Chapel Hill Consensus Conference Definition Research Articles

#3038 Plasma exchange for refractory IgA Vasculitis

Abstract Background and Aims IgA Vasculitis (IgAV) frequently has a relapsing/refractory course despite glucocorticoids and immunosuppressive therapies and the management of severe disease remains controversial [1]. Plasma exchange (PLEX) has been used as a rescue treatment in other vasculitides, particularly in cases with rapidly progressive glomerulonephritis, but little is known about its role in IgAV. Here we present outcomes of patients with refractory IgAV treated with PLEX at our centre. Method Clinical records of patients who met 1990 American College of Rheumatology classification criteria and 2012 Chapel Hill Consensus Conference definitions for IgAV were analysed and those receiving ≥1 course of PLEX (5 sessions) identified from our PLEX database. We assessed demographic and clinical features at diagnosis and at starting of PLEX. Response was defined as an improvement in vasculitis activity measured with Birmingham Vasculitis Activity Score (BVAS) 1 month after PLEX course completion and classified as “partial” (BVAS<3 and prednisolone <10 mg/day) or “complete” (BVAS = 0). Both definitions included changes in eGFR and proteinuria. Relapse was defined as an increase in BVAS after initial response. Early adverse events occurring during PLEX course or within one week after completion of this were recorded. Results Among 174 patients with IgAV, 12 (7%) received ≥1 course of PLEX. This was started a median of 15 months after diagnosis (interquartile range, IQR 3-40). All patients received glucocorticoids and immunosuppressive therapy prior to PLEX (Table). At the time of starting PLEX, 8/12 patients had active skin involvement (7/8 had purpura and 2/8 ulcers) and 10/12 nephritis, with a median eGFR 34 mL/min (IQR 30-43) and a median urine albumin:creatinine ratio (UACR) of 298 mg/mmol (IQR 240-486). PLEX was combined with glucocorticoids and various immunosuppressive agents, most commonly cyclophosphamide (42%) or mycophenolate mofetil (33%). All but one patient had a response at 1 month, and this was “complete” in five (42%). The median eGFR of patients with active nephritis increased up to 44 mL/min/1.73 m2 (IQR 36-58) and the median UACR drop to 182 (IQR 159-408). Ten patients (91%) relapsed a median of 3 months (IQR 2-7) after completion of the PLEX course and 8/10 (80%) resumed PLEX and achieved response. Six patients (50%) continued a “chronic” regimen of PLEX (1-2 monthly sessions) for a median of 85 months (25-141), as this was the only therapy that could control skin (4/6) and/or kidney manifestations (3/6). Three patients experienced infection within a week of PLEX discontinuation and two reported reactions to FFP/albumin, but all recovered completely. Three patients (25%) developed kidney failure during follow-up and two died (one of whom had kidney failure), with death occurring 9 and 146 months after discontinuation of PLEX. Conclusion In this small cohort of adult patients with severe and refractory IgAV, PLEX was associated with improved disease control, stabilisation of renal parameters, and few early adverse events. The clinical response to PLEX appeared temporary, but some patients maintained remission through a “chronic” PLEX regimen. As highlighted by the high risk of death or kidney failure, more effective therapies for IgAV are needed but PLEX should be considered as a rescue treatment in severe/refractory cases.

Development and organization of Tabriz University of Medical Sciences Vasculitis Registry: TUOMS-VR

This manuscript describes the establishment and initial results of a patient-driven registry in Tabriz, Iran to collect demographic, clinical, and paraclinical data, treatment and outcomes of patients with vasculitis. The Tabriz University of Medical Sciences Vasculitis Registry (TUOMS-VR), a patient-driven, prospective and web-based disease registry system, is conducted at the Connective Tissue Diseases Research Center, TUOMS located in Tabriz, Iran. The primary objective of this registry is to comprehensively document prospective data of patients diagnosed with systemic or single-organ vasculitis according to the Chapel Hill Consensus Conference nomenclature and definitions. To date, the registry has successfully enrolled 743 patients. The gender distribution within this existing cohort is balanced, with 50.5% male and 49.5% female participants. The most frequently diagnosed condition was Behcet’s disease, representing 56.5% of cases. Polymyalgia rheumatica also emerged as a notable diagnosis, accounting for 13.7% of cases. By providing a comprehensive and prospective documentation of vasculitis cases, the TUOMS-VR aims to enhance vasculitis patients care and outcomes.

#2754 EPIDEMIOLOGY OF PAUCI-IMMUNE ANCA-ASSOCIATED GLOMERULONEPHRITIS – REPORT FROM AN AUSTRALIAN POPULATION-BASED STUDY

Abstract Background and Aims ANCA-associated vasculitis is a group of autoimmune vasculitides of unknown aetiology that predominantly affect small blood vessels among different organ systems, with different phenotypic manifestations. Although vasculitides were reported to account for 12 percent of all renal biopsies in the state of Victoria [1] and crescentic glomerulonephritis was reported to account for 6 percent of all renal biopsies in the state of Queensland [2], the epidemiology data on renal predominant ANCA vasculitis, particularly renal biopsy confirmed ANCA associated glomerulonephritis (AAGN) is limited. Method This retrospective study was performed at the Royal Brisbane and Women's Hospital, a major tertiary hospital that service a population of 1,030,006 in North Brisbane, Australia. The 2012 Chapel Hill Consensus Conference definitions were used to identify renal predominant ANCA vasculitis. Patients with pauci-immune glomerulonephritis confirmed on kidney biopsy between 1st January 2005 to 1st October 2021 were selected. Clinical data was collected via electronic and paper medical records. Modified Monash Model classification was used to determine rurality of cases. Results 1433 kidney biopsy results were reviewed. 80 cases of biopsy-confirmed pauci-immune AAGNs were identified. There was no significant difference in gender (Male; 42/80 (53%), p = 0.87). There was a preponderance towards MPO-positive AAGN (53/80), as opposed to PR3-positive disease (21/80), 5/80 were ANCA negative and 1/80 did not have ANCA serology available. The mean age of diagnosis was similar between MPO and PR3 (63.7 vs 59.5 years, p = 0.34) and between males and females (63.3 vs 59.3, p = 0.42). There was no seasonal variation in AAGN diagnoses – 23/80 in spring, 20/80 in summer, 14/80 in autumn, 23/80 in winter ( χ2 = 1.48, p = 0.69). Fourteen (18%) patients died during the study period, 3 of which died prematurely before age 65. Within our cohort, 16% (13/80) of cases lived in regional/rural areas. Interestingly, all 3 premature deaths were from these areas. This may reflect poorer access to health care in regional/rural settings. Conclusion Pauci-immune ANCA-associated glomerulonephritis remains rare in North Brisbane, with estimated annual incidence of 4.6/million population, representing 5.6% of all kidney biopsies. The incidence is significantly lower than an American-based study that reported an incidence of 20 cases/million population [3] whilst a Swedish study reported an incidence of 13.2 cases/million population [4]. The reason behind the geoepidemiology variation is unclear, though there are evidence suggesting complex interaction of polygenic genetic susceptibility, epigenetic influences, and environmental associations such as rurality of living. Within our cohort, the incidence of MPO AAGN was 2.5 fold higher than PR3 AAGN, this is similar to other observed European and American data [5]. Our findings add to the current literature, particularly where epidemiological data on AAGN from the southern hemisphere is limited.

#4683 CHARACTERISTICS AND OUTCOMES OF MPO VERSUS PR3 ANCA ASSOCIATED GLOMERULONEPHRITIS: A REPORT FROM AN AUSTRALIAN POPULATION-BASED STUDY

Abstract Background and Aims ANCA-associated vasculitis is a group of autoimmune vasculitides of unknown aetiology that predominantly affect small blood vessels among different organ systems, with different phenotypic manifestations. Myeloperoxidase (MPO) and Proteinase 3 (PR3) have emerged as two main serological subtypes and growing evidence has shown there are differences between their disease characteristics [1,2]. We investigate into the difference in histological presentation, disease manifestation and progression, as well as mortality rate in patients with biopsy confirmed ANCA associated glomerulonephritis (AAGN). Method This retrospective study was performed at the Royal Brisbane and Women's Hospital, a major tertiary hospital that service a population of 1,030,006 in North Brisbane, Australia. The 2012 Chapel Hill Consensus Conference definitions was used to identify renal predominant ANCA vasculitis. Patients with pauci-immune glomerulonephritis confirmed on kidney biopsy between 1st January 2005 to 1st October 2021 were selected for review. Biopsies were categorised according to Berden's histopathologic classification. Clinical data were collected via medical records. Results Of 80 cases of AAGN identified during the study period, 53 cases were MPO/pANCA positive and 21 cases were PR3/cANCA positive, there were 5 ANCA negative cases and one indeterminate case due to unavailable serology results. There was no statistical significant difference between gender and ANCA subtype (Male MPO 53% and Male PR3 48%, p=0.57). Lung involvement was the most common extra-renal manifestation of AAGN. Similar rates were found between MPO and PR3 positive diseases, 30% (16/53) and 29% (6/21), respectively. PR3 AAGN were much more likely to have sinus involvement, 14% (3/21) vs 4% (2/53) (Relative Risk 3.8, p=0.13). Berden classification was used to classify renal biopsy results (Table 1). There were more cases of sclerotic AAGN within the MPO group whereas crescentic AAGN cases were more common in the PR3 group (Fisher Exact test, p=0.43) Estimated Glomerular Filtration Rate (eGFR) were measured at time of AAGN diagnosis compared to at 3 years. In the MPO group, 45% cases had recovery of eGFR by at least 5mls/min, compared to 62% in PR3 group (P = .30). In addition, 91% (40/44) had improvement of MPO titre following induction treatment, compared to 83% (15/18) in PR3 group had improvement in their titre (p=0.40). Eighteen percent (14/80) of AAGN cases died during the study period. The crude mortality rate for MPO, PR3 and ANCA negative cases were 21% (11/53), 10% (2/21) and 20% (1/5) respectively (p=0.33). Conclusion In our cohort, MPO AAGN was more prevalent (RR 2.5), more likely to have sclerotic class on biopsy (i.e. typically carries the worst prognosis), less likely to have eGFR recovery following treatment and had a higher mortality rate. This is despite the MPO group having a higher titre response rate. Both MPO and PR3 are associated with lung involvement but sinus involvement was significantly more common in PR3 disease. ANCA negative pauci-immune GN remains an uncommon, recognised subtype. Allowing for rarity of disease, larger longitudinal cohort studies are desirable to further define the disease characteristics between AAGN subtypes.

Long‐term survival, causes of death, and prognostic factors for mortality in patients with microscopic polyangiitis and those with anti‐neutrophil cytoplasmic antibody‐positive interstitial lung disease: A single‐center retrospective study

To elucidate the clinical features, long-term survival, and prognostic factors for mortality among patients with microscopic polyangiitis (MPA), including those with anti-neutrophil cytoplasmic antibody-positive interstitial lung disease (ILD) (ANCA-ILD), which could be a subset of its variant phenotype. We retrospectively included 76 consecutive patients between 2006 and 2014, diagnosed with MPA according to the European Medicines Agency algorithm using the Chapel Hill Consensus Conference definitions or ANCA-ILD. ILD was classified as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia pattern using chest computed tomography. The mean (standard deviation) age of the patients (female, 68%) was 69 (12) years. The median (interquartile range) follow-up period was 68 (33-95) months. Comorbid ILD and glomerulonephritis were observed in 44 (58%) (68% UIP) and 54 (71%) patients, respectively. Comorbid ILD was associated with low survival (P=.0563). There were 17 (39%) and 5 (16%) deaths in the ILD and non-ILD groups, respectively (P=.0404). In the ILD group, 6 and 5 of the deaths were attributed to infection and ILD progression, respectively. In the non-ILD group, 1 and 2 patients expired from subsequently developed ILD and aspiration pneumonia, respectively. Age ≥ 70 years (hazard ratio=2.78; 95% confidential interval 1.15-6.70) and UIP (3.95; 1.60-9.77) were independent risk factors for mortality. Age ≥ 70 years and ILD with a UIP pattern were associated with high mortality, owing to susceptibility to infection and ILD progression. A more effective and less toxic treatment is required for progressive ILD.

The Reclassification of Patients With Previously Diagnosed Eosinophilic Granulomatosis With Polyangiitis Based on the 2022 ACR/EULAR Criteria for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

The American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) have proposed the 2022 classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). This study applied the 2022 ACR/EULAR criteria to Korean patients with previously diagnosed EGPA to investigate the concordance rate between the 2022 ACR/EULAR criteria and the old criteria for EGPA. In total, 51 patients with EGPA who met the 1990 ACR criteria, the 2007 European Medicines Agency algorithm, and the 2012 Chapel Hill Consensus Conference definitions were reclassified based on the 2022 ACR/EULAR criteria. Of 51 patients, 44 (86.3%) were reclassified as having EGPA according to the 2022 ACR/EULAR criteria. Among the 7 patients who failed to meet the 2022 ACR/EULAR criteria, 3 patients were reclassified as having microscopic polyangiitis (MPA) and 1 was reclassified as having granulomatosis with polyangiitis (GPA) based on the 2022 ACR/EULAR criteria; as well, 3 patients were reclassified as having unclassifiable vasculitis. Moreover, 6 patients who met the 2022 ACR/EULAR criteria for EGPA simultaneously met the criteria for MPA based on the 2022 ACR/EULAR criteria for MPA, and 1 who met the criteria for EGPA simultaneously met the criteria for GPA based on the 2022 ACR/EULAR criteria for GPA. The concordance rate between the 2022 ACR/EULAR criteria for EGPA and the old criteria was 86.3%. The most important factor in the failure to reclassify patients as having EGPA was the exclusion of nonfixed pulmonary infiltrates in the 1990 ACR criteria for EGPA. We cautiously suggest reconsidering nonfixed pulmonary infiltrates in cases reclassified as unclassifiable vasculitis. Further, additional classification strategies are needed for patients who simultaneously satisfy both antineutrophil cytoplasmic antibody-associated vasculitis subtypes.

Prevalence of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Spatial Association With Quarries in a Region of Northeastern France: A Capture-Recapture and Geospatial Analysis.

Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs. Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture-recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region. Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture-recapture analysis was 6.4 (95% confidence interval [95% CI] 3.6-11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3-93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3-34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7-35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 [95% CI 1.66-3.80]), and geographic-weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed. In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease.

Performance of the 2017 American College of Rheumatology/European League Against Rheumatism Provisional Classification Criteria for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Peruvian Tertiary Care Center.

To validate the new classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis in a real-life Peruvian cohort of antineutrophil cytoplasmic antibody-associated vasculitis patients. We reviewed medical records from a Peruvian tertiary care center from January 1990 to December 2019. Antineutrophil cytoplasmic antibody-associated vasculitis was diagnosed based on the 1990 American College of Rheumatology (ACR) criteria, the 2012 Chapel Hill Consensus Conference definitions, the European Medicines Agency (EMEA) algorithm, and the clinical acumen of the treating rheumatologists. We classified all patients using the "former criteria" (the 1990 ACR criteria for granulomatosis with polyangiitis [GPA] and eosinophilic GPA [EGPA] and the 1994 Chapel Hill Consensus Conference definition for microscopic polyangiitis [MPA]), the EMEA algorithm, and the "new criteria" (the 2017 ACR/European League Against Rheumatism Provisional Criteria). The level of agreement (using Cohen κ) was calculated using the clinical diagnosis as the criterion standard. We identified 212 patients, 12 of whom were excluded. One hundred fifty-four (77%) had MPA, 41 (20.5%) GPA, and 5 (2.5%) EGPA. The new criteria performed well for MPA (κ = 0.713) and EGPA (κ = 0.659), whereas the EMEA algorithm performed well for GPA (κ = 0.938). In the overall population, the new criteria showed better agreement (κ = 0.653) than the EMEA algorithm (κ = 0.506) and the former criteria (κ = 0.305). The 2017 ACR/European League Against Rheumatism Provisional Criteria showed better agreement for the clinical diagnosis of all the patients overall and had the best performance for MPA and EGPA. The EMEA algorithm had the best performance for GPA.

Use of new diagnostic criteria for reclassification of polyarteritis nodosa

With the recognition of antineutrophil cytoplasmic antibodies (ANCA)-related vasculitis and widespread vaccination against viral hepatitis B, the prevalence of polyarteritis nodosa (PAN) varied considerably. In our study, patients diagnosed as polyarteritis nodasa (PAN)based on the 1990 American College of Rheumatology(ACR) criteria were reclassified using 2007 European Medicines Agency(EMA) algorithm modified by 2012 Chapel Hill Consensus Conference(CHCC) definitions, aiming to evaluate the new classification criteria for the diagnosis of PAN. A total of 113 PAN patients admitted to Peking Union Medical College Hospital from January 2002 to December 2018 were retrospectively analyzed, who were classified into three subtypes including 9 patients with cutaneous, 80 with classic and 24 Hepatitis B virus (HBV) associated PAN. All patients were reclassified according to 2007 EMA algorithm using CHCC 2012 definitions. As a result, 7 patients were diagnosed as microscopic polyangiitis(MPA) and 19 patients with unclassified vasculitis based on the new classification criteria. The diagnostic rate of PAN was gradually declined as the classification criteria of vasculitides was update. However, there are quite a few PAN patients in China, whom rheumatologists should pay attention to the early diagnosis and treatment.

P0450END-STAGE RENAL DISEASE PREDICTION IN ANCA-ASSOCIATED GLOMERULONEPHRITIS AT BASELINE: UTILITY OF DIFFERENT APPROACHES IN CLINICAL PRACTICE

Abstract Background and Aims Despite significant progress in treatment of ANCA-associated vasculitis (AAV), at least 20% of patients with renal involvement develop end-stage renal disease (ESRD). Histopathologic classification by Berden et al, which addresses only glomerular pathology, has been used to predict renal outcome in ANCA-assoicted glomerulonephritis (ANCA-GN) since 2010.1 In 2018 Brix et al proposed ANCA renal risk score (ARRS), which combines assessment of morphological (percentage of normal glomeruli, tubular atrophy and interstitial fibrosis) and clinical parameters (estimated glomerular filtration rate) to predict probability of ESRD.2 The aim of our study was to compare clinical utility of these two methods. Methods In our retrospective study we enrolled 57 patients with ANCA-associated vasculitis, diagnosed according to Chapel Hill Consensus Conference (2012) definition and/or American College of Rheumatology (1990) criteria, with histologically proven renal involvement. There were 14 (24.6%) males and 43 (75.4%) females, median age at AAV onset was 48 (33; 57) years. Fifty-one (89.5%) patients were ANCA-positive. Eight (14.0%) patients were diagnosed with renal-limited AAV. Median Birmingham vasculitis activity score (BVAS v.3) at onset was 16 (13; 19). In each case ANCA-GN class was established according to Berden classification: focal (>50% normal glomeruli); crescentic (>50% cellular crescents); mixed (<50% normal, <50% crescentic, and <50% globally sclerotic glomeruli) or sclerotic (>50% globally sclerotic glomeruli). ARRS at onset was also retrospectively assessed and all patients were divided into three groups depending on the risk of ESRD: low risk (0 points), intermediate risk (2 to 7 points), or high risk (8 to 11 points). Thirteen patients (22.8%) developed ESRD after a median of 12 (6.5; 28) months. Renal survival rates were assessed by Kaplan-Meier method and compared by log-rank test. Results Among the 57 patients seven (12.3%) had focal, 10 (17.5%) – crescentic, 24 (43.2%) – mixed, and 16 (28.1%) – sclerotic ANCA-GN class according to Berden et al classification. 1- and 3-year renal survival rates were the highest (100% and 100% respectively) in focal, and the lowest in sclerotic class (67% and 50.2% respectively). 1- and 3- year renal survival was similar in crescentic (80% and 80% respectively) and mixed (80.6% and 80.6% respectively) classes (Fig. 1A). The differences were not statistically significant (Log-rank (Mantel-Cox) p = 0.17). Then we retrospectively re-evaluated all cases according to ARSS: 12 cases were classified as low-risk, 27 – as medium risk, 18 – as high risk. One-year and three-year survival rates were 100% and 100% in low-risk group, 86.1% and 74.2% in medium risk group, 50.6% and 50.6% in high risk group (Figure 1B). The differences were statistically significant (Log-rank (Mantel-Cox) p=0.003). Conclusion In our limited group of patients ANCA renal risk score classification provided better and more clear stratification of patients in terms of ESRD prediction than Berden classification. ARRS is a simple and valuable tool for assessment of renal survival prognosis which can contribute to personalized approach to the management of AAV.

The complexity of classifying ANCA-associated small-vessel vasculitis in actual clinical practice: data from a multicenter retrospective survey.

The different sets of criteria for diagnosis or classification of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) lead to numerous overlapping and reclassified diagnoses in clinical practice. We designed this study to assess the difficulties in classifying patients with AAV. As a secondary objective, different variables were tested to predict prognosis. We conducted a retrospective chart review in a Western Spain multicentre survey. A total of 115 adult patients diagnosed with AAV from 2002 to 2013 and followed for at least 3years were included. They were classified according to (1) Chapel Hill Consensus Conference (CHCC), (2) European Medicines Agency algorithm and (3) French Vasculitis Study Group/European Vasculitis Society phenotypes. Fifty-three patients (46%) had neither distinctive histopathological data of a single AAV definition nor any surrogate markers for granulomatous inflammation and thus did not fulfill any diagnostic criteria. Ocular, ear, nose, throat, skin, and lung involvement were more frequent with proteinase 3 (PR3) antibodies, whereas peripheral neuropathy was more frequent with myeloperoxidase (MPO) antibodies. When the disease was severe at diagnosis, the HR for mortality was 10.44. When induction treatment was not given in accordance with the guidelines, the HR for mortality was 4.00. For maintenance treatment, the HR was 5.49 for mortality and 2.48 for relapse. AAV classification is difficult because many patients had neither specific clinical data nor distinctive histological features of a single CHCC definition. A structured clinical assessment of patient severity is the best tool to guide the management of AAV.

Anti-Neutrophil Cytoplasmic Antibodies Positivity and Anti-Leukotrienes in Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Monocentric Study on 134 Italian Patients

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with asthma, anti-neutrophil cytoplasmic antibodies (ANCA) positivity, and tissue eosinophilia. Objective: To describe the presenting clinical features, significant biochemical alterations, and also potential pathogenic factors in adult patients diagnosed in our Center over a period of >20 years. Method: A retrospective study of EGPA patients diagnosed from 1994 to 2019 at ASST Grande Ospedale Metropolitano Niguarda Ca’ Granda, Milan (Italy), which was performed according to the 1990 American College of Rheumatology criteria and Chapel Hill Consensus Conference definition. A dataset was compiled, registering demographic and clinical features, biochemical analysis at onset, and also the therapies received 3 months prior to EGPA diagnose. Statistical analyses were subsequently conducted dividing patients in 2 groups based on ANCA positivity and comparing them. Results: Two groups were clearly identified by ANCA serology and specific organ involvement in accordance with literature reports; however, our data underline for the first time the association between anti-leukotriene receptor antagonists (LTRAs) and ANCA positivity. The group of previously treated patients presents an OR of 6.42 to be ANCA positive. This finding could be attributed to an imbalanced stimulation of leukotriene receptors, inducing both mast cells activation and an increased neutrophil extracellular traps release from neutrophils. Conclusion: Despite the limitations of this retrospective study, the association between LTRAs and ANCA antibodies elucidates the mechanism by which innate immunity is directly involved in tolerance breakdown and autoantibodies production. Validation of our results with targeted studies could clarify the differences between ANCA-positive and ANCA-negative patients with important consequences on the use of some drug classes in the treatment of EGPA and asthmatic subjects.

Orbital mass in ANCA-associated vasculitides: data on clinical, biological, radiological and histological presentation, therapeutic management, and outcome from 59 patients.

Orbital mass is a rare and sight-threatening manifestation of ANCA-associated vasculitides, which remains a therapeutic challenge. We aimed to describe the presentation, therapeutic management and outcome of ANCA-associated vasculitides-related orbital mass. We conducted a French nationwide retrospective study of patients with orbital mass in the setting of ANCA-associated vasculitides according to ACR criteria and/or Chapel Hill Consensus Conference definitions. Fifty-nine patients [33 women, median age 46 (range 7-90) years] were included. Fifty-six (95%) patients had granulomatosis with polyangiitis, two eosinophilic granulomatosis with polyangiitis and one microscopic polyangiitis. Orbital mass was unilateral in 47 (80%) cases, and seemed to develop from ENT involvement in most cases. Orbital mass biopsy was available in 32 (54%) patients, showing lymphoplasmacytic infiltration in 65%, fibrosis in 55%, granulomas in 48% and vasculitis in 36%. All patients but one received glucocorticoids as first-line therapy associated with immunosuppressive agents in 82%, mainly cyclophosphamide. Response to therapy was noted in 52% of patients treated with cyclophosphamide compared with 91% of those treated with rituximab. Twenty-seven (46%) patients required a second-line therapy because of relapse (59%) or refractory course (41%). Sequelae included visual impairment in 28%, with definitive blindness in 17%. Refractory course was associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis. Orbital mass is associated with refractory course and high frequency of sequelae, especially blindness. Refractory course is associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis.

Relationship between serologic profile (ANCA type) and clinical features of renal involvement in ANCA-associated vasculitides.

To compare the frequency, clinical features and outcomes of renal involvement in ANCA-associated vasculitides (AAV) in patients with antibodies against proteinase-3 (pr3-ANCA) and myeloperoxidase (MPO-ANCA). In our retrospective study we enrolled 264 patients, 94 males and 170 females, median age 53 [36; 62] years. Among them 157 were pr3-ANCA positive and 107 were MPO-ANCA positive. AAV was diagnosed according to ACR criteria and Chapel Hill consensus conference definition (2012). Median follow up was 44 [18; 93] months. We assessed baseline BVAS and VDI by the end of the follow up. Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and daily proteinuria were estimated. Diagnosis and stage of chronic kidney disease (CKD) and acute kidney injury (AKI) were established according to KDIGO guidelines (2012) and Scientific Society of Russian Nephrologists (2016). Renal involvement was present in 181 (68.6%) patients, and its frequency was similar in pr3-ANCA and MPO-ANCA subgroups. Patients with MPO-ANCA developed rapidly progressive glomerulonephritis and hypertension significantly more often than patients with pr3-ANCA: 50.7% vs 35.6% (p=0.049) and 46.1% vs 29.8% (p=0.029) respectively. At disease onset, median sCr was significantly higher and eGFR was significantly lower in patients with MPO-ANCA (p<0.05). 1-year and 5-year renal survival rates were similar in pr3-ANCA-positive (93.9% and 87.4% respectively) and MPO-ANCA positive patients (87.4% and 83.1% respectively). Median BVAS and VDI scores were significantly higher in pr3-ANCA subgroup. The number of patients who developed AAV relapse during 1-year follow up was also significantly higher in pr3-ANCA subgroup. The frequency of eye and ENT involvement was significantly higher in pr3-ANCA positive patients than in MPO-ANCA-positive patients. The frequency of extrarenal manifestations, clinical features of renal involvement and relapse rate are associated with AAV serotype.

Clinical features of kidney involvement in microscopic microscopic polyangiitis.

To evaluate clinical features and outcomes of renal involvement in patients with microscopic polyangiitis (MPA). We enrolled 99 patients with MPA, diagnosed in accordance with the algorithm of the European Medicines Evaluation Agency (EMEA) and the Chapel Hill consensus conference definition (2012). Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and proteinuria were estimated. Frequency of rapidly progressive renal failure (a twofold increase in the sCr level in ≤3 months) was regarded as the clinical equivalent of rapidly progressive glomerulonephritis (RPGN). Renal involvement was present in 92 (92.9%) patients. RPGN developed in 51 (55,4%) patients. The most common features of kidney involvement were hematuria and subnephrotic proteinuria. Arterial hypertension was revealed in 32 (34.7%) patients and was associated with RPGN (p<0.004). End-stage renal disease (ESRD) developed in 11 (11.9%) patients. Despite effective induction therapy disease relapses occurred in 20 (21.1%) patients during the 1st year, including renal relapses in 12 (13.3%) cases. During 5-year follow up 34 (37.1%) patients developed disease relapses, including renal relapses in 22 (24.4%) patients. Renal involvement is one of the most common manifestations of MPA with a high frequency of RPGN. More than one third of patients develop disease relapses despite adequate therapy.

Evolving concepts in classification of systemic vasculitis: where are we and what is the way forward?

The classification of the systemic vasculitides has been controversial for several decades. The Chapel Hill consensus Conference definitions originally developed in 1994, but revised and extended in 2012 are now widely accepted. The American College of Rheumatology (ACR) criteria were first published in 1990, are now generally accepted to be out of date and new criteria are needed. More recently the classical division of the ANCA vasculitides using clinical phenotype has come under scrutiny with evidence from epidemiological, genetic and outcome studies that perhaps these conditions should be classified on the basis of ANCA specificity into PR3-ANCA positive and MPO-ANCA positive groups. The traditional distinction between giant cell arteritis and Takayasu arteritis has been questioned and some recent studies of GCA have included patients with only extra-cranial disease. The Diagnostic and Classification Criteria of Vasculitis study (DCVAS) will provide new validated classification criteria for the systemic vasculitides.

Maintenance of Remission in antineutrophil cytoplasm antibody-associated vasculitides.

The classification of the systemic vasculitides has been controversial for several decades. The Chapel Hill consensus Conference definitions originally developed in 1994, but revised and extended in 2012 are now widely accepted. The American College of Rheumatology (ACR) criteria were first published in 1990, are now generally accepted to be out of date and new criteria are needed. More recently the classical division of the ANCA vasculitides using clinical phenotype has come under scrutiny with evidence from epidemiological, genetic and outcome studies that perhaps these conditions should be classified on the basis of ANCA specificity into PR3-ANCA positive and MPO-ANCA positive groups. The traditional distinction between giant cell arteritis and Takayasu arteritis has been questioned and some recent studies of GCA have included patients with only extra-cranial disease. The Diagnostic and Classification Criteria of Vasculitis study (DCVAS) will provide new validated classification criteria for the systemic vasculitides.

Determinants of renal and patient outcomes in a Spanish cohort of patients with ANCA-associated vasculitis and renal involvement.

The classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. The main objective of this study was to define the respective values of ANCA serotype-based classification, clinicopathological classification, and histopathological classification in predicting patient and renal outcomes in a Spanish cohort of patients with ANCA with specificity for myeloperoxidase, MPO-ANCA, versus ANCA with specificity for proteinase 3, PR3-ANCA. Two hundred and forty-five patients with ANCA-AAV and biopsy-proven renal involvement diagnosed between 2000 and 2104 were recruited in 12 nephrology services. Clinical and histologic data, renal outcomes, and mortality were analyzed. We applied the Chapel Hill Consensus Conference definition with categories for granulomatosis with the polyangiitis (GPA) and microscopic polyangiitis (MPA), the classification based on ANCA specificity, and the histopathological classification proposed in 2010. Eighty-two percent were MPO-ANCA positive and 18.0% PR3-ANCA positive. Altogether, 82.9% had MPA and 17.1% GPA. The median follow-up was 43.2months (0.1-169.3). Neither ANCA-based serological nor clinical classification was predictive of renal outcomes or patient survival on bivariate or multivariate Cox regression analysis. Histopathological classification was found to predict development of end-stage renal disease (p = 0.005) in Kaplan-Meier analysis. ANCA specificity was more predictive of relapse than clinicopathological classification in multivariate analysis (HR 2.086; 95% CI 1.046-4.158; p = 0.037). In our Spanish cohort, a majority of patients had an MPO-ANCA-AAV. A classification based on ANCA specificity has a higher predictive value for relapse occurrence and could be used for decision-making with respect to induction treatment and maintenance therapies.

Eosinophilic granulomatosis with polyangiitis in childhood: retrospective experience from a tertiary referral centre in the UK.

To describe the presenting clinical features, treatment and outcome in children with eosinophilic granulomatosis with polyangiitis (EGPA) and to define factors that predicted mortality. A retrospective case notes review of patients fulfilling the Chapel Hill Consensus Conference definition and/or ACR criteria for EGPA seen at Great Ormond Street Hospital, London. Demographics, clinical features, histopathology, treatment and outcomes were recorded. Descriptive statistics were expressed as median and range. Fisher's exact test was used for group comparisons. The Paediatric Vasculitis Activity Score and Paediatric Vasculitis Damage Index (PVDI) were calculated. Thirteen children (38% female) aged at diagnosis 14.1 (4-15.6) years were identified. The median time to diagnosis was 2 (0-7.3) years. History of asthma was documented in 76%. The most common presenting features were pulmonary (69%), skin (61%), gastrointestinal (46%), cardiac involvement (46%), paranasal sinus abnormality (38%), arthritis/arthralgia (38%) and neurological involvement (15%). Paediatric Vasculitis Activity Score at presentation was 8/63 (2-25/63); ANCA was negative in all 10/13 patients tested. Treatment included corticosteroids in all, combined with CYC in 38% or AZA in 23%. PVDI at 12 (3-48) months follow-up was 3/72 (0-13/72). Relapses were recorded in 46%. Mortality was 15%; cardiomyopathy and PVDI scores ⩾5 significantly associated with mortality risk (P = 0.012). EGPA in the paediatric population is a rare and potentially life-threatening vasculitis. Increased awareness is essential to secure a timely diagnosis and to promptly initiate treatment since our data emphasize a high mortality, particularly in those with cardiac involvement and significant accrued damage.

THU0216 Subglottic stenosis and tracheobronchitis in granulomatosis with polyangiitis (GPA, wegener’s) are associated with a high burden of disease and damage

BackgroundLocalized disease manifestations including inflammatory subglottic stenosis in GPA have been associated with a refractory disease course in case series and small cohorts [1, 2].ObjectivesTo identify and characterize GPA patients...