Ji Ae Yang’s research while affiliated with Seoul National University Hospital and other places

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Publications (13)


Elderly Patients Exhibit Stronger Inflammatory Responses during Gout Attacks
  • Article
  • Full-text available

December 2017

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51 Reads

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13 Citations

Journal of Korean medical science

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Ji Ae Yang

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Gout attacks are often accompanied by systemic inflammatory response. The aim of the retrospective study was to compare gout patients in different age groups in terms of their clinical features at gout attacks. Patients, who were treated for gout attack in two tertiary medical centers between January 2000 and April 2014, were divided into young (≤ 50 years), middle-aged, and elderly (> 65 years) groups. Patients in three age groups were compared in terms of presence of fever (> 37.8°C), C-reactive protein (CRP) levels, and erythrocyte sedimentation ratio (ESR) at the gout attacks. Monocytes, which were isolated from 10 consecutive patients who previously experienced gout attacks, were stimulated with monosodium urate (MSU) crystals and cytokine production was measured by flow cytometry. Among 254 patients analyzed in this study, 48 were young, 65 were middleaged, and 141 were elderly. The elderly patients were more likely to have fever (51.1%) during the attack than the young (20.8%) and middle-aged (30.8%) patients (P < 0.001 by χ² test). They were also more likely to have higher ESR and CRP levels than the young patients (P = 0.002 for ESR, P < 0.001 for CRP). Patients' age correlated significantly with CRP and ESR levels (both P < 0.001). After stimulation with MSU, the production of interleukin-1ß by monocytes increased with patients' age (r = 0.670, P = 0.03). In conclusion, gout attacks in elderly patients are associated with fever and higher ESR and CRP levels, often resembling a septic arthritis.

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Figure 1. Serial changes in (A) erythrocyte sedimentation rate (ESR) and (B) C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) compared to those without ILD over the 10-year follow-up. 
Clinical characteristics associated with occurrence and poor prognosis of interstitial lung disease in rheumatoid arthritis

March 2017

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130 Reads

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45 Citations

The Korean Journal of Internal Medicine

Background/aims: To analyze clinical characteristics of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA), especially in patients with poor prognosis. Methods: Seventy-seven RA patients with ILD and 231 age, sex, and disease duration-matched RA patients without ILD were enrolled in this retrospective study. Epidemiologic, clinical, and laboratory information were obtained through a medical chart review. Logistic regression analysis was used to estimate the risk of mortality in RA patients with ILD. Results: Compared to the RA without ILD group, the RA with ILD group had significantly higher titers of rheumatoid factor and the anti-cyclic citrullinated peptide (p = 0.001 for both), higher levels of C-reactive protein (CRP) at the time of RA diagnosis (p = 0.014), and a higher erythrocyte sedimentation rate (p = 0.022) and CRP levels (p < 0.001) throughout the 10-year follow-up period. These patients also received a higher mean daily dose of corticosteroids (p < 0.001). In the subgroup analysis of RA patients with ILD, 28 patients (36.4%) died during follow-up. Multivariate analysis revealed that older age at the time of ILD diagnosis was significantly associated with mortality. Usual interstitial pneumonia (UIP) subtype on high-resolution computed tomography (HRCT) was also suggested as a poor prognostic factor. Conclusions: The survival of RA patients with ILD is adversely affected by age at the time of ILD diagnosis. RA-ILD patients diagnosed after age 65 or with a UIP subtype on HRCT may have a poor prognosis.



Figure 1: Kaplan-Meier survival curves for cancer patients with gastric cancer (a), colon cancer (b), lung cancer (c) and breast cancer (d) were compared with those for matched cancer patients without rheumatic diseases. Tick marks indicate censoring events. The p value was calculated using the log rank test. DM, dermatomyositis; ND, not determined; PM, polymyositis; RA, rheumatoid arthritis; RD, rheumatic disease; SLE, systemic lupus erythematosus; SSc, systemic sclerosis.*p < 0.05, **p < 0.01 and ***p < 0.001 compared with the non-RD exposed cancer cohort
Table 1 Characteristics of 122 patients with rheumatic diseases and 366 cancer-matched controls without RD
Figure 2: Hazard ratios (HR) and 95 % confidence intervals for overall survival of patients with lung a or breast b cancer. HR was calculated by adjusting for cancer stage, performance status, comorbidity index, and age at the time of cancer diagnosis. HR for lung cancer was adjusted also for the presence of ILD. ND, not determined; DM, dermatomyositis; PM, polymyositis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SSc, systemic sclerosis
Table 2 Baseline cancer-related characteristics of the 122 RD patients with cancer and the 366 age-, sex-, and cancer-matched controls without RD
Table 3 Cause of death of 45 patients with rheumatic disease and cancer
Survival rates of cancer patients with and without rheumatic disease: A retrospective cohort analysis

July 2016

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58 Reads

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30 Citations

BMC Cancer

Background: To compare the outcomes of gastric, colon, lung, and breast cancer patients with and without rheumatic diseases (RD). Methods: This retrospective study compared the cancer survival rates of a cohort of 122 cancer patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis/polymyositis (DM/PM), or systemic sclerosis with that of a cohort of 366 age-, sex-, and, cancer type-matched patients without RD who received medical care from 2000 to 2014. Staging, comorbidities, and functional status were ascertained. Survival was compared using the Kaplan-Meier method. Relative risk of death was estimated as a hazard ratio (HR) using Cox regression analysis. Results: The mean age of the RD patients at the time of cancer diagnosis was 58.7 ± 11.5 years. The overall survival rate of gastric cancer patients did not differ between the cohorts. The survival of lung or breast cancer was worse in patients with RA or DM/PM than in those without RD (all, p < 0.05). After adjusting for cancer stage, comorbidity index, performance status and age at the time of cancer diagnosis (as well as interstitial lung disease for lung cancer group), the mortality rate among lung cancer patients with RA was significantly higher (HR, 1.81; 95 % CI, 1.03-3.18) than that of lung cancer patients without RD, whereas SSc was associated with decreased mortality of lung cancer (HR, 0.16; 95 % CI, 0.04-0.58). DM/PM were associated with increased mortality of breast cancer patients (HR, 297.39; 95 % CI, 4.24-20842.33). Conclusions: RA and DM/PM seemed to be associated with a higher mortality in patients with lung or breast cancers, whereas SSc seemed to be associated with decreased mortality in patients with lung cancer. It is warranted to explore the survival effect of tailored cancer treatments according to specific RD.



Table 1 . Clinical features of 17 patients identified to have recurrent fever and multi-system inflammation without infectious or autoimmune evidence 
Table 2 . Scores according to the provisional Eurofever clinical classification criteria 
Table 3 . Genetic features of 17 patients identified to have recurrent fever and multi-system inflammation without infectious or autoimmune evidence 
Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence

February 2016

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74 Reads

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3 Citations

Journal of Korean medical science

Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.



Figure 1: Cancer incidence in patients with rheumatic disease. The incidence of cancer was higher in patients with systemic lupus erythematosus and dermatomyositis, but lower in those with rheumatoid arthritis, compared with that in the general population. SIR, Standardized incidence ratio; CI, Confidence interval.
Table 1 Demographic characteristics of the rheumatic disease patients a
Table 2 Standardized incidence ratios for each cancer according to type of rheumatic disease a
Comparison of cancer incidence among patients with rheumatic disease: A retrospective cohort study

August 2014

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48 Reads

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52 Citations

Arthritis Research & Therapy

IntroductionRheumatic diseases (RDs) are associated with different cancers; however, it is unclear whether particular cancers are more prevalent in certain RDs. Here, we examined the relative incidence of several cancers in a single homogenous cohort of patients with different RDs.Methods Patients (n¿=¿3,586) diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), or polymyositis were included. Cancer diagnosis was based on histopathology. The 2008 Korean National Cancer Registry served as the reference for calculating standardized incidence ratios (SIRs).ResultsDuring the follow-up period of 31,064 person-years (PYs), 187 patients developed cancer. RA and SLE patients showed an increased risk of non-Hodgkin¿s lymphoma (SIR, 3.387; 95% CI, 1.462 to 6.673, SIR, 7.408; 95% CI, 2.405 to 17.287, respectively). SLE patients also had a higher risk of cervical cancer (SIR, 4.282; 95% CI, 1.722 to 8.824). SSc patients showed a higher risk of lung cancer (SIR, 4.17; 95% CI, 1.977 to 10.131). Endometrial cancer was increased only in patients with DM (SIR, 30.529; 95% CI, 3.697 to 110.283). RA patients had a lower risk for gastric cancer (SIR, 0.663; 95% CI, 0.327 to 0.998). The mean time between the RD and cancer diagnosis ranged from 0.1 to 16.6 years with the shortest time observed in patients with DM (2.0¿±¿2.1 years).Conclusions Different RDs are associated with particular cancers. Thus, cancer surveillance tailored to specific RD might be beneficial.


A Case of Relapsing Polychondritis Improved by Infliximab Treatment

January 2014

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19 Reads

Journal of Rheumatic Diseases

Relapsing polychondritis is an episodic, systemic inflammation of the cartilage with unknown autoimmune etiology. It leads to the destruction of cartilaginous structures of the ear, eye, nose, respiratory tract, joints, skin, and heart valve, and its presented symptoms are diverse. It can be improved mainly by corticosteroid or immunosuppressive agents. Recently, the use of biologic agents (TNF inhibitors, rituximab, tocilizumab et al) was reported from abroad. However, there is no reported case of relapsing polychondritis, which is treated by biologic agents in Korea. We report this first case of refractory relapsing polychondritis, which was improved with a treatment of Infliximab.


Figure 1. A mild hepatosplenomegaly was shown in abdominal CT scan taken at the diagnosis of Felty syndrome. 
Figure 2. Bone marrow aspiration and biopsy revealed no abnormalities except partial maturation arrest of myeloid lineage at the diagnosis of Felty syndrome. (A) Bone marrow aspirate (magnification ×400) and (B) biopsy (Hematoxylin and eosin stain, magnification ×400). 
Treatment with Rituximab in a Patient with Refractory Felty Syndrome and Low Rheumatoid Arthritis Disease Activity: A Case Report

January 2014

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181 Reads

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1 Citation

Journal of Rheumatic Diseases

Felty syndrome (FS) is a rare manifestation in rheumatoid arthritis (RA) characterized by neutropenia and splenomegaly. Treatment for FS is not well established because there has been no randomized controlled study. A few recent reports found rituximab effective in patients with refractory FS. According to those reports, most patients with RA and FS had active arthritis. Here we report a case of a patient with glucocorticoid dependent and disease-modifying anti-rheumatic drugs (DMARDs) refractory FS and quiescent RA who was successfully treated with rituximab.


Citations (7)


... Mechanistic studies have indicated a negative correlation between magnesium intake and CRP levels (44-48). Excessive serum uric acid crystallization can induce inflammation in joints and surrounding tissues (49), with patients experiencing uric acid crystals often showing markedly elevated serum CRP concentrations during acute episodes (50). Magnesium is essential for DNA folding and functional activity (22), with its role in DNA stability being concentration-dependent; low concentrations can lead to DNA deficiency and instability (51). ...

Reference:

Association between magnesium depletion score and prevalence of hyperuricemia in American adults: a study based on NHANES 2007-2018
Elderly Patients Exhibit Stronger Inflammatory Responses during Gout Attacks

Journal of Korean medical science

... In the previous issue of the Journal of Rheumatic Diseases, Kwon et al. [9] reported that among the Korean RA patients, bDMARDs did not increase the risk of developing HZ compared to cDMARDs (crude incidence rate, 2.6 [95% CI=1.6∼4] vs. 2.4 [95% CI=1.4∼3.9]), although the number of patients and observed patient-years was low for treatment with several biologic agents. ...

Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy
  • Citing Article
  • January 2017

Journal of Rheumatic Diseases

... Previous studies have shown that the specificity and sensitivity of ACPA detection for the diagnosis of RA are 96-99% and 47-88%, respectively, depending on the features of the RA population [79,80]. ACPA titers are significantly increased in patients with RA-ILD compared to those in patients with RA without ILD [16,81,82], suggesting that abnormal citrullination may contribute to the development of lung fibrosis in patients with RA. Klester et al. found that the ACPA titer was the most strongly associated risk factor for RA-ILD in a univariate analysis [46]. ...

Clinical characteristics associated with occurrence and poor prognosis of interstitial lung disease in rheumatoid arthritis

The Korean Journal of Internal Medicine

... apy. 35) In addition, a study evaluating treatment, including ICI therapy, for advanced NSCLC patients with ADs have reported a trend toward poorer prognosis in these patients. 17) Thus, because the presence of AD may affect mortality in advanced NSCLC patients, analyses that compared survival between patients with and without ADs, particularly focusing on patients receiving ICI therapy, should be interpreted with caution. ...

Survival rates of cancer patients with and without rheumatic disease: A retrospective cohort analysis

BMC Cancer

... 1,3 In the previous Korean study where 1777 patients were analyzed for an AID, none was found to possess a pathogenic mutation in the TNFRSF1A gene. 4 Herein, we report the first case of a Korean patient with a pathogenic TN-FRSF1A mutation who was initially diagnosed with systemic juvenile idiopathic arthritis (sJIA), but was then correctly diagnosed with TRAPS after 15 years. ...

Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence

Journal of Korean medical science

... In addition, the relationship between ADs and cancer is established, and the two kinds of diseases often occur together [4]. Some patients with ADs always have an increased susceptibility to cancers [5]. Cathepsins are involved in both immune regulation and tumor progression which may play a crucial role in this association [6]. ...

Comparison of cancer incidence among patients with rheumatic disease: A retrospective cohort study

Arthritis Research & Therapy

... Network of evidence. Six studies [22,23,26,29,32,33] reported Functional Index for Hand score, involving 7 interventions and 677 participants. The network of evidence was centered ...

The Efficacy of Diacerein in Hand Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Study
  • Citing Article
  • March 2013

Clinical Therapeutics