The Clinical Utility of Serum Alpha-1-Acid Glycoprotein in Reflecting the Cross-Sectional Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Centre Retrospective Study.

Background and Objectives: This study investigated whether serum alpha-1-acid glycoprotein (AGP) at diagnosis could reflect the cross-sectional activity represented by the Birmingham vasculitis activity score (BVAS) and further predict poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 70 patients with AAV. Clinical data at diagnosis, including AAV-specific indices and acute-phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were reviewed. All-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident, and acute coronary syndrome were evaluated as poor outcomes of AAV. Serum AGP was measured using the sera obtained and stored at diagnosis. Results: The median age of the patients was 63.0 years, with 29 male and 41 female patients. The median serum AGP was 150.9 µg/mL. At diagnosis, serum AGP was significantly correlated with BVAS and ESR but not CRP or serum albumin. Additionally, serum AGP showed significant correlations with the sum scores of ear-nose-throat and pulmonary manifestations; however, no significant differences in serum AGP according to each poor outcome were observed. Although serum AGP at diagnosis tended to be associated with ESKD occurrence during follow-up, serum AGP at AAV diagnosis was not significantly useful in predicting the future occurrence of poor outcomes of AAV during follow-up. Conclusions: In this study, we demonstrated the clinical utility of serum AGP at AAV diagnosis in assessing the cross-sectional activity represented by BVAS in patients with AAV for the first time.

A new index for distinguishing hypereosinophilic syndrome and antineutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis.

BACKGROUND: It is difficult to differentiate between hypereosinophilic syndrome (HES) and antineutrophil cytoplasmic antibody (ANCA)-negative eosinophilic granulomatosis with polyangiitis (EGPA). OBJECTIVE: We compared laboratory data at diagnosis between Korean patients with HES and ANCA-negative EGPA and investigated independent laboratory predictors suggesting HES. METHODS: We reviewed the medical records of 41 HES patients and 16 ANCA-negative EGPA patients. The cut-offs were extrapolated by the receiver operator characteristic (ROC) curve. The odds ratio (OR) and relative risk (RR) were assessed using the multivariable logistic regression analysis and the chi-square test, respectively. We developed a new equation by assigning a weight to each variable according to the slopes (B) and expressed a decimal as the nearest integer. RESULTS: HES patients had a higher median WBC and eosinophil counts than ANCA-negative EGPA patients. The cutoffs of WBC and eosinophil counts for HES were set at 9,900.0/mm3 and 2,400.0/mm3. In the multivariable analysis, WBC count ≥ 9,900.0/mm3 (B 1.763) and eosinophil count ≥ 2,400.0/mm3 (B 1.515) were significantly associated with HES. An equation was as follows: HES-suggesting laboratory index (HSLI) = 2 × (WBC count ≥ 9,900.0/mm3 (1 = No or 2 = Yes)) + 1.5 × (eosinophil count ≥ 2,400.0/mm3 (1 = No or 2 = Yes)). The cut-off of HSLI for HES was 4.25. Patients with HSLI ≥ 4.25 exhibited a significantly high RR (51.429) for HES, compared to those without. CONCLUSIONS: In conclusion, the cut-off of HSLI derived from WBC and eosinophil counts could be an independent predictor of HES in patients suspected of both HES and ANCA-negative EGPA.

Art Play with Daddy: Father-Child Play with Art Materials at Home.

Paternal involvement in household and childcare has increased over the past century, but global studies show that most mothers still remain responsible for a significantly higher proportion of total household care and childcare. Moreover, the COVID-19 pandemic has further negatively impacted mothers, who take on the majority of childcare responsibilities. However, scholars agree that a father's devotion to playing with the child fosters the child's cognitive, linguistic, and socio-emotional development. Acknowledging and approaching art as a dynamic and integrated play, this qualitative case study investigates five South Korean father-child dyads and their interactions while playing with art materials. The participants engaged in three thematic art sessions designed by the author. Data collection involved audio and video recordings of each session, surveys of adult participants, and photos of finished artworks. The study found that fathers' varied educational backgrounds and perceptions of their abilities to facilitate arts learning influenced their confidence in teaching the arts at home. Furthermore, having a theme and prompting questions assisted the fathers to facilitate more focused art play. The art play also provided the father-child dyads with arts learning opportunities, including learning and distinguishing colors and recognizing stereotypes associated with colors. Moreover, one-on-one interaction between the dyads helped them build a more intimate bond. This study presents specific examples of art activities and participants' responses, which might offer insights and educational implications for paternal involvement in child play and thematic art play at home.

Clinical characteristics and long-term outcomes in patients with mixed Class III/IV + V and pure proliferative lupus nephritis: A single-center experience.

OBJECTIVES: Proliferative lupus nephritis (LN) is a crucial complication in systemic lupus erythematosus (SLE). This study evaluated the clinical implications of coexistence of membranous LN in proliferative LN in terms of clinical characteristics and long-term outcome. METHODS: We retrospectively reviewed the medical records of patients with SLE who underwent renal biopsy between 2005 and 2018. Patients with proliferative LN based on the 2003 International Society of Nephrology/Renal Pathology Society classification were subclassified into pure (Class III or IV only) and mixed (Class III or IV + Class V) proliferative LN. The clinical features at the time of renal biopsy, incidence of end-stage renal disease (ESRD), and all-cause mortality were compared between patients with mixed or pure proliferative LN. RESULTS: Of the 171 patients, 30 and 141 were classified into mixed and pure proliferative LN groups, respectively. Patients with pure proliferative LN showed higher anti-dsDNA antibody and lower hemoglobin, platelet, and complement 3 levels than patients with mixed proliferative LN. The SLE disease activity index was also higher in patients with pure proliferative LN (p = 0.047). The pure proliferative LN group showed a higher proportion of Class IV and higher histologic activity index scores (p < 0.001 and p = 0.004, respectively). During the follow-up period of 58.3 months, 18 patients developed ESRD and 15 patients died. ESRD was exclusively observed in patients with pure proliferative LN, although the incidence of ESRD was not statistically different (p = 0.055). All-cause mortality was comparable between the two groups. CONCLUSION: Pure proliferative LN was associated with higher clinical and histological activities and modestly increased risk of ESRD. Active immunosuppressive treatment would be required to control the renal inflammation in patients with proliferative LN, regardless of the coexistence of membranous LN.

Risk of Stroke in Systemic Necrotizing Vasculitis: A Nationwide Study Using the National Claims Database.

Objective: Evidences indicate that the risk of stroke is increased in autoimmune rheumatic diseases. This study aimed to investigate the incidence of stroke in patients with systemic necrotizing vasculitis (SNV) using the national health database. Methods: Data were obtained from the Korean National Claims database between 2010 and 2018 to identify incident SNV [anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN)] cases. The standardized incidence ratio (SIR) and incidence rate ratio (IRR) were calculated to estimate the risk of stroke in patients with SNV compared to the general population and among disease subgroups. Time-dependent Cox's regression analysis was performed to identify risk factors for stroke. Results: Among 2644 incident SNV cases, 159 patients (6.0%) were affected by stroke. The overall risk of stroke was significantly higher in patients with SNV compared to the general population (SIR 8.42). Stroke event rates were the highest within the first year of SNV diagnosis (67.3%). Among disease subgroups, patients with microscopic polyangiitis (MPA) exhibited higher IRR compared to PAN (adjusted IRR 1.98). In Cox's hazard analysis, older age and MPA were associated with higher risk of stroke [hazard ratio (HR) 1.05 and 1.88], whereas the administration of cyclophosphamide, azathioprine/mizoribine, methotrexate, and statins were protective in stroke (HR 0.26, 0.34, 0.49, and 0.50, respectively). Conclusion: A considerable number of SNV patients experienced stroke, especially in the early phase of disease. Older age and MPA diagnosis were associated with elevated risk of stroke, while the administration of immunosuppressive agents and statins was beneficial in preventing stroke.

Serum granzyme B is associated with otorhinolaryngological, pulmonary, and renal involvement of antineutrophil cytoplasmic antibody-associated vasculitis.

We investigated whether serum granzyme B (GrB) can reflect the inflammatory burden such as cross-sectional disease activity and organ-specific involvement in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Seventy-eight immunosuppressive drug-naïve patients with AAV were included in this study. At the time of the first classification, whole blood was obtained from each patient and sera was immediately isolated and stored at - 80℃. On the day of the blood sampling, we performed routine laboratory tests including antineutrophil cytoplasmic antibody tests and collected both clinical and laboratory data. AAV-specific indices included Birmingham Vasculitis Activity Score (BVAS) and Five-Factor Score (FFS). The median age of patients with AAV was 62 years and 26 patients were men. Serum GrB was not associated with the cross-sectional BVAS; however, patients with serum GrB positivity exhibited higher frequencies of otorhinolaryngological manifestation than those without (p=0.037). When serum GrB levels were compared after dividing the patients into two groups based on the presence of organ-specific involvement, patients with pulmonary involvement exhibited a significantly higher serum GrB than those without (p=0.042). On the other hand, patients with renal involvement showed a significantly lower serum GrB than those without (p=0.023). In addition, serum GrB was inversely correlated with the cross-sectional FFS (r=-0.249, p=0.028). Even though serum GrB could not reflect the inflammatory burden of AAV, serum GrB was associated with otorhinolaryngological, pulmonary, and renal involvement in immunosuppressive drug-naïve patients with AAV.

Evaluation of body composition using computed tomography in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND/AIMS: Measures of body composition, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA), are considered important prognostic factors in chronic diseases. The association of these measures with auto-inflammatory disorders, such as anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), remains unclear. We investigated the clinical significance of VAT, SAT, and SMA in patients with AAV. METHODS: Patients with AAV subjected to chest computed tomography (CT), abdominal CT, or positron emission tomography-CT on diagnosis of AAV were evaluated. Quantitative assessment of VAT, SAT, and SMA was performed at the third lumbar vertebral level and computed by summing the pixel attenuation for tissue-specific Hounsfield units in the corresponding region. Associations of VAT, SAT, and SMA with clinical and laboratory data and clinical outcome measures were evaluated. RESULTS: Of the 117 patients, 61 (52.1%) were classified as having microscopic polyangiitis, 28 (23.9%) as granulomatosis with polyangiitis, and 28 (23.9%) as eosinophilic granulomatosis with polyangiitis. VAT significantly correlated with age, weight, body mass index (BMI), and Birmingham Vasculitis Activity Score, whereas SAT correlated with weight, BMI, and creatinine levels. A significant association was found between SMA and age, height, weight, BMI, and the Five-Factor Score. Cox proportional hazards analysis showed that creatinine levels (odds ratio [OR], 1.346; 95% confidence interval [CI], 1.034 to 1.753; p = 0.027) and high VAT (OR, 7.137; 95% CI, 1.343-37.946; p = 0.021) were independently associated with all-cause mortality during follow-up. CONCLUSION: Evaluation of VAT using CT is useful for estimating disease activity and all-cause mortality in patients with AAV.

Reclassification of Korean patients with polymyositis and dermatomyositis based on the Bohan and Peter criteria by the 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies.

BACKGROUND/AIMS: We investigated the concordance rate of the classification of polymyositis (PM) and dermatomyositis (DM) between the Bohan and Peter criteria and the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) (the 2017 EULAR/ACR criteria) in Korean patients. METHODS: We retrospectively reviewed the medical records of 137 patients with PM and DM. We finally included 72 PM patients and 49 DM patients who fulfilled the Bohan and Peter criteria for PM and DM and reclassified them by the 2017 EULAR/ ACR criteria. RESULTS: Three patients (4.2%) with probable PM were newly reclassified as non-IIM due to a total score of 5.3 or smaller. Meanwhile, one patient with possible PM was newly reclassified as probable PM due to the presence of dysphagia. In addition, eight patients (16.3%) with possible DM with DM-specific typical skin rash were newly reclassified as amyopathic DM (ADM) due to the absence of proximal muscle weakness. The concordance rate of the classification between the Bohan and Peter criteria and the 2017 EULAR/ACR criteria was 95.8% for PM patients and 83.7% for DM patients. CONCLUSION: The Bohan and Peter criteria were comparable to the 2017 EULAR/ ACR criteria for classifying PM and DM in Korean patients. Considering the convenience of the Bohan and Peter criteria in the real clinical settings, we suggest that the old criteria should be preferentially applied and then performing muscle biopsy should be considered in a patient suspected of PM without antihistidyl tRNA synthetase (anti-Jo-1). Moreover, we suggest that ADM could also clinically be classified by the old criteria.

Incidence of Tuberculosis in Systemic Necrotizing Vasculitides: A Population-Based Study From an Intermediate-Burden Country.

Objective: Tuberculosis (TB) has a significant impact on public health; however, its incidence in patients with systemic necrotizing vasculitides (SNV) remains unknown. Therefore, we evaluated the incidence of TB in patients with SNV using a nationwide claims database. Methods: The Health Insurance and Review Agency database was used to identify patients diagnosed with SNV between 2010 and 2018. The standardized incidence ratio (SIR) was calculated to compared the risk of TB between patients and the general population, based on the 2016 annual national TB report. The incidence of TB after SNV diagnosis was compared by estimating age- and sex- adjusted incidence rate ratio (IRR). A time-dependent Cox regression analysis was performed to estimate factors associated with TB. Results: Among the included 2,660 patients, 51 (1.9%) developed TB during the follow-up period. The risk of TB was significantly higher in patients with SNV [SIR 6.09, 95% confidence interval (CI) 4.53-8.00], both in men (SIR 5.95) and women (SIR 6.26), than in the general population; this increased risk was consistent in all disease subtypes, except eosinophilic granulomatosis with polyangiitis. Additionally, the incidence of TB was the highest in patients with SNV within the first 3 months after diagnosis (adjusted IRR: 8.90 compared to TB ≥ 12 months). In Cox regression analysis, the diagnosis of microscopic polyangiitis [hazard ratio (HR) 3.22, 95% CI 1.04-9.99], granulomatosis with polyangiitis (HR 4.63, 95% CI 1.53-14.02), and polyarteritis nodosa (HR 3.51, 95% CI 1.13-10.88) were independent factors associated with TB. Conclusion: Even when considering the high incidence of TB in the geographic region, the risk of TB increased in patients with SNV, with a difference based on disease subtypes. Moreover, taking into account of the high incidence of TB in SNV, vigilant monitoring for TB is required especially during the early disease period.

Comparison of clinical features and outcomes between patients with early and delayed lupus nephritis.

BACKGROUND: Lupus nephritis is associated with increased risk of end-stage renal disease (ESRD) and all-cause mortality. We evaluated the clinical features and outcomes of patients with early and delayed lupus nephritis. METHODS: The medical records of 171 patients who met the 1997 revised classification criteria for systemic lupus erythematosus (SLE) with pathologic confirmation of lupus nephritis were reviewed. Early lupus nephritis was defined when lupus nephritis was histopathologically confirmed as the first clinical manifestation of SLE, whereas delayed lupus nephritis was defined as lupus nephritis that was identified after the diagnosis of SLE. Clinical and laboratory data, as well as kidney histopathology and medication usage were investigated. Kaplan-Meier and Cox-proportional hazard analysis was performed to compare the outcomes of early and delayed lupus nephritis and evaluate factors associated with ESRD and all-cause mortality. RESULTS: Patients with early lupus nephritis had higher disease activity (median non-renal SLE disease activity index-2000, 6.0 vs. 4.0; p < 0.001) and more frequent skin rash, oral ulcer and serositis; however, the proportion of patients with higher renal chronicity index was greater in the delayed lupus nephritis group (p = 0.007). Nevertheless, no difference was found regarding ESRD and all-cause mortality between the groups. In Cox-proportional hazard analysis, C-reactive protein level, creatinine level and chronicity index were factors associated with ESRD, while age and haemoglobin level were associated with all-cause mortality. CONCLUSIONS: In conclusion, clinical outcomes of early and delayed lupus nephritis are not significantly different. Rigorous adherence to current treatment recommendations is essential for the treatment of lupus nephritis.

Serum Mannose-Binding Lectin Levels Are Correlated with the Disease Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Center Study.

Mannose-binding lectin (MBL) is a soluble pattern-recognition molecule, which plays a crucial role in the innate immune system and the activation of lectin complement pathway. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease affecting the small vasculatures and is characterized by the alteration of innate and adaptive immunity and complement activation. In this study, we investigated whether serum MBL is associated with disease activity of AAV, which was measured by ELISA. Associations between serum MBL and AAV-specific indices, as well as clinical and laboratory data were assessed using Kendall's tau. Among the 80 patients, 42 (52.5%), 21 (26.3), and 17 (21.3%) patients were classified as microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), respectively. The median values of erythrocyte sedimentation rate, C-reactive protein, and serum MBL were 36.5 (normal range < 20) mm/h, 2.4 (normal range < 8) mg/dL, and 8.6 ng/mL, respectively. The median serum levels of MBL in MPA, GPA, and EGPA patients were 8.4, 9.3, and 8.2 ng/mL. Correlation analysis showed that serum MBL was associated with Birmingham Vasculitis Activity Score (BVAS) (R = 0.169, p = 0.027), but not with other AAV-specific indices and clinical and laboratory data. In addition, serum MBL was significantly associated with the pulmonary manifestation score based on BVAS (R = 0.247, p = 0.001). In summary, among the AAV-specific indices and clinical and laboratory variables analyzed, serum MBL is correlated with BVAS and pulmonary manifestation score based on the BVAS.

Definite IgG4-related disease had no overlap with eosinophilic granulomatosis with polyangiitis in Korean patients: a pilot study in one centre.

OBJECTIVES: Serum IgG4 may often increases in allergic diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has an allergic phase. For this reason, it was questionable whether IgG4-RD and EGPA may share some clinical and laboratory features. In this study, we investigated whether definite IgG4-RD might share those features with EGPA. METHODS: We retrospectively reviewed the medical records of 42 Korean immunosuppressive drug-naïve patients with definite IgG4-RD. The American College of Rheumatology 1990 criteria for classification (the 1990 ACR criteria) for Churg-Strauss syndrome (CSS, known as EGPA) were applied to patients who were previously diagnosed with definite IgG4-RD and had no antineutrophil cytoplasmic antibody (ANCA). Definite IgG4-RD was defined when 3 components of the comprehensive diagnostic criteria were met. RESULTS: The median age of 42 patients was 61.0 years and 69% of them were men. The median serum IgG4 level was 379.0 mg/dL and the median IgG4+/IgG+ cells ratio was 50.0%. The most common biopsy site was the salivary gland (14.3%). Antinuclear antibody was detected in 6 patients, and test results for ANCA were negative in all patients. Among 42 patients with definite IgG4-RD without ANCA, none of them met the 1990 ACR classification criteria for EGPA. CONCLUSIONS: Definite IgG4-RD found to have no overlap with EGPA when the 1990 ACR criteria for CCS were applied to Korean patients. Key Points • None of 42 Korean patients with definite IgG4-RD without ANCA met the 1990 ACR classification criteria for EGPA. • Definite IgG4-RD found to have no overlap with EGPA in Korean patients without ANCA.

Hyperuricemia is associated with decreased renal function and occurrence of end-stage renal disease in patients with microscopic polyangiitis and granulomatosis with polyangiitis: a retrospective study.

Current evidence suggests that high uric acid levels are associated with accelerated renal damage. However, the clinical impact of serum uric acid level on patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) is unknown. We aimed to evaluate the impact of hyperuricemia on such patients. A retrospective study was performed to obtain patients' demographic, clinical, and laboratory data from when they were diagnosed with MPA and GPA. Multivariable logistic regression and Cox hazard model analyses were performed to evaluate factors associated with hyperuricemia at diagnosis and predictive factors of end-stage renal disease (ESRD) development. Among 156 patients, 35 (22.4%) had hyperuricemia at baseline. Hyperuricemic patients had renal manifestation and impaired renal function more frequently than non-hyperuricemic patients. Logistic regression analysis revealed that serum creatinine was significantly associated with hyperuricemia at diagnosis [odds ratio 1.995; 95% confidence interval (CI), 1.503-2.648; P < 0.001]. Cox hazard model analysis revealed that body mass index and serum creatinine were significantly associated with ESRD when all variables were included, but hyperuricemia was independently associated with ESRD [hazard ratio (HR), 3.799; 95% CI 1.719-8.222; P < 0.001) when serum creatinine was excluded. Additionally, in a subgroup analysis of patients with decreased glomerular filtration rates (GFRs), serum uric acid was the sole predictor of ESRD (HR, 1.243; 95% CI 1.048-1.475; P = 0.013). Hyperuricemia is associated with renal damage and ESRD occurrence in MPA and GPA patients. Serum uric acid level is associated with ESRD occurrence in patients with decreased GFRs.

Serum Amyloid A Is a Biomarker of Disease Activity and Health-Related Quality-of-Life in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Serum amyloid A (SAA) is one of the acute phase proteins synthesized in hepatocytes and secreted by various inflammation or infectious stimuli. We investigated the clinical implication of measuring SAA in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). Seventy-five patients who had been classified as AAV and enrolled in our prospective observational cohort for AAV patients were included. Clinical and laboratory data were obtained on the day of blood sampling, and SAA was measured by ELISA kits. Birmingham Vasculitis Activity Score (BVAS) and Short-Form 36-Item Health Survey (SF-36) were assessed for disease activity and health-related quality-of-life (HRQoL) measures. We stratified patients into having high BVAS when the BVAS was over the median values, and those with either low SF-36 PCS or low SF-36 MCS were defined as having poor HRQoL. Multivariate logistic regression analysis was conducted to estimate independent predictors of high BVAS. The relative risk (RR) was analyzed using the contingency tables and the chi-squared test. SAA was positively correlated with BVAS (r = 0.642) and FFS (r = 0.367) and was inversely correlated with both the SF-36 physical component summary (r = -0.456) and mental component summary scores (r = -0.394). Furthermore, SAA was significantly correlated with acute phase reactants ESR (r = 0.611) and CRP (r = 0.629). Patients with high BVAS exhibited significantly higher SAA than those with low BVAS (1317.1 ng/mL vs. 423.1 ng/mL). In multivariable logistic regression analysis, serum albumin (odds ratio (OR) 0.132) and SAA > 1173.6 ng/mL (OR 15.132) were independently associated with high BVAS. The risk of having high BVAS and poor HRQoL in patients with SAA > 1173.6 ng/mL was higher than in those with SAA ≤ 1173.6 ng/mL (RR 3.419 and 1.493). Our results suggest that SAA might be a useful biomarker in assessing disease activity and HRQoL in AAV.

Risk of Cancers in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results from the Korea National Health Insurance Claims Database 2010-2018.

The association between antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and cancer remains poorly understood. In this study, we searched the Korea National Health Insurance Claims Database to obtain data for 2097 AAV patients, and evaluated the risk of cancers in AAV. The standardized incidence ratios (SIRs) of overall and site-specific cancers were estimated in patients with AAV compared to the general population. The overall risk of cancer was significantly higher in patients with AAV (SIR 1.90); this remained true in both males (SIR 1.74) and females (SIR 2.06). For site-specific cancers, the risks of lung (SIR 2.23) and hematological (SIR 11.39) cancers were higher in AAV patients. For males, the risks of gallbladder and hematological cancers were increased, while the risks of bladder and hematological cancers were increased in females. Among AAV subtypes, patients with granulomatosis with polyangiitis had the highest risk of cancers, and cyclophosphamide, azathioprine/mizoribine, and methotrexate ever-users had increased risk of overall cancer. The risks of overall and hematological cancers were elevated in AAV patients younger than 60 years old. Patients with AAV have increased risks of overall, lung, and hematological cancers. Distinct patterns of cancer incidence are present according to age, sex, AAV subtypes, and immunosuppressant usage.

Anti-Smith antibody is associated with disease activity in patients with new-onset systemic lupus erythematosus.

Although anti-Smith (Sm) antibody is a highly specific antibody for systemic lupus erythematosus (SLE), the significance of anti-Sm antibody in patients with SLE is unclear. This study aimed to evaluate the association between anti-Sm antibodies and disease activity in patients with new-onset SLE. We included patients who were tested for anti-Sm antibodies at SLE diagnosis and within 12 months after diagnosis. SLE disease activity index (SLEDAI) was obtained at the time of the anti-Sm antibody test. The baseline disease activity was compared between patients with and without anti-Sm antibodies. The longitudinal association between disease activity and anti-Sm antibodies was also evaluated in total patients and in those with anti-Sm antibodies. Among 92 patients who were tested for anti-Sm antibodies at SLE diagnosis, 67 and another 67 patients were followed up for the presence of anti-Sm antibodies at 6 and 12 months, respectively. Although the baseline SLEDAI was comparable in patients with and without anti-Sm antibodies, the serum level of anti-Sm antibody was significantly correlated with SLEDAI (P = 0.003). At 12 months, anti-Sm antibody positivity was associated with higher SLEDAI and anti-dsDNA titer (P = 0.002, both). In addition, the changes in anti-Sm antibody titer over 12 months were correlated with the alterations in SLEDAI (P = 0.029).Anti-Sm antibody was associated with the baseline disease activity and the alteration of disease activity in patients with new-onset SLE. Monitoring of anti-Sm antibody titer may help assess the disease activity in SLE.

Clinical characteristics of patients with systemic lupus erythematosus showing a false-positive result of syphilis screening.

A false-positive result of syphilis screening test (FPST) is a characteristic finding in patients with systemic lupus erythematosus (SLE). We evaluated the clinical characteristics of SLE patients with FPST at SLE diagnosis. We reviewed the medical records of patients with SLE who underwent the Venereal Disease Research Laboratory or Rapid Plasma Reagin tests at SLE diagnosis at Severance Hospital between 2006 and 2016. The baseline characteristics and clinical outcomes were compared between patients with FPST and those with a negative result of syphilis screening test. Of 145 patients with SLE, 20 patients showed FPST and 125 patients showed a negative syphilis screening result. At SLE diagnosis, patients with a negative result had higher SLE disease activity index (5.0 vs. 8.0, P < 0.001) and were more commonly complicated with nephritis (15.0% vs. 41.6%, P = 0.026). High level of serum total protein (> 8 g/dL) and the presence of anti-cardiolipin antibodies were independently associated with FPST (P = 0.010 and 0.037, respectively). During the follow-up (median 61 months), 5 patients with FPST (20.0%) and 12 patients without FPST (9.6%) were finally diagnosed with APS. The long-term risk of de novo thrombosis was higher in the FPST group (n = 4/20, 20% vs n = 6/125, 4.8%, P = 0.041). However, all-cause mortality showed no difference between the FPST group and the negative group. Patients with SLE showing FPST showed lower disease activity at SLE diagnosis but higher thrombotic risk and similar overall survival compared to those without FPST.

Persistent antiphospholipid antibodies are associated with thrombotic events in ANCA-associated vasculitis: A retrospective monocentric study / Los anticuerpos antifosfolípidos persistentes se asocian a eventos trombóticos en la vasculitis asociada con ANCA: un estudio monocéntrico retrospectivo

AIM: We investigated whether persistent antiphospholipid syndrome (APLAs) at diagnosis are associated with the risk of thrombotic events during follow-up in patients with ANCA-associated vasculitis (AAV). METHODS: We retrospectively reviewed the medical records of 138 AAV patients. Thrombotic events were defined as arterial and venous thrombosis confirmed by magnetic resonance imaging, computed tomography, angiography and Doppler ultrasonography. Clinical and laboratory variables at diagnosis and during follow-up between patients with and without thrombotic events were compared. The univariable and multivariable Cox hazard model analyse to appropriately obtain hazard ratio (HR) considering the follow-up duration were conducted. RESULTS: The mean age of 138 AAV patients was 55.1 years and 44 were male. Persistent APLAs were detected in 18 patients with AAV (13.0%). Thrombotic events were observed in 26 patients with AAV (18.8%) during follow-up. At the time of a retrospective study point, persistent APLAs at diagnosis were observed more frequently in patients with thrombotic events than those without. In the multivariable Cox hazard model analysis, age at diagnosis (HR 1.075) and persistent APLAs (HR 2.902), but not ANCAs. Thrombotic events were identified more frequently in patients with persistent APLAs at diagnosis than those without (38.9% vs. 15.8%, relative risk 3.383). CONCLUSION: Persistent APLAs at diagnosis are significantly associated with the risk of thrombotic events during follow-up of AAV. We suggest that physicians should closely monitor the development of thrombotic events during follow-up

OBJETIVO: Se investigó si el síndrome antifosfolipídico (SAF) persistente en el momento del diagnóstico se asocia a un riesgo de eventos trombóticos durante el seguimiento en pacientes con vasculitis asociada con ANCA (VAA). MÉTODOS: Se revisaron de forma retrospectiva las historias clínicas de 138 pacientes con VAA. Los eventos trombóticos se definieron como aquellos de trombosis arterial y venosa confirmada mediante resonancia magnética, tomografía computarizada, angiografía o ecografía Doppler. Se compararon las variables clínicas y analíticas en el momento del diagnóstico y durante el seguimiento entre los pacientes con y sin eventos trombóticos. Se realizó un análisis con un modelo de riesgos de Cox univariable y multivariable para obtener de forma adecuada el cociente de riesgos instantáneos (hazard ratio [HR]) teniendo en cuenta la duración del seguimiento. RESULTADOS: La edad media de los 138 pacientes con VAA fue de 55,1 años, y 44 pacientes eran varones. Se detectó SAF persistente en 18 pacientes con VAA (13,0%). Se observaron eventos trombóticos en 26 pacientes con VAA (18,8%) durante el seguimiento. En un punto de análisis retrospectivo del estudio se observó SAF persistente en el momento del diagnóstico de forma más frecuente en pacientes con eventos trombóticos que en aquellos sin este tipo de eventos. En el análisis con un modelo de riesgos de Cox multivariable, la edad en el momento del diagnóstico (HR: 1,075) y SAF persistente (HR: 2,902), pero no ANCA. Los eventos trombóticos se identificaron de forma más frecuente en los pacientes con SAF persistente en el momento del diagnóstico que en aquellos sin SAF (38,9% frente a 15,8%; riesgo relativo 3,383). CONCLUSIÓN: El SAF persistente en el momento del diagnóstico se asoció de forma significativa a un riesgo de eventos trombóticos durante el seguimiento de la VAA. Se sugiere que los médicos deberían monitorizar de forma exhaustiva el desarrollo de eventos trombóticos durante el seguimiento

Predictor of depressive disorders in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

We investigated the frequency of depressive disorders and determined the predictors of depressive disorders in Korean patients with antineutrophil cytoplasmic antibody-associated vasculitis. Sixty-one patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were enrolled in this study. We assessed the Birmingham vasculitis activity score (BVAS), vasculitis damage index (VDI) and the Korean version of the short form 36-item Health Survey (SF-36). SF-36 consists of the mental component score (MCS) and physical component score (PCS). Depression disorder was identified based on the Korean version of the Center for Epidemiologic Studies Depression Scale-Revised (K-CESD-R) ≥ 16. Mood states including depression were assessed by the Korean edition of the Profile of Mood States (K-POMS) subscales. The mean age was 62.2 years (19 men). Twenty-eight AAV patients (45.9%) had depressive disorders based on K-CESD-R ≥ 16. Both SF-36 MCS and SF-36 PCS were negatively correlated with K-CESD-R (r = - 0.687 and r = - 0.594) and K-POMS depression (r = - 0.604 and r = - 0.480), respectively. The optimal cut-offs of SF-36 MCS and SF-36 PCS for depressive disorders based on K-CESD-R ≥ 16 were obtained as 48.07 and 55.63. Patients with SF-36 MCS ≤ 48.07 exhibited a significantly high RR for depressive disorders, compared with those without (RR 42.667). Also, patients with SF-36 PCS ≤ 55.63 showed a significantly high RR depressive disorder, compared with those without (RR 13.619). We demonstrated that SF-36 could help to estimate the current depressive disorders. We also suggest a method to obtain the optimal cut-offs of SF-36 to predict depressive disorders.Key points• Both SF-36 MCS and SF-36 PCS were negatively correlated with K-CESD-R and K-POMS depression.• Patients with SF-36 MCS ≤ 48.07 exhibited a significantly high relative risk (RR) for depressive disorders, compared with those without (RR 42.667).• Patients with SF-36 PCS ≤ 55.63 showed a significantly high RR depressive disorder, compared with those without (RR 13.619).

Could hypereosinophilia at diagnosis estimate the current activity or predict relapse in systemic immunosuppressive drug-naïve patients with eosinophilic granulomatosis with polyangiitis?

In this study, we investigated whether hypereosinophilia (peripheral eosinophil ≥ 1500/mm3) at diagnosis could estimate the increased current activity and predict the poor prognosis during follow-up in patients with eosinophilic granulomatosis with polyangiitis (EGPA). We retrospectively reviewed the medical records of 42 patients with EGPA and finally included 30 systemic immunosuppressive drug-naïve patients. We obtained clinical and laboratory data including clinical manifestations, Birmingham vasculitis activity score (BVAS), five-factor score (FFS) (2009), and routine laboratory results. Hypereosinophilia was defined as peripheral eosinophil ≥ 1500/mm3. We divided EGPA patients based on hypereosinophilia and compared variables between the two groups. The cumulative relapse-free survival rates were compared by the Kaplan-Meier survival analysis. Patients with hypereosinophilia more commonly exhibited cutaneous manifestation than those without (50.0% vs. 14.3%, P = 0.038), but there were no significant differences in BVAS and FFS (2009) at diagnosis. Patients with hypereosinophilia showed the higher median WBC (14,200.0/mm3 vs. 7940.0/mm3) and CRP (17.6 mg/L vs. 2.0 mg/L) at diagnosis than those without. During follow-up, patients with hypereosinophilia at diagnosis exhibited the similar cumulative relapse-free survival rate to those without (P = 0.393). Whereas, patients with FFS (2009) at diagnosis ≥ 2, which was a well-known predictor of the poor prognosis of EGPA, exhibited the lower cumulative relapse-free survival rate than those with FFS (2009) < 2 (P = 0.030). Hypereosinophilia at diagnosis could neither estimate the current activity nor predict relapse in systemic immunosuppressive drug-naïve patients with EGPA unlike theoretical assumption.