Chapel Hill Consensus Conference Research Articles

Performance of the 2022 ACR/EULAR Classification Criteria in Comparison With the European Medicines Agency Algorithm in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

This study aimed to compare the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria with the European Medicines Agency (EMA) algorithm for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). All consecutive, newly diagnosed patients with AAV according to the 2012 Chapel Hill Consensus Conference who visited Keio University Hospital between March 2012 and May 2022 were retrospectively reviewed. Patients were reclassified according to the EMA algorithm and the 2022 ACR/EULAR criteria, and their clinical characteristics were statistically analyzed. A total of 114 patients with AAV were included in the analyses. Using the EMA algorithm as a reference, reclassification of the patients revealed sensitivity and specificity of the 2022 ACR/EULAR criteria of 100% and 96% for eosinophilic granulomatosis with polyangiitis, 40% and 97% for granulomatosis with polyangiitis (GPA), and 90% and 49% for microscopic polyangiitis (MPA), respectively. Approximately half of patients classified as EMA-GPA or EMA-unclassifiable were reclassified as 2022-MPA; these patients were older, were more disposed to be positive for myeloperoxidase (MPO)-ANCA, and had interstitial lung disease (ILD) more frequently than patients with 2022-GPA or non-2022-MPA. Further, some patients positive for MPO-ANCA with biopsy-proven granulomatous inflammation were also reclassified from EMA-GPA to 2022-MPA. Over the mean observation period of 4.0 years, 16 patients died. Overall survival for each classification group differed significantly from the 2022 ACR/EULAR criteria (P = 0.02), but not with the EMA algorithm (P = 0.21). Among the patients classified as EMA-GPA or EMA-unclassifiable, older patients with MPO-ANCA and ILD tended to be reclassified as 2022-MPA. The 2022 ACR/EULAR criteria were more useful in prognostic prediction than the EMA algorithm.

The Evaluation of Changing the Eponym Churg-Strauss Syndrome Due to the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

Background: Eponyms do not describe any pathogenesis of a disease. So, there is no other way than to memorize the disease or anatomical area. Over the years, new nomenclatures have been suggested for some diseases due to a better understanding of the pathogenesis. In this article, the changes in the use of Churg-Strauss syndrome were investigated. Methods: In the study, a computerized search was performed using the PubMed database. Books and documents, clinical trials, editorials, meta-analyses, reviews, and case reports were included in the study. Data were obtained from the title of the database, and the variations or distribution by year for the nomenclature of the most related studies were evaluated. Results: Overall, 68.3% of the articles included CSS, 25.7% included eosinophilic granulomatous polyangiitis (EGPA), and 6.0% included both nomenclatures. When evaluated in terms of the distribution according to years, it was determined that there was a statistically significant increase in use in terms of EGPA. When evaluated among specific section journals, the highest rate was in Rheumatology (29.4%). The highest rate of using CSS was in the Rheumatology (25.1%) journals, followed by Pulmonary/Respiratory (17%), Cardiovascular (12%), and Allergy/Immunology/Biology (9.8%). The use of EGPA combined with CSS decreased in all the specific journals from 2012 to the present. Conclusions: The findings of the study revealed that the number of articles with the eponym of EGPA showed an increased frequency in contrast to a decreasing frequency for those with CSS during recent years. Today, with the elaboration of the disease pathogenesis and the increase in knowledge, the trend has shifted in this direction.

#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.

E078 Long term outcomes of diffuse alveolar haemorrhage in antineutrophil cytoplasmic antibody-associated vasculitis: a single centre study

Abstract Background/Aims ANCA associated vasculitis (AAV) is a heterogeneous disease with significant mortality and morbidity. Diffuse Alveolar Hemorrhage (DAH) is a life-threatening condition and presents with hemoptysis, cough, breathlessness and respiratory failure. Studies have shown a prevalence of about 25%. This study was designed to assess the clinical features, serology, efficacy of treatment and long term outcomes in DAH patients secondary to AAV. Methods This was an observational study which included adult AAV Patients diagnosed based on Revised International Chapel Hill Consensus Conference classification criteria from January 2016 to August, 2023 after IEC approval. DAH was diagnosed based on clinical symptoms, Imaging (Diffuse alveolar infiltrates), drop in hemoglobin, hypoxia and Bronchoalveolar lavage in cases where feasible. Demographic details, clinical features, laboratory data including ANCA serology, treatment, disease activity, outcomes of patients were assessed prospectively. DAH and Non DAH groups were compared using Kruskal Wallis test for median values. Student t-test for mean values and Chi square for categorical variables were used to test association between two groups with statistical significance of P-Value <0.05. Results 133 AAV patients were included in the study. DAH was seen in 42(31.5%) patients. The mean (± SD) age of patients was 49.4(±18.9) years. Males (52.3%) were marginally higher in number then females (47.6%). Patients presented with a median of 8 weeks after AAV diagnosis. Hemoptysis (61.9%), cough (47.6%) and breathlessness(64.3%) were the presenting complaints. Renal, Sinusitis, Gastrointestinal involvement was seen in 83.3%, 61.9% and 14.2% respectively. Musculoskeletal and Ophthalmic features were seen in 33.3% each. RPRF was seen in 42.8%. c-ANCA, p-ANCA were seen in 73.8%,21.4% while Anti PR3 antibody and Anti MPO antibody were seen in 78.5%, 21.4% patients respectively. Median (IQR) BVAS score at presentation was 20(13-24) compared to 11(7-11) in Non DAH group which was statistically significant (p < 0.001). 10(23.8%) patients required ventilator support. IVIg was given in 3(7.1%), while plasmapheresis was used in 7(16.7%). Induction regimen with Cyclophosphamide was used in 73.8% and Rituximab (RTX) in 8(19%) patients. Maintenance RTX was used in 42.8% and 45.2% patients received Azathioprine. 23.8% patients relapsed and 54.6% patients were in remission. 10(23.8%) required Mechanical Ventilation. No patients were on long term oxygen therapy. 7(16.6%) patients died. Morbidity was seen in 16(38%) including CKD in 8(19%) patients. Median(IQR) duration of follow up was 10(6-24) months. Conclusion DAH is a serious manifestation of AAV and an important Rheumatological emergency. DAH was present in 31.5% with majority patients in remission. Mortality was seen in 16.6% and morbidity in 38% cases. Management with combination of Pulse steroids, Cyclophosphamide /Rituximab and Plasmapheresis is the key to better outcomes. Ventilator support may be necessary in severe cases. Timely diagnosis and aggressive management is the key to survival and prevents morbidity. Disclosure J.R. Yadavalli: None. K. Telang: None. P. Khatri: None. S. Dhuria: None. G. Ekbote: None. R. Gupta: None.

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.

Comparison of clinical and laboratory data of adult patients with cutaneous IgA vasculitis and non-IgA vasculitis.

Immune complex vasculitides may be subdivided into adult IgA small vessel vasculitis (aIgA-SVV; i.e. adult Henoch-Schönlein purpura) and non-IgA-SVV (hypersensitivity vasculitis, etc.). To evaluate the clinical and laboratory parameters of inpatients fulfilling the diagnostic criteria for aIgA-SVV and non-IgA-SVV. Twenty-nine adults aged ≥ 20 years with aIgA-SVV [according to the European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) criteria] and 53 adults with non-IgA-SVV (according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides) were compared with respect to a variety of clinical and laboratory parameters by uni- and multivariable analyses. Compared with patients with aIgA-SVV, the platelet-to-lymphocyte ratio was significantly higher in patients with non-IgA-SVV. Serum C3 levels and mean corpuscular haemoglobin concentration in patients with non-IgA-SVV were significantly lower compared with patients with aIgA-SVV. Proteinuria and haematuria were significantly more common in patients with aIgA SVV, and were significantly correlated with systemic immune-inflammation biomarkers only in patients with aIgA-SVV. In patients with aIgA-SVV, higher lactate dehydrogenase and C-reactive protein were strong independent predictors for the presence of proteinuria and proteinuria. In patients with non-IgA-SVV, female sex was a protective factor for proteinuria, while skin lesions on the upper extremities proved to be a significant independent predictor of haematuria. We detected several clinical and laboratory differences between patients with aIgA-SVV and non-IgA-SVV. Distinct predictors for renal involvement were not observed in either group, indicating that aIgA-SVV and non-IgA-SVV are similar conditions but do not appear to represent the same entity.

Nationwide epidemiological survey of polyarteritis nodosa in Japan in 2020.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that predominantly affects medium-sized arteries. With advances in our understanding of the pathogenesis and classification of vasculitis, PAN and microscopic polyangiitis (MPA), a disease of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), were separated from the group of diseases previously diagnosed as periarteritis nodosa (PN) at the Chapel Hill Consensus Conference (CHCC) in 1994 (1).

Polyarteritis nodosa and Kawasaki syndrome : Vasculitis predominantly of medium size and small vessels

Polyarteritis nodosa (PAN) and Kawasaki syndrome (KS) are rare forms of primary vasculitis with heterogeneous manifestations and courses of the disease. According to the Chapel Hill Consensus Conference 2012 they belong to the vasculitis of medium size vessels. In contrast to microscopic polyangiitis (MPA), PAN and KS do not affect microscopic vessels such as arterioles, venules or capillaries and are not associated with antineutrophil cytoplasmic antibodies (ANCA). The diagnostics are based on the typical constellation of clinical symptoms, on angiographic findings, the exclusion of other differential diagnoses and, in the case of PAN, in the histopathological confirmation. The therapeutic options of KS in childhood and PAN in adults and children, which are dependent on the severity and the prognosis, are presented.

#5010 INCIDENCE AND CLINICAL PRESENTATION OF ANCA ASSOCIATED VASCULITIS AMONGST INDO-ASIAN PATIENTS IN LANCASHIRE, UK

Abstract Background and Aims ANCA associated vasculitis (AAV) is a rare autoimmune condition that is predominately seen in white Caucasian populations [1]. Across the UK, Europe and the USA, the prevalence of AAV is between 4.6 -18.4 per 100,000. Studies have shown significant geographical differences in the presentation and phenotype of AAV. PR3 positivity and granulomatosis with polyangiitis (GPA) is more common in Northern European countries at higher latitudes. In contrast MPO positivity is seen more frequently in Japanese, Chinese and Southern European populations [1]. Comparatively, few studies have looked at the incidence, phenotype and outcomes in ethnic minority patients in particular Indo-Asian populations. Method We completed a retrospective cohort study of patients with AAV from a central referral centre in Lancashire, UK between December 2010 and December 2022. Patients with a diagnosis of AAV according to the Chapel Hill consensus conference and who belonged to the following ethic groups; ‘Indian, British Indian, Pakistani, British Pakistani, Asian or Asian British’, were included. Using data from the 2021 census, available from the Office of National Statistics, denominator populations were obtained [2]. Patients ethnic group were determined by self-reported ethnicity records on hospital e-health records or via GP summary care records. Ethical approval was obtained (IRAS 257174). Results Using 2021 census data, the total population of Lancashire (Fig. 1), aged >18 years old was 1,149,826. Of this population, the majority identified as white (1,059,000) and the second most common ethnic group was Asian / Asian British (74,523). Black/ African/ Caribbean/ Black British made up <1% of the population and mixed / multiple ethnic groups and other ethnic groups made up just over 1%. Eighteen Indo-Asian patients with newly diagnosed AAV were identified. The mean age was 46 ±16.7 yrs, which is younger than our cohort of white patients who had a mean age of 65.1 ± 14.6 yrs. There was an equal gender split, the majority were PR3 positive (n = 12, 67%) and 6 patients had MPO positive AAV. Nine patients had renal involvement, with only 2 having renal limited disease and 1 requiring dialysis at presentation. Over half of the patients (n = 11, 61%) had ENT involvement. The crude incidence of AAV in Indo-Asian patients in Lancashire was 20.1 per million person years (95% CI 10.7, 28.5). This is higher than that reported in other areas of the UK [3]. When compared to age and gender matched white patients, white patients had more renal involvement (89.5% V's 50%, P = 0.01) and more renal limited disease (31.6% V's 11.1% P = 0.13). Pulmonary involvement was similar between the ethnic groups whereas ENT involvement was more prevalent in Indo-Asian patients (61.1% V's 26.3%, P = 0.03). Conclusion Our findings demonstrate that whilst the crude incidence of AAV is lower in Indo-Asian populations compared to white Caucasians, there is a significantly high incidence rate in the Lancashire area, which is greater than in other areas of the UK. Pearce et al. reported an incidence of 10.6 per million person years in Nottingham which was almost half that seen in our cohort [3]. Our Indo-Asian patients were on average younger and had less renal involvement compared to our cohort white patients. This contrasts some studies which report Indo-Asian populations to have more PR3 positivity and higher rates or renal involvement [1]. This may reflect an under diagnosis of extra renal disease and non-renal phenotypes in Indian subcontinent populations. There remains a gap in our understanding as to the genetic role in the pathogenesis and clinical phenotype of AAV disease. Further research is needed to determine if the differences seen between ethnic minorities are due to genetic or environmental factors.

#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.

Clinical significance of microscopic polyangiitis with interstitial lung disease and bronchiectasis: probability of preexisting comorbidities

Background The association between pulmonary involvement and microscopic polyangiitis (MPA) has been increasingly recognized in recent years. Whether interstitial lung disease (ILD) and bronchiectasis (BE) are disease manifestations of MPA, preexisting comorbidities or important complications remains unclear. The purpose of this study was to determine the clinical characteristics and prognosis of MPA with pulmonary involvement to further guide clinical management. Methods The data for 97 patients with a definitive diagnosis of MPA were retrospectively reviewed. The MPA diagnosis was based on the 2012 revised Chapel Hill Consensus Conference (CHCC) criteria. The baseline clinical information and laboratory parameters were collected and analysed at each patient’s initial diagnosis. Results Forty-seven out of the 97 (48.5%) patients who were diagnosed with MPA presented with pulmonary involvement, including 37 patients with ILD, 12 patients with BE and two patients with diffuse alveolar haemorrhage (DAH). ILD and BE antedated MPA in 56.76% and 75.00% of the patients, respectively. Compared with that in the MPA-BE group, the serum LDH level (222.86 ± 68.19 vs. 171.58 ± 31.43, p = .016) in the MPA-ILD group was significantly higher. In the multivariate Cox analysis, elevated serum creatinine (HR 4.08, confidence interval (CI) 1.38–12.05, p = .011) was an independent risk factor for shorter survival in MPA patients with pulmonary involvement, and treatment with glucocorticoid pulse cyclophosphamide therapy (HR 0.095, 95% CI 0.019–0.47, p = .004) was independently associated with prolonged survival. Among the patients in the MPA-ILD group, acute exacerbations of ILD (HR 4.55 CI 1.16–17.86, p = .029) and elevated serum creatinine (HR 4.95, CI 1.39–17.54, p = .014) were independently associated with a poor prognosis, and treatment with glucocorticoids (HR 0.057, 95% CI 0.012–0.28, p < .001) was independently associated with significant prolongation of survival. Conclusions Patients with MPA have a high prevalence of pulmonary involvement, and ILD is the most common subtype of MPA. ILD and BE can be considered preexisting comorbidities of MPA. Elevated serum creatinine was associated with shorter survival. However, remission induction regimens with glucocorticoids and/or immunosuppressants may improve this outcome.

Intimal granulomatous angiitis in sarcoid pulmonary vasculitis: worth remembering.

Intimal granulomatous angiitis is a facet of pulmonary sarcoidosis vasculitis that has almost been forgotten. Its observation may offer new understanding of the various patterns of pulmonary hypertension associated with sarcoidosis. https://bit.ly/3g6Ms76.

Wounds caused by vasculitis-Current classification, diagnostics and treatment

Wounds of the skin can have very different causes. Especially in clinically atypical or non-healing wounds, the very heterogeneous group of vasculitides is of particularly important differential diagnostic significance. Nowadays, the classification of vasculitis is based on the affected vessels according to the Chapel Hill consensus conference. Thus, potentially any part of the vascular system can be affected. It becomes clear that there is often arisk of systemic diseases with high interdisciplinary relevance.Clinically, the usually very painful wounds in cutaneous vasculitis develop from necrosis and are typically surrounded by an erythematous-livid rim in the florid phase. In addition to clinical inspection, the histopathological examination of biopsies is of particular importance in the usually extensive diagnostic work-up.Therapeutically, adequate wound treatment should always be performed with afocus on pain prevention and infection prophylaxis. In the case of edema, compression therapy also supports wound healing. In addition, it is often necessary to initiate systemic treatment with immunosuppressive or immunomodulating drugs. Whenever possible, causally relevant factors and comorbidities should be diagnosed early and avoided or treated. Otherwise, there is arisk of severe or even fatal disease progression.

Biases in large-vessel vasculitis.

Dear Sir, I read the paper from Yamaguchi et al. published in the January 2023 edition of Modern Rheumatology with great interest [1]. I thank them for sharing their observations and insights with the world about the differences between those individuals who appear to have extracranial giant cell arteritis (GCA) and those with just cranial arterial disease. I would like to debate the following points with them. The Chapel Hill Consensus Conference effectively defines large vessels as those that are outside an organ [2]. The superficial temporal artery and the maxillary artery are third-generation branches of the aorta and are defined as large vessels with very clear anatomical differentiation of the vessel wall into adventitia, media, and intima. For that reason, it would be inaccurate to name the two groups of their analysis as those involving large vessels and those not involving, since the cranial arteries are also large vessels. I propose the use of anatomically more accurate terms for their groups—cranial verus extracranial OR carotid system versus those with additional aortic and/or subclavian system disease.

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.

Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis

Results of randomized clinical trials have demonstrated rituximab's noninferiority to cyclophosphamide as induction therapy for antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), with neither treatment having a specific advantage for granulomatosis with polyangiitis (GPA). However, post hoc analysis results have suggested that rituximab might be more effective than cyclophosphamide in inducing remission in patients with proteinase 3-positive AAV. To compare the effectiveness of rituximab and cyclophosphamide in inducing GPA remission in a large population of unselected patients. This comparative effectiveness study used multicenter target trial emulation observational data from 32 French hospitals in the French Vasculitis Study Group Registry. Groups were determined according to treatments received, without any intervention from the investigators. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Participants included patients with newly diagnosed or relapsing GPA who satisfied American College of Rheumatology classification criteria and/or Chapel Hill Consensus Conference nomenclature. Data were analyzed from October 1, 2021, to May 31, 2022. At least 1 infusion of rituximab or cyclophosphamide for induction therapy between April 1, 2008, and April 1, 2018. The primary outcome was remission rate at month 6 (±2 months), with remission defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and prednisone dose of 10 mg/d or less. The BVAS is a validated tool for small-vessel vasculitis and used to assess the level of disease activity, with a numerical weight attached to each involved organ system. The BVAS has a range of 0 to 63 points; a score of 0 indicates no disease activity. Subgroup analyses included the primary outcome for patients with a new diagnosis, for most recently treated patients, and for patients with myeloperoxidase-ANCA positivity. Among 194 patients with GPA included in the analysis (mean [SD] age, 54 [15] years; 110 men [56.7%]), 165 (85.1%) had a new diagnosis, and 147 of 182 with data available (80.8%) had proteinase 3-ANCA positivity. Sixty-one patients received rituximab and 133 received cyclophosphamide for induction therapy. In the weighted analysis, the primary outcome was reached for 73.1% of patients receiving rituximab vs 40.1% receiving cyclophosphamide (relative risk [RR], 1.82 [95% CI, 1.22-2.73]; risk difference, 33.0% [95% CI, 12.2%-53.8%]; E value for RR, 3.05). Similar results were observed in the subgroup of patients with newly diagnosed GPA and those with a more recent treatment. In the subset of 27 patients with myeloperoxidase-ANCA-positive GPA, 8 of 10 rituximab recipients and 8 of 17 cyclophosphamide recipients met the primary end point (unweighted RR, 1.73 [95% CI, 0.96-3.11]). In this comparativeness effectiveness study using clinical data, rituximab induction therapy for GPA was more frequently associated with remission than cyclophosphamide. These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.

Analysis of treatment outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis on rituximab therapy.

This study aimed to analyze a group of patients with severe and refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) managed with rituximab and to report on treatment outcomes. A total of 78 patients (41 females, 37 males; mean age: 50.1±13.4 years; range, 18 to 76 years) with AAV on rituximab treatment were included in the single-center, retrospective study conducted between 2009 and 2018. The diagnosis was established based on the 1990 classification criteria of the American College of Rheumatology and the definitions of vasculitis of Chapel Hill Consensus Conference. Laboratory and immunological tests were conducted. Disease activity was determined through the Birmingham Vasculitis Activity Score. Rituximab was preferred over cyclophosphamide in 37 patients and used as a second-line therapy after cyclophosphamide in 41 cases. Rituximab treatment showed favorable outcomes with regard to serum creatinine levels, proteinuria, and hematuria, as well as in cases of isolated lung involvement. Nearly half of patients with pulmonary renal syndrome also improved, with 22.2% achieving remission. ANCAs were positive in 85.9% of patients at the onset of rituximab treatment and became negative in 82% of the positive cases. Adverse events were rare and included infusion reactions (one case of reactivation of a herpes zoster infection and one case of allergic reaction). Rituximab is an efficient and safe therapeutic option in patients with AAV who are difficult to treat, have insufficient response, or have not tolerated other treatments.

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITHOUT ANY PERIPHERAL EOSINOPHILIA

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITHOUT ANY PERIPHERAL EOSINOPHILIA

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.