류마티스 관절염 환자에서 혈장 호모시스테인, 혈청 비타민 B12, 엽산 농도에 관한 연구

차훈석 ( Hoon Suk Cha ),전찬홍 ( Chan Hong Jeon ),고재현 ( Jay Hyun Koh ),이창근 ( Chang Keun Lee ),김진석 ( Jin Seok Kim ),김종원 ( Jong Won Kim ),강성욱 ( Seong Wook Kang ),송영욱 ( Yeong Wook Song ),고은미 ( Eun Mi Koh ) 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.3

Objective: Cardiovascular disease is the most frequent cause of death in rheumatoid arthritis(RA) patients and hyperhomocysteinemia is an independent risk factor for cardiovascular disease. We evaluated the status of homocysteine, vitamin B12 and folate in RA patients and the influence of the drugs used in RA on homocysteine and vitamin levels Methods: Fifty-six RA patients and 22 controls were studied. Plasma total homocysteine was measured by HPLC method and serum folate and vitamin B12 were measured by chemiluminescence immunoassay. In RA patients, age, sex, disease duration, medications and laboratory findings were analyzed. Results: Serum vitamin B12 level was significantly lower in RA patients compared to controls(p=0.033). No significant difference in serum folate level was found between RA patients and controls but plasma total homocysteine level was significantly higher in RA patients. There was no difference in plasma total homocysteine level between patients taking MTX with folate and controls, but plasma total homocysteine level was significantly higher in patients not taking MTX compared with controls(p=0.028). In RA patients taking only hydroxyl-chloroquine(HCQ) as a DMARD, there was significantly lower serum folate level(p=0.033) and higher plasma total homocysteine level(p=0.043) compared with controls. There was a significant negative correlation between plasma total homocysteine level and serum folate level in RA patients(r=-0.319, p=0.017). Conclusion: Plasma total homocysteine level was increased in RA patients but not in patients taking MTX and folate. These findings suggested that folate supplementation may be effective to prevent hyperhomocysteinemia in RA patients.

류마티스 관절염 활막에서 종양단백질의 발현

김진석 ( Jin Seok Kim ),차훈석 ( Hoon Suk Cha ),고재현 ( Jay Hyun Koh ),서기현 ( Gi Hyun Seo ),이창근 ( Chang Keun Lee ),김병준 ( Byoung Joon Kim ),최화정 ( Hwa Jung Choi ),한정호 ( Joung Ho Han ),오원환 ( Won Hwan Oh ),고은미 ( E 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.3

Objective: The synovium in rheumatoid arthritis(RA) is characterized by an increase in the thickness of lining layer and infiltration of cells into the sublining area. Histomorphologic studies of RA have indicated that initial destruction is more closely related to the presence of transformed appearing proliferating synovial cells than to the presence of subsynovial or periarticular inflammation. Based on the fact that synovial lining cells have some properties of transformed appearing cells, we examined the expressions of Fos, Jun and Myc oncoproteins in the synovial tissue from patients with rheumatoid arthritis and osteoarthritis. Methods: Synovial tissues from 15 patients with RA and 15 with osteoarthritis(OA) were studied by the immunohistochemical staining technique. Nine of 15 RA sped men were from arthroscopic synovectomy and the other 6 were from total knee replacement arthroplasty. Result: In all specimen studied, Myc and Fos were expressed in the synovial lining cells and Myc, Fos and Jun were expressed in the sublining cells, including lymphocytes, other inflammatory cells and blood vessels. Lymphocytes in the diffuse infiltrates showed increased expression of three oncoproteins compared to lymphocytes in the nodular aggregates. When oncoprotein expressions in RA were compared to OA, Fos and Myc expressions in the synovial lining cell layer were significantly higher in RA than in OA and Jun, Fos and Myc expressions in inflammatory cells were significantly higher in RA than in OA. The expressions of Fos and Myc were significantly correlated with the degree of synovial hypercellularity. In RA, the expressions of all three oncoproteins were increased in synovectomy group than joint replacement group. Conclusion: We observe that there are increased expressions of Myc, Fos and Jun in RA synovium than OA. These changes are more prominent in synovectomy group than joint replacement group, which suggest the differential expression of oncoproteins according to disease progression.

전신성 괴사성 혈관염에서 다발성 단신경염의 임상적 고찰

김진석 ( Jin Seok Kim ),차훈석 ( Hoon Suk Cha ),서기현 ( Gi Hyun Seo ),안홍준 ( Hong Joon Ahn ),이창근 ( Chang Keun Lee ),고재현 ( Jae Hyun Koh ),김현숙 ( Hyeon Sook Kim ),최동철 ( Dong Chull Choi ),고은미 ( Eun Mi Koh ) 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.1

Background: The vasculitides are heterogeneous clinical syndromes characterized by inflammation of blood vessels. There are no pathognomonic symptoms. Mononeuritis multiplex is an acute or subacute asymmetric sensory motor syndrome involving discrete peripheral nerves and is known to occur in many illnesses including certain types of systemic vasculitis. Our purpose was to evaluate the clinical manifestations and significance of mononeuritis multiplex in systemic necrotizing vasculitis. Patients & Methods: Eight patients who were diagnosed as systemic necrotizing vasculitis at Samsung Medical Center between 1995 and 1997 were reviewed. Vasculitis was diagnosed by ACR criteria for each vasculitis and microscopic polyangiitis was diagnosed by the Chapel Hill Consensus Conference on the nomenclature of systemic vasculitis. Three were diagnosed as Churg-Strauss syndrome, 3 as polyarteritis nodosa, and 2 as microscopic polyangiitis. In most cases, vasculitis was confirmed by a biopsy specimen showing infiltration of granulocytes, lymphocytes, and/or plasma cell into vessel walls. Occasionally, polyarteritis nodosa was confirmed by mesenteric or renal arteriography which showed microaneurysms. EMG/NCV was performed in seven patients who had neuropathy. Results: Seven of the eight patients presented with mononeuritis multiplex and one had no neuropathy. Four patients presented with neuropathy as the first symptom, and three developed neuropathy within 3 weeks after the onset of vasculitis symptoms. The peroneal nerve and sural nerve were involved in all seven patients. The median nerve, ulnar nerve and posterior tibial nerve were involved in four, two and six patients, respectively. All seven patients had lower extremity involvement. Two showed only lower extremity involvement and five had both lower and upper extremity involvement. Isolated upper extremity involvement was not seen. All patients with mononeuritis multiplex were improved by treatment with cyclophosphamide and steroid therapy. Conclusion: Mononeurtis multiplex is a common manifestation of vasculitis and occurs early in the course of systemic vasculitis. Prognosis of mononeuritis multiplex is excellent, although it may take up to one year to recover.

전신성 홍반성 루푸스 환자에서 자가항체 검출을 위한 이중면역확산법, ELISA, Western Blot법의 비교 및 자가항체와 임상양상의 연관에 관한 연구

유창달 ( Chang Dal Yoo ),차훈석 ( Hoon Seok Cha ),김성욱 ( Seong Wook Kang ),이은봉 ( Eun Bong Lee ),백한주 ( Han Joo Baek ),임용성 ( Yong Seong Im ),김현아 ( Hyun A Kim ),신찬수 ( Chan Su Shin ),송영욱 ( Yeong Wook Song ),최강원 대한류마티스학회 1996 대한류마티스학회지 Vol.3 No.2

Objective: To investigate the autoantibody profile and its clinical association in patients with systemic lupus erythematosus. Methods: The frequency and clinical correlation of autoantibodies were studied in 73 patients with systemic lupus erythematosus who have been followed in Seoul National University Hospital. Double immunodiffusion, ELISA and immunoblot were used for the detection of autoantibodies. Results: The frequency of each autoantibody measured by double immunodiffusion was as follows; anti-Ro 53.4%, anti-La 11.0%, anti-Sm 20.5%, anti-U1 RNP 20.5%. The frequency of each autoantibody by ELISA was as follows; anti-Ro 69.9%, anti-La 27.4%, anti-Sm 54.8%, anti-Ul RNP 68.5%, anti-dsDNA 72.6%, anti-cardiolipin 47.2% (IgG 43.1%, igM 15.3%). The frequency of each autoantibody by immunoblot was as follows; anti-Ro 15.1%, anti-La 42.5%, anti-Sm 46.6%, anti-Ul RNP 42.5%. anti-ribosomal P(P0) 27.4%. Anti-Ro was associated with decreased frequency of nephrotic syndrome. Anti-Ul RNP was associated with increased frequency of malar rash, Raynaud phenomenon and decreased frequency of nephritis. Patients with both anti-Ro and anti-La had more frequent serositis than those with anti-Ro only. Patients with both anti-Sm and anti-Ul RNP had less frequent thrombocytopenia than those with anti-Ul RNP only. And patients with anti-Sm and anti-dsDNA had more frequent arthritis than those with only one of both antibodies. There was a positive correlation of autoantibody titers between anti-Ro and anti-La, anti-Sm and anti-Ul RNP, anti-dsDNA and anti-cardiolipin (IgG). Taking the result of immunoblot as a standard, both of double immunodiffusion and ELISA showed low sensitivity but high specficity for anti La. As for anti-Sm and anti-Ul RNP, double immunodiffusion showed low sensitivity but high specificity, whereas ELISA showed high sensitivity but low specificity. Conclusions: In our study, some autoantibodies (anti-Ro, anti-Ul RNP) were associated with certain clinical manifestations while others not. Immunoblot being used as a standard method, ELISA showed higher sensitivity but lower specificity for anti-La, anti-Sm and anti-Ul RNP compared with immunodiffusion. It is recommended that in interpretating the laboratory findings of these autoantibodies these parameters of each method should be considered.

통풍환자에서 Allopurinol 투여 후 나타난 간기능이상

서기현 ( Gi Hyeon Seo ),안홍준 ( Hong Joon Ahn ),차훈석 ( Hoon Suk Cha ),김진석 ( Jin Seok Kim ),고광철 ( Kwang Cheol Koh ),고은미 ( Eun Mi Koh ) 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.1

Objective: To investigate the incidence and clinical course of the patients who had liver function test abnormalities during treatment with allopurinol. Methods: 62 patients who were diagnosed as gout and were treated with allopurinol at Samsung Medical Center between 1995 and 1997 were reviewed. In these patients, liver function tests were checked before and during treatment for 6 months. The term of `abnormalities of liver function test` was defined when there was an increase of more than 1.5 times of upper limit of normal values or baseline values in anyone of bilirubin, asparate transaminase, alanine transaminase and alkaline phosphatase. Results: During treatment with allopurinol, 25 patients(40.2%) showed abnormalities of liver function test. 10(25.0%) of 40 patients who had normal liver function tests before treatment showed abnormalities of liver function tests during treatment, while 15(68.2%) of 22 patients who had abnormal liver function tests before treatment showed abnormalities during treatment. In 12 of the 25 patients who showed abnormalities of liver function tests during treatment with allopurinol, allopurinol was stopped and all patients showed improvement of liver function tests. In remaining 13 patients, 10 patients were improved and other 2 patients showed only mild abnormalities of liver function tests despite of continuing allopurinol and 1 patient was lost during follow-up. Conclusions: Abnormalities of liver function tests were common during treatment with allopurinol. Most patiensts who had mild abnormalities of liver functions tests during treatment with allopurinol were improved regardless of continuing allopurinol.

Adult onset Still`s disease 환자에서 질환의 활동지표로서의 혈중 Ferritin의 역할

서기현 ( Gi Hyeon Seo ),안홍준 ( Hong Joon Ahn ),차훈석 ( Hoon Suk Cha ),김진석 ( Jin Seok Kim ),고은미 ( Eun Mi Koh ) 대한류마티스학회 1998 대한류마티스학회지 Vol.5 No.1

Objective: Adult onset Still`s disease is an acute systemic inflammatory disorder. There are no pathognomonic symptoms or specific laboratory abnormalities. In recent reports, serum ferritin concentration is increased in active disease phase and decreased after defervescence. Our purpose was to determine the clinical significance of serum ferritin as an indicator for disease activity. Methods: Seven patients who were diagnosed as adult onset Still`s disease at Samsung Medical Center between October 1994 and March 1997, were reviewed. In these patients we checked leukocyte count, ESR, CRP and serum ferritin concentrations at the time of diagnosis and during follow-up periods and recorded febrile events during follow-up periods. Results: At the time of diagnosis and during febrile periods, the concentrations of ferritin were extremely high(927ng/ml to 96,650ng/ml; normal 10-290.8 ng/ml). The values were unrelated to other manifestations of the disease or laboratory findings. The ferritin concentrations decreased rapidly after adequate treatment. Eleven febrile reattacks happened in 7 patients. Serum ferritin concentrations were increased in 8 febrile attacks, while leukocyte count, ESR, and CRP were increased in 5, 5, 6 febrile attacks respectively. There were 10 events of increased serum ferritin concentrations in 7 patients during follow-up periods and 8 events were related with fever. The increases of other laboratory tests were similar. Conclusions: In all patients, serum ferritin concentrations were increased at the time of diagnosis and closely related to fever. During follow-up periods, serum ferritin concentrations are helpful in monitoring disease activity and guiding decisions about treatment.

전신성 경화증의 임상상에 관한 연구

강성욱(Seong Wook Kang),이윤종(Yun Jong Lee),차훈석(Hoon Seok Cha),김현아(Hyun Ah Kim),박명희(Myung Hee Park),오명돈(Myoung Don Oh),송영욱(Yeung Wook Song),최강원(Kang Won Choi),이은봉(Eun Bong Lee),한창완(Chang Wan Han),백한주(Han J 대한내과학회 1999 대한내과학회지 Vol.57 No.6

N/A Background : Systemic sclerosis (scleroderma) is a connective tissue disorder of unknown etiology characterized by fibrosis of the skin and internal organs. It is remarkably heterogeneous in initial presentations and internal organ involvement. Limited and diffuse cutaneous subsets of systemic sclerosis (SSc) are known to be different in clinical and laboratory features. The aim of the present study was to determine the clinical characteristics of systemic sclerosis in Koreans. Methods : Fifty-six patients with systemic sclerosis at the Rheumatology Clinic of Seoul National University Hospital were studied for age, sex, symptoms, signs, and laboratory results. The differences in clinical and laboratory features between limited and diffuse cutaneous subsets were investigated. Results : The mean age at diagnosis of 56 patients (male:female=1:4.6) was 42.4 years (range 11-72 years). The patients consisted of 30 limited and 26 diffuse cutaneous SSc. Cutaneous involvement was as follows: sclerodactyly (100%), Raynaud's phenomenon (94.6%), digital pitting scar (66.1%), subcutaneous calcinosis (1.8%). In musculoskeletal system, 25 cases (46.3%) developed arthralgia/arthritis, 14 cases (25.9%) myalgia. In gastrointestinal system, esophagus was affected in 11 cases (20.7%). Respiratory involvement consisted of interstitial lung disease (24 cases, 43.7%) and pulmonary hypertension (2 cases, 3.6%). Total skin score and functional vital capacity showed significant negative correlation (p<0.05). Cardiovascular involvement consisted of congestive heart failure (3 cases, 5.5%) and pericardial effusion (1 case, 1.8%). Azotemia was found in one patient (1.8%). Antinuclear antibody was positive in 53 cases (94.6%) and anticentromere antibody 2 cases (3.6%). Anti-Scl 70 antibody was positive in 46.4% of all patients, 40.0% of limited scleroderma and 53.8% of diffuse scleroderma. When comparing clinical features between limited and diffuse cutaneous subsets, musculoskeletal involvement was more common in limited scleroderma. Conclusion : Systemic sclerosis in Koreans showed various systemic and organ involvement, musculoskeletal system, lung and esophagus being commonly affected. There was no significant difference between limited and diffuse scleroderma in clinical features except musculoskeletal involvement. Investigation of major internal organs, especially lung and esophagus, is needed, regardless of cutaneous subsets in systemic sclerosis. (Korean J Med 57:979-987, 1999)

불명열로 발현한 재발성 다발성 연골염

김지향 ( Ji Hyang Kim ),안석진 ( Suk Jin Ahn ),김진석 ( Jin Seok Kim ),차훈석 ( Hoon Suk Cha ),한정호 ( Jeong Ho Han ),고은미 ( Eun Mi Koh ),송재훈 ( Jae Hoon Song ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.1

Relapsing polychondritis is a rare autoimmune disease of unknown etiology with episodic but potentially progressive inflammatory manifestations. Auricular, articular and nasal manifestations are the most frequent disturbances. Fever is one of the manifestations of this disease but it rarely appears as an initial presentation. In this situation, the diagnosis is delayed until other manifestations are obvious. We report a case of relapsing polychondritis, which was presented as fever of unknown origin. Ten months after the onset of fever, auricular chondritis appeared and gave us the key to diagnosis.

미만성 폐포출혈을 동반한 전신성 홍반성 루푸스 환자에서 Plasmapheresis를 이용한 치험

고재현 ( Jay Hyun Koh ),송서영 ( Seo Young Song ),이창근 ( Chang Keun Lee ),서기현 ( Gi Hyeon Seo ),안홍준 ( Hong Joon Ahn ),차훈석 ( Hoon Suk Cha ),김진석 ( Jin Seok Kim ),고은미 ( Eun Mi Koh ),송재훈 ( Jae Hoon Song ) 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.2

Pulmonary alveolar hemorrhage (PAH) is a rare and often fatal presenting feature of systemic lupus erythematosus (SLE) and enters the differential diagnosis of diffuse lung disease in patients with SLE. Reported mortality rates are extremely high, between 70 and 90 percents. Because death frequently occurs within the first several days of the hemorrhage, the diagnosis needs to be established promptly and treatment should be initiated immediately. Treatment of alveolar hemorrhage has included various combinations of corticosteroids, cytotoxic agents, and plasmapheresis, but survival rates have been extremely low despite aggressive therapy. We experienced a case of diffuse alveolar hemorrhage in a 29 year-old SLE male patient. PAH was diagnosed by hemoptysis, anemia, infiltration on chest X-ray and hemosiderin-laden macrophages in bronchoalveolar lavage. After high dose intravenous steroid, cyclophosphamide intravenous therapy and plasmapheresis, the condition of patient was markedly improved. He was discharged and received monthly intravenous pulse cyclophosphamide. He has done well since, showing no further pulmonary hemorrhage with steroid tapering.

초기 류마티스 관절염에서 적혈구 침강속도, 혈청 C-반응성 단백과 방사선학적 진행의 상관관계

고재현 ( Jay Hyun Koh ),김재형 ( Jae Hyung Kim ),이창근 ( Chang Keun Lee ),전찬홍 ( Chan Hong Jeon ),서기현 ( Gi Hyeon Seo ),안홍준 ( Hong Joon Ahn ),차훈석 ( Hoon Suk Cha ),김진석 ( Jin Seok Kim ),안중모 ( Joong Mo Ahn ),고은미 ( 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.4

Objective: To investigate the clinical usefulness of serial measurement of erythrocyte sediment rate(ESR) and C-reactive protein(CRP) for monitoring the radiological progression in early rheumatoid arthritis(RA). Methods: Thirty one patients with RA according to the 1987 ACR criteria, with joint symptoms for less than one year, and who had not previously received disease modifying antirheumatic drugs(DMARDs) were assessed from Oct. 1994 to Aug. 1998 in retrospective study. Area under curve(AUC) of ESR and CRP were calculated in these patients. Joint damage in the hands was assessed by modified Sharp`s method. Results: Male to female ratio was 1: 3.4. Median age of this group was 45.8±13.2 years. Patients who had positive rheumatoid factor were 82%. Mean duration until first visit was 271.9±145.8 days. At the first clinic visit, mean ESR and CRP were 50mm/hr and 2.0mg/dL. Mean erosions and joint space narrowing score by modified Sharp`s method were 55.2 and 12.4, respectively. Correlation analysis showed that ESR AUC and CRP AUC were significantly associated with radiologic progression. Conclusions: Elevated over-time ESR and CRP provide a convenient short term correlation with radiologic outcome(i. e. erosions). Elevated over-time ESR and CRP can be used as a guide for therapy.