Birmingham Vasculitis Activity Score Score Research Articles

#1800 Cascade filtration in severe pulmonary-kidney syndrome: an one-center experience

Abstract Background and Aims In some forms of rapidly progressive glomerulonephritis (RPGN), the effect of plasma exchange (PE) is not well understood. Cascade filtration (CF) differs from standard PE in that it uses a double filter system, where the first filter is used to separate plasma from whole blood and the second filter is used to filter high-molecular weight substances. In this study, we investigated the efficacy and safety of CF in patients with ANCA-associated vasculitis (AAV) and Goodpasture's syndrome (GPS). Method During one year we included 18 patients with RPGN whose received CF in the study. The eligibility criteria was eGFR ≤15 ml/min/1.73 m2 and/or diffuse alveolar hemorrhage (DAH), presence of antineutrophilic antibodies or anti-GBM-antibodies. CF was performed on a Plasauto Sigma using a Plasmaflo OP-05W plasma separator and a Cascadeflo EC-30W separator with a fresh frozen plasma or 25% albumin solution. All patients received immunosuppressive therapy with steroids and cyclophosphamide, one patient with AAV received rituximab due to anemia and thromobocytopenia. All data were obtained from one hospitalization with the median of 43 days. Results Eight patients with AAV and three patients with GPS met the eligibility criteria. The median age of the patients in the AAV group was 59.8 (48; 66) years, with a female to male ratio of 1:1. All patients had evidence of systemic disease: seven patients had lung damage, including DAH, two patients had arthralgia, one had purpura and one had severe sinonasal involvement. The median creatinine level was 588 µmol/l (382; 1352), dialysis was initiated in 6 patients, and the median Birmingham Vasculitis Activity Score (BVAS) was 17 (15; 20). After three procedures of CF, all patients showed positive changes on CT scan, and dialysis was stopped in three patients. The immunological response to CF was observed quite rapidly in seven patients, with decreasing ANCA titer after three exchanges and decreasing antibody levels after six exchanges in one patient. There was a significant decrease in inflammatory markers, median C-reactive protein at baseline 179 (147; 226) decreased to 23 (2.8; 30.9) mg/l (p = 0.041). The CF was well tolerated with no significant adverse events. One patient receiving rituximab died after 4 months due to a severe COVID 19 infection. Three patients with GPS, one male 23 years old and two females 56 and 60 years old, also received CF. Creatinine concentrations at baseline were 1285, 1299 and 661 µmol/l, BVAS scores were 18, 20 and 15, respectively. After three procedures of CF, there was an immunological response: decrease in antibody levels from 121 U/ml to 15 U/ml, from 88.2 to 18.4 U/ml, from > 200.0 to 85.4 U/ml, CRP from 252 to 0.7 mg/l, from 120 to 5 mg/l, from 81.9 to 12.58 mg/l. There were no deaths and all three patients remained on dialysis. Conclusion CF was an effective and well tolerated method of treating severe AAV and GPS in addition to immunosuppressive treatment. Possibly due to the different filtration principle and the absence of donor plasma, we did not observe any infection-related adverse events and a lower number of procedures of CF was required compared to standard plasma exchanges. Further larger studies are needed to evaluate the benefits and safety of CF in combination with immunosuppressive treatment in RPGN patients.

Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People's Hospital from May 2020 to August 2022 were selected. A total of 52 AAV patients were divided into active phase (>15 points) and remission phase (≤15 points) based on the Birmingham vasculitis activity score (BVAS). Serum IL-18 level was detected by enzyme-linked immunosorbent assay in three groups. Pearson product moment correlation analysis was performed to investigate the correlation between serum IL-18 levels and clinical laboratory indicators, and receiver operating characteristic (ROC) curve analysis was performed on serum IL-18, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and NLR in AAV patients. The levels of serum creatinine, parathyroid hormone, β2-microglobulin (β2-MG), ESR, CRP, and IL-18 in active stage of AAV were significantly higher than those in remission stage of AAV. Moreover, the serum IL-18 level of active AAV patients was significantly higher than that of disease control group (P < 0.05). The levels of eGFR, hemoglobin, and complement C3 were significantly lower than those during the remission (P < 0.05). Pearson product moment correlation analysis showed that serum IL-18 level in AAV patients was positively correlated with BVAS score and ESR level. The area under the curve of serum IL-18, NLR, CRP, ESR levels evaluated by ROC curve was 0.921, 0.899, 0.83, and 0.75, respectively. Kaplan-Meier survival curve showed that the cumulative survival rate of patients in low NLR group was significantly higher than that in high NLR group (68.36 vs 42.89%), with significant difference (Log-Rank = 6.745, P = 0.025 < 0.05). IL-18 may be adopted as one of the important biological markers to judge the disease of AAV, and the cumulative survival rate of patients with high NLR is low, which may be applied as an indicator to evaluate the poor prognosis of patients with AAV.

Intravenous immunoglobulin therapy in antineutrophil cytoplasmic antibody-associated vasculitis

IntroductionAnti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) includes three heterogeneous and difficult to treat clinical entities. Intravenous immunoglobulins (IVIG) may constitute a good therapeutic option, although data hitherto are scarce. The aim of this study was to assess the effectiveness and safety of IVIG in AAV in a real-world setting. MethodsSingle center observational study of patients with AAV with at least one cycle of IVIG since January of 2000 to December of 2020. AAV diagnosis was based on a compatible clinical presentation and positive ANCA serology and/or compatible histology. Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). The effectiveness was evaluated by clinical and laboratory parameters (CRP, ESR) and its glucocorticoid-sparing effect. These variables were measured at one, six, twelve and twenty-four months of IVIG treatment. The doses of IVIG were 2g/kg in the following cycles of administration: 1 g/kg/day in 2 days (n=12); 0.5 g/kg/day in 4 days (n=11); 0.4 g/kg/day in 5 days (n=5). The clinical improvement was classified according to BVAS categories in remission, partial response and no response. ResultsTwenty-eight patients (15 granulomatosis-polyangiitis, 10 microscopic polyangiitis and 3 eosinophilic granulomatosis with polyangiitis) were included. Reasons for using IVIG were relapse/refractory disease (n=25), active or suspected infection (n=3), and both (n=5). We observed a rapid and maintained BVAS score improvement, increasing from 34.6% at 1 month to 56.5% at 2 years of follow-up (p=0.12), and a reduction of glucocorticoids dose. Therapy was well tolerated and adverse events mild and scarce. ConclusionIVIG represents an effective and relative safe therapeutic alternative in relapsing/refractory AAV or in presence of a concomitant active infection.

Evaluation of three scoring systems for predicting renal prognosis in antineutrophil cytoplasmic antibody-associated glomerulonephritis

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) is characterized by rapidly progressive glomerulonephritis, and timely initiation of treatment and evaluation is critical to prevent the progression of renal disease to end-stage renal disease (ESRD). The aim of this study was to evaluate predictive value of the renal risk score (RRS), Birmingham vasculitis activity score (BVAS), and renal vascular lesions (RVLs) score for renal prognosis in AAGN.MethodsA retrospective analysis of ninety-four patients diagnosed with AAGN after renal biopsy was performed. The RRS, BVAS, and RVLs score were evaluated in relation to clinicopathologic features and renal prognosis. A receiver operating characteristic curve (ROC) was used to evaluate their renal prognostic value.ResultsThe median follow-up time was 36 months. Thirty-eight patients progressed to ESRD. Survival analysis showed that renal prognosis worsened in the RRS group in order of low, medium, and high RRS (P < 0.05). Within the RVLs group, the renal prognosis of the groups with severe and moderate RVLs was worse than that of the group without RVLs (P = 0.012, P < 0.001), and the group with mild RVLs was close to that of the group without RVLs. ROC analysis showed that the AUC of RRS, BVAS, RVLs score, RVLs score combined with RRS (RVLs score & RRS, RR), RVLs score, and RRS combined with BVAS (RVLs score & RRS & BVAS, RRB) were 0.865, 0.624, 0.763, 0.910, and 0.942, respectively. The predictive power of RRB and RR was comparable and significantly better than the RRS, BVAS, and RVLs score. Based on simplicity and validity, RR was selected as the best predictor, and the relationship between RRS, RVLs score, and RR was calculated using a linear fit, resulting in the linear equation RR = -0.4766 + 0.1231 × RVLs score + 0.395 × RRS (P < 0.001).ConclusionsIn AAGN, the predictive power of RR for renal prognosis was superior to that of RRS, BVAS, and RVLs score. RR may serve as a new predictor of renal prognosis in AAGN.

Clinical characteristics and long-term outcome of patients with gastrointestinal involvement in eosinophilic granulomatosis with polyangiitis.

This study aims to investigate clinical characteristics, potential risk factors, as well as long-term outcome in EGPA patients with GI involvement. A total of 94 EGPA patients were included in this cohort study. We retrospectively reviewed the clinical data, treatment, and outcome of 21 EGPA patients with GI involvement and compared them with other 73 EGPA patients without GI involvement. Multivariate logistic regression was used to find potential risk factors associated with GI involvement in EGPA patients. Compared with EGPA patients without GI involvement, EGPA patients with GI involvement had higher level of hs-CRP (65.1 (24.5-138.9) vs. 21.3 (5.7-39.1) mg/L, p=0.005), higher grades of Birmingham vasculitis activity score (BVAS) (20 (13-29.5) vs. 12 (16-19), p=0.022), higher Five Factor Score (FFS) (1 (1-2) vs. 0 (0-1), p<0.001), and were more likely to have weight loss (66.7% vs. 38.4%, p=0.021) at baseline. In EGPA patients with GI involvement, the most common gastrointestinal symptoms were abdominal pain (90.5%) and diarrhea (42.9%). Weight loss was identified as a potential risk factor for GI involvement in EGPA patients (OR = 4.304, 95% CI 1.339-13.841). During follow-up, EGPA patients with GI involvement showed lower 1-year cumulative survival rate (75.2% vs. 100.0%, P <0.0001) and 3-year cumulative survival rate (67.7% vs. 100.0%, P<0.0001), lower long-term remission rate (33.3% vs. 86.3%, P<0.001), but higher 1-year cumulative relapse rate (19.2% vs. 3.8%, P=0.03) and 3-year cumulative relapse rate (54.6% vs. 13.1%, P<0.001) compared with patients without GI involvement. EGPA patients with GI involvement had distinct features from those without GI involvement, including higher hs-CRP level, higher BVAS and FFS scores. EGPA patients with GI involvement showed lower cumulative survival rate, lower long-term remission rate and higher cumulative relapse rate compared with those without GI involvement.

Analysis of the risk factors forend‑stage renal disease and mortality inANCA-associated vasculitis: a study fromasingle center of the Chinese Rheumatism Data Center.

The purpose of this study was to describe the clinical features of AAV and identify possible risk factors for end-stage renal disease (ESRD) and mortality in AAV based on the experience of a single center in China. A prospective cohort study of AAV was conducted based on data acquired by the Chinese Rheumatism Data Center (CRDC). The cohort involved 140 patients diagnosed with AAV in the Second Affiliated Hospital of Nanchang University from January 2013 to April 2022. Clinical characteristics and prognostic data were prospectively collected. The patients were divided into an ESRD group and a non-ESRD group, a death group and a survival group, Then, univariate and multivariate COX regression models were used to determine the risk factors associated with ESRD and mortality by AAV. Multivariate Cox regression results showed that high initial serum creatinine (hazard ratio (HR) = 1.001, 95% confidence interval (CI): 1.000-1.002, P = 0.024), high initial Birmingham vasculitis activity score (BVAS) (HR = 1.081, 95% CI: 1.027-1.138, P = 0.003), and the need for dialysis treatment (HR = 4.918, 95% CI: 1.727-14.000, P = 0.003) were independent risk factors for the progression of ESRD in AAV patients.Multivariate Cox regression results showed that alveolar hemorrhage (HR = 3.846, 95% CI: 1.235-11.973, P = 0.020), interstitial lung disease (HR = 4.818, 95% CI: 1.788-12.982, P = 0.002), and low initial estimated glomerular filtration rate (EGFR) (HR = 0.981, 95% CI: 0.968-0.995, P = 0.009) were independent risk factors for the prediction of death in AAV patients. These findings suggest that high initial serum creatinine, a high initial BVAS score, and the need for dialysis were independent risk factors for the progression of ESRD in AAV patients.Alveolar hemorrhage, interstitial lung disease, and low initial EGFR were independent risk factors for death. Key Points • The risk factors for ESRD in AAV determined in this study are high initial serum creatinine, a high initial BVAS score, and the need for dialysis. • The risk factors for mortality in AAV are alveolar hemorrhage, interstitial lung disease, and low initial EGFR.

Serum B cell activating factor (BAFF) as a biomarker for induction of remission with rituximab in ANCA-associated vasculitis

We examined whether serum B cell activating factor (BAFF) is useful for predicting the remission of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) following rituximab treatment. We used the Birmingham Vasculitis Activity Score (BVAS) 2008 version 3 for the evaluation of 27 patients with AAV 6 months after rituximab treatment. Those with BVAS = 0 achieved remission, whereas those with BVAS score > 0 did not achieve remission. We considered changes in serum BAFF before rituximab treatment, 1 month after treatment, and 6 months after treatment. In the remission group, the serum BAFF increased consistently. In the non-achieved group, serum BAFF was within the normal range. In addition, there was no statistically significant difference between the two groups in terms of serum BAFF before and 1 month after rituximab treatment. However, the serum BAFF level at 6 months after rituximab treatment was significantly higher in the remission group than in the non-achieved group. If serum BAFF does not increase after 6 months of rituximab in AAV, it may be assumed that there are residual B cells and plasma cells in the tissues. Enhanced treatment targeting B cells, including re-administration of rituximab or the addition of other immunosuppressive drugs, should be considered.

Predicting factors for relapse in patients with granulomatosis with polyangiitis: results from a long-term cohort.

To investigate the predictive factors and the best predictive model for relapse in granulomatosiswithpolyangiitis (GPA) patients. All patients referred to our tertiary university hospital with confirmed diagnosis of GPA based on 1990-ACR criteria and/or revised Chapel Hill nomenclature, who were followed more than 24months between 2012 and 2021 were included. Patients were classified into relapsing and non-relapsing groups. Disease activity was assessed based on Birmingham Vasculitis Activity Score (BVAS) and BVASforGPA (BVAS-GPA). All demographic, clinical, laboratory, and radiologic parameters were compared between two groups. Data of 133 patients (male = 52 (39.1%); mean age = 46.5 ± 14.5years) with a mean follow-up period of 49.4 ± 24.1months were evaluated. Of those, 91 (68.4%) experienced at least one relapse episode. The mean duration of relapse-free-survival (RFS) was 12.5months with 1-year, 3-year, and 5-year RFS rates of 46.6%, 34.6%, and 31.6%, respectively. The risk of relapse was higher if patients had higher BVAS or BVAS-GPA score (P-values < 0.001), constitutional syndrome (P-value = 0.01), neutrophil-to-lymphocyte ratio (NLR) (P-value = 0.01), C-reactive-protein (P-value = 0.03), alanine transaminase > 40 units/L (P-value = 0.04), and microscopic hematuria (P-value = 0.001). In backward logistic regression analysis, baseline BVAS score ≥ 12 (Ex(B) = 4.21, P-value = 0.03), and NLR > 2.5 (Ex(B) = 12.00, P-value = 0.007) remained statistically significant at the last step of the model with 75.8% sensitivity, 76.9% specificity, and 76.3% accuracy in predicting the relapsing patients. The frequency of relapse episodes was significantly lower in treatment group of rituximab-rituximab (0.3 ± 0.6) compared to cyclophosphamide-methotrexate (1.2 ± 1.3) and cyclophosphamide-azathioprine (1.8 ± 1.5) treatment protocols (P-value = 0.002). High-risk patients according to proposed model should be prioritized for more intensive care, more aggressive treatment, and closer follow-ups. • During the mean follow-up period of 50months, 68.4% experienced at least one relapse episode • Patients with baseline BVAS > 12, renal involvement, and elevated NLR are more vulnerable to relapsing disease • Patients on rituximab for induction and maintenance less experienced relapse episodes compared to other treatment regimens.

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores. Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively. Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r = - 0.675) and ITAS scores (r = - 0.385), as well as with CRP and CRI. Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.

Anti-ETAR and suPAR as markers of disease activity in renal ANCA-associated vasculitis

PurposeIn anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a lack of reliable biomarkers of disease activity. The aim of the study was to evaluate soluble urokinase plasminogen activator receptor (suPAR) and anti-endothelin-1 type A receptor (anti-ETAR) antibodies levels in active phase and remission of AAV. Patients and methodsWe enrolled 60 patients (median age 63.0 years) with renal AAV into this study. Plasma suPAR, urine suPAR (expressed as urine suPAR/creatinine ratio) and serum anti-ETAR antibodies were assayed by ELISA. Disease activity was assessed using Birmingham Vasculitis Activity Score (BVAS) and patients were divided into 2 subgroups based on their BVAS scores, namely: active AAV subgroup (BVAS≥1) and remission subgroup (BVAS ​= ​0). Median follow-up was 12 months. ResultsPatients with active AAV had higher levels of all candidate biomarkers in comparison to those in remission (p ​< ​0.05). C-statistics for plasma suPAR, urine suPAR/creatinine ratio and serum anti-ETAR were 0.807, 0.713 and 0.783, respectively. In multivariable analysis, no clear associations were found between serum anti-ETAR and BVAS, while both plasma suPAR and serum anti-ETAR were independently influenced by estimated glomerular filtration rate (eGFR). ConclusionsPlasma suPAR better discriminated between active AAV and remission in comparison to urine suPAR/creatinine ratio and serum anti-ETAR antibodies.

Serum chitinase-3-like 1 protein is a useful biomarker to assess disease activity in ANCA-associated vasculitis: an observational study

BackgroundTo investigate whether serum chitinase-3-like 1 protein (YKL-40) is associated with disease activity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).MethodsELISA was performed in serum samples from AAV patients who were enrolled in our prospective observational cohort to estimate levels of YKL-40. Birmingham vasculitis activity score (BVAS) (version 3), five factor score (FFS), and short form-36 (SF-36), as well as clinical and laboratory data were collected. Kidney expression of YKL-40 was assessed by immunohistochemical staining using renal biopsy tissues from ANCA-associated glomerulonephritis patients (AAGN). Severe AAV and FFS were defined as BVAS ≥ 12 and FFS ≥ 2, and the correlations between laboratory variables, BVAS, FFS, and SF-36 score were assessed using linear regression analysis. The optimal cut-off of serum YKL-40 for severe AAV and high FFS was calculated using the receiver operator characteristic curve analysis.ResultsOf the included 60 patients, 32 (53.3%), 17 (28.3%), and 11 (18.3%) were classified as microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis. The median BVAS and FFS were 7.0 and 1.0, whereas the mean SF-36 physical and mental component scores were 50.5 and 58.3. Serum YKL-40 level was higher in patients with severe AAV and high FFS compared to those without (p = 0.007 and p < 0.001); multivariable linear regression analysis revealed that serum YKL-40 was independently associated with BVAS, FFS, and SF-36 scores. On kidney tissues obtained from AAGN patients, strong cytoplasmic staining of YKL-40 was found in cells present in inflammatory lesions. In addition, AAV patients had higher levels of serum YKL-40 compared to those with systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, and healthy control. The proportion of patients having severe AAV and high FFS was significantly higher in those with serum YKL-40 > 221.3 ng/mL and > 227.1 ng/mL than those without (relative risk 2.852 and 7.000). In 12 patients with serial YKL-40 testing, 11 patients (91.7%) exhibited a reduction in serum YKL-40 levels following a decrease in disease activity (p < 0.001).ConclusionOur findings suggest that serum YKL-40 may be a clinically useful biomarker to assess AAV disease activity.Trial registrationRetrospectively registered.

Value of prognostic scores in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis patients in intensive care unit: a multicenter retrospective cohort study from Turkey

Background/aimThere is a need for a scoring system for predicting ICU prognosis of patients with ANCA-associated vasculitis (AAV), but there are limited data on it in the literature. Therefore, we aimed to determine the scores that can estimate the prognosis of patients with AAV during intensive care follow up.Materials and methodsAll adult patients admitted to the medical ICUs of 4 reference university hospitals in Turkey due to AAV activation and/or disease/treatment complications in the last 10 years were included in this study. Demographic data, treatments before ICU, the Birmingham Vasculitis Activity Score (BVAS) score at the time of vasculitis diagnosis, and BVAS, APACHE II, SOFA, and SAPS II scores at the ICU admission, treatments, procedures, and complications during ICU stay were recorded for all AAV patients.ResultsThirty-four patients were included in the study. The median age of the patients was 60 (42–70) years, and 64.7% were male. Twenty-five patients were diagnosed with Granulomatosis with polyangiitis, and 9 were diagnosed with Microscopic polyangiitis. The most common ICU admission causes were hemorrhage (85.3%) and sepsis/septic shock (67.6%). Twenty patients (58.8%) died in the ICU follow up. There were significant differences in APACHE II (P = 0.004) and SAPS II (P = 0.044) scores between survivors and nonsurvivors, while there were no significant differences in BVAS (during diagnosis P = 0.089 and ICU admission P = 0.539) and SOFA (P = 0.097) scores. APACHE II score was found to be an independent risk factor for ICU mortality (OR = 1.231, CI 95% = 1.011–1.498, P = 0.038) according to logistic regression analysis. An APACHE II score of greater than 20.5 predicted ICU mortality with 80% sensitivity and 70% specificity (AUC = 0.8, P = 0.004, Likelihood ratio = 2.6) according to the ROC curve analysis.Conclusion APACHE II score can be used for the prediction of ICU mortality in AAV patients.

Presence of purpura is related to active inflammation in association with IL-5 in eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a relatively rare necrotizing vasculitis that causes asthma, nasal involvement, peripheral nerve disturbance, renal disorder, and cutaneous lesions like purpura and is characterized by eosinophil infiltration into the damaged tissue. Purpura is the most common cutaneous lesion, but it remains unknown whether this skin lesion is associated with disease activity of EGPA and laboratory data including interleukin (IL)-5, a target cytokine of this disease. We conducted a search of our hospital electronic records for cases of EGPA from the last 10 years. Symptoms related to EGPA (fever, asthma, nasal and cutaneous manifestations, neuropathy), the Birmingham Vasculitis Activity Score (BVAS), and laboratory parameters, such as eosinophil count, urinalysis, antineutrophil cytoplasmic antibody (ANCA), CRP, IgE and IL-5, before and during treatment were compared among the eligible cases. A total of 28 EGPA patients (21 females and 7 males) were selected. Almost all developed peripheral neuropathy. Fever occurred in 25%, nasal symptoms in 38.1% and purpura in 44%. Glomerulonephritis developed in 7.7%. One patient had cardiac involvement (3.6%). The laboratory data showed a marked increase in peripheral eosinophil count, CRP, serum IgE and serum IL-5. ANCA was positive in 15.4%. In the univariate analysis, presence of purpura was associated with increased CRP and IL-5, and high BVAS score. Multivariate analysis revealed a robust relationship between purpura and CRP. Our findings showed that presence of purpura was associated with increased CRP and IL-5, and high disease activity in EGPA.

P0446OUTCOMES OF CYCLOPHOSPHAMIDE FOR ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODIES-ASSOCIATED VASCULITIS: DIFFERENT PROTOCOLS, SINGLE-CENTER EXPERIENCE AND LITERATURE REVIEW

Abstract Background and Aims Cyclophosphamide (CYC), associated with corticosteroids has been considered the mainstay of treatment for severe antineutrophil cytoplasmic antibody−associated vasculitis (AAV) for decades. This protocol is effective in 70-90% of patients resulting in drastic improvement in both renal and patient survival. Nevertheless, cyclophosphamide is associated with significant rates of adverse events, namely severe infections and malignancies. The authors present the single-center experience of the use of CYC for AAV treatment regarding clinical presentation, immunosuppression protocol, outcomes and adverse events, as well as a comparison with the main RCTs and studies using CYC for induction of remission of AAV. Method Retrospective analysis of clinical records of patients with AAV diagnosis (de novo or relapse) treated with CYC in the ward of the Nephrology Department of Centro Hospitalar Universitário Lisboa Norte between January 2006 and December 2019. Results Thirty patients with AAV diagnosis treated with CYC for induction of remission were identified. Average age was 69.4 ± 11.5 years. On admission, serum creatinine (SCr) was 5.03 mg/dL ± 2.24 mg/dL (eGFR 13.3 mL/min/1.73 m2 ± 11.1 mL/min/1.73 m2). Twenty patients (67%) required renal replacement therapy at admission and 12 (40%) had alveolar hemorrhage. The average Birmingham Vasculitis Activity Score (BVAS) was 27.5 ± 11.5. Immunosuppressive regimens varied considerably, as they were left to the clinician's consideration. Intravenous methylprednisolone pulses were performed in 29 (96.7%) patients, with total dose ranging from 1000 mg to 5000 mg. Cyclophosphamide was also prescribed at clinician’s choice, with only one patient receiving oral CYC and 29 patients receiving from 1 to 11 pulses in different doses. Plasma exchange was performed in 12 (40%) patients due to alveolar hemorrhage and/or rapidly progressive renal insufficiency. After induction of remission, twenty patients received maintenance therapy. On a 12-month follow-up, 9 (30%) patients were on renal replacement therapy and, in the remaining patients, mean SCr was 2.23 ± 0.98 mg/dL (eGFR 33.4 mL/min/1.73 m2 ± 19.8 mL/min/1.73m2). Fifteen (50%) patients experienced severe infection at 6 months, 3 (10.7%) patients developed malignancies and 7 (23.3%) patients died on a 12-month follow-up. Conclusion Our cohort of patients treated with CYC is unlike the population that underwent clinical trials. In our cohort, SCr at presentation was considerably higher, being only comparable to MEPEX and the control arm of RITUXVAS. The BVAS score of our patients was also significantly superior than all other studies. Furthermore, most clinical trials do not include patients with alveolar hemorrhage, present in 40% of the patients in our study, nor RRT requirement, present in 67% of our patients. The higher rate of severe infections and mortality registered in our cohort reflects the severity of the disease at presentation, but also highlights the importance of modifying immunosuppression to the population and the need for future regimens which can reduce the rate of adverse effects.

Serum interleukin-16 significantly correlates with the Vasculitis Damage Index in antineutrophil cytoplasmic antibody-associated vasculitis

BackgroundInterleukin (IL)-16 is a T cell chemoattractant produced by peripheral mononuclear cells. We investigated whether IL-16 plays a pro- or an anti-inflammatory role in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Furthermore, we investigated whether the level of IL-16 could predict the activity and extent of organ damage in AAV based on AAV-specific indices.MethodsSeventy-eight patients with AAV from a prospective observational cohort were included in this analysis. Blood sampling and clinical assessments, including the Birmingham Vasculitis Activity Score (BVAS), Five-Factor Score (FFS), Short Form 36-item Health Survey (SF-36), and Vasculitis Damage Index (VDI), were performed, and laboratory data were collected. Serum IL-16 was measured from stored sera.ResultsThe median age was 62.0 years, and 27 patients were male. The median serum IL-16 concentration was 84.1 pg/dL, and the median BVAS, FFS, VDI, and SF-36 scores were 7.0, 1.0, 3.0, and 48.0, respectively. Among the AAV-related indices, the serum IL-16 concentration was correlated with VDI (R2 = 0.306, P = 0.006), but not with BVAS (R2 = 0.024, P = 0.834), FFS (R2 = − 0.069, P = 0.550), or SF-36 (R2 = − 0.015, P = 0.898). The serum IL-16 concentration also did not correlate with either the erythrocyte sedimentation rate or the C-reactive protein concentration. Per our analysis based on organ involvement, only patients with ear, nose, and throat manifestations had higher serum IL-16 concentrations relative to those with other conditions (P = 0.030).ConclusionsThis was the first study to elucidate the clinical implication of serum IL-16 in patients with AAV. We found that the serum IL-16 level may reflect the cross-sectional VDI scores among AAV-specific indices. Future studies with larger numbers of patients and serial measurements could provide more reliable data on the clinical implications of serum IL-16 in AAV.

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.

Risk factors of peritonitis during earlyperitoneal dialysis in patients with ANCA-associated systemic vasculitis .

This study investigated the risk factors of peritonitis during early peritoneal dialysis for renal failure in patients with antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (AASV). This study enrolled hospitalized AASV patients with renal failure who underwent peritoneal dialysis at the Department of Nephrology of our hospital between 2008 and 2015. The primary aim of this study was to perform a retrospective analysis to characterize peritonitis during the early period (≤8weeks) of dialysis, and to compare the differences in initial clinical manifestations, vasculitis activity, immunosuppressive therapies prior to the renal replacement therapy, and prognosis between patients with or without peritonitis. The secondary aim of this study was to conduct a literature review of peritoneal dialysis in patients with vasculitis. All 14 enrolled AASV patients had myeloperoxidase (MPO)-positive microscopic polyangiitis (MPA). Six patients (of whom 2 died) withdrew from peritoneal dialysis due to peritonitis caused by enteric bacteria during the early period of dialysis. Their mean Birmingham vasculitis activity score (BVAS) during the early AASV onset was 31.67±3.98, with significant symptoms of gastrointestinal involvement. Also, their BVAS score, anti-MPO antibody titer, erythrocyte sedimentation rate, C-reactive protein level, serum ANCA level, and glucocorticoid dose were higher than the AASV patients without peritonitis (all p<0.05). AASV patients with a higher level of vasculitis (BVAS score >30) during onset as well as gastrointestinal symptoms had a higher risk for intestinal peritonitis. Therefore, peritoneal dialysis is not recommended as a first-choice renal replacement therapy for such patients. .

Anti-neutrophil cytoplasmic autoantibodies associated vasculitis – Clinical profile and outcomes

Background: Studies on antineutrophil cytoplasmic autoantibodies-associated vasculitis (AAV) from India are scarce. The aim of the present study was to characterize the profile of AAV and experience with rituximab in ocular granulomatous with polyangiitis (GPA) in our cohort. Methods: Clinical, laboratory, and treatment details of AAV from January 2010 to May 2017 were noted. Continuous variables were reported as mean and standard deviation (SD). In GPA, clinical variables between survivors and nonsurvivors were compared using independent sample t -test and Fisher's exact test. Cox regression analysis was done to estimate the hazard ratios. Our cohort of GPA was compared with other large single-center cohorts from India, USA, Germany, and France. Results: Thirty-one patients were diagnosed to have AAV. Seventeen were females. GPA was most common phenotype (23/31). Mean (SD) age at onset was 39.8 (15.7) years. Median (IQ) time to diagnosis was 6 (22) months. The most common manifestations in GPA were ocular ( n = 20) and lower respiratory tract ( n = 13). Mean (SD) Birmingham Vasculitis Activity Score (BVAS) at disease onset was 9.4 (6.9). Pulse methylprednisolone with cyclophosphamide was used as induction regime followed by maintenance with azathioprine. Rituximab was given to four patients with refractory GPA. Six patients succumbed to illness. Remission was achieved in 19/25 survivors. Mean (SD) BVAS at disease onset was significantly higher in nonsurvivors (17.6 ± 10.2) compared to survivors (9.4 ± 4.9) ( P = 0.018). Higher proportion of renal involvement was seen in nonsurvivors ( P = 0.03). There was three-fold increased mortality with renal and lung involvement. In addition, the risk of death increases by 1.13 fold with each point increase in BVAS score. Conclusion: Ocular involvement was higher in our GPA cohort. Baseline BVAS, renal, and lung involvement predicts poor prognosis in GPA. Sustained remission with rituximab was seen in all patients with refractory ocular disease.

The efficiency of treatment of cryoglobulinemic vasculitis associated with hepatitis C virus: analysis of 60&#x0D; cases

Aim. To evaluate the results of immunosuppressive and/or antiviral treatment of patients with hepatitis C virus (HCV)-induced mixed cryoglobulinemic (MC) vasculitis. Material and methods. This prospective study included 60 patients (m/f - 23/49, age - 45,9±11,1) with HCV-MC vasculitis. The Birmingham vasculitis activity score (BVAS) was used before the treatment and during follow-up (3,5±4,1 years). The rate of clinical and immunological responses to the treatment, the frequency of relapses and the influence of different treatment approaches on the prognosis of the disease were evaluated. Logistic regression analysis was used to assess factors influencing the effectiveness of treatment. Results. 23 (38%) patients had liver cirrhosis. BVAS scores before treatment ranged from 2 to 36. 25 (41,6%) patients had BVAS≥15. 6 (10%) patients presented with B-cell non-Hodgkin lymphomas. The antiviral treatment resulted in the elimination of the virus in 48.0% of the cases, complete clinical and immunological responses were achieved in 68,0% and 32,0% respectively. It had an advantage over immunosuppressive therapy in terms of long-term results of the treatment. We established the superiority of anti-CD monoclonal antibodies (rituximab) over conventional immunosuppressive drugs: complete clinical response 73% vs 13% (p=0,001). Combined therapy (rituximab and antiviral treatment) was more effective in patients with severe vasculitis (BVAS≥15). A case of successful treatment using direct-acting antivirals (DAAs) is reported. Causes of MC-vasculitis relapses after achieving sustained viral response are discussed. Conclusion. Antiviral therapy is the treatment of choice in all patients with HCV- HCV-MC vasculitis. Preference should be given to highly effective and safe modern therapy regimens with the use of DAAs. The antiviral treatment of severe forms of vasculitis must be combined with rituximab therapy.

Kidney injury molecules (KIM-1, MCP-1) and type IV collagen in the assessment of activity of antineutrophil cytoplasmic antibody-associated glomerulonephritis

To assess the significance of determining the serum and urinary concentrations of monocyte chemotactic protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), and type IV collagen in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to estimate the activity of renal involvement in AAV. 78 patients (32 men and 46 women) (median age 55 (45; 61) years) with AAV were examined. The patients were divided into 3 groups according to the AAV activity estimated using the Birmingham vasculitis activity Score (BVAS): 1) 25 patients with active ANCA-associated glomerulonephritis (GN); 2) 26 patients with active AAV without renal involvement; 3) 27 patients in sustained AAV remission. The serum and urinary concentrations of the markers were measured by enzyme immunoassay. The urinary concentration of all 3 biomarkers was higher in patients with renal involvement (Group 1); the differences in the levels of MCP-1 and type IV collagen were statistically significant as compared to Groups 2 and 3 (p<0.01), while that in KIM-1 level was only in Group 2. There were statistically significant correlations between the urinary concentration of these biomarkers and the traditional GN activity indices (erythrocyturia, daily proteinuria (DPU), total BVAS scores that reflect renal involvement, as well as serum creatinine levels and estimated glomerular filtration rate (p<0.05). ROC curve analysis showed that the urinary MCP-1 excretion of ≥159 pg/ml had the highest (92%) sensitivity and urinary type IV collagen excretion of ≥3.09 µg/l had the highest (86%) specificity in assessing the activity of ANCA-associated GN. At the same time, their diagnostic value increased in terms of a combination of DPU and ESR (96% sensitivity, 84.9% specificity). The urinary excretion of MCP-1, KIM-1, and type IV collagen reflects the severity of local renal inflammation in AAV patients and a study of these indicators is a promising diagnostic tool for assessing the activity of ANCA-associated GN.