To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactiv... more To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA). Medical records of all patients who received JAKi at a tertiary referral center between August 2015 and June 2021 were retrospectively reviewed. Data from patients who developed HZ reactivation were collected, and the HZ-related safety of those who continued JAKis after reactivation was evaluated. Of the 416 patients who received JAKis, 33 (7.9%) developed HZ reactivation during treatment (tofacitinib, n = 22; baricitinib, n = 11). The mean age of the patients was 60.2 ± 11.8 years. Fourteen patients (42.4%) received glucocorticoids with a median dose of 3.75 mg of prednisone (IQR, 2.5–5.0). The median duration of JAKi administration before HZ reactivation was 11 months (IQR, 4–29). JAKi was continued in 24 (72.7%) patients during the HZ episode, while it was temporarily discontinued and then resumed after the HZ episode in 5 (15.2%) patients. Three (9.1%) patients had acute complications, such as encephalitis with HZ ophthalmicus. Four (12.1%) patients, including the 3 with complications, permanently discontinued JAKis. Of the 29 patients who were observed for a median of 12 months (IQR, 6–21) after the initial HZ reactivation episode, reactivation recurred in one (3.4%); this patient maintained JAKi treatment for a further 18 months without additional HZ recurrence. JAKis were commonly continued or re-administered in patients with HZ reactivation, and the majority of these patients did not experience significant complications or recurrence of HZ reactivation. Thus, the use of JAKi after HZ reactivation episode seems to be tolerated. Key Points • JAK inhibitor was generally continued or re-administered after HZ reactivation • Most patients receiving JAK inhibitor after the HZ episode did not experience recurrence of HZ • Resuming JAK inhibitor following HZ seems to be safe
The Korean Journal of Internal Medicine, Aug 7, 2023
Background/Aims: Although non-proliferative lupus nephritis (LN) (class I, II or V) has been cons... more Background/Aims: Although non-proliferative lupus nephritis (LN) (class I, II or V) has been considered as a less severe type of LN, data on long-term renal prognosis are limited. We investigated the long-term outcomes and prognostic factors in non-proliferative LN. Methods: We retrospectively reviewed patients with systemic lupus erythematosus who were diagnosed with LN class I, II, V, or II + V by kidney biopsy from 1997 to 2021. A poor renal outcome was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m 2. Results: We included 71 patients with non-proliferative LN (class I = 4; class II = 17; class V = 48; class II+V = 2), and the overall rate of poor renal outcomes was 29.6% (21/71). The univariate analysis indicated that older age, low eGFR at 6 or 12 months, failure to reach complete remission at 6 months, and LN chronicity score > 4 or activity score > 6 were significantly associated with poor renal outcomes. The multivariate analysis revealed that low eGFR at 6 months (HR 0.971, 95% CI
antibody (anti-Sm) on BBB integrity via matrix metalloproteinase (MMP)-2 and evaluate the effect ... more antibody (anti-Sm) on BBB integrity via matrix metalloproteinase (MMP)-2 and evaluate the effect of captopril, a MMP-2 inhibitor on preventing BBB breach. Methods Human umbilical vein endothelial cells (HUVEC) were stimulated with monoclonal anti-Sm or anti-RNP antibody (anti-RNP). BBB integrity was evaluated with claudin-5 expression, the tight junction composing protein by q-PCR, and western blot. MMP-2 activity was measured by gelatin zymography. Results Antibody stimulation with anti-Sm or anti-RNP did not affect the expression of MMP-2 and claudin-5 at mRNA level. However, Claudin-5 protein expression was significantly reduced by anti-Sm stimulation compared to isotype control (p=0.004), but not by anti-RNP (p=0.496) (figure 1A). Active MMP-2 in culture supernatant was significantly increased after anti-Sm stimulation (p=0.015), but not by anti-RNP (p=0.688) (figure 1B). Addition of captopril restored claudin-5 mRNA expression that was reduced by anti-Sm stimulation (p=0.031) (figure 1C). Conclusions Anti-Sm reduced claudin-5 expression in HUVEC through up-regulation of active MMP-2 expression. Our results suggest that Captopril can be protective for BBB breaches mediated by anti-Sm in patients with NPSLE.
Background Serologically active clinically quiescent (SACQ) is a clinical state of systemic lupus... more Background Serologically active clinically quiescent (SACQ) is a clinical state of systemic lupus erythematosus (SLE) characterized by high levels of serologic markers without clinical activity. The outcome and treatment strategy after SACQ achievement remains unclear. After achieving the treatment goal, maintaining low-dose glucocorticoids has always been both a blessing and a curse. 1 2 In this multi-center prospective study, we aimed to identify the risk of flares, organ damage accumulation, and the glucocorticoids discontinuation feasibility of SLE patients who achieved the clinical state as SACQ. Methods This study was conducted based on data from the Chinese SLE treatment and research (CSTAR) registry. Demographic characteristics, autoantibody profiles, clinical manifestations, organ damage, and treatment profile were collected at recruitment and during follow-up. SACQ was defined as persistent serologic activity (positive anti-dsDNA antibody, and/or hypocomplementemia), and without clinical activity. Serologically quiescent clinically quiescent (SQCQ) was defined as a persistent serologic and clinical quiescent stage. Organ damage is principally assessed using the SLICC damage index (SDI). Results Of 4107 SLE patients, 1889 reached the clinical quiescent stage (990 achieved SACQ, and 899 achieved SQCQ). Among SACQ patients, 364 (36.7%) underwent flares, 163 (16.5%) showed organ damage, 47 (4.7%) developed renal damage, and 21 (2.1%) died during a mean follow-up of 7.30 years. Compared with SQCQ, SACQ patients were at a higher risk of flares (HR=1.47, 95% CI 1.25-1.73, p<0.001) and renal damage accumulation (HR=2.02, 95% CI 1.23-3.33, p=0.004). Furthermore, 224 (22.6%) SACQ patients withdraw glucocorticoids and 125 (55.8%) of them did not flare. Glucocorticoids discontinuation was a favorable factor of survival (HR=0.22, 85% CI, 0.05-0.96, P=0.044). As shown in the figure, withdrawing glucocorticoids can reduce organ damage (p=0.0075), especially renal damage accumulation (p=0.045), even experience flares after discontinuation. Conclusions Glucocorticoids withdrawal under tight survallance could be considered after achieving the clinical state as SACQ to prevent the accrual of renal damage.
without SLE. On the other hand, the pregnancy adverse outcomes are common in pregnant women with ... more without SLE. On the other hand, the pregnancy adverse outcomes are common in pregnant women with SLE. However, the pregnancy rates in women with SLE was not fully understood. In addition, comparison of the pregnancy adverse outcomes with general population is limited. Objectives: We estimated the pregnancy rates and adverse pregnancy outcomes in Korean women with SLE and compared them with women without SLE. Methods: Among all women aged 15-49 years in the Korean National Health Insurance claim database from January 2013 to December 2015, pregnant women were identified by using ICD-10 code for delivery and abortion. Pregnant women were categorized into women with SLE and control group. Adverse pregnancy outcomes classified into five categories as follows: fetal loss, intrauterine growth retardation (IUGR), preterm delivery, pre-eclampsia or eclampsia, and gestational diabetes mellitus. Crude incidence rates (IRs) of pregnancy and adverse pregnancy outcomes were calculated. Incidence rate ratios (IRRs) of those were estimated and adjusted for age. Results: In SLE, 994 pregnancy cases were observed during the study period. The crude estimated IRs of pregnancy were lower in SLE patients than general population (Table 1). Age-adjusted IRR was also lower in SLE patients (Table1). The adjusted-IRR of live birth in SLE pregnant women was 0.92 (95% CI 0.85-0.99) compared with control group. The adjusted-IRR of fatal loss, IUGR, and preterm delivery was 1.27 (95% CI 1.11-1.45), 4.52 (95% CI 3.45-5.91), and 3.25 (95% CI 1.62-6.52), respectively. The IRR of pre-eclampsia or eclampsia was 3.21 (95% CI 2.52-4.08), but those of gestational diabetes mellitus was not significant (IRR 0.89, 95% CI 0.80-1.00). Conclusion: Pregnancy rates in SLE women were lower about 30% compared with general population. Pregnancy adverse outcomes were higher in SLE pregnant women with more than 4-fold IUGR and pre-eclampsia/ eclampsia, 3.2-fold preterm delivery. REFERENCES: [1] EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.
Background: Anaphylaxis to tocilizumab has been reported anecdotally. Therefore, we evaluated the... more Background: Anaphylaxis to tocilizumab has been reported anecdotally. Therefore, we evaluated the incidence of anaphylaxis in patients starting tocilizumab. Materials &amp;amp; methods: This retrospective study included patients with rheumatic disease who were administered tocilizumab from 2013 to 2020. The incidence of anaphylaxis was examined during the first 6 months. Results: During follow-up, four of 171 patients developed anaphylaxis within the third course of infusions. The incidence of anaphylaxis to tocilizumab was higher in patients with adult-onset Still’s disease (AOSD) than in those with other rheumatic disease (21.4% in AOSD vs 0.7% in rheumatoid arthritis vs 0% in Takayasu arteritis). Conclusions: When we consider tocilizumab treatment, especially in AOSD, we should keep in mind that intensive monitoring for anaphylaxis is necessary.
Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder that has defects in ... more Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder that has defects in glucose-6-phosphatase (G6Pase) in liver, kidney and intestinal mucosa. The defect leads to inadequate conversion of glucose-6-phospate to glucose in the liver and thus makes affected individuals susceptible to fasting hypoglycemia, hyperuricemia, lactic acidemia and hyperlipidemia. Hyperuricemia has been observed in a considerable number of patients and in some of those, clinical gout has occurred. Inhibited tubular secretion of uric acid due to hyperlacticacidemia and ketonemia, and overproduction of uric acid have been postulated as a mechanism for hyperuricemia in patients with GSD-Ia. A 30-year-old male was admitted with fatigue, foot pain and multiple gouty tophi on knee, ankle, and elbow. GSD-Ia and gout were confirmed by analysis of the G6Pase gene and tophi aspiration respectively. He was treated with allopurinol and uncooked cornstarch. After treatment, foot pain improved and the number and size of tophi were decreased.
Background: Patients with immune thrombocytopenia (ITP) have a risk of developing systemic lupus ... more Background: Patients with immune thrombocytopenia (ITP) have a risk of developing systemic lupus erythematosus (SLE). We sought to examine the clinical characteristics of patients with primary ITP who later developed SLE and identified the risk factors for the development of SLE. Methods: We retrospectively examined patients who were diagnosed with primary ITP at a tertiary hospital between August 2001 and November 2019. We compared the clinical characteristics according to the development of SLE. Logistic regression analysis was performed to identify the factors associated with the development of SLE. Results: Of 130 patients with primary ITP, 10 (7.7%) were later diagnosed with SLE during follow-up (median, 30 months [IQR, 15.5-105]). The presence of skin bleeding, organ bleeding, lymphocytopenia, anemia, and antinuclear antibody (ANA) positivity (≥ 1:160) were more common among patients who later developed SLE than did those who did not develop SLE. Multivariate analysis showed that young age (< 40 years; odds ratio [OR], 6.307 [95% confidence interval (CI), 1.114-34.908]; P = 0.035), organ bleeding (OR, 13.672 [95% CI, 2.437-76.689]; P = 0.003), and ANA positivity (1:160; OR, 6.638 [95% CI, 1.399-31.504]; P = 0.017) were significantly associated with the development of SLE. Conclusions: Young age (< 40 years), organ bleeding, and ANA positivity (≥ 1:160) were risk factors for the development of SLE in patients with primary ITP. Close follow-up is needed to detect the development of SLE in patients with ITP and the abovementioned risk factors.
We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on ... more We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis receiving bisphosphonate. A total of 199 RA patients, who were newly diagnosed with osteoporosis and receiving bisphosphonate between January 2005 and March 2017, were reviewed. Changes in BMD after 1 year were compared between patients treated with and without TNFi. The inverse probability of treatment weighting (IPTW) method using the propensity score was performed to minimize confounding factors, and logistic regression analysis was applied to identify any factors associated with significant BMD improvement (≥ 3%) at the lumbar spine and femur neck. Among patients receiving bisphosphonate, 29 were exposed to TNFi, and 170 patients were not exposed. The percentage change in BMD and the proportion of significant improvements at the lumbar spine and femur neck were similar between patients treated with and without TNFi, before and after IPTW adjustment. In addition, the disease activity score 28 (DAS28) with three variables [adjusted odds ratio (OR) 0.741, 95% confidence interval (CI) 0.592-0.927, p = 0.009] and cumulative steroid dose (adjusted OR 0.639, 95% CI 0.480-0.851, p = 0.002) were inversely associated with an improvement in BMD. Conversely, TNFi use was not associated with any improvement in BMD after adjustment by IPTW using the propensity score. TNFi did not influence BMD improvement in RA patients with osteoporosis receiving bisphosphonate, suggesting that TNFi cannot be considered as a preferred therapeutic option for increasing BMD.
Objective. Previous studies investigating the beneficial effect of rituximab on lupus nephritis (... more Objective. Previous studies investigating the beneficial effect of rituximab on lupus nephritis (LN) reported controversial results. There have been few reports of renal response to rituximab according to renal function. We investigated the efficacy of rituximab in refractory/relapsing LN and the role of renal function as a predictor of renal response. Methods. From 2016 to 2019, we retrospectively reviewed 22 patients with refractory/relapsing LN receiving rituximab. Renal responses (complete and partial) at 6 and 12 months were compared between normal (glomerular filtration rate [GFR]≥90 mL/min/1.73 m 2 , n=11) and decreased (GFR＜90 mL/min/1.73 m 2 , n=11) GFR groups. Multivariate Cox regression analysis was used to assess predictors of renal response. Results. At baseline, the decreased GFR group had a higher urine proteinuria to creatinine ratio (p=0.008) and proportion of refractory LN (p=0.010) and previous cyclophosphamide therapy (p=0.035) than the normal GFR group. The overall renal response rate was 45.5% (10 patients) at 6 months and 54.5% (12 patients) at 12 months. Renal response rates were higher in the normal GFR group (81.8% and 90.9% at 6 and 12 months, respectively) than in the decreased GFR group (9.1% and 18.2% at 6 and 12 months, respectively; p＜0.001). Normal GFR and anti-La were associated with renal response to rituximab, with hazard ratios of 9.256 (p=0.008) and 5.478 (p=0.041), respectively. Conclusion. Rituximab is an effective therapy for refractory/relapsing LN, particularly in patients with preserved renal function.
Objectives Macrophage activation syndrome (MAS) is a hyperinflammatory condition that is known to... more Objectives Macrophage activation syndrome (MAS) is a hyperinflammatory condition that is known to be secondary hemophagocytic lymphohistiocytosis (HLH) in patients with rheumatic disease. The aim of study was to evaluate the clinical manifestations and outcomes in patients with MAS with rheumatic disease. Materials and methods We performed a retrospective study of 20 adult patients who were diagnosed with MAS from 2012 to 2020. MAS was classified according to the HLH-2004 criteria. Patients’ information, including clinical features, laboratory findings, and treatment regimens, was collected, and the overall survival rate was estimated by the Kaplan–Meier method. Results Twenty patients (18 women, 35.6 ± 18.3 years) who met the HLH-2004 criteria also fulfilled the 2016 EULAR/ACR/PRINTO classification criteria for MAS, and HScore was higher than 169 (mean, 241.1). Fourteen patients with systemic lupus erythematosus and 6 patients with adult-onset Still’s disease were included. All pat...
Background The purpose of this study was to stratify patients with rheumatoid arthritis (RA) acco... more Background The purpose of this study was to stratify patients with rheumatoid arthritis (RA) according to the trend of disease activity by trajectory-based clustering and to identify contributing factors for treatment response to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) according to trajectory groups. Methods We analyzed the data from a nationwide RA cohort from the Korean College of Rheumatology Biologics and Targeted Therapy registry. Patients treated with second-line biologic and targeted synthetic DMARDs were included. Trajectory modeling for clustering was used to group the disease activity trend. The contributing factors using the machine learning model of SHAP (SHapley Additive exPlanations) values for each trajectory were investigated. Results The trends in the disease activity of 688 RA patients were clustered into 4 groups: rapid decrease and stable disease activity (group 1, n = 319), rapid decrease followed by an increase (group 2, ...
Background: We developed a model to predict remissions in patients treated with biologic disease-... more Background: We developed a model to predict remissions in patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify important clinical features associated with remission using explainable artificial intelligence (XAI).Methods: We gathered the follow-up data of 1204 patients treated with bDMARDs (etanercept, adalimumab, golimumab, infliximab, abatacept, and tocilizumab) from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. Remission was predicted at one-year follow-up using baseline clinical data obtained at the time of enrollment. Machine learning methods (e.g., lasso, ridge, support vector machine, random forest, and XGBoost) were used for the predictions. The Shapley additive explanation (SHAP) value was used for interpretability of the predictions.Results: The ranges for accuracy and area under the receiver operating characteristic of the newly developed machine learning model for predicting remission were 52.8%–72....
Background: Because of the highly variable clinical course, it is important to predict the progno... more Background: Because of the highly variable clinical course, it is important to predict the prognosis of rheumatoid arthritis related interstitial pneumonia (RA-IP) at the time of diagnosis. The aim of the study was to find out the blood biomarker that can predict the disease progression and/or survival in the patients with RA-IP at the time of diagnosis. Method: The plasma levels of biomarkers (KL-6, MMP-7, IL-6, IL-22, and IL-32) were retrospectively compared with the clinical course of 79 patients with RA-IP (biopsy-proven: 33). Results: The mean age of the patients was 63 years and 45.6% was male. The median follow-up period was 42 months. Among the 5 biomarkers, only KL-6 has clinical significance. KL-6 level was significantly higher in the patient with acute exacerbation (≥1447.80 ng/mL) compared to stable state (AUC, 0.938; P<0.001). There was no correlation between the level of KL-6 and the treatment response. Among the patients followed-up without treatment (n=38), KL-6 l...
To the Editor: Lupus nephritis (LN) is the leading cause of morbidity and mortality in patients w... more To the Editor: Lupus nephritis (LN) is the leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). 1 Noninvasively obtainable biomarkers for LN could greatly improve early LN detection. In this study, we found that urine alpha-1-acid glycoprotein (ORM1) is a promising biomarker for early LN detection. Furthermore, with regard to histologic features, urine haemoglobin subunit delta (HBD) accurately discriminated proliferative LN from nonproliferative LN and correlated with activity index. Using sequential window acquisition of all theoretical mass spectra combined with liquid chromatography (SWATH LC-MS) platform, a novel mass spectrometrybased proteome analysis, 2 we screened potential biomarker candidates in urine samples from 20 healthy controls (HCs) and 39 patients with SLE with or without newly diagnosed LN (n-LN). All patients with SLE met the 2012 Systemic Lupus International Collaborating Clinics classification criteria for SLE. 3 Sample preparation and in-house urine proteome spectral library generation were performed as described previously. 2 In our spectral library, 2323 proteins and 8371 peptides were identified using data-dependent acquisition analysis. A total of 1157 protein groups (581 ± 31, 506 ± 25 and 457 ± 22 in HCs, patients with SLE without nephritis, and patients with n-LN, respectively) were quantified from individual samples using an in-house spectral library. Among the 1157 protein groups, 143 protein groups (false discovery rate ≤.05, log2 fold change ±1) were increased in patients with SLE without nephritis than those in HCs (Figure 1A), and 67 protein groups were increased in patients with n-LN than those in patients with SLE without nephritis (Figure 1B). Among these protein groups, 23 protein groups were identified to be common between the two comparative analyses. Among these 23 urine proteins, five proteins (ORM1, antithrombin-III [SERPINC1], ceruloplasmin [CP], haemoglobin subunit beta [HBB] and HBD) were selected for enzyme-linked immunosorbent assay This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
To assess the clinical features, laboratory findings, and response to therapy according to diseas... more To assess the clinical features, laboratory findings, and response to therapy according to disease course, and analyse the predictive factors for unfavourable outcomes in patients with adult-onset Still's disease (AOSD). We retrospectively reviewed the medical records of 82 patients from January 1992 to December 2010 at a single tertiary hospital. Thirty-three had monocyclic disease, 33 experienced at least one relapse, and 14 had chronic disease. Patients were divided into those with favourable (monocyclic, n=33) and unfavourable (polycyclic or chronic and death, n=49) outcomes. The major clinical features were high spiking fever (96.3%), polyarthralgia (85.4%), skin rash (80.5%), myalgia (70.7%), and sore throat (68.3%). Analysis of prognostic factors for the 2 groups showed that polyarthralgia, elevated erythrocyte sedimentation rate, high serum lactate dehydrogenase, and low dose of initial glucocorticoids were related with unfavourable outcomes. An insufficient starting dos...
Although chronic kidney disease (CKD) may constitute a chronic inflammatory state indicated by el... more Although chronic kidney disease (CKD) may constitute a chronic inflammatory state indicated by elevated inflammatory mediators such as tumor necrosis factor alpha (TNF-α), the impact of anti-TNF-α therapy on progression of CKD in patients with rheumatoid arthritis (RA) is unclear. Seventy patients with RA and CKD were retrospectively analyzed. Outcomes were evaluated using the difference in the annual change of estimated glomerular filtration rate (eGFR) between patients treated with anti-TNF-α or without. Anti-TNF-α therapy significantly decreased disease activity score (DAS) 28 from 5.32 ± 0.78 to 3.59 ± 0.85 (p < 0.001). There was a tendency toward stabilization of eGFR after a mean of 2.9 ± 1.1 years from 50.3 ± 8.4 ml/min/1.73 m(2) to 54.5 ± 16.0 ml/min/1.73 m(2) in patients received anti-TNF-α therapy along with decreased DAS28 (p = 0.084). Conversely, eGFR decreased significantly in patients not receiving anti-TNF-α therapy after a mean of 2.8 ± 1.7 years from 52.6 ± 7.5 m...
To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactiv... more To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA). Medical records of all patients who received JAKi at a tertiary referral center between August 2015 and June 2021 were retrospectively reviewed. Data from patients who developed HZ reactivation were collected, and the HZ-related safety of those who continued JAKis after reactivation was evaluated. Of the 416 patients who received JAKis, 33 (7.9%) developed HZ reactivation during treatment (tofacitinib, n = 22; baricitinib, n = 11). The mean age of the patients was 60.2 ± 11.8 years. Fourteen patients (42.4%) received glucocorticoids with a median dose of 3.75 mg of prednisone (IQR, 2.5–5.0). The median duration of JAKi administration before HZ reactivation was 11 months (IQR, 4–29). JAKi was continued in 24 (72.7%) patients during the HZ episode, while it was temporarily discontinued and then resumed after the HZ episode in 5 (15.2%) patients. Three (9.1%) patients had acute complications, such as encephalitis with HZ ophthalmicus. Four (12.1%) patients, including the 3 with complications, permanently discontinued JAKis. Of the 29 patients who were observed for a median of 12 months (IQR, 6–21) after the initial HZ reactivation episode, reactivation recurred in one (3.4%); this patient maintained JAKi treatment for a further 18 months without additional HZ recurrence. JAKis were commonly continued or re-administered in patients with HZ reactivation, and the majority of these patients did not experience significant complications or recurrence of HZ reactivation. Thus, the use of JAKi after HZ reactivation episode seems to be tolerated. Key Points • JAK inhibitor was generally continued or re-administered after HZ reactivation • Most patients receiving JAK inhibitor after the HZ episode did not experience recurrence of HZ • Resuming JAK inhibitor following HZ seems to be safe
The Korean Journal of Internal Medicine, Aug 7, 2023
Background/Aims: Although non-proliferative lupus nephritis (LN) (class I, II or V) has been cons... more Background/Aims: Although non-proliferative lupus nephritis (LN) (class I, II or V) has been considered as a less severe type of LN, data on long-term renal prognosis are limited. We investigated the long-term outcomes and prognostic factors in non-proliferative LN. Methods: We retrospectively reviewed patients with systemic lupus erythematosus who were diagnosed with LN class I, II, V, or II + V by kidney biopsy from 1997 to 2021. A poor renal outcome was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m 2. Results: We included 71 patients with non-proliferative LN (class I = 4; class II = 17; class V = 48; class II+V = 2), and the overall rate of poor renal outcomes was 29.6% (21/71). The univariate analysis indicated that older age, low eGFR at 6 or 12 months, failure to reach complete remission at 6 months, and LN chronicity score > 4 or activity score > 6 were significantly associated with poor renal outcomes. The multivariate analysis revealed that low eGFR at 6 months (HR 0.971, 95% CI
antibody (anti-Sm) on BBB integrity via matrix metalloproteinase (MMP)-2 and evaluate the effect ... more antibody (anti-Sm) on BBB integrity via matrix metalloproteinase (MMP)-2 and evaluate the effect of captopril, a MMP-2 inhibitor on preventing BBB breach. Methods Human umbilical vein endothelial cells (HUVEC) were stimulated with monoclonal anti-Sm or anti-RNP antibody (anti-RNP). BBB integrity was evaluated with claudin-5 expression, the tight junction composing protein by q-PCR, and western blot. MMP-2 activity was measured by gelatin zymography. Results Antibody stimulation with anti-Sm or anti-RNP did not affect the expression of MMP-2 and claudin-5 at mRNA level. However, Claudin-5 protein expression was significantly reduced by anti-Sm stimulation compared to isotype control (p=0.004), but not by anti-RNP (p=0.496) (figure 1A). Active MMP-2 in culture supernatant was significantly increased after anti-Sm stimulation (p=0.015), but not by anti-RNP (p=0.688) (figure 1B). Addition of captopril restored claudin-5 mRNA expression that was reduced by anti-Sm stimulation (p=0.031) (figure 1C). Conclusions Anti-Sm reduced claudin-5 expression in HUVEC through up-regulation of active MMP-2 expression. Our results suggest that Captopril can be protective for BBB breaches mediated by anti-Sm in patients with NPSLE.
Background Serologically active clinically quiescent (SACQ) is a clinical state of systemic lupus... more Background Serologically active clinically quiescent (SACQ) is a clinical state of systemic lupus erythematosus (SLE) characterized by high levels of serologic markers without clinical activity. The outcome and treatment strategy after SACQ achievement remains unclear. After achieving the treatment goal, maintaining low-dose glucocorticoids has always been both a blessing and a curse. 1 2 In this multi-center prospective study, we aimed to identify the risk of flares, organ damage accumulation, and the glucocorticoids discontinuation feasibility of SLE patients who achieved the clinical state as SACQ. Methods This study was conducted based on data from the Chinese SLE treatment and research (CSTAR) registry. Demographic characteristics, autoantibody profiles, clinical manifestations, organ damage, and treatment profile were collected at recruitment and during follow-up. SACQ was defined as persistent serologic activity (positive anti-dsDNA antibody, and/or hypocomplementemia), and without clinical activity. Serologically quiescent clinically quiescent (SQCQ) was defined as a persistent serologic and clinical quiescent stage. Organ damage is principally assessed using the SLICC damage index (SDI). Results Of 4107 SLE patients, 1889 reached the clinical quiescent stage (990 achieved SACQ, and 899 achieved SQCQ). Among SACQ patients, 364 (36.7%) underwent flares, 163 (16.5%) showed organ damage, 47 (4.7%) developed renal damage, and 21 (2.1%) died during a mean follow-up of 7.30 years. Compared with SQCQ, SACQ patients were at a higher risk of flares (HR=1.47, 95% CI 1.25-1.73, p<0.001) and renal damage accumulation (HR=2.02, 95% CI 1.23-3.33, p=0.004). Furthermore, 224 (22.6%) SACQ patients withdraw glucocorticoids and 125 (55.8%) of them did not flare. Glucocorticoids discontinuation was a favorable factor of survival (HR=0.22, 85% CI, 0.05-0.96, P=0.044). As shown in the figure, withdrawing glucocorticoids can reduce organ damage (p=0.0075), especially renal damage accumulation (p=0.045), even experience flares after discontinuation. Conclusions Glucocorticoids withdrawal under tight survallance could be considered after achieving the clinical state as SACQ to prevent the accrual of renal damage.
without SLE. On the other hand, the pregnancy adverse outcomes are common in pregnant women with ... more without SLE. On the other hand, the pregnancy adverse outcomes are common in pregnant women with SLE. However, the pregnancy rates in women with SLE was not fully understood. In addition, comparison of the pregnancy adverse outcomes with general population is limited. Objectives: We estimated the pregnancy rates and adverse pregnancy outcomes in Korean women with SLE and compared them with women without SLE. Methods: Among all women aged 15-49 years in the Korean National Health Insurance claim database from January 2013 to December 2015, pregnant women were identified by using ICD-10 code for delivery and abortion. Pregnant women were categorized into women with SLE and control group. Adverse pregnancy outcomes classified into five categories as follows: fetal loss, intrauterine growth retardation (IUGR), preterm delivery, pre-eclampsia or eclampsia, and gestational diabetes mellitus. Crude incidence rates (IRs) of pregnancy and adverse pregnancy outcomes were calculated. Incidence rate ratios (IRRs) of those were estimated and adjusted for age. Results: In SLE, 994 pregnancy cases were observed during the study period. The crude estimated IRs of pregnancy were lower in SLE patients than general population (Table 1). Age-adjusted IRR was also lower in SLE patients (Table1). The adjusted-IRR of live birth in SLE pregnant women was 0.92 (95% CI 0.85-0.99) compared with control group. The adjusted-IRR of fatal loss, IUGR, and preterm delivery was 1.27 (95% CI 1.11-1.45), 4.52 (95% CI 3.45-5.91), and 3.25 (95% CI 1.62-6.52), respectively. The IRR of pre-eclampsia or eclampsia was 3.21 (95% CI 2.52-4.08), but those of gestational diabetes mellitus was not significant (IRR 0.89, 95% CI 0.80-1.00). Conclusion: Pregnancy rates in SLE women were lower about 30% compared with general population. Pregnancy adverse outcomes were higher in SLE pregnant women with more than 4-fold IUGR and pre-eclampsia/ eclampsia, 3.2-fold preterm delivery. REFERENCES: [1] EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.
Background: Anaphylaxis to tocilizumab has been reported anecdotally. Therefore, we evaluated the... more Background: Anaphylaxis to tocilizumab has been reported anecdotally. Therefore, we evaluated the incidence of anaphylaxis in patients starting tocilizumab. Materials &amp;amp; methods: This retrospective study included patients with rheumatic disease who were administered tocilizumab from 2013 to 2020. The incidence of anaphylaxis was examined during the first 6 months. Results: During follow-up, four of 171 patients developed anaphylaxis within the third course of infusions. The incidence of anaphylaxis to tocilizumab was higher in patients with adult-onset Still’s disease (AOSD) than in those with other rheumatic disease (21.4% in AOSD vs 0.7% in rheumatoid arthritis vs 0% in Takayasu arteritis). Conclusions: When we consider tocilizumab treatment, especially in AOSD, we should keep in mind that intensive monitoring for anaphylaxis is necessary.
Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder that has defects in ... more Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder that has defects in glucose-6-phosphatase (G6Pase) in liver, kidney and intestinal mucosa. The defect leads to inadequate conversion of glucose-6-phospate to glucose in the liver and thus makes affected individuals susceptible to fasting hypoglycemia, hyperuricemia, lactic acidemia and hyperlipidemia. Hyperuricemia has been observed in a considerable number of patients and in some of those, clinical gout has occurred. Inhibited tubular secretion of uric acid due to hyperlacticacidemia and ketonemia, and overproduction of uric acid have been postulated as a mechanism for hyperuricemia in patients with GSD-Ia. A 30-year-old male was admitted with fatigue, foot pain and multiple gouty tophi on knee, ankle, and elbow. GSD-Ia and gout were confirmed by analysis of the G6Pase gene and tophi aspiration respectively. He was treated with allopurinol and uncooked cornstarch. After treatment, foot pain improved and the number and size of tophi were decreased.
Background: Patients with immune thrombocytopenia (ITP) have a risk of developing systemic lupus ... more Background: Patients with immune thrombocytopenia (ITP) have a risk of developing systemic lupus erythematosus (SLE). We sought to examine the clinical characteristics of patients with primary ITP who later developed SLE and identified the risk factors for the development of SLE. Methods: We retrospectively examined patients who were diagnosed with primary ITP at a tertiary hospital between August 2001 and November 2019. We compared the clinical characteristics according to the development of SLE. Logistic regression analysis was performed to identify the factors associated with the development of SLE. Results: Of 130 patients with primary ITP, 10 (7.7%) were later diagnosed with SLE during follow-up (median, 30 months [IQR, 15.5-105]). The presence of skin bleeding, organ bleeding, lymphocytopenia, anemia, and antinuclear antibody (ANA) positivity (≥ 1:160) were more common among patients who later developed SLE than did those who did not develop SLE. Multivariate analysis showed that young age (< 40 years; odds ratio [OR], 6.307 [95% confidence interval (CI), 1.114-34.908]; P = 0.035), organ bleeding (OR, 13.672 [95% CI, 2.437-76.689]; P = 0.003), and ANA positivity (1:160; OR, 6.638 [95% CI, 1.399-31.504]; P = 0.017) were significantly associated with the development of SLE. Conclusions: Young age (< 40 years), organ bleeding, and ANA positivity (≥ 1:160) were risk factors for the development of SLE in patients with primary ITP. Close follow-up is needed to detect the development of SLE in patients with ITP and the abovementioned risk factors.
We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on ... more We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis receiving bisphosphonate. A total of 199 RA patients, who were newly diagnosed with osteoporosis and receiving bisphosphonate between January 2005 and March 2017, were reviewed. Changes in BMD after 1 year were compared between patients treated with and without TNFi. The inverse probability of treatment weighting (IPTW) method using the propensity score was performed to minimize confounding factors, and logistic regression analysis was applied to identify any factors associated with significant BMD improvement (≥ 3%) at the lumbar spine and femur neck. Among patients receiving bisphosphonate, 29 were exposed to TNFi, and 170 patients were not exposed. The percentage change in BMD and the proportion of significant improvements at the lumbar spine and femur neck were similar between patients treated with and without TNFi, before and after IPTW adjustment. In addition, the disease activity score 28 (DAS28) with three variables [adjusted odds ratio (OR) 0.741, 95% confidence interval (CI) 0.592-0.927, p = 0.009] and cumulative steroid dose (adjusted OR 0.639, 95% CI 0.480-0.851, p = 0.002) were inversely associated with an improvement in BMD. Conversely, TNFi use was not associated with any improvement in BMD after adjustment by IPTW using the propensity score. TNFi did not influence BMD improvement in RA patients with osteoporosis receiving bisphosphonate, suggesting that TNFi cannot be considered as a preferred therapeutic option for increasing BMD.
Objective. Previous studies investigating the beneficial effect of rituximab on lupus nephritis (... more Objective. Previous studies investigating the beneficial effect of rituximab on lupus nephritis (LN) reported controversial results. There have been few reports of renal response to rituximab according to renal function. We investigated the efficacy of rituximab in refractory/relapsing LN and the role of renal function as a predictor of renal response. Methods. From 2016 to 2019, we retrospectively reviewed 22 patients with refractory/relapsing LN receiving rituximab. Renal responses (complete and partial) at 6 and 12 months were compared between normal (glomerular filtration rate [GFR]≥90 mL/min/1.73 m 2 , n=11) and decreased (GFR＜90 mL/min/1.73 m 2 , n=11) GFR groups. Multivariate Cox regression analysis was used to assess predictors of renal response. Results. At baseline, the decreased GFR group had a higher urine proteinuria to creatinine ratio (p=0.008) and proportion of refractory LN (p=0.010) and previous cyclophosphamide therapy (p=0.035) than the normal GFR group. The overall renal response rate was 45.5% (10 patients) at 6 months and 54.5% (12 patients) at 12 months. Renal response rates were higher in the normal GFR group (81.8% and 90.9% at 6 and 12 months, respectively) than in the decreased GFR group (9.1% and 18.2% at 6 and 12 months, respectively; p＜0.001). Normal GFR and anti-La were associated with renal response to rituximab, with hazard ratios of 9.256 (p=0.008) and 5.478 (p=0.041), respectively. Conclusion. Rituximab is an effective therapy for refractory/relapsing LN, particularly in patients with preserved renal function.
Objectives Macrophage activation syndrome (MAS) is a hyperinflammatory condition that is known to... more Objectives Macrophage activation syndrome (MAS) is a hyperinflammatory condition that is known to be secondary hemophagocytic lymphohistiocytosis (HLH) in patients with rheumatic disease. The aim of study was to evaluate the clinical manifestations and outcomes in patients with MAS with rheumatic disease. Materials and methods We performed a retrospective study of 20 adult patients who were diagnosed with MAS from 2012 to 2020. MAS was classified according to the HLH-2004 criteria. Patients’ information, including clinical features, laboratory findings, and treatment regimens, was collected, and the overall survival rate was estimated by the Kaplan–Meier method. Results Twenty patients (18 women, 35.6 ± 18.3 years) who met the HLH-2004 criteria also fulfilled the 2016 EULAR/ACR/PRINTO classification criteria for MAS, and HScore was higher than 169 (mean, 241.1). Fourteen patients with systemic lupus erythematosus and 6 patients with adult-onset Still’s disease were included. All pat...
Background The purpose of this study was to stratify patients with rheumatoid arthritis (RA) acco... more Background The purpose of this study was to stratify patients with rheumatoid arthritis (RA) according to the trend of disease activity by trajectory-based clustering and to identify contributing factors for treatment response to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) according to trajectory groups. Methods We analyzed the data from a nationwide RA cohort from the Korean College of Rheumatology Biologics and Targeted Therapy registry. Patients treated with second-line biologic and targeted synthetic DMARDs were included. Trajectory modeling for clustering was used to group the disease activity trend. The contributing factors using the machine learning model of SHAP (SHapley Additive exPlanations) values for each trajectory were investigated. Results The trends in the disease activity of 688 RA patients were clustered into 4 groups: rapid decrease and stable disease activity (group 1, n = 319), rapid decrease followed by an increase (group 2, ...
Background: We developed a model to predict remissions in patients treated with biologic disease-... more Background: We developed a model to predict remissions in patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify important clinical features associated with remission using explainable artificial intelligence (XAI).Methods: We gathered the follow-up data of 1204 patients treated with bDMARDs (etanercept, adalimumab, golimumab, infliximab, abatacept, and tocilizumab) from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. Remission was predicted at one-year follow-up using baseline clinical data obtained at the time of enrollment. Machine learning methods (e.g., lasso, ridge, support vector machine, random forest, and XGBoost) were used for the predictions. The Shapley additive explanation (SHAP) value was used for interpretability of the predictions.Results: The ranges for accuracy and area under the receiver operating characteristic of the newly developed machine learning model for predicting remission were 52.8%–72....
Background: Because of the highly variable clinical course, it is important to predict the progno... more Background: Because of the highly variable clinical course, it is important to predict the prognosis of rheumatoid arthritis related interstitial pneumonia (RA-IP) at the time of diagnosis. The aim of the study was to find out the blood biomarker that can predict the disease progression and/or survival in the patients with RA-IP at the time of diagnosis. Method: The plasma levels of biomarkers (KL-6, MMP-7, IL-6, IL-22, and IL-32) were retrospectively compared with the clinical course of 79 patients with RA-IP (biopsy-proven: 33). Results: The mean age of the patients was 63 years and 45.6% was male. The median follow-up period was 42 months. Among the 5 biomarkers, only KL-6 has clinical significance. KL-6 level was significantly higher in the patient with acute exacerbation (≥1447.80 ng/mL) compared to stable state (AUC, 0.938; P<0.001). There was no correlation between the level of KL-6 and the treatment response. Among the patients followed-up without treatment (n=38), KL-6 l...
To the Editor: Lupus nephritis (LN) is the leading cause of morbidity and mortality in patients w... more To the Editor: Lupus nephritis (LN) is the leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). 1 Noninvasively obtainable biomarkers for LN could greatly improve early LN detection. In this study, we found that urine alpha-1-acid glycoprotein (ORM1) is a promising biomarker for early LN detection. Furthermore, with regard to histologic features, urine haemoglobin subunit delta (HBD) accurately discriminated proliferative LN from nonproliferative LN and correlated with activity index. Using sequential window acquisition of all theoretical mass spectra combined with liquid chromatography (SWATH LC-MS) platform, a novel mass spectrometrybased proteome analysis, 2 we screened potential biomarker candidates in urine samples from 20 healthy controls (HCs) and 39 patients with SLE with or without newly diagnosed LN (n-LN). All patients with SLE met the 2012 Systemic Lupus International Collaborating Clinics classification criteria for SLE. 3 Sample preparation and in-house urine proteome spectral library generation were performed as described previously. 2 In our spectral library, 2323 proteins and 8371 peptides were identified using data-dependent acquisition analysis. A total of 1157 protein groups (581 ± 31, 506 ± 25 and 457 ± 22 in HCs, patients with SLE without nephritis, and patients with n-LN, respectively) were quantified from individual samples using an in-house spectral library. Among the 1157 protein groups, 143 protein groups (false discovery rate ≤.05, log2 fold change ±1) were increased in patients with SLE without nephritis than those in HCs (Figure 1A), and 67 protein groups were increased in patients with n-LN than those in patients with SLE without nephritis (Figure 1B). Among these protein groups, 23 protein groups were identified to be common between the two comparative analyses. Among these 23 urine proteins, five proteins (ORM1, antithrombin-III [SERPINC1], ceruloplasmin [CP], haemoglobin subunit beta [HBB] and HBD) were selected for enzyme-linked immunosorbent assay This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
To assess the clinical features, laboratory findings, and response to therapy according to diseas... more To assess the clinical features, laboratory findings, and response to therapy according to disease course, and analyse the predictive factors for unfavourable outcomes in patients with adult-onset Still's disease (AOSD). We retrospectively reviewed the medical records of 82 patients from January 1992 to December 2010 at a single tertiary hospital. Thirty-three had monocyclic disease, 33 experienced at least one relapse, and 14 had chronic disease. Patients were divided into those with favourable (monocyclic, n=33) and unfavourable (polycyclic or chronic and death, n=49) outcomes. The major clinical features were high spiking fever (96.3%), polyarthralgia (85.4%), skin rash (80.5%), myalgia (70.7%), and sore throat (68.3%). Analysis of prognostic factors for the 2 groups showed that polyarthralgia, elevated erythrocyte sedimentation rate, high serum lactate dehydrogenase, and low dose of initial glucocorticoids were related with unfavourable outcomes. An insufficient starting dos...
Although chronic kidney disease (CKD) may constitute a chronic inflammatory state indicated by el... more Although chronic kidney disease (CKD) may constitute a chronic inflammatory state indicated by elevated inflammatory mediators such as tumor necrosis factor alpha (TNF-α), the impact of anti-TNF-α therapy on progression of CKD in patients with rheumatoid arthritis (RA) is unclear. Seventy patients with RA and CKD were retrospectively analyzed. Outcomes were evaluated using the difference in the annual change of estimated glomerular filtration rate (eGFR) between patients treated with anti-TNF-α or without. Anti-TNF-α therapy significantly decreased disease activity score (DAS) 28 from 5.32 ± 0.78 to 3.59 ± 0.85 (p < 0.001). There was a tendency toward stabilization of eGFR after a mean of 2.9 ± 1.1 years from 50.3 ± 8.4 ml/min/1.73 m(2) to 54.5 ± 16.0 ml/min/1.73 m(2) in patients received anti-TNF-α therapy along with decreased DAS28 (p = 0.084). Conversely, eGFR decreased significantly in patients not receiving anti-TNF-α therapy after a mean of 2.8 ± 1.7 years from 52.6 ± 7.5 m...
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