Risk for Parkinson’s disease in patients with Behcet’s Disease: A nationwide population-based dynamic cohort study in Korea

( Min Ji Kang ),( Ji Min Seo ),( Joo Hee Lee ),( Dong Soo Yu ),( Young Bok Lee ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.2

Background: Although several studies have reported a correlation between Behcet’s disease and Parkinson’s disease, this association has not yet been clarified. Objectives: The aim of this study is to determine the risk of Parkinson’s disease in patients with Behcet’s disease. Methods: Behcet’s disease patients (n = 17,179; mean age, 51.12±8.09 years; male, 34.95%) without known previous diagnosis of Parkinson’s disease were selected from the Korean National Health Insurance Database between 2010 and 2013. An age and gender-matched control population of individuals without Behcet’s disease was randomly sampled at a ratio of 3:1 (n = 34,575). Both cohorts were followed for development of Parkinson’s disease until 2015. Results: Among a total of 11,525 Behcet’s disease patients, 50 (0.43%) developed Parkinson’s disease, whereas only 51 among the 34,575 individuals in the non- Behcet’s disease group developed Parkinson’s (0.15%, P < 0.0001). The incidence of Parkinson’s disease was significantly higher in Behcet’s disease patients than in controls. In addition, during the follow-up period, patients with Behcet’s disease were more likely to be diagnosed with Parkinson’s disease than those in the non- Behcet’s disease group. Conclusion: Behcet’s disease patients had a higher risk of Parkinson’s disease compared to non- Behcet’s disease controls. Physicians should carefully monitor patients with Behcet’s disease for potential development of Parkinson’s disease.

베체트병환자에서 회상항원에 대한 피부 지연과민반응의 연구

김병천,송준영,이규석 啓明大學校 醫科大學 1998 계명의대학술지 Vol.17 No.1

To assess cell-mediated immunity of patients with Behcet's disease, many studies have been performed by in vitro method. However, there is a little known about cell-mediated immunity of patients with Bechcet's disease by in vivo method. Thus, we investigated delayed cutaneous hypersensitivity using Multitest CMI, which is a disposable applicator preloaded with 7 recall antigens, in 82 cases including 62 cases of Behect's disease and 20 cases of control, Sixty two patients with Behcet's disease were classified into 3 types : complete, incomplete and suspected type according to the revised Shimizu method. The results were obtained as follows: 1) Sum of average diameter of positive antigens was 6.71±1.10 mm in complete type of Behcet's disease, 12.59±3.48 mm in incomplete type 7.0±2.0 mm in suspected type, 11.13±3.36 in total of Behcet's disease and 20.38±6.06 mm in control. There was statistically significant difference between Behcet's disease and control (p<0.05). 2) Number of positive antigen was 1.7±0.51 in complete type, 2.29±0.89 in incomplete type, 3.0±1.0 in suspected type, 3.32±0.78 in total of Behcet's disease and 4.01±1.51 in control. There was statistically significant difference between Behcet's disease and control (p<0.05). 3) The rate of hyponergy in Behcet's disease and control was 32.2% and 0%, respectively. The rate of energy in Behcet's disease and control was 4.8% and 0%, respectively. 4) Antigens acquired strongest reaction were all tuberculin in Behcet's disease (positivity; 81%) and control (95%). Antigens acquired weakest reaction were all tetanus in Behcet's disease (7%) and control (10%). Unexpectedly, the positivity of streptococcus suggested as one of etiologic agents in Behcet's disease was 10% in Bechet's disease and 56% in control. Taken altogether, our study revealed cell-mediated immunity of Behcet's disease measured by multitest CMI was decreased and it is suggested that decreased cell-mediated immunity in Behcet's disease is related, at least in part, to the disease severity and involved in the pathogenesis of this disease.

Increased cardiovascular risk and all-cause death in patients with Behcet’s disease: a nationwide population-based dynamic cohort study

( Soo Young Lee ),( Min Ji Kang ),( Joo Hee Lee ),( Young Bok Lee ),( Dong Soo Yu ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.2

Background: Behcet’s disease is a inflammatory multiorgan disease. An increased risk of cardiovascular disease and heightened death rate with Behcet’s disease have been suggested, but, to our knowledge, a nationwide large-scale study has not been conducted to date. Objectives: This study aimed to determine the overall cardiovascular risk and death rate in Behcet’s disease patients versus controls using the Korean National Health Insurance Service claim database. Methods: Patients with Behcet’s disease (n = 5,576) with no previous history of cardiovascular disease were selected from 2010 to 2014. An age- and sex-matched control population of individuals without Behcet’s disease (n = 27,880) was randomly sampled at a ratio of 5:1. Both cohorts were followed for incident cardiovascular disease or all-cause death until 2015. Results: The risks of myocardial infarction [hazard ratio (HR): 1.72, 95% CI: 1.01-2.73] and stroke [HR: 1.65, 95% CI: 1.09-2.50] were significantly higher in Behcet’s disease patients than in control patients. Behcet’s disease patients also had a significantly higher risk of all cause death [HR: 1.82, 95% CI: 1.40-2.37] compared to controls. Conclusion: Korean Behcet’s disease patients had a higher overall risk of cardiovascular disease than did those without Behcet’s disease. Therefore, patients with Behcet’s disease must be carefully monitored for the potential development of cardiovascular disease to ensure that appropriate early treatments are delivered.

베체트병에서의 혈액응고 이상에 관한 연구

강성욱 ( Seong Wook Kang ),신기철 ( Ki Chyul Shin ),이윤종 ( Yun Jong Lee ),이은봉 ( Eun Bong Lee ),백한주 ( Han Joo Baek ),김현아 ( Hyun Ah Kim ),송영욱 ( Yeong Wook Song ) 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.3

Objective: The predominant histopathologic lesion in Behcet`s disease is vasculitis. Thrombotic complications have been reported in approximately 10~40% of patients with Behcet`s disease, but the precise mechanisms are not known. To investigate the coagualtion abnormalities in patients with Behcet`s disease, coagulation and fibrinolytic activities were examined. Methods: Thirty-two patients with Behcet`s disease and thirty-two healthy individuals as a control group were included in the study. The presence of thrombosis and risk factors for hypercoagulability, and blood components concerning coagulation and fibrinolytic activites were evaluated. Results: Of thirty-two patients with Behcet`s disease, thrombosis was found in four patients(13%). No patient had risk factors for hypercoagulability except one with lymphoma. Levels of white blood cell count(mean±SD 8,362±2,893 vs 5,934±1,755/mm3, p<0.001), erythrocyte sedimentation rate(40.5±37.6 vs 3.3±2.73 mm/hr, p<0.001), C reactive protein(2.26±3.99 vs 1.20±0.26mg/dl, p=0.008), fibrinogen(387.7±128.5 vs 240.6±49.5mg/dl, p<0.001) and von Willebrand factor antigen(131.9±46.6 vs 105.2±1.75%, p=0.008) were significantly higher in patients with Behcet`s disease compared with controls. The level of fibrinogen correlated with erythrocyte sedimentation rate(r=0.721, p<0.001) and C reactive protein (r=0.454, p=0.018). High density lipoprotein(HDL) cholesterol(46.6±12.7 vs 65.5±16.1mg/dl, p<0.001), apolipoprotein A-1(118.8±24.7 vs 134.6±18.5mg/dl, p=0.018) and antithrombin III (92.8±16.7 vs 106.3±14.7%, p=0.004) were significantly lower in patients with Behcet`s disease. No differences were observed in lipoprotein(a), plasminogen, protein C, and protein S activities. Activated protein C(APC) resistance was not observed in any patients with Behcet`s disease. Lupus anticoagulant was positive in four patients(13%). one of whom had deep vein thrombosis. Antiphospholipid antibody was found in one patient(3%), but thrombosis was not found. Conclusions: Significantly higher level of von Willebrand factor antigen was observed in Behcet`s disease, which suggested injury of vascular endothelium. Levels of HDL cholesterol, apolipoprotein A-1 and antithrombin III were decreased in Behcet`s disease. APC resistance was not found.

베체트병 환자에서 TNF-α와 TNF 수용체 유전자의 다양성

서욱장 ( Wook Jang Seo ),김용길 ( Yong Gil Kim ),양석균 ( Suk Kyun Yang ),박경숙 ( Kyung Sook Park ),이창근 ( Chang Keun Lee ),유빈 ( Bin Yoo ),문희범 ( Hee Bum Mon ) 대한류마티스학회 2007 대한류마티스학회지 Vol.14 No.2

Objective: TNF-α has a pivotal role in the development of inflammation on mucous lesion in Behcet`s disease like Crohn`s disease. We examined three single nucleotide polymorphisms (SNPs) of TNF receptor gene of intestinal Behcet`s disease and Behcet`s disease without gastrointestinal involvement. Methods: DNA of peripheral blood samples was obtained from 43 patients with intestinal Behcet`s disease, 59 patients with Behcet`s disease without gastrointestinal involvement and 60 healthy controls. After polymerase chain reaction (PCR), we examined SNPs of TNF-α gene (-308, -238) and TNF receptor gene (-1493, -196, -1466) by SNaPshot assay. We also analyzed reconstruction of haplotypes of three TNF receptor genes. Results: No significant difference was observed in the distribution of TNF-α gene (-308, -238) and TNF receptor gene (-1493, -196, -1466) polymorphisms among the groups. Haplotype reconstruction analysis of three TNF receptor genes showed difference in allele group of (T-T-G) (-1493/-196/-1493) between patients with intestinal Behcet`s disease and Behcet`s disease without gastrointestinal involvement (p<0.05). However, other allele groups revealed no difference among the groups. Conclusion: The role of TNF-α gene (-308, -238) polymorphisms and TNF receptor gene (-1493, -196, -1466) polymorphisms in the pathogenesis of Behcet`s disease is not supported by this data. Haplotype reconstruction analysis showed that haplotype of T-T-G (TNFR2, -1493/-196/-1466) in Behcet`s disease may have protective effect on gastrointestinal involvement of this disease.

Association between smoking and Behcet’s disease: A nationwide population-based study in Korea

( Ji Min Seo ),( Soo Young Lee ),( Joo Hee Lee ),( Dong Soo Yu ),( Young Bok Lee ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.2

Background: There have been conflicting results about the asssociation between Behcet’s disease and smoking. Smoking has been reported to be a protective factor for Behcet’s disease, but smoking may have a role in triggering Behcet’s disease. Objectives: This study aimed to investigate the incidence of Behcet’s disease in Korea according to smoking status using nationwide population data. Methods: We analysed clinical data from individuals 20 years of age and older who received a health examination arranged by the Korean national insurance programme between 2009 and 2012. The incidence of Behcet’s disease was analysed according to smoking status reported by individuals during their health examination. Newly diagnosed cases of Behcet’s disease were identified using claims data from baseline to the date of diagnosis or until 31 December 2016. Results: The risk of Behcet’s disease was lower in current smokers compared with never-smokers regardless of the amount and duration of smoking. The decreased risk of Behcet’s disease in current smoker persisted after adjusting for age, sex, regular exercise, drinking status, BMI, diabetes mellitus, hypertension, and dyslipidemia, history of stroke and/or history of ischemic heart diseases. Conclusion: This study found a decreased incidence of Behcet’s disease in current smokers compared with never smokers. Further investigation of the pathophysiology responsible for the negative association between smoking and Behcet’s disease is needed.

베체트병 환자에서 혈청 대식세포 유주 억제 인자 (Macrophage Migration Inhibitory Factor, MIF)의 상승

김성동 ( Sung Dong Kim ),김상현 ( Sang Hyon Kim ),김해림 ( Hae Rim Kim ),박미경 ( Mi Kyung Park ),윤종현 ( Chong Hyeon Yoon ),김완욱 ( Wan Uk Kim ),이상헌 ( Sang Heon Lee ),박성환 ( Sung Hwan Park ),조철수 ( Chul Soo Cho ),김호연 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.3

Objective: Macrophage migration inhibitory factor (MIF) has emerged recently as an important regulator of inflammatory and immune responses. This work was undertaken to evaluate serum levels of MIF and in vitro MIF production by whole blood cells in patients with Behcet`s disease and investigate the relationship between serum levels of MIF and clinical manifestations. Methods: Sixty-five patients with Behcet`s disease and forty-eight healthy controls were studied to evaluate serum levels of MIF. Six patients with Behcet`s disease and Five healthy controls were studied for evaluating the production of MIF by whole blood cells. Serum and culture supernatant levels of MIF were measured by enzyme-linked immuno-sorbent assay (ELISA). The production of MIF by whole blood cells was investigated by culturing peripheral blood cells in the absence or presence of Concanavalin A (Con A). Results: Serum levels of MIF were higher in patients with Behcet`s disease than in healthy controls. Serum levels of MIF were changed in each patient with Behcet`s disease according to clinical disease activity (higher at active state). The MIF production by Con A-stimulated peripheral blood cell culture was higher in patients with Behcet`s disease than in healthy controls. Conclusion: Circulating levels of MIF are higher in patients with Behcet`s disease than in healthy controls and the levels of MIF may be associated with clinical disease activity. MIF may play an important role as a mediator of inflammation in Behcet`s disease and provide opportunity for the development of anti-MIF strategy for the treatment of patients with Behcet`s disease.

Expression of Pro-inflammatory Protein S100A12 (EN-RAGE) in Behcet`s Disease and Its Association with Disease Activity: A Pilot Study

( Eun Chun Han ),( Sung Bin Cho ),( Keun Jae Ahn ),( Sang Ho Oh ),( Ji Hyun Kim ),( Dong Soo Kim ),( Kwang Hoon Lee ),( Dong Sik Bang ) 대한피부과학회 2011 Annals of Dermatology Vol.23 No.3

Background: S100A12 is a member of the S100 family of calcium-binding proteins and is secreted either in inflamed tissues or in the bloodstream by activated neutrophils. Expression of S100A12 has been reported in various diseases, especially non-infectious inflammatory diseases, such as Kawasaki disease, giant cell arteritis and inflammatory bowel disease. Objective: This study was conducted to determine both the tissue expression and the serum levels of S100A12 in Behcet`s disease (BD) patients and the correlation of the S100A12 serum level with disease activity of BD. Methods: We included in this study ten BD patients who fulfilled the criteria for diagnosis, according to the International Study Group for BD. The activity of BD was calculated using the BD Current Activity Form. The serum concentrations of both S100A12 and interleukin-8 were measured by the enzyme-linked immunosorbent assay, before and after treatment. Immunohistochemical studies were also performed to detect S100A12 expression in the skin. Results: The serum S100A12 level was significantly increased in the active BD period (p<0.001), in the inactive BD period (p=0.041) and in patients with active Kawasaki disease (p=0.028), compared with the serum level in the healthy controls. The serum S100A12 level decreased significantly from baseline, compared to post-treatment (p=0.017). The activity score of BD was significantly correlated with the serum level of S100A12 (Spearman`s coefficient=0.464, p=0.039). Immunohistochemical studies showed that S100A12 was strongly expressed in the erythema nodosum-like skin lesions of patients. Conclusion: S100A12 contributes to the pathogenesis of BD related to neutrophil hyperactivity and reflects the disease activity in BD patients.

Incidence, prevalence, and mortality of Behcet’s disease in Korea: a nationwide, population-based study (2006-2015)

( Young Bok Lee ),( Soo Young Lee ),( Jin Young Choi ),( Ji Hyun Lee ),( Jin-wou Kim ),( Dong Soo Yu ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.2

Background: The epidemiology of Behcet’s disease varies among ethnic populations worldwide. Trends in the incidence of Behcet’s disease have not been investigated based on the Korean National Health Insurance database. Objectives: This study investigated the incidence and mortality of Behcet’s disease by age using nationwide population data in Korea. Methods: A nationwide population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2006 to 2015. Results: The annual incidence of Behcet’s disease per 100,000 person-years was 3.976 (2.587 for males and 5.373 for females) from 2006 to 2015. The incidence of Behcet’s disease peaked among people in their 40s (6.561 per 100,000 person-years). Incidence was significantly higher in subjects with comorbid metabolic conditions, such as diabetes mellitus, hypertension, and dyslipidemia. The mortality rate per 1,000 person-years increased with age in Behcet’s disease patients. Conclusion: This study showed the incidence, prevalence, and mortality of Behcet’s disease. Metabolic conditions increased the risk of Behcet’s disease among Koreans.

악성혈액질환이 동반된 베체트병에서 동종골수이식을 시행한 2예

권남희,전경만,박세훈,김동희,이순일,차훈석,이홍기 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2

골수 이식 후 자가면역질환의 관해는 수 차례 보고 되었다. 그러나 베체트병과 악성혈액질환이 동반된 예에서 골수 이식을 시행한 경우는 보고된 바가 없다. 저자 등은 재생불량성빈혈 혹은 골수이형성 증후군과 각각 동반된 베체트병에서 동종 골수 이식을 시행하여 베체트병의 임상 증상이 호전된 후 양호한 임상 경과를 보이는 한 예와 정확한 분석이 어려운 한 예를 경험하였다. 현재까지 보고된 다른 자가면역질환에서와 같이 베체트병에서도 혈액질환이 동반되어 있는 경우 동종 골수 이식을 새로운 치료법으로 사용할 수 있으나, 장기적인 경과 및 치료 성적은 정리되지 않은 상태이다. 따라서 향후 더 많은 증례를 분석하여 그 의미를 찾아보아야 할 것이다. Allogeneic or autologous bone marrow transplantation (BMT) in autoimmune disease is a new approach for treating the patients who either do not respond to the standard treatments or require long-term administration of toxic drugs to maintain a clinical remission. We report two cases of allogeneic BMT in patients with Behcet"s disease which was accompanied with either aplastic anemia or myelodysplastic syndrome. A 36-year old woman who had abdominal pain, oral ulcer, and vaginal ulcer was diagnosed to have Behcet"s disease and severe aplastic anemia. Prednisolone, colchicine, and sulfasalazine were administered for the treatment of Behcet"s disease; however, patient had the persistent symptoms and signs without improvement. She underwent allogeneic BMT for the treatment of severe aplastic anemia. Following the transplantation, she recovered completely from Behcet"s disease as well as aplastic anemia. In the second case, a 33-year old woman was diagnosed to have Behcet"s disease, which was based on her recurrent oral ulcer, genital ulcer, and erythema nodosum. In the meantime, she was diagnosed to have myelodysplastic syndrome (RARS). Although her Behcet"s disease responded partially to colchicine, sulfasalazine, prednisolone, and dapsone, she required these drugs in high dosages for a long time. We performed allogeneic BMT for her myelodysplastic syndrome. She had successful engraftment after transplantation, and the symptoms and signs associated with Behcet"s disease temporarily disappeared. In conclusion, allogeneic BMT can be a promising curative treatment for Behcet"s disease accompanied with hematologic malignancies.