Association between Mycobacterium tuberculosis infection and the risk of inflammatory arthritides.

OBJECTIVES: Tuberculosis is a highly contagious disease that has a significant impact on global health. Emerging evidence suggests that tuberculosis can lead to an altered immune response. We investigated the association between tuberculosis and the onset of inflammatory arthritides (IA). METHODS: Patients with incident tuberculosis in the South Korean National Claims database from 2010 to 2021 were included, and those who had undergone appendectomy during 2010-2011 served as controls. The onset of IA (including seropositive rheumatoid arthritis [SPRA], ankylosing spondylitis [AS], and psoriatic arthritis [PsA]) after tuberculosis was compared between patients with tuberculosis and the control group. Sensitivity analysis was performed using stabilised inverse probability of treatment weighting (sIPTW). RESULTS: A total of 408,685 patients with tuberculosis and 159,675 controls were included. During the mean follow-up of 7.5 years, a total of 1,957 (0.3%) were diagnosed with IA (SPRA, 1,397; AS, 481; and PsA, 79). Multivariable Cox hazard analysis indicated that the overall risk of IA was elevated in the tuberculosis group (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.51-1.93) compared with controls. This increased incidence in patients with tuberculosis was identical among IA subgroups even after adjustment (SPRA [HR, 1.72; 95% CI, 1.49-2.00], AS [HR, 1.64; 95% CI, 1.30-2.06], and PsA [HR, 2.59; 95% CI, 1.32-5.07]) and was replicated in the sIPTW. CONCLUSIONS: The increased overall risk of developing IA after tuberculosis corroborates the hypothesis that tuberculosis can trigger dysregulated immunity. This necessitates an increased awareness of autoimmunity in this patient group.

Incidence of systemic vasculitides after Mycobacterium tuberculosis infection: A population-based cohort study in Korea.

BACKGROUND: Tuberculosis (TB) is a highly prevalent disease associated with significant morbidity and mortality globally, and is reported to be associated with the onset of autoimmunity. This study investigated the association between TB and the incidence of systemic vasculitides (SV). METHODS: Data were obtained from the South Korean National Claims database to identify patients with TB and controls (who had undergone appendectomy). The overall occurrence of SV and disease subtypes during the observation period was compared between the two groups. Adjusted Cox proportional hazards regression and Kaplan-Meier analysis were performed to identify the relationship between TB and SV and to compare SV incidence. RESULTS: We identified 418 677 patients with TB and 160 289 controls. The overall SV incidence rate was 192/1,000 000 person-years during a mean follow-up of 7.5 years and was higher in patients with TB than controls. Cox regression revealed that the risk of SV was elevated in the TB group independently (adjusted hazard ratio [aHR]: 1.72, 95% confidence interval [CI]: 1.45-2.05). Furthermore, the risk of SV was significantly higher in extrapulmonary TB (aHR: 4.28, 95% CI: 3.52-5.21) when the TB group was categorized into pulmonary and extrapulmonary TB. The findings remained identical even after applying a stabilized inverse probability of treatment weighting analysis. CONCLUSIONS: Patients with TB have increased risk of SV, which is prominent in extrapulmonary TB. As well as confirming TB is associated with increased incidence of immune-related vasculitis, our findings highlight the need for clinical vigilance for early diagnosis and initiation of treatment.

Earliest total vascular damage index scores independently predict all-cause mortality in patients with ANCA-associated vasculitis.

OBJECTIVES: This study investigated whether the earliest total Vasculitis Damage Index (VDI) score could significantly predict all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: This study included AAV patients who were first diagnosed at this hospital from 2001 to 2022. The earliest total VDI score was defined as the first VID assessed more than 3 months after AAV diagnosis in 93.5% of patients or after the first AAV presentation in 6.5% of patients. The optimal cut-off of the earliest total VDI score for all-cause mortality was obtained using the receiver operating characteristic curve. RESULTS: The median age and earliest VDI score were 60.0 years (35.5% men), and 3.0. The most common damaged system in the earliest VDI was the pulmonary (55.3%) system. Among the AAV patients, 39 (13.3%) died. When the optimal cut-off of the earliest total VDI score for all-cause mortality was set at 3.0 (sensitivity 64.1%, specificity 75.2%), AAV patients with the earliest total VDI score ≥3.0 exhibited a significantly higher risk for all-cause mortality than those without (relative risk 6.090). AAV patients with the earliest total VDI score ≥3.0 exhibited a significantly lower cumulative patients' survival rate than those without. In the multivariable Cox hazards model analyses, not only the earliest total VDI score but also the earliest total VDI score ≥3.0 were independently associated with all-cause mortality. CONCLUSIONS: This study was the first to demonstrate that the earliest total VDI score could predict all-cause mortality during follow-up in AAV patients.

Overlap syndrome of systemic sclerosis with antineutrophil cytoplasmic antibody-associated vasculitis according to 2022 ACR/EULAR criteria.

BACKGROUND/AIMS: This study applied the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients with systemic sclerosis (SSc) and investigated the frequency of overlap syndrome of SSc and AAV (SSc-AAV-OS). METHODS: Among the 232 patients diagnosed with SSc, 105 with signs suggestive of small- or medium-vessel vasculitis, which were defined as the present of interstitial lung disease (ILD), peripheral neuropathy, or suspected renal vasculitis, were included in this study and analyzed. RESULTS: Among the 105 SSc patients, the detection rate of ANCA was 19.0%. When the 2022 ACR/EULAR criteria were applied, the frequency of SSc-AAV-OS was 20.0%, which was much higher than 1.7% reported with previous criteria for AAV. ANCA positivity contributed to the reclassification of SSc-AAV-OS more than ANCA negativity in SSc patients with signs suggestive of small- or medium-vessel vasculitis. CONCLUSION: The frequency of SSc-AAV-OS in SSc patients with signs suggestive of small- or medium-vessel vasculitis at diagnosis was 20.0%. Therefore, we suggest that physicians should perform ANCA tests in SSc patients exhibiting signs suggestive of small- or medium-vessel vasculitis and apply the new criteria for AAV.

Circulating cold-inducible RNA-binding protein levels in microscopic polyangiitis and granulomatosis with polyangiitis : Correlation with disease activity.

OBJECTIVE: This study investigated whether circulating cold-inducible RNA-binding protein (CIRP) could be a biomarker to reflect the current activity, function, and damage status in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: This study selected 39 MPA and 26 GPA patients. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-specific indices include the Birmingham Vasculitis Activity Index (BVAS), five-factor score (FFS), the Korean version of the Short-Form 36-Item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), and the vasculitis damage index (VDI). The highest tertile of BVAS was defined as high activity of AAV. RESULTS: The median age of the study subjects was 65.0 years and 53.8% were women. The median BVAS, FFS, SF-36 PCS, MCS, and VDI scores were 12.0, 2.0, 47.5, 50.3, and 3.0, respectively. The median circulating CIRP level was 6.4 ng/mL. Among the four AAV-specific indices, circulating CIRP was significantly correlated with BVAS (r = 0.256). Using the receiver operator characteristic curve, the cut-off of circulating CIRP for high activity of AAV was 6.16 ng/mL. High activity of AAV was identified more frequently in patients with circulating CIRP ≥ 6.16 ng/mL than in those with circulating CIRP < 6.16 ng/mL (48.6% vs. 21.4%). In addition, patients with circulating CIRP ≥ 6.16 ng/mL exhibited a significantly higher risk for high activity of AAV than those with circulating CIRP < 6.16 ng/mL (relative risk 3.474). CONCLUSION: This study suggests the clinical potential of circulating CIRP as a biomarker for reflecting the current BVAS and predicting high activity of AAV in patients with MPA and GPA.

Clinical association of health-related quality of life and mortality in an antineutrophil cytoplasmic antibody-associated vasculitis cohort.

OBJECTIVES: To evaluate the association between health-related quality of life (HRQoL) and mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We searched patients with AAV assessed for HRQoL at initial diagnosis using Short Form 36 (SF-36). Relationships between SF-36 physical component summary (PCS) and mental component summary (MCS) scales and variables were estimated using Pearson's correlation analysis. Contal's and O'Quigley's methods were used to determine optimal SF-36 PCS cut-off for predicting all-cause mortality. The Cox proportional hazards model and inverse probability of treatment weighting (IPTW) analysis were used to ascertain prognostic implications of SF-36 scales and mortality. RESULTS: The median SF-36 PCS and MCS values of the 189 patients were 47.5 and 53.3, respectively, and 21 (11.1%) patients (microscopic polyangiitis [MPA], n=15; granulomatosis with polyangiitis [GPA], n=6) died during follow-up. SF-36 PCS was significantly but weakly associated with Birmingham Vasculitis Activity Score, Five-factor score, erythrocyte sedimentation rate (ESR), and C-reactive protein. However, SF-36 MCS was not associated with ESR. In the multivariable Cox analysis, a decrease of SF-36 PCS score by one unit indicated a higher death risk (hazard ratio [HR]: 1.030; 95% confidence interval [CI]: 1.007, 1.052; p=0.041), which was not for SF-36 MCS. IPTW analysis in a subgroup of MPA and GPA patients revealed increased patient mortality with SF-36 PCS <53.75 independently (HR: 3.249; 95% CI: 1.169, 9.033; p=0.024). CONCLUSION: Poor baseline physical functioning associated with premature death in patients with MPA and GPA. HRQoL assessment during initial diagnosis may provide clinical insights for this population.

Clinical implications of peripheral eosinophil count at diagnosis in patients newly diagnosed with microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: This study investigated the clinical implications of peripheral eosinophil count at diagnosis in estimating cross-sectional antineutrophil cytoplasmic antibody-associated vasculitis (AAV) activity and predicting all-cause mortality during follow-up in patients newly diagnosed with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: This study included 224 immunosuppressive drug-naïve patients with peripheral eosinophil count at diagnosis < 1,000/mm3. The Birmingham Vasculitis Activity Score (BVAS), the Five-Factor Score (FFS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at diagnosis were assessed. RESULTS: The median age of the 224 patients (152 MPA and 72 GPA) was 62.0 years; 35.3% of them were men. At diagnosis, peripheral eosinophil count was significantly correlated with BVAS (P = 0.001), FFS (P = 0.046), ESR (P < 0.001), and CRP (P < 0.001). Deceased patients had a significantly higher median peripheral eosinophil count at diagnosis than surviving patients (310.0/mm3 vs. 170.0/mm3, P = 0.004). In addition, patients with MPA and those with cardiovascular and renal manifestations at diagnosis exhibited significantly higher peripheral eosinophil counts than those without. When the optimal cut-off of peripheral eosinophil count at diagnosis for all-cause mortality during follow-up was set at 175.0/mm3, Patients with peripheral eosinophil count at diagnosis ≥ 175.0/mm3 exhibited a significantly lower cumulative patients' survival rate than those with peripheral eosinophil count at diagnosis < 175.0/mm3 (P = 0.008). CONCLUSIONS: This study was the first to demonstrate that peripheral eosinophil count at diagnosis could estimate cross-sectional AAV activity at diagnosis and contribute to predicting all-cause mortality during follow-up in MPA and GPA patients.

Overlap Syndrome Consisting of Polymyositis/Dermatomyositis and ANCA-Associated Vasculitis According to the 2022 ACR/EULAR Criteria for Vasculitis: A Korean Single-Centre Study.

The present study applied the 2022 American College of Rheumatology and European Alliance of Associations for Rheumatology classification criteria (the 2022 ACR/EULAR criteria) for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to ANCA-positive patients with polymyositis (PM)/dermatomyositis (DM). Also, this study investigated how many patients could be diagnosed with overlap syndrome consisting of PM/DM and AAV. Twelve ANCA-positive patients with PM/DM were included and analysed in this study. The 2022 ACR/EULAR classification criteria for microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA (EGPA) are scoring systems, and when a total score is over five in cases of MPA and GPA and over six in cases of EGPA, AAV can be classified. The median age of 12 ANCA-positive patients (six with PM and six with DM) was 54.0 years and one patient (8.3%) was male. Of the 12 ANCA-positive patients with PM/DM, 11 had myeloperoxidase (MPO)-ANCA (or perinuclear [P]-ANCA) and the remaining one had proteinase 3 (PR3)-ANCA (or cytoplasmic [C]-ANCA). Nine (75.5%) and one (8.3%) ANCA-positive patients with PM/DM were diagnosed with overlap syndrome consisting of PM/DM and MPA and overlap syndrome consisting of PM/DM and GPA, respectively. The main contributors to the classification of MPA and GPA were interstitial lung disease and renal vasculitis, along with ANCA positivity, respectively. In conclusion, this study was the first to demonstrate that 83.3% of them could be diagnosed with overlap syndrome consisting of PM/DM and AAV according to the 2022 ACR/EULAR criteria for AAV.

Prevalence, clinical significance, and persistence of autoantibodies in COVID-19.

BACKGROUND: Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. METHODS: We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. RESULTS: A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-ß2Glycoprotein1 antibody (aß2-GPI) in 32 patients, and IgG aß2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aß2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. CONCLUSION: A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation.

Soluble triggering receptor expressed on myeloid cell-1 reflects the cross-sectional activity of microscopic polyangiitis and granulomatosis with polyangiitis.

Objectives: We investigated whether soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflects cross-sectional activity of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods: Forty-seven MPA and 32 GPA patients with well-documented clinical records and stored sera were enrolled. sTREM-1 levels were evaluated using Magnetic Luminex® assay, and disease activity was assessed using Birmingham vasculitis activity score (BVAS). Patients were divided into two groups according to the upper and lower halves of BVAS. Receiver operator characteristic (ROC) curve analysis was used to identify cut-off for determining upper half of BVAS. Linear and binary logistic regression was performed to evaluate the association between sTREM-1 and disease activity and status. Results: The median age of patients was 67.0 years, and 58.2 % were women. The median BVAS and sTREM-1 were 12.0 and 467.1 pg/mL. sTREM-1 was significantly correlated with BVAS along with five-factor score, Short-Form 36-Item Health Surveys, and C-reactive protein. In multivariable linear regression analysis, erythrocyte sedimentation rate (standardised ß 0.241), and sTREM-1 (standardised ß 0.288) were correlated with BVAS. ROC analysis revealed that the cut-off of sTREM-1 for the upper half of BVAS was 474.1 pg/mL. MPA and GPA patients with sTREM-1 ≥474.1 pg/mL exhibited a significantly higher risk for the upper half of BVAS than those without (relative risk 5.932). Multivariable logistic regression analysis demonstrated sTREM-1 ≥474.1 pg/mL (odds ratio 5.662) was associated with the upper half of BVAS. Conclusion: sTREM-1 reflects the activity of MPA and GPA, suggesting its role as a potential biomarker for assessing disease severity.

Vasculitis Activity-Predicting Ability of IL-12 Family Cytokines in Patients with Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

PURPOSE: The present study investigated and compared the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) activity-predicting ability of the serum concentrations of the four interleukin (IL)-12 family cytokines including IL-23, IL-27, IL-35, and IL-39 in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). MATERIALS AND METHODS: The present study included 70 patients with MPA and GPA. Clinical and laboratory data, particularly Birmingham Vasculitis Activity Score (BVAS), at the time of blood collection were obtained. The serum concentrations of IL-23, IL-27, IL-35, and IL-37 were measured using sera stored at -80℃. Patients were divided into two groups: the upper half of BVAS (BVAS ≥12) and the lower half of BVAS (BVAS <12). RESULTS: The serum concentrations of IL-23 and IL-27 reflected AAV activity. Patients with the upper half of BVAS exhibited significantly higher serum concentrations of IL-23 and IL-27 than those without. Patients with the serum concentrations of IL-23 ≥132.1 pg/mL or IL-27 ≥684.7 pg/mL exhibited higher frequency and risk for the upper half of BVAS than those without [relative risks (RR) 5.143 and RR 4.091, respectively]. The serum concentrations of IL-27 were associated with age ≥65 years and proteinase 3-ANCA (or C-ANCA) negativity, whereas, those of IL-23 were associated with MPA. However, the serum concentrations of IL-35 and IL-39 were not useful in predicting AAV activity in this study. CONCLUSION: The present study is the first to demonstrate that among the various members of IL-12 family cytokines, the serum concentrations of IL-23 and IL-27 possess AAV activity-predicting ability.

Total Globulin Fraction at Diagnosis Could Forecast All-Cause Mortality during the Disease Course in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Total globulin fraction (TGF) is calculated by subtracting serum albumin levels from serum total protein levels. The present study examined whether TGF at diagnosis could forecast all-cause mortality during the disease course in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The present study included 283 patients with AAV. The variables at AAV diagnosis such as demographic data, AAV-specific data including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and laboratory data including ANCA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were collected. The number of deceased patients during the follow-up duration based on all-cause mortality was counted. The median age of the 283 AAV patients was 60 years, and 35.7% were men. ANCAs were detected in 228 patients, and the median TGF was 2.9. A total of 39 patients (13.8%) died within a median follow-up duration of 46.9 months. TGF at AAV diagnosis was significantly correlated with ESR and CRP rather than AAV activity. Patients with ANCA positivity exhibited a significantly higher median TGF at AAV diagnosis than those without. Patients with TGF ≥ 3.1 g/dL at AAV diagnosis exhibited a significantly lower cumulative survival rate than those without. Furthermore, in the multivariable Cox hazards model analysis, TGF ≥ 3.1 g/dL (hazard ratio 2.611) was independently associated with all-cause mortality, along with age, male sex, and body mass index. The present study is the first to demonstrate that TGF at AAV diagnosis can forecast all-cause mortality during the disease course in AAV patients.

Acute Brain Infarction in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Korean Single-Center Study.

OBJECTIVES: This study investigated the clinical and radiological features of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with acute brain infarction, using a cohort of Korean patients with AAV. METHODS: This study included 263 patients with AAV. Acute brain infarction was defined as infarction that occurred within 7 days or less. The brain territories affected by acute brain infarction were investigated. Active AAV was arbitrarily defined as the highest tertile of Birmingham Vasculitis Activity Score (BVAS). RESULTS: The median age at diagnosis was 59.0 years, and 35.4% were male. Fourteen cases of acute brain infarction occurred in 12 patients (4.6%), which was calculated as 1332.2 per 100,000 patient-years and 10 times higher than the incidence rate in the Korean general population. Patients with AAV with acute brain infarction exhibited significantly older age, increased BVAS at diagnosis, and a more frequent history of prior brain infarction compared with those without. The brain territories affected in AAV patients were middle cerebral artery (50.0%), multiple territories (35.7%), and posterior cerebral artery (14.3%). Lacunar infarction and microhemorrhage were observed in 42.9% and 71.4% of cases, respectively. Prior brain infarction and BVAS at diagnosis were independently associated with acute brain infarction (hazard ratios, 7.037 and 1.089). Patients with AAV with prior brain infarction or BVAS for active AAV exhibited significantly lower cumulative acute brain infarction-free survival rates than those without. CONCLUSION: Acute brain infarction was observed in 4.6% of AAV patients, and both prior brain infarction and BVAS at diagnosis were independently associated with acute brain infarction.

Predictive potential of albumin-alkaline phosphatase ratio for cerebrovascular accident in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: This study investigated the predictive potential of the albumin-to-alkaline phosphatase ratio (AAPR) for cerebrovascular accident (CVA) occurrence in patients with antineutrophil cytoplasmic antibody-associated vasculitis. METHODS: This study included 239 AAV patients and reviewed their medical records retrospectively. AAPR was calculated using the following formula: AAPR = serum albumin (g/dL)/serum alkaline phosphatase (IU/L). CVA was defined only as cerebral infarction after AAV diagnosis in this study. In patients with CVA and those without CVA, the follow-up duration based on CVA was defined as the period from AAV diagnosis to CVA occurrence and to the last visit day, respectively. RESULTS: The median age of 239 AAV patients (130 microscopic polyangiitis, 64 granulomatosis with polyangiitis, and 45 eosinophilic granulomatosis with polyangiitis) was 59.0 years and 32.6% were men. The median serum albumin and alkaline phosphatase levels, and AAPR were 3.7 g/dL, 70.5 IU/L and 0.051, respectively. Nineteen patients had CVA during the median follow-up duration of 34.8 months. Using the receiver operator characteristic curve analysis, the optimal cut-off of AAPR for CVA occurrence was obtained as ≤ 0.035. AAV patients with AAPR ≤ 0.035 showed a significantly higher risk of CVA occurrence after AAV diagnosis than those with AAPR >0.035 (relative risk 5.000, p < 0.001). In the multivariable Cox analysis, only AAPR ≤ 0.035 was independently associated with CVA occurrence among AAV patients (hazard ratio 3.195, 95% confidence interval 1.014, 10.062). CONCLUSION: This study demonstrated the predictive potential of AAPR calculated at AAV diagnosis for CVA occurrence after AAV diagnosis among AAV patients.

A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and interstitial lung disease in systemic sclerosis.

Anti-cyclic citrullinated peptide antibody testing is used to diagnose rheumatoid arthritis and associated with interstitial lung disease in RA. Herein, we investigate the relationship between anti-CCP antibody and ILD in SSc. We performed a retrospective analysis at a tertiary medical center between 2005 and 2019. Patients with SSc, systemic lupus erythematosus, and polymyositis/dermatomyositis (PM/DM) were evaluated for anti-CCP antibody and ILD. Additionally, medical records of SSc patients with ILD were reviewed. SSc patients had the highest anti-CCP antibody positivity rate compared to those with SLE and PM/DM. The incidence of ILD was higher in SSc patients with anti-CCP antibody than in those without. The usual interstitial pneumonia (UIP) incidence was higher in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. The DLCO was lower in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. On multivariable analysis, factors associated with SSc-ILD were anti-CCP antibody or rheumatoid factor (ß coefficient, 2.652 [95% CI 1.472 to 4.776]) and anti-Scl70 antibody (ß coefficient, 4.011 [95% CI 2.142 to 7.508]). Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. SSc patients with anti-CCP antibody may have more UIP pattern and lower DLCO.Trial Registration Retrospectively registered.

Clinical impact of antineutrophil cytoplasmic antibody positivity on the occurrence of interstitial lung disease in patients with polymyositis/dermatomyositis.

BACKGROUND: This study investigated the clinical impact of antineutrophil cytoplasmic antibody (ANCA) positivity on the occurrence of interstitial lung disease (ILD) in patients with probable and definite polymyositis (PM)/dermatomyositis (DM) who met both the Bohan and Peter and the 2017 European League Against Rheumatism/American College of Rheumatology criteria. METHODS: The medical records of 75 PM/DM patients were retrospectively reviewed. ANCA and anti-Jo 1 positivity at diagnosis were obtained, and pulmonary function test and chest high-resolution computed tomography results at ILD occurrence were collected. The follow-up duration based on ILD was defined as the period from the time of PM/DM diagnosis to the occurrence of ILD in PM/DM patients with ILD and to the last visit for those without ILD. RESULTS: The median age was 50.0 years and 21.3% were male. ANCA and anti-Jo 1 were detected in 12 (16.0%) and 26 patients (34.7%), respectively. ILD occurred in 32 patients, 24 of whom had ILD at the time of PM/DM diagnosis. Anti-Jo 1 was detected more often in PM/DM patients without ANCA than those with (39.7% vs. 8.3%). ILD occurred more frequently in PM/DM patients with ANCA than those without ANCA (75.0% vs. 36.5%). However, the occurrence of ILD was not affected by anti-Jo 1 positivity. Furthermore, ANCA-positive PM/DM patients exhibited a significantly lower cumulative ILD-free survival rate than ANCA-negative PM/DM patients (P=0.009). CONCLUSIONS: ANCA positivity at the time of PM/DM diagnosis might be an important risk factor for ILD in PM/DM patients.

BVAS version 3 and BVAS/GPA: standing on the same line?

INTRODUCTION/OBJECTIVES: Birmingham vasculitis activity score (BVAS) version 3 (BVAS 3.0) and BVAS/granulomatosis with polyangiitis (BVAS/GPA) are used as indicators of disease activity in anti-neutrophil cytoplasmic antibody-associated vasculitis. We evaluated the association between these indices and the significance in patients with GPA and microscopic polyangiitis (GPA/MPA). METHODS: We retrospectively reviewed the records of 203 patients with GPA/MPA in our hospital. The correlation between BVAS 3.0 and BVAS/GPA with the five-factor score (FFS) and laboratory data was investigated. The episodes of all-cause mortality, end-stage renal disease, and disease relapse were counted as adverse clinical outcomes. Multivariate Cox hazard analyses were performed to assess the relationships between both indices and patient outcomes. RESULTS: Sixty-five (32.0%) and 138 (68.0%) patients with GPA and MPA were included. The median BVAS 3.0 was significantly higher in patients with MPA than in those with GPA (13.0 vs. 11.0, p = 0.015), whereas BVAS/GPA was higher in patients with GPA (4.0 vs. 3.0, p = 0.001). BVAS 3.0 and BVAS/GPA correlated significantly (r = 0.670, p < 0.001); both BVAS 3.0 and BVAS/GPA were shown to be associated with the outcomes investigated in separate Cox models. However, the correlation between BVAS 3.0 and BVAS/GPA was especially higher in a subgroup of patients with MPA than in those with GPA (MPA: r = 0.817, p < 0.001 vs. GPA: r = 0.570, p < 0.001) and with renal involvement (r = 0.676, p < 0.001). CONCLUSIONS: Although both BVAS 3.0 and BVAS/GPA significantly correlated and predicted outcomes well in those with GPA/MPA, a discord was observed based on disease subtypes and organ involvement. Key Points • BVAS 3.0 and BVAS/GPA significantly correlated and predicted outcomes in those with GPA/MPA. • A discordance was also observed based on disease subtypes and organ involvement.

Incidence and Patterns of Interstitial Lung Disease and Their Clinical Impact on Mortality in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Korean Single-Centre Observational Study.

Objectives: This study investigated the frequency and patterns of interstitial lung disease (ILD) and their clinical effect on all-cause mortality during the follow-up period in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) in Korea. Methods: The medical records of 255 AAV patients with ILD were retrospectively reviewed. ILD and its patterns, the usual interstitial pneumonia (UIP) and non-UIP patterns, were confirmed using high-resolution computed tomography both at AAV diagnosis and during follow-up. Forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) were also obtained. Results: The median age was 65.0 years, and 34.9% were male. ILD occurred in 53 patients, among whom 49.1% developed ILD after AAV diagnosis. Among AAV subtypes, the frequencies of ILD were significantly higher in both patients with microscopic polyangiitis (MPA) and those with AAV having myeloperoxidase (MPO)-ANCA (or P-ANCA) compared to other subtypes. However, there was no statistical significance in AAV subtypes or FVC/DLCO ratio between patients with the UIP and non-UIP patterns. In particular, the cumulative patients' survival rate was lower in patients with AAV and ILD than in those without ILD. Conclusions: ILD occurred in one-fifth of Korean patients with AAV in this study and was associated with MPA and MPO-ANCA (or P-ANCA). In addition, ILD significantly increased the rate of all-cause mortality in these patients with AAV. Therefore, we suggest the need for more attention and more frequent regular visit for patients with AAV and ILD regardless of the time of ILD occurrence.

Nutrition Risk Index Score at Diagnosis Can Effectively Predict Poor Prognosis in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVES: This study investigated whether the nutritional risk index (NRI) score at diagnosis might be useful for anticipating poor prognosis, in particular, all-cause mortality and end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: The medical records of 242 immunosuppressive drug-naïve patients with AAV were retrospectively reviewed. Data at diagnosis and poor prognosis and medications during follow-up were assessed. The NRI score was calculated by 1.519 × serum albumin (g/L) + 41.7 × present (kg)/ideal body weight (kg). RESULTS: The median age at diagnosis of patients with AAV (131 microscopic polyangiitis, 62 granulomatosis with polyangiitis, and 49 eosinophilic granulomatosis with polyangiitis) was 60 years (85 male). During follow-up, twenty-nine patients (12.0%) died after a period of 35.9 months, and 42 patients (17.4%) had ESRD for a period of 30.0 months. Using the receiver operator characteristic curve, the cutoffs of the NRI scores for all-cause mortality and ESRD were calculated as NRI ≤ 101.95 (sensitivity, 46.5%; specificity, 89.7%) and NRI ≤ 99.85 (sensitivity, 57.0%; specificity, 83.3%). In the multivariable Cox hazard model analyses, age (hazard ratio [HR], 1.035), five-factor score (HR, 1.623), and the NRI score ≤ 101.95 (HR, 4.262) were independent predictors of all-cause mortality, whereas, five-factor score (HR, 1.516), hypertension (HR, 1.906), and the NRI score ≤ 99.85 (HR, 3.623) were independent predictors of ESRD occurrence during follow-up in patients with AAV. CONCLUSIONS: The NRI score at diagnosis may be a useful index to anticipate all-cause mortality and ESRD occurrence during follow-up in patients with AAV.

Rheumatoid factor positivity in antineutrophil cytoplasmic antibody-associated vasculitis: a distinct clinical entity or innocent bystander?

OBJECTIVE: To investigate the significance of RF positivity in ANCA-associated vasculitis (AAV) patients. METHODS: AAV patients were divided into groups as follows: RF (+)/ANCA (+) (n = 94), RF (-)/ANCA (+) (n = 80), RF (+)/ANCA (-) (n = 15) and RF (-)/ANCA (-) (n = 25). Their clinical data, organ involvement patterns, laboratory data, and patient outcomes were assessed. Kaplan-Meier analysis and propensity score matching (PSM) were performed to compare outcomes and analyse differences between the groups. RESULTS: Of the 214 patients, RF and ANCA positivity was found in 109 (50.9%) and 174 (81.3%) patients, respectively. RF (+)/ANCA (+) patients more frequently presented with general manifestations (58.5%) than the other groups. Additionally, compared with those of RF (-)/ANCA (+) group, RF (+)/ANCA (+) patients were older, had higher white blood cell, neutrophil, platelet counts and acute phase reactants; however, creatinine and albumin levels were lower. The end-stage kidney disease-free survival rate was significantly higher in the RF (+)/ANCA (+) group (P =0.013), while the proportion of renal involvement was comparable to the RF (-)/ANCA (+) group. PSM showed no difference in patient outcomes between the two groups after adjustment. CONCLUSION: RF positivity was associated with a distinct phenotype in AAV patients. In particular, difference was observed in clinical features and outcomes between RF (+)/ANCA (+) and RF (-)/ANCA (+) groups, although the direct prognostic implication of RF was not evident.