The Efficacy of Mycophenolate Mofetil in Remission Maintenance Therapy for Microscopic Polyangiitis and Granulomatosis with Polyangiitis

표정윤,이은주,안성수,송정식,박용범,이상원 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.6

Purpose: The present study compared the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) in Koreanpatients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: The medical records of 69 patients with MPA and GPA who received cyclophosphamide and subsequentlyreceived AZA or MMF for remission maintenance therapy were reviewed. All-cause mortality, relapse, end-stage renal disease(ESRD), cerebrovascular accident, and cardiovascular disease were evaluated as poor outcomes. Having a lower BirminghamVasculitis Activity Score (BVAS) was defined as the lowest tertile of BVAS (BVAS ≤11 in this study). Results: In comparative analysis of the occurrence of poor outcomes among patients taking AZA only, MMF only, and MMF afterAZA, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than patients taking AZA only(p=0.028). In terms of ESRD occurrence between the groups based on BVAS at diagnosis, among patients with MPA and GPA withhigher BVAS at diagnosis, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than thosetaking AZA only (p=0.047). Among patients with MPA and GPA with the lowest tertile of BVAS at diagnosis, cumulative ESRD-freesurvival rates did not differ. Conclusion: With regard to ESRD occurrence, the efficacy of MMF in remission maintenance therapy was less effective than AZAin patients with MPA and GPA. However, among patients with lower BVAS, there was no difference in the occurrence of poor outcomesbetween patients taking MMF and those taking AZA.

Pregnancy Morbidities in Korean Patients with Takayasu Arteritis: A Monocentric Pilot Study

표정윤,송정식,박용범,이상원 연세대학교의과대학 2020 Yonsei medical journal Vol.61 No.11

We investigated pregnancy morbidities in Korean patients with Takayasu arteritis (TA) in a single tertiary hospital as a pilot study. We retrospectively reviewed the medical records of 12 pregnancies in seven patients with TA. All patients were diagnosed with TAbased on the 1990 American College of Rheumatology classification criteria. The medical records of patients were well-documented,allowing review of clinical data including pregnancy morbidities. The angiographic and Ishikawa classifications at diagnosisand TA activity at delivery were assessed. Of the 12 pregnancies, two pregnancies ended in spontaneous abortion (16.7%), andone pregnancy (8.3%) had therapeutic abortion at 9 weeks due to maternal morbidity. Among the remaining nine pregnancies,only one child was delivered via normal spontaneous vaginal delivery, and the remaining eight were delivered by Caesarean section. Two out of nine (22.2%) neonates were born with low birth weight, and one of them was born at 30 weeks of gestation. Themost common maternal complication was hypertension affecting 7/12 (58.3%) pregnancies. Preeclampsia occurred in one pregnancy,and gestational diabetes mellitus (GDM) occurred in two pregnancies. At delivery, disease activity of TA was stable in allpregnancies, and glucocorticoids were administered in nine pregnancies. Live birth rate of pregnant Korean patients with TA was75%. Future studies are needed to reduce pregnancy-related complications.

Ventricular Tachyarrhythmias in a Patient with Andersen-Tawil Syndrome

표정윤,정보영,박진수,이승준,이한철,김원진,조동후 대한심장학회 2013 Korean Circulation Journal Vol.43 No.1

Andersen-Tawil syndrome (ATS), a rare autosomal dominant disorder, is characterized by periodic paralysis, dysmorphic features and car-diac arrhythmias. This syndrome is caused by mutations of KCNJ2 gene, which encodes inward rectifying potassium channel. Here, we re-port an 18-year-old girl who was presented with life-threatening cardiac arrhythmia and acute respiratory distress. She was diagnosed with ATS, based on dysmorphic features, ventricular arrhythmia, and periodic paralysis. This is the first case to be reported in Korea who experienced a fatal cardiac arrest and respiratory failure caused by ATS.

Subsequent Thrombotic Outcomes in Patients with Ischemic Stroke with Antiphospholipid Antibody Positivity

표정윤,박용범,정승민,이상원,송정식,이수곤 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.6

Purpose: International consensus criteria for antiphospholipid syndrome (APS) require persistently positive antiphospholipid antibodies (aPL) and medium or high titers in association with clinical manifestations. However, the clinical relevance of persistenceand titers of aPL in patients with stroke has not been identified. We aimed to investigate the risk of subsequent thrombotic events in patients with ischemic stroke with aPL positivity in terms of aPL status. Materials and Methods: We reviewed the medical records of 99 patients with ischemic stroke with at least one or more aPL-positivity (i.e., positivity for aCL, anti-β2-glycoprotein-1, and/or lupus anticoagulants). The patients were divided into two groups: “definite APS” who fulfilled the laboratory criteria and “indefinite APS” who fell short of the criteria. We compared the risk of subsequent thromboticevents between the two groups. Cox proportional hazards model and Kaplan-Meier survival curves were used for the analyses. Results: Of the 99 patients, 46 (46%) were classified as having definite APS and 53 (54%) as having indefinite APS. The mean follow-up was 51.6 months. Overall event numbers were 14 (30.4%) in definite APS and 16 (30.2%) in indefinite APS. Increased subsequentthrombotic events (hazard ratio 1.039; 95% confidence interval 0.449−2.404; p=0.930) and decreased time to thrombotic events (log-rank p=0.321) were not associated with aPL status. Conclusion: There was no increased risk of subsequent thrombotic events in ischemic stroke patients with definite APS, compared with those with indefinite APS.

Takayasu arteritis associated with ulcerative colitis and optic neuritis: first case in Korea

표정윤,박진수,송창호,이상원,박용범,이수곤 대한내과학회 2013 The Korean Journal of Internal Medicine Vol.28 No.4

Takayasu arteritis (TA) is a chronic vasculitis that affects the aortic arch and its primary branches. Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Patients diagnosed with both TA and UC have rarely been reported. The pathogenesis of TA and UC is uncertain, but cell-mediated mechanisms play an important role in both diseases, and a genetic factor is thought to have an effect on the coincidence of these two diseases. We herein report a 38-year-old female with TA who had a history of UC with optic neuritis. We believe that this is the first case of the coexistence of TA and UC in Korea.

Comparison of the 2022 ACR/EULAR Classification Criteria for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Previous Criteria

이상원,표정윤,이은주,박용범 연세대학교의과대학 2023 Yonsei medical journal Vol.64 No.1

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises group of small vessel vasculitides, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In 2022, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) jointly proposed new classification criteria for AAV (the 2022 ACR/EULAR criteria). In this review, we briefly summarize the 2022 ACR/EULAR criteria for GPA, MPA, and EGPA, and introduce our clinical experience with applying them to patients who were previously diagnosed with AAV based on three criteria: firstly, the classification criteria for GPA and EGPA proposed by the ACR in 1990; secondly, the algorithm for the classification of AAV and polyarteritis nodosa proposed by the European Medi cines Agency algorithm in 2007 (the 2007 EMA algorithm); and thirdly, the revised International Chapel Hill Consensus Confer ence nomenclature of vasculitides in 2012 (the 2012 CHCC definitions). We found that concordance rate was highest in patients with MPA (96.6%), followed by those with EGPA (86.3%) and GPA (73.8%). In addition, compared to previous criteria, we noted several issues of the undervalued or overvalued items in the 2022 ACR/EULAR criteria for classifying AAV and provided several suggestions. To increase the diagnostic accuracy and reduce the discordance rate among the new and previous criteria for AAV, we suggest that the previous criteria should be considered together with the 2022 ACR/EULAR criteria when applying the classifi cation criteria for AAV to patients suspected of AAV.

Implication of Serious Infections in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis for the First Cycle of Rituximab: A Pilot Study in a Single Korean Center

도현수,표정윤,송정식,박용범,이상원 대한류마티스학회 2023 대한류마티스학회지 Vol.30 No.1

Objective: This study investigated the clinical implications of serious infections in patients with antineutrophil cytoplasmic antibody- associated vasculitis (AAV) who received the first cycle of rituximab (RTX) during the first 6 months of follow-up. Methods: The medical records of 36 AAV patients treated with RTX were reviewed. A weekly dose of 375 mg/m2 RTX was administered for 4 weeks to all patients along with glucocorticoids. Serious infections were defined as those requiring hospitalization. All-cause mortality during the first 6 months of follow-up was counted. The follow-up duration was defined as the period from the first RTX infusion to 6 months after the first RTX infusion. Results: The median age was 60.5 years, and 16 patients were male. Seven of 36 patients (19.4%) died and three AAV patients had five cases of serious infection such as enterocolitis, pulmonary aspergillosis, atypical pneumonia, cytomegalovirus pneumonia, and cellulitis. AAV patients with serious infections during the first 6 months of follow-up exhibited a significantly lower cumulative survival rate than those without serious infections (p<0.001). However, we found no independent predictor of serious infections using the Cox hazard model analysis. Conclusion: Serious infection is an important predictor of all-cause mortality in Korean patients with AAV who received their first cycle of RTX but there were no significant variables to predict the occurrence of serious infections at the first RTX. Thus, in cases refractory to other induction therapies, RTX should be strongly considered, despite an increase in mortality rate.

Serum Clusterin Level Could Reflect the Current Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

윤태준,안성수,표정윤,송정식,박용범,이상원 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.11

Purpose: We investigated whether serum clusterin levels could reflect the current antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-specific indices. Materials and Methods: Fifty-seven patients with AAV and 40 healthy controls were included in this study. AAV-specific indices included the Short-Form 36-Item Health Survey Physical and Mental Component Summaries (SF-36 PCS and MCS) scores, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index. Clinical and laboratory data and AAV-specific indices were obtained at blood collection. The highest tertile of BVAS (≥16) was defined as high activity of AAV. Results: The median age of AAV patients was 64.0 years and 19 patients were male. SF-36 PCS score (r=0.328), SF-36 MCS score (r=0.289), BVAS (r=-0.404), erythrocyte sedimentation rate (r=-0.336), and C-reactive protein levels (r=-0.421) were significantly correlated with serum clusterin levels. In the multivariable linear regression analysis using AAV-specific indices and serum clusterin levels, both FFS (β=0.412) and serum clusterin levels (β=-0.250) were significantly associated with BVAS. When the optimal serum clusterin cut-off level for high activity of AAV was identified as 130.45 μg/mL, patients with serum clusterin level ≤130.45μg/mL had a significantly higher risk for high activity of AAV than did those without (relative risk 7.194). Patients with AAV exhibited significantly lower serum clusterin levels than did healthy controls (168.2 μg/mL vs. 230.5 μg/mL). Conclusion: Serum clusterin levels could reflect the current disease activity in patients with AAV.

Successful treatment of Adult-onset Still’s disease after influenza vaccination: A case report

김민혜,김정호,표정윤,최준용,염준섭 대한내과학회 2022 대한내과학회 추계학술대회 Vol.2022 No.2

Delta Neutrophil Index as an Early Marker for Differential Diagnosis of Adult-Onset Still’s Disease and Sepsis

박희진,이상원,하유정,표정윤,박용범,이수곤 연세대학교의과대학 2014 Yonsei medical journal Vol.55 No.3

Purpose: To investigate clinical implications of delta neutrophil index (DNI) to discriminate adult onset Still’s disease (AOSD) from sepsis. Materials and Methods:We reviewed the medical records of 13 patients with AOSD and 33 gender and age-matched patients with sepsis. In all subjects, microbial tests were performedto exclude or confirm sepsis. All laboratory data were measured two or three times during the first 3 days and represented by their mean levels. DNI was measured automatically by ADVIA 2120 for the first 3 days. Results: There were no significant differences in white blood cell counts, neutrophil proportion, erythrocytesedimentation rate and C-reactive protein between two groups. AOSD patientshad notably lower DNI than sepsis patients regardless of the presence of bacteremia or not. However, both DNI and ferritin were not significant independentfactors for predicting sepsis in the multivariate logistic regression analysis. Meanwhile, the area under the receiver operating characteristic curve (AUROC) of DNI was slightly higher than that of ferritin. When we set DNI of 2.75% as the cut-off value for predicting sepsis, 11 (84.6%) of AOSD patients had a DNI value below 2.75% and 2 (15.4%) of them had a DNI over 2.75% (relative risk for sepsis176). Conclusion: We suggest that DNI may be a useful marker for differential diagnosis of AOSD from sepsis in the early phase as supplementary to ferritin.