Baseline use of hydroxychloroquine or immunosuppressive drugs and the risk of coronavirus disease 2019

Background/Aims@#The preventive role of hydroxychloroquine (HCQ) on coronavirus disease 2019 (COVID-19) remains unclear. The aim of this study was to examine the effects of HCQ and other immunosuppressive drugs on the incidence of COVID-19. @*Methods@#The data were collected from the South Korea National Health Insurance Sharing-COVID-19 database. All individuals who underwent nasopharyngeal and oropharyngeal swab tests for COVID-19 from January 2020 to May 2020 are included. The association between COVID-19 risk and HCQ use was examined in a propensity score-matched population. Factors associated with COVID-19 were identified using multiple logistic regression analysis. @*Results@#Total 8,070 patients with COVID-19 and 121,050 negative controls were included from the database. Among all participants, 381 were HCQ users. In a propensity score-matched population, the incidence of COVID-19 was 7.1% in HCQ users and 6.8% in non-users. The odds ratio (OR) for HCQ use was 1.05 with a 95% confidence interval (CI) of 0.58 to 1.89. Among the subpopulation of patients with rheumatoid arthritis (RA), 33 were diagnosed with COVID-19 and 478 were not. Use of HCQ, glucocorticoids, or other immunosuppressive drugs was not associated with COVID-19 risk, whereas abatacept use was. Chronic lung disease was an independent risk factor for COVID-19 diagnosis in patients with RA (adjusted OR, 6.07; 95% CI, 1.10 to 33.59). @*Conclusions@#The risk of COVID-19 did not differ between HCQ users and non-users. Glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs other than abatacept did not increase the risk of COVID-19.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data

Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Erratum: Correction of Ethics Statement: Metastatic Insulinoma Presenting as a Liver Cyst

We found an error in our published article.

Metastatic Insulinoma Presenting as a Liver Cyst

No abstract available.

The Risk of Malignancy in Korean Patients with Rheumatoid Arthritis

PURPOSE: To investigate the overall cancer risk and risk for specific cancers in rheumatoid arthritis (RA) patients in Korea by comparing cancer incidence between RA patients and the general population. MATERIALS AND METHODS: Individuals diagnosed with RA between 1996 and 2009 who underwent treatment at the Daegu Catholic University Medical Center were retrospectively examined. 1885 patients with RA were included in the analyses. Occurrence of cancer and death during follow up was ascertained by linking medical records to the Korean Central Cancer Registry and national death certificates. For comparing cancer incidence between RA patients and general population, standardized incidence ratios (SIR) were calculated. The 95% confidence intervals (CIs) of SIRs were calculated using the shortcut method introduced by Vandenbroucke. RESULTS: The total follow-up time was 10218.9 person-years. During follow up, 100 patients (31 men and 69 women) were diagnosed with cancer. Both men and women had greater risks of having malignancy, although cancer risk was greater in men. Men showed increased risks of lung cancer (SIR=5.46, 95% CI: 2.60–9.36) and leukemia (SIR=16.7, 95% CI: 1.58–47.9). Women showed increased risks of thyroid cancer (SIR=1.75, 95% CI: 1.02–2.68), cervical cancer (SIR=3.65, 95% CI: 1.65–6.42), non-Hodgkin's lymphoma (SIR=6.47, 95% CI: 2.04–13.4), and gallbladder cancer (SIR=3.87, 95% CI: 1.01–8.60). Disease-modifying anti-rheumatic drugs usage and cancer were not related: the relative risks of developing malignancy were not elevated for each medicine. CONCLUSION: The overall cancer incidence was increased in Korean men and women with RA. Increased risk of specific malignancy differed according to sex.

Korean rheumatology workforce from 1992 to 2015: current status and future demand

BACKGROUND/AIMS@#Rheumatology in Korea has rapidly advanced in the 24 years since the subspecialty board certification program was established in 1992. The objective of this investigation was to analyze the distribution of rheumatology practices in Korea in order to better understand the rheumatology workforce.@*METHODS@#Using a membership list from the Korean College of Rheumatology (KCR), we obtained information on practicing rheumatologists. We mapped the ratio of rheumatologists to the general population and to patients with rheumatologic disease using data from Statistics Korea and the 2015 Health Insurance Review & Assessment Service (HIRA).@*RESULTS@#In the 16 administrative districts of Korea in 2015, there were 311 practicing rheumatologists on the list of KCR members. There were 218 members practicing in metropolitan areas and 93 members in the provinces. The mean number of rheumatologists per 100,000 people was 0.60, with 0.33/100,000 in the provinces, but 0.92/100,000 in metropolitan areas, a 2.7-fold difference. The number of rheumatologists per 100,000 patients with chronic rheumatic disease was 17.21 in metropolitan areas but 6.57 in the provinces, according to 2015 HIRA data. This geographic maldistribution emerged as a problem; indeed, the regional disparity in the distribution of Korean rheumatologists was striking when compared to the published medical professional distribution in 2014.@*CONCLUSIONS@#Because of the uneven distribution of rheumatologists, it is likely that some patients with chronic rheumatic conditions have limited access to rheumatology care. Thus, a policy-based approach is needed to alleviate this disparity.

Efficacy of luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist priming protocol in poor responders undergoing in vitro fertilization

OBJECTIVES: We investigated whether luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist (E/G-ant) priming protocol improves clinical outcomes in poor responders to controlled ovarian stimulation for in vitro fertilization (IVF)-embryo transfer, and identified underlying mechanisms. METHODS: This restrospective study consisted of 65 poor responders who underwent the E/G-ant priming protocol. Sixty-four other poor responders undergoing conventional protocols without pretreatment were included as the control group. Clinical outcomes were compared between 2 groups. RESULTS: The E/G-ant priming protocol group exhibited improvements over the control group in terms of the number of retrieved oocytes (3.58±2.24 vs. 1.70±1.45; P=0.000), mature oocytes (2.68±2.11 vs. 1.65±1.23; P=0.000), fertilized oocytes (2.25±1.74 vs. 1.32±1.26; P=0.001), good embryos (1.62±0.91 vs. 1.14±0.90, P=0.021). Day 3 follicle-stimulating hormone (FSH; 8.40±4.84 vs. 16.39±13.56; P=0.000) and pre-ovulation progesterone levels (0.67 vs. 1.28 ng/mL; P=0.016) were significantly higher in the control group than in the E/G-ant priming group. The overall rate of positive human chorionic gonadotropin tests was higher in the E/G-ant priming group than in the control group (32.3% vs.16.1%; P=0.039). Also, clinical pregnancy rate (26.2% vs. 12.5%; P=0.048) and the rate of live births (23.1% vs. 7.1%; P=0.023) were significantly higher in the E/G-ant priming group than in the control group. CONCLUSION: The E/G-ant priming protocol would lead to promising results in poor responders to IVF by suppressing endogenous FSH and by preventing premature luteinization.

Idiopathic Noncirrhotic Portal Hypertension: An Appraisal

Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity.

Factors Associated with Airway Disease and Interstitial Lung Disease in Rheumatoid Arthritis

OBJECTIVE: This study examined lung involvement in patients with rheumatoid arthritis (RA) and identified factors associated with airway disease (AD) and interstitial lung disease (ILD). METHODS: A total of 507 RA patients were enrolled in a cross-sectional study. Lung involvement was assessed by high-resolution computed tomography scan. The patient groups were classified according to normal, AD, and ILD. Multinomial logistic regression analysis was performed to identify factors associated with AD and ILD. RESULTS: The most frequent lung involvement was AD (38.3%) followed by ILD (12.6%). Old age (adjust odds ratio [aOR] 2.58, 95% confidence interval [CI] 1.70 to 3.90 for AD; aOR 4.38, 95% CI 2.30 to 8.35 for ILD), male gender (aOR 2.57, 95% CI 1.22 to 5.42 for AD; aOR 5.48, 95% CI 2.20 to 13.65 for ILD) were factors associated with AD and ILD in RA patients. ILD was associated with short disease duration (aOR 0.30, 95% CI 0.14 to 0.62), AD was associated with high titers of anti-cyclic citrullinated peptides antibodies (anti-CCP; aOR 1.61, 95% CI 1.07 to 2.44). CONCLUSION: AD was the most frequent lung involvement in patients with RA. Old age and male gender were both associated with AD and ILD. Short disease duration was associated with ILD. High titers of anti-CCP was associated with AD.

Effect of Formal Education Level on Measurement of Rheumatoid Arthritis Disease Activity

OBJECTIVE: The aim of this study is to analyze the capacity of three demographic variables - age, sex, and formal education level - as well as disease duration to explain variation in 7 Core Data Set variables and 4 indices used to assess rheumatoid arthritis (RA), in a cohort of Korean patients seen in usual care. METHODS: All RA Core Data Set measures were collected in usual care of 397 RA patients, including tender/swollen joint counts (TJC, SJC) 28, physician global estimate of status, erythrocyte sedimentation rate, C-reactive protein, and a multidimensional health assessment questionnaire to assess physical function, pain, and patient global estimate of status (PATGL). Four indices were computed: disease activity score with 28 joint count (DAS28), simplified disease activity index (SDAI), clinical disease activity index (CDAI), and routine assessment of patient index data 3 (RAPID3). Descriptive statistics and multivariate generalized linear models were used in data analysis. RESULTS: Patients with lower education had higher scores, indicating greater severity, for all 7 Core Data Set measures and 4 indices (significant for TJC, function, pain, PATGL, DAS28, SDAI, CDAI, RAPID3). In a series of regressions that included age, sex, disease duration, and education, formal education level was the only significant variable to explain variation in TJC, pain, PATGL, physician global estimate of status (DOCGL), DAS28, SDAI, CDAI, and RAPID3. CONCLUSION: Significant associations with education were found in Korean RA patients according to most RA Core Data Set measures and 4 indices. Education was more likely than age, sex, or disease duration to explain variation in most measures and indices.

Renal Infarction in Antiphospholipid Antibody-negative Pediatric Systemic Lupus Erythematosus Patient

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems, and is characterized by the deposition of immune complexes and a large array of autoantibodies. Thrombosis is a relatively frequent and serious complication of SLE; however, renal infarction in young patients with antiphospholipid antibody-negative lupus has rarely been reported, and no pediatric case has been reported in Korea. A 12-year-old female patient was presented to our hospital with a 3-day history of nausea, vomiting, and right flank pain. She was diagnosed with SLE and lupus nephritis two years ago and was treated with corticosteroids and hydroxychloroquine, azathioprine. Abdominal computed tomography (CT) showed renal infarction in the upper pole of the right kidney. Subcutaneous low molecular weight heparin was started, and warfarin was also started simultaneously and continued for 3 months. After 3 months, only minimal atrophic changes were seen on the abdominal CT. She is doing well by maintaining oral anticoagulant therapy and is being followed up regularly through outpatient clinic visits.

Development of Crohn's Disease during Etanercept Treatment in Juvenile Idiopathic Arthritis

No abstract available.

Resting energy expenditure is not associated with disease activity in women with rheumatoid arthritis: cross-sectional study

BACKGROUND/AIMS: Increased resting energy expenditure (REE) in rheumatoid arthritis (RA) patients is thought to be caused by hypermetabolism associated with production of proinflammatory cytokines. Our aim in the present study was to explore the possible association between REE and disease activity in females with RA. METHODS: A total of 499 female RA patients were recruited to this cross-sectional study assessing REE scores on disease activity indices (the routine assessment of patient index data 3 [RAPID3], the disease activity score 28, and the clinical/simplified disease activity index [CDAI/SDAI]) and the levels of RA-associated autoantibodies (rheumatoid factor and anticyclic citrullinated peptide [anti-CCP] antibodies). Age-matched healthy female controls (n = 131) were also enrolled. RESULTS: REE did not differ between RA patients (all patients, and those in remission or not) and controls, or between RA patients in remission or not (p > 0.05 for all comparisons). Increased REE in total RA patients was associated with younger age and a higher body mass index (BMI) (p < 0.001 and p < 0.001, respectively), but not with disease activity index scores on any of RAPID3, CDAI, or SDAI. BMI was the only clinical parameter exhibiting a significant relationship with REE quartiles (Q1 to Q4; p < 0.001); none of disease duration, functional status, or anti-CCP antibody titer in RA patients was significantly related to REE, based on analysis of covariance. CONCLUSIONS: We found no association between REE and disease activity in RA patients, implying that energy metabolism in RA patients might be independent of RA-associated systemic inflammation.

Pandemic H1N1 Influenza Vaccination Responses in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients

OBJECTIVE: We investigated the efficacy and safety of pandemic H1N1 vaccine in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients, and evaluated its correlation with serum cytokine level. METHODS: A total of 43 RA patients and 31 SLE patients were enrolled in the study and were compared with age, sex-matched 40 healthy controls (HC). The blood samples drawn from selected patients before vaccination and in post-vaccination at week 4 were assayed in one session to measure the titers of antibodies against haemagglutinin specific for influenza virus strains: A/California/7/2009 NYMC X-179A (H1N1). Serum IL17 and CXCL13 levels were measured in the same session by enzyme-linked immunosorbent assay. The association of serum cytokine level with anti-influenza antibody titer and mean fold increase (MFI) was investigated. Each specific side effect after vaccination was monitored in both the patients and control groups. RESULTS: The geometric mean antibody titer (GMT) for pre- and post-vaccination at week 4 was not significantly different between RA and HC, SLE and HC. The seroconversion rate in HC and RA was not significantly different, whereas the seroprotection rate is significantly higher in HC (82.5%) than RA (55.8%) (p<0.05). MFI in HC, RA, SLE were 19.65, 6.00 and 6.06, which were significantly higher in HC. Serum IL17 level was 6.28+/-2.89 pg/mL and 7.56+/-3.34 pg/mL in pre-, post-vaccination SLE patients, 33.85+/-15.62 pg/mL and 38.04+/-18.60 pg/mL in RA patients and was significantly lower in SLE patients. Serum CXCL13 level was 518.73+/-720.29 pg/mL and 431.53+/-601.23 pg/mL in pre-, post-vaccination SLE patients, which was significantly higher than HC (149.64+/-248.81 pg/mL and 147.36+/-213.92 pg/mL in each pre-, post-vaccination) and was not significantly different with the level of RA patients. In SLE patients, significant correlations were detected between cytokine level and post-vaccination antibody titer (r=0.22 p=0.026 between IL 17 and GMT; r=0.44, p<0.05 between CXCL13 and GMT). CONCLUSION: The increase in post-vaccination antibody titer is weaker in both RA and SLE patients group than the HC group. Post-vaccination antibody titer was positively correlated with B lymphocyte chemoattractant and CXCL13 in SLE patients, but not in RA patients.

Prognostic Factors of the RA Patients with ILD

OBJECTIVE: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA), and an important cause of morbidity and mortality in RA. We compared demographic and clinical characteristics of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) patterns in RA patients and determined the prognostic factors that influence the survival of RA-ILD patients. METHODS: 51 enrolled RA patients (male n=21, female n=30) with ILD underwent HRCT. We categorized ILD into two groups, as the UIP pattern and the NSIP pattern, using HRCT. HRCT scans were scored to investigate the extent of the ILD. We divided the extent of the interstitial lung disease into 4 groups 1~14%, 15~19%, 20~24%, >25%. RESULTS: There were no significant differences between the UIP and NSIP pattern in the clinical characteristics, except for age at the time of the study (RA-NSIP pattern vs RA-UIP pattern 62.3+/-11.7 vs 68.2+/-8.4, p=0.042). There were no significant differences in survival time between the RA-UIP and RA-NSIP pattern (Log rank p=0.985). The extent of ILD on chest HRCT was significantly associated with mortality (HR=1.044, 95% CI 1.019~1.069) and patients that were diagnosed with ILD at an older age (HR=1.109, 95% CI 1.024~1.200) were associated with a worse prognosis. Comparing four groups divided by the extent of the lung disease, there were significant differences in survival estimates (Log-rank p-value<0.001) based on an ILD extent of 15%. CONCLUSION: Our study reveals that the extent of ILD on chest HRCT was found to be significantly associated with poor prognosis of RA-ILD patients.

Prognostic Factors of the RA Patients with ILD

OBJECTIVE: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA), and an important cause of morbidity and mortality in RA. We compared demographic and clinical characteristics of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) patterns in RA patients and determined the prognostic factors that influence the survival of RA-ILD patients. METHODS: 51 enrolled RA patients (male n=21, female n=30) with ILD underwent HRCT. We categorized ILD into two groups, as the UIP pattern and the NSIP pattern, using HRCT. HRCT scans were scored to investigate the extent of the ILD. We divided the extent of the interstitial lung disease into 4 groups 1~14%, 15~19%, 20~24%, >25%. RESULTS: There were no significant differences between the UIP and NSIP pattern in the clinical characteristics, except for age at the time of the study (RA-NSIP pattern vs RA-UIP pattern 62.3+/-11.7 vs 68.2+/-8.4, p=0.042). There were no significant differences in survival time between the RA-UIP and RA-NSIP pattern (Log rank p=0.985). The extent of ILD on chest HRCT was significantly associated with mortality (HR=1.044, 95% CI 1.019~1.069) and patients that were diagnosed with ILD at an older age (HR=1.109, 95% CI 1.024~1.200) were associated with a worse prognosis. Comparing four groups divided by the extent of the lung disease, there were significant differences in survival estimates (Log-rank p-value<0.001) based on an ILD extent of 15%. CONCLUSION: Our study reveals that the extent of ILD on chest HRCT was found to be significantly associated with poor prognosis of RA-ILD patients.

Greater prevalence of seropositivity for anti-cyclic citrullinated peptide antibody in unaffected first-degree relatives in multicase rheumatoid arthritis-affected families

BACKGROUND/AIMS: This study determined the prevalence and determinants of seropositivity for rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and anti-mutated citrullinated vimentin (anti-MCV) antibody in unaffected first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients. METHODS: A total of 337 subjects (135 with RA and 202 FDRs) were enrolled in this case-control study. Serum RF, anti-CCP antibody, and anti-MCV antibody were assayed. Subjects in multicase families (> or = 2 affected FDRs within the same family) were identified. Multivariate logistic regression analysis was used to identify risk factors associated with RA-related autoantibodies. RESULTS: Seropositivity for RF, anti-CCP antibody, or anti-MCV antibody was detected in 14.4%, 5.0%, or 13.4% of unaffected FDRs, respectively. Anti-CCP antibody seropositivity was more prevalent in FDRs in multicase families (17.8%) than in those not in multicase families (1.3%, p < 0.0001). Significant correlations between RA-associated autoantibodies were detected in the FDR group (between RF and anti-CCP antibody: r = 0.366, p < 0.0001; between RF and anti-MCV antibody: r = 0.343, p < 0.0001; and between anti-CCP antibody and anti-MCV antibody: r = 0.849, p < 0.0001). After adjustment for age and sex, anti-CCP antibody seropositivity in FDRs was significantly associated with being in a multicase family (odds ratio, 49.8; 95% confidence interval, 5.6 to 441.6). CONCLUSIONS: The association between anti-CCP antibody seropositivity in unaffected FDRs and being in a multicase family suggests that genetic and/or environmental factors may increase the risk for RA development in unaffected FDRs.