였 70 Korean Journal of National Health Insurance Service Ilsan Hospital

2 박진수외. 다고한다. 3 전신면역질환과동반된포도막염의치료에있어면역 억제치료의중요성이점점증가하고있고, 이로인해치료결과가 향상되고, 스테로이드의사용을줄일수있다. 10 따라서면역질환 과동반된포도막염의치료를위해서는안과의사와류마티스내 과의사의협진이필요하다. 하지만, 류마티스내과에서진료받은 환자로포도막염상병을동반한환자의임상적인특성에대한국 내보고는많지않아, 본원류마티스내과에서진료받은환자 로포도막염상병을동반한환자의임상적인특성을알아보고자 하였다. 1. 연구대상 대상및방법 이환자들의남녀비는 1:1 이었고, 류마티스내과에내원할당 시의나이는 42.8 세였으며, 포도막염을진단받은나이는 42.6세 였다. 포도막염이양쪽에모두온경우보다는한쪽에만온경우가 더많았으며, 대부분의환자(81.0%) 가포도막염을처음진단받고 류마티스질환에대한평가를위해류마티스내과에내원하였다. 구강궤양을동반한환자는 31.8% 였으며, 요통은 27.3% 에서확 인되었다. 류마티스인자나항씨씨피인자가양성인환자는없었으 나, 항핵항체는 2 명에서양성반응을보였고, 10 명(45.5%) 에서 HLA-B27 이양성이었으며, 4명에서 HLA-B51 이양성이었다. 이들환자중류마티스질환이동반된환자는모두 6명이었다 (27.3%, Table 1). 동반된류마티스질환은척추관절병증 (4 명), 베체트병 (1 명), 혈관염 (1 명) 이었다. 본원안과에서포도막염을진 단받은 11명의환자중 10 명에서경구스테로이드를투여받았고, 2012 년 1월 1일부터 2016 년 12월 31일사이에본원류마티스 내과에서진료받은환자중포도막염상병을동반한환자를대상으 로하였다. 이들환자중 2012 년 1월 1일이전에포도막염을진단 받은환자, 19세미만의환자및 65 세이상의환자는제외하였다. 2. 방법 류마티스내과에서진료받은환자로포도막염상병을동반한 환자의임상양상을알아보고자나이(; 류마티스내과내원시의 나이및포도막염진단시의나이), 성별, 포도막염의양상, 구강궤 양, 외음부궤양, 요통동반여부, 백혈구, 혈색소, 혈소판, 적혈구 침강속도(erythrocyte sedimentation rate; ESR), C-반응성 단백질 (C-reactive protein, CRP), 류마티스인자, 항 cyclic cit- rullinated peptide (CCP) 항체, 항핵항체, HLA-B27, HLA- B51, 류마티스질환동반여부, 포도막염치료법등을비교하였다. 두군간의비교는카이제곱검정이나 T-test 를이용하였고, p값 이 0.1 이하인경우의미있는것으로정의하였다. 본연구는국 민건강보험일산병원기관생명윤리위원회의승인을받았다 (Institutional review board No: ). 결과 2012년 1월 1일부터 2016 년 12월 31일사이에국민건강보 험공단일산병원류마티스내과에서진료받은환자중포도막염 상병을동반한환자는총 38 명이었고, 이중 2012 년 1월 1일이 전에포도막염을진단받은환자와 19세미만의환자및 65세이 상의환자를제외한환자는총 22 명이었다. Table 1. Demographic, clinical and laboratory findings of uveitis patients visiting rheumatology clinic. N=22 Male: female 11:11 Visit Rheumatology clinic 42.8 ± 12.4 Diagnose uveitis 42.6 ± 12.4 Right/left/both * 7/7/3 * Anterior/posterior/pan 4/2/5 First/second/more than second 17/2/2 Oral ulcer (%) 7 (31.8) Genital ulcer (%) 0 Back pain (%) 6 (27.3) WBC (/mm3) 8,430 ± 3,040 Hemoglobin (g/dl) ± 1.38 platelet (mg/dl) ± 73.8 ESR (mm/hr) 14.9 ± 15.8 CRP(mg/dL) 1.40 ± 4.15 Proteinuria (%) 2 (9.5) Rheumatoid factor (IU/L) 0 Anti-CCP antibody 0 Antinuclear antibody positivity (%) 2 (20.0) HLA-B27 (%) 10 (45.5) HLA-B51 (%) 4 (20.0) Abnormal chest x-ray (%) 0 Follow-up duration (month) 5.4 ± 9.4 With rheumatologic disease (%) 6 (27.3) WBC: white blood cell, ESR: erythrocyte sedimentation rate, CRP: c-reactive protein, CCP: cyclic citrullinated peptide, HLA: human leukocyte antigen, * 17 patients had a result, 11 patients had a result, 21 patients had a result, 20 patients had a result. Volume 17 Number 2 December

3 JS Park et al. Clinical Characteristics of Patients Visiting Rheumatology Clinics 그중 4 명에서는안과적수술도시행받았다. 포도막염이있는환자들을 HLA-B27 양성여부에따라비교해 보면, 양성인군과음성인군사이에성별이나, 포도막염발병연 령, 포도막염의양안발생여부, 구강궤양이나, 요통의동반여부, HLA-B51 양성여부에는큰차이를보이지않았다. 하지만, HLA- B27 양성인환자들중절반에서류마티스질환이동반되어, HLA- B27 음성인군에비해류마티스질환의동반률이높았다 (p=0.06, Table 2). HLA-B51 은총 20 명에서검사되었고, 4명에서양성 반응을보였으나, HLA-B51 양성여부에따른통계학적차이를 보이는결과는확인되지않았다 (Table 3). 류마티스질환이동반된군과동반되지않은군을비교해보 면, 두군사이에성별이나, 연령, 구강궤양이나, 요통의동반여 부, HLA-B51 양성여부에는큰차이를보이지않았으나, 류마티 스질환이동반된환자의 83.3% 에서 HLA-B27 양성이확인되 어, 류마티스질환이동반되지않은환자군 (31.3%) 보다 HLA-B27 양성률이높았다 (p=0.06, Table 4). 평균추적관찰기간은 5.4개 월이었으며, 류마티스질환이동반된 6명의환자모두 follow-up loss 가되어류마티스질환에대한장기적인추적관찰은하지못 하였다. 고찰 본연구를통해, 포도막염상병을가지고류마티스내과에서 진료받은환자의 27% 에서류마티스질환이동반됨을확인하였 다. 동반된류마티스질환은척추관절병증이 4명으로가장많았 으며, 베체트병과혈관염이각각 1 명이었다. HLA-B27 양성인 환자의류마티스질환동반률은음성인환자보다높았으나, HLA- B51 양성인환자의류마티스질환동반률은음성인환자와차이 Table 2. Comparison of clinical and laboratory findings between uveitis patients with and without HLA-B27. Positive HLA-B27 Negative Number Male: female 5:5 6:6 1.0 Visit Rheumatology clinic Diagnose uveitis Both eye 2 (2/8 * ) 2 (2/9 * ) More than first 0 (0/8 * ) 4 (4/12 * ) Oral ulcer 3 (30.0%) 4 (33.3%) Back pain 3 (30.0%) 3 (25.0%) WBC (/mm 3 ) 8,970 7, Hemoglobin (g/dl) platelet (mg/dl) ESR (mm/hr) CRP(mg/dL) HLA-B51 1 (1/8 * ) 3 (3/12 * ) 0.62 Follow-up duration (month) With rheumatologic disease 5 (50.0%) 1 (8.3%) 0.06 Table 3. Comparison of clinical and laboratory findings between uveitis patients with and without HLA-B51. Positive HLA-B51 Negative Number 4 16 Male: female 1:3 8: Visit Rheumatology clinic Diagnose uveitis Both eye 1 (1/3 * ) 2 (2/13 * ) More than first 0 (0%) 4 (25.0%) Oral ulcer 0 (0%) 6 (37.5%) Back pain 1 (25.0%) 4 (25.0%) WBC (/mm 3 ) 9,450 8, Hemoglobin (g/dl) platelet (mg/dl) ESR (mm/hr) CRP(mg/dL) HLA-B27 1 (25.0%) 7(43.8%) 0.62 Follow-up duration (month) With rheumatologic disease 1 (25.0%) 3 (18.8%) Korean Journal of National Health Insurance Service Ilsan Hospital

4 박진수외. Table 4. Comparison of clinical and laboratory findings between uveitis patients with and without rheumatologic disease. Rheumatologic disease With Without Number 6 16 를보이지않았다. 류마티스질환이동반된환자의 83% 에서 HLA- B27 이양성으로확인되어, 류마티스질환이동반되지않은환자 군의 HLA-B27 양성률보다높음을알수있었다. Male: female 4:2 7: Visit Rheumatology clinic Diagnose uveitis Both eye 2 2 More than first 0 4 Oral ulcer 2 (33.3%) 5 (31.3%) Back pain 2 (33.3%) 4 (25.0%) WBC (/mm 3 ) 8,300 8, Hemoglobin (g/dl) platelet (mg/dl) ESR (mm/hr) CRP(mg/dL) HLA-B27 5 (83.3%) 5 (31.3%) 0.06 HLA-B51 1 (1/4 * ) 3 (3/16 * ) 0.78 Follow-up duration (month) 대부분의환자(81.0%) 에서첫포도막염을진단받고류마티스 질환동반여부에대한평가를진행하였다. 이를통해본원에서의 포도막염에대한안과와류마티스내과의다학제적접근은원활 하게이루어지고있는것으로추정된다. 포도막염상병을가지고 류마티스내과에서진료받은환자중류마티스질환이동반된환 자는 27.3% 로이는 Llorenc 의연구(25%) 와유사한양상이었다. 3 기연구에의하면동반된류마티스질환 25% 중베체트병이 5%, HLA-B27 연관전방포도막염이 5%, 강직성척추염이 5% 로, HLA- B27 연관포도막염 (HLA-B27 연관전방포도막염 + 강직성척추 염) 이약 10% 일것으로추정되며, 본연구에서도 HLA-B27 양성 이 46%, HLA-B51 양성이 20% 로 HLA-B27 연관포도막염이베 체트병연관포도막염의 2 배정도가됨을알수있었다. 또한 HLA-B27 양성인환자의 50% 에서류마티스질환이동반되었고, 류마티스질환이동반된환자의 83% 에서 HLA-B27 이양성으로 확인되었다. 류마티스질환이동반된포도막염의경우, 중증도가 더높다는보고도있어, 12 포도막염이있으면서 HLA-B27 양성인 경우류마티스질환동반여부에대한주의깊은평가가필요할것 으로사료된다. 본연구는단일기관에서시행한연구로, 대상환자수가많지 않다는제한점이있다. 아울러추적관찰기간도길지않기에더많 은환자를대상으로한추가적인다기관장기추적관찰연구가필 요할것으로생각된다. 대부분의류마티스질환은만성전신성염증질환으로, 안과질 환도잘동반되는것으로알려져있다. 본연구에서도포도막염 환자의 27% 에서류마티스질환이동반된것을확인하였다. 포도 막염은심한경우시력상실까지초래될수있으므로, 안과전문의 와류마티스전문의의포도막염에대한다학제진료가환자의진 단및치료, 예후의향상에도움을줄수있을것이다. REFERENCES 1. Baldassano VF. Ocular manifestations of rheumatic diseases. Curr Opin Ophthalmol 1998;9(6): Sève P, Kodjikian L, Adéla ïde L, Jamilloux Y. in adults: What do rheumatologists need to know? Joint Bone Spine 2015;82(5): Lloren ç V, Mesquida M, Sainz de la Maza, Maite, Keller J, Molins B, Espinosa G, et al. Epidemiology of uveitis in a Western urban multiethnic population. The challenge of globalization. Acta Ophthalmol 2015;93(6): Smith JR. HLA-B27-associated uveitis. Ophthalmol Clin North Am 2002;15(3): Selmi C, Gershwin ME. Diagnosis and classification of reactive arthritis. Autoimmun Rev 2014;13(4-5): Wendling D. in seronegative arthritis. Curr Rheumatol Rep 2012;14(5): Pan J, Kapur M, McCallum R. Noninfectious immunemediated uveitis and ocular inflammation. Curr Allergy Asthma Rep 2014;14(1): Generali E, Cantarini L, Selmi C. Ocular Involvement in Systemic Autoimmune Diseases. Clin Rev Allergy Immunol 2015;49(3): Selmi C. Diagnosis and classification of autoimmune uveitis. Autoimmun Rev 2014;13(4-5): Prete M, Dammacco R, Fatone MC, Racanelli V. Auto- Volume 17 Number 2 December

5 JS Park et al. Clinical Characteristics of Patients Visiting Rheumatology Clinics immune uveitis: clinical, pathogenetic, and therapeutic features. Clin Exp Med 2016;16(2): Kim JJ, Kim TH. in Rheumatic Diseases. J Rheum Dis 2012;19: Kim NK, Park MY, Lee JH, Lee DH, Yoon BY. and Rheumatic Diseases in a Community Based Practice - Korean Population. J Rheum Dis 2011;18: Koo BS, Hong SC, Kim YJ, Lee CK, Yoo B, Kim TG. The Incidence of in Ankylosing Spondylitis Patients Undergoing Tumor Necrosis Factor Inhibiting Therapy in Korea. J Rheum Dis 2015;22: Kim YJ, Lee JY. Eye and Rheumatic Disease. J Rheum Dis 2013;20: Korean Journal of National Health Insurance Service Ilsan Hospital

012임수진

012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar