The role of tobacco smoking in anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic review.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV. METHODS: Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases. RESULTS: The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients. CONCLUSIONS: Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.

Co-existence of ANCA-associated vasculitides with immune-mediated diseases: a single-center observational study.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) is a group of systemic necrotizing small vessel autoimmune diseases, with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) being the two most common. The co-existence of AAV with different immune-mediated diseases (autoimmune disesases - AID) might affect the clinical presentation of the primary disease. The purpose of the study was to assess the co-existence of AAV with AID and to investigate whether it affects the characteristics and the course of AAV. METHODS: A retrospective single-center study was performed to identify patients with a diagnosis of MPA or GPA and concomitant AID, and to investigate their clinical features and characteristics. The group consisted of consecutive unselected AAV patients treated at a large university-based hospital, since 1988 with follow-up until 2022. RESULTS: Among 284 patients diagnosed either with GPA (232) or MPA (52), 40 (14,1%) had co-existing AIDs. The most frequent were: Hashimoto thyroiditis (16 cases), rheumatoid arthritis (8 cases), followed by psoriasis (6 cases), pernicious anemia (3 cases), and alopecia (3 cases). Patients with autoimmune comorbidities had a significantly longer time between the onset of symptoms and the diagnosis (26 vs. 11 months, p < 0.001). Laryngeal involvement (20.0% vs. 9.0%, p = 0,05), peripheral nervous system disorders (35.0% vs. 13.9%, p < 0.001), and neoplasms (20.0% vs. 8.6%, p = 0,044) were more common in patients with AID comorbidities, compared to subjects without AID. In contrast, renal involvement (45.0% vs. 70.9%, p = 0.001) and nodular lung lesions (27.5% vs. 47.5%, p = 0.044) were significantly less frequent in patients with co-morbidities. Following EUVAS criteria, patients with autoimmune co-morbidities had a generalized form of the disease without organ involvement (52.5% vs. 27.2%, p = 0.007), while the others had a higher percentage of generalized form with organ involvement (38.3% vs. 20.0%, p = 0.007). CONCLUSIONS: The coexistence of AAV with different autoimmune diseases is not common, but it might affect the clinical course of the disease. Polyautoimmunity prolonged the time to diagnosis, but the AAV course seemed to be milder. Particular attention should be paid to the increased risk of cancer in these patients. It also seems reasonable that AAV patients should receive a serological screening to exclude the development of overlapping diseases.

Neuro-ophthalmic challenges and multi-morbidity in vasculitis among the older adults.

INTRODUCTION: Vasculitides are a heterogeneous group of disorders producing inflammation of blood vessels (e.g. arteries or veins). All major vasculitides potentially have ophthalmological symptoms and signs including visual loss. Co-morbidity, multimorbidity, polypharmacy, and geriatric syndromes all play important roles in patient outcomes for these rheumatic conditions in the elderly. This monograph reviews the NCBI PubMed database (Feb 2023) literature on the neuro-ophthalmic and geriatric considerations in vasculitis. AREAS COVERED: Cogan Syndrome, Granulomatosis with Polyangiitis, Giant Cell Arteritis, Polyarteritis Nodosa, Takayasu Arteritis, Vasculitis epidemiology, and neuro-ophthalmological symptoms. EXPERT OPINION: Geriatric patient care for vasculitis with neuro-ophthalmological manifestations can be complicated by the interplay of multiple co-morbidities, polypharmacy, and specific geriatric syndromes. The valuation and treatment of vasculitis and the complications associated with the disease can negatively impact patient care. Advances in noninvasive imaging and updates in diagnostic criteria have enabled increased identification of patients at earlier stages with less severe disease burden. Novel therapeutic agents can be glucocorticoid sparing and might reduce the adverse effects of chronic steroid use. Holistic care models like the 5 M geriatric care model (mind, mobility, medications, multicomplexity, and matters most) allow patients' needs to be in the forefront with biopsychosocial aspects of a patient being addressed.

The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 266 AAV patients.

OBJECTIVES: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry. METHODS: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019. RESULTS: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%). CONCLUSIONS: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.

Epidemiology and treatment outcome of ANCA-associated vasculitis in South Korea: a nationwide, population-based cohort study.

OBJECTIVES: To investigate the epidemiological features of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in South Korea. METHODS: We identified the index cases of GPA and MPA using the 2010-2018 Korean National Health Insurance Service database and the Rare Intractable Disease registry for the entire Korean population. Each disease's incidence and prevalence rates and trends over time were analysed. To assess the impact of disease on morbidity and mortality, a comparator group comprising the general population was established using nearest-neighbour matching by age, sex, income, and comorbidity index, at a 5:1 ratio. Morbidity outcomes included the initiation of renal replacement therapy and admission to the intensive care unit. RESULTS: We identified 546 and 795 patients with GPA and MPA, respectively. The incidence rates of both diseases increased with age, with peak incidence rates observed among patients aged ≥70 years. The incidence of MPA increased continuously over time, whereas that of GPA showed no significant changes. During the observation period, 132 (28.7%) and 277 (41.1%) patients in the GPA and MPA groups, respectively, died, which were significantly higher than that in the general population (standardised mortality ratio: 3.53 and 5.58, respectively) and comparator group (hazard ratio: 4.02 and 5.64, respectively). Higher mortality and morbidity rates were observed among patients with MPA than among those with GPA. CONCLUSIONS: In South Korea, the incidence of MPA has increased over time. Although both GPA and MPA had high rates of mortality and morbidity, MPA has a poorer prognosis than GPA.

Data quality and patient characteristics in European ANCA-associated vasculitis registries: data retrieval by federated querying.

OBJECTIVES: This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS: Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS: A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS: In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.

Childhood-Onset ANCA- Associated Vasculitis: single center experience from Central California.

BACKGROUND: Childhood-onset ANCA-associated vasculitides (AAV) are characterized by necrotizing inflammation and include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pediatric data is scare and there have been no prior studies examining the characteristics of pediatric AAV in Central California. METHODS: This retrospective study comprised AAV patients ≤18 years of age, diagnosed between 2010 and 2021, in Central California. We analyzed initial presentation including demographics, clinical, laboratory characteristics, treatment, and initial outcomes. RESULTS: Of 21 patients with AAV, 12 were categorized as MPA and 9 with GPA. Median age at diagnosis was 13.7 years in MPA cohort and 14 years in GPA. MPA cohort were majority females (92% versus 44%). 57% of the cohort were racial/ethnic minority including Hispanics (n = 9), Asians (n = 2), multiracial (n = 1) and 43% were white (n = 9). MPA patients were more frequently Hispanic (67%), meanwhile GPA patients were frequently white (78%). Median duration of symptoms prior to diagnosis was 14 days in MPA cohort and 21 days in GPA cohort. Renal involvement was frequent (100% in MPA and 78% in GPA). GPA cohort had frequent ear, nose and throat (ENT) involvement (89%). All patients were ANCA positive. All Hispanic patients were MPO positive, meanwhile 89% of white patients were PR3 positive. MPA cohort tended towards more severe disease with 67% requiring ICU admission and 50% requiring dialysis. Two deaths were reported in MPA cohort, related to Aspergillus pneumonia and pulmonary hemorrhage. In MPA cohort, 42% received cyclophosphamide in combination with steroids and 42% received rituximab in combination with steroids. GPA patients received cyclophosphamide, either with steroids alone (78%) or in combination with steroids and rituximab (22%). CONCLUSIONS: Microscopic polyangiitis was the most frequent AAV subtype with female preponderance, shorter duration of symptoms at onset and higher proportion of racial/ ethnic minority patients. Hispanic children demonstrated frequent MPO positivity. Trends towards higher rates of ICU requirement and need for dialysis upon initial presentation was noted in MPA. Patients with MPA received rituximab more frequently. Future prospective studies are needed to understand differences in presentation and outcomes in childhood onset AAV between diverse racial-ethnic groups.

The Association Between Age at Diagnosis and Disease Characteristics and Damage in Patients With ANCA-Associated Vasculitis.

OBJECTIVE: This study examined the relationship between age at diagnosis and disease characteristics and damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Analysis of a prospective longitudinal cohort of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA) in the Vasculitis Clinical Research Consortium (2013-2021). Disease cohorts were divided by age at diagnosis (years): children (<18), young adults (18-40), middle-aged adults (41-65), and older adults (>65). Data included demographics, ANCA type, clinical characteristics, Vasculitis Damage Index (VDI) scores, ANCA Vasculitis Index of Damage (AVID) scores, and novel disease-specific and non-disease-specific damage scores built from VDI and AVID items. RESULTS: Analysis included data from 1020 patients with GPA/MPA and 357 with EGPA. Female predominance in GPA/MPA decreased with age at diagnosis. AAV in childhood was more often GPA and proteinase 3-ANCA positive. Children with GPA/MPA experienced more subglottic stenosis and alveolar hemorrhage; children and young adults with EGPA experienced more alveolar hemorrhage, need for intubation, and gastrointestinal involvement. Older adults (GPA/MPA) had more neurologic manifestations. After adjusting for disease duration, medications, tobacco, and ANCA, all damage scores increased with age at diagnosis for GPA/MPA (P < 0.001) except the disease-specific damage score, which did not differ (P = 0.44). For EGPA, VDI scores increased with age at diagnosis (P < 0.009), whereas all other scores were not significantly different. CONCLUSION: Age at diagnosis is associated with clinical characteristics in AAV. Although VDI and AVID scores increase with age at diagnosis, this is driven by non-disease-specific damage items.

Common clinical pattern of antineutrophil cytoplasmic antibody -associated vasculitis: An experience from a multicenter study in Saudi Arabia.

OBJECTIVES: To understand the most common type and clinical manifestations of associated vasculitis (AAV) in the Saudi Arabia. METHODS: This retrospective study was conducted at King Fahad Medical City and the Security Forces Hospital Program, Riyadh, Saudi Arabia, between January 2014 and May 2022. Patients aged ≥18 years were included in the study and diagnosed based on clinical manifestations, serology, or histopathology according to the EMA algorithm. Univariate analysis was carried out to compare different groups; a series of independent samples t-tests was applied for continuous data. RESULTS: A total of 53 patients were enrolled: eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). Overall, proteinase-3 was the most prevalent (52.8%), and myeloperoxidase, myeloperoxidase MPO was the least prevalent antineutrophil cytoplasmic antibody (ANCA)-type (18.9%) among patients; other patients showed negative ANCA test results. The clinical manifestations differed significantly between EGPA and GPA groups in pulmonary, neurological, cardiological, and renal signs and symptoms (p<0.05); there was a higher incidence of the former 3 in the EGPA group. Although upper airway was predominant in all groups, there was no statistical difference between both groups. CONCLUSION: This study validated international reports on AAV clinical manifestations in the Saudi population. The GPA was associated with more upper airway and pulmonary signs and symptoms. Further investigation is needed to understand the treatments and quality of life of patients with AAV.

Stable incidence but increase in prevalence of ANCA-associated vasculitis in southern Sweden: a 23-year study.

OBJECTIVE: To update the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in a defined geographical area of southern Sweden. METHODS: The study area comprised 14 municipalities with a combined adult population (≥18 years) of 623 872 in 2019. All cases diagnosed with AAV in 1997-2019 in the study area were included in the estimate of incidence. Diagnosis of AAV was verified by case record review, and cases were classified using the European Medicines Agency algorithm. Point prevalence was estimated on 01 January 2020. RESULTS: Three hundred and seventy-four patients (median age 67.5 years, 47% female) were diagnosed with new-onset AAV during the study period. One hundred and ninety-two were classified as granulomatosis with polyangiitis (GPA), 159 as microscopic polyangiitis (MPA) and 23 as EGPA. The average annual incidence/million adults was 30.1 (95% CI 27.0 to 33.1) for AAV: 15.4 (95% CI 13.3 to 17.6) for GPA, 12.8 (95% CI 10.8 to 14.8) for MPA and 1.8 (95% CI 1.1 to 2.6) for eosinophilic GPA (EGPA). Incidence was stable during the study period, 30.3/million 1997-2003, 30.4/million 2004-2011 and 29.5/million 2012-2019. The incidence increased with age and was highest in age group 70-84 years (96/million adults). On 1 January 2020, the prevalence was 428/million adults and was higher in males than in females (480 vs 378/million). CONCLUSIONS: The incidence of AAV in southern Sweden was found stable over the course of 23 years; while the prevalence has increased, which might indicate better management and treatment of AAV resulting in improved survival.

Score to assess the probability of relapse in granulomatosis with polyangiitis and microscopic polyangiitis.

OBJECTIVE: To develop a score assessing the probability of relapse in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS: Long-term follow-up data from GPA and MPA patients included in five consecutive randomised controlled trials were pooled. Patient characteristics at diagnosis were entered into a competing-risks model, with relapse as the event of interest and death the competing event. Univariate and multivariate analyses were computed to identify variables associated with relapse and build a score, which was then validated in an independent cohort of GPA or MPA patients. RESULTS: Data collected from 427 patients (203 GPA, 224 MPA) at diagnosis were included. Mean±SD follow-up was 80.6±51.3 months; 207 (48.5%) patients experienced ≥1 relapse. Relapse risk was associated with proteinase 3 (PR3) positivity (HR=1.81 (95% CI 1.28 to 2.57); p<0.001), age ≤75 years (HR=1.89 (95% CI 1.15 to 3.13); p=0.012) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² (HR=1.67 (95% CI 1.18 to 2.33); p=0.004) at diagnosis. A score, the French Vasculitis Study Group Relapse Score (FRS), from 0 to 3 points was modelised: 1 point each for PR3-antineutrophil cytoplasmic antibody positivity, eGFR ≥30 mL/min/1.73 m² and age ≤75 years. In the validation cohort of 209 patients, the 5-year relapse risk was 8% for a FRS of 0, 30% for 1, 48% for 2 and 76% for 3. CONCLUSION: The FRS can be used at diagnosis to assess the relapse risk in patients with GPA or MPA. Its value for tailoring the duration of maintenance therapy should be evaluated in future prospective trials.

Eosinophilic granulomatosis with polyangiitis.

This review aims to describe the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophilic granulomatosis with polyangiitis is a small to medium vessel necrotizing vasculitis, typically classified with granulomatosis with polyangiitis (GPA) and microscopic polyangitis (MPA) as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, less than 50% of patients with EGPA have a positive ANCA test. Among all the vasculitides, asthma and eosinophilia are unique features of EGPA. Eosinophilic granulomatosis with polyangiitis is very rare and the diagnosis may be missed as the disease evolves over time. Polyneuropathies are common and may be severe, requiring aggressive immunosuppressive therapy. Heart involvement is the most common cause of death in EGPA. Biopsy of involved tissue supports a clinically suspected diagnosis but is not always feasible. Treatment of EGPA is primarily dictated by the severity of disease and prognostic factors. More severe disease frequently requires the use of aggressive therapy such as cyclophosphamide. Once treatment is initiated, patients can achieve good control of symptoms; unfortunately, disease relapses are common and prolonged treatment with corticosteroids is often necessary for asthma management. A better understanding of the disease heterogeneity is needed for the development of better therapies.

Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.

OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Cancer-associated vasculitides: a single-centre case series.

OBJECTIVES: This study investigated the frequency of cancer-associated vasculitis, the types of associated cancers and vasculitides, and the temporal relationship in Korean patients who were diagnosed with both cancers and vasculitides. METHODS: This study performed a digital search of the clinical data repository using selected diagnostic terms of vasculitides among patients diagnosed with cancers from May 2001 to May 2021. The time gap between the time of diagnosis of 'cancers' and that of 'vasculitides' was limited to 3 years. The types of cancers and vasculitides were reviewed. RESULTS: The mean age of 73 patients with both cancers and vasculitides with a time gap of fewer than 3 years was 53.0 years and 42.5% were men. Of the 215,897 patients with cancers, 73 patients were also diagnosed with vasculitides (0.034%). The most common type of cancer was thyroid cancer (28.8%), followed by lymphoma (13.7%), whereas the most frequent type of vasculitis associated with cancer was Behcet disease (52.1%), followed by granulomatosis with polyangiitis (12.3%). The median time gap between cancer and vasculitis was - 17.0 days. Among vasculitides, Behcet disease was closely associated with various cancers compared to other types. Twenty-one patients exhibited both cancers and vasculitides between 0 and 90 days after the diagnosis of the corresponding cancer. CONCLUSION: The frequency of cancer-associated vasculitis was 0.034% in Korean patients. The types of cancers and vasculitides in cancer-associated vasculitis and the distributions of sex and age may be dependent on ethnic and geographic differences. Key Points • The frequency of cancer-associated vasculitis was 0.034% in Korean patients. • The most common cancer and vasculitis in cancer-associated vasculitis were thyroid cancer and Behcet disease. • The types of cancers and vasculitides in cancer-associated vasculitis seemed to be dependent on ethnic and geographic differences.

COVID-19 course in granulomatosis with polyangiitis: single center experience with review of the literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19) shares some clinical features with new-onset granulomatosis with polyangiitis (GPA) or GPA flare that may lead to a challenge in differential diagnosis. To date, little is known whether GPA can be induced by COVID-19. Herein, we aimed to seek the frequency and mortality rates of COVID-19 in our GPA cohort, and along with the literature cases, to evaluate clinical features and treatments of GPA patients with COVID-19. We also tried to identify clinical features of COVID-19 induced GPA. METHODS: As of July 2021, we conducted a systematic literature review using different spelling combinations of "COVID-19 and GPA" in the PUBMED database. In total, 18 cases were found in the literature, 6 of them had COVID-19 induced GPA. The remaining 12 of literature cases and 6 cases in our GPA cohort (n = 81) had a COVID-19 infection while followed-up with GPA. We grouped these 18 patients as GPA+COVID-19. RESULTS: The frequency of COVID-19 was 7.4% in GPA cohort and mortality rate was 33% in GPA patients with COVID-19. The most common symptoms of GPA+COVID-19 patients were fever, cough, arthralgia/myalgia, and malaise. The most frequent treatments for GPA before the COVID-19 infection were steroids (72%) and rituximab (56%). Three patients who received rituximab also had COVID-19 reinfection. In the literature cases, mortality was observed in 4 (22%) of 18 patients with GPA+COVID-19. The most common symptoms of COVID-19 induced GPA were dyspnea, fever and cough. DISCUSSION: In our GPA cohort, we observed a higher mortality rate compared to global WHO data. In patients followed up with GPA, rituximab treatment may be precarious for both COVID-19 disease and reinfection. Our study also provided some clues about the diagnostic challenge of GPA induced by COVID-19.

Cluster analysis of patients with granulomatosis with polyangiitis (GPA) based on clinical presentation symptoms: a UK population-based cohort study.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is small vessel vasculitis with heterogeneous clinical presentation. In the present population-based cohort study, we classified patients with GPA based on clinical features at presentation using an unsupervised clustering approach and compared their mortality, infections and frequency of comorbidities. METHODS: In this open cohort study, de-identified primary care data of patients with GPA included in the IQVIA Medical Research Data database between 1 January 1995 and 25 September 2019 was analysed retrospectively. Latent class analysis was performed to create symptom clusters of patients based on 16 categories of symptoms representing various organ involvement. All-cause mortality of resultant clusters was compared after adjusting for age, sex, Townsend deprivation quintile and smoking status at index date using extended Cox proportional hazards models. Prescription of antibiotics, considered as an indirect indicator of recurrent bacterial infection, was compared using a recurrent event model, after adjusting for quarterly use of steroid as a time-dependent covariate. Cumulative frequencies of common comorbidities were compared among the clusters at index visit, 1-year and 3-year follow-up. RESULTS: Altogether, 649 patients with GPA [median age 60.0 (IQR: 49.6-70.1)] were included. Three clusters were identified: patients with limited disease mainly with involvement of ENT and cough were classified into cluster 1 (n = 426); cluster 2 had generalised non-renal disease (n = 176); while patients in cluster 3 had renal-predominant disease (n = 47). Many patients in cluster 1 developed generalised disease at the end of 1 year. Mortality in clusters 2 and 3 was higher compared with cluster 1. Mortality in cluster 1 itself was 68% higher than the general population without GPA. The duration of antibiotics prescription and frequency of coexisting medical illnesses was also higher in clusters 2 and 3. CONCLUSIONS: In a primary care setting, patients with GPA can be classified into three distinct clusters with different prognosis, susceptibility to recurrent infections and presence of comorbidities. The tendency of cluster 1 to evolve into a more generalised disease raises questions about current immunosuppressive treatment approaches in these patients.

Hypertrophic pachymeningitis in ANCA-associated vasculitis: a cross-sectional and multi-institutional study in Japan (J-CANVAS).

BACKGROUND: This study investigated the characteristics of hypertrophic pachymeningitis (HP) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), using information from a multicenter study in Japan. METHODS: We analyzed the clinical information of 663 Asian patients with AAV (total AAV), including 558 patients with newly diagnosed AAV and 105 with relapsed AAV. Clinical findings were compared between patients with and without HP. To elucidate the relevant manifestations for HP development, multivariable logistic regression analyses were additionally performed. RESULTS: Of the patients with AAV (mean age, 70.2 ± 13.5 years), HP was noted in 30 (4.52%), including 20 (3.58%) with newly diagnosed AAV and 10 (9.52%) with relapsed AAV. Granulomatosis with polyangiitis (GPA) was classified in 50% of patients with HP. A higher prevalence of GPA was significantly observed in patients with HP than in those without HP in total AAV and newly diagnosed AAV (p < 0.001). In newly diagnosed AAV, serum proteinase 3 (PR3)-ANCA positivity was significantly higher in patients with HP than in those without HP (p = 0.030). Patients with HP significantly had ear, nose, and throat (ENT) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.03-2.14, p = 0.033) and mucous membrane/eye manifestations (OR 5.99, 95% CI 2.59-13.86, p < 0.0001) in total AAV. Moreover, they significantly had conductive hearing loss (OR 11.6, 95% CI 4.51-29.57, p < 0.0001) and sudden visual loss (OR 20.9, 95% CI 5.24-85.03, p < 0.0001). CONCLUSION: GPA was predominantly observed in patients with HP. Furthermore, in newly diagnosed AAV, patients with HP showed significantly higher PR3-ANCA positivity than those without HP. The ear and eye manifestations may be implicated in HP development.

Increased risk of venous thromboembolism in patients with granulomatosis with polyangiitis: A population-based study.

We assessed the risk and time trends of venous thromboembolism (VTE) including pulmonary embolism (PE) and deep venous thrombosis (DVT) in new granulomatosis with polyangiitis (GPA) cases compared to the general population. Using a population-level database from the entire province of British Columbia, Canada, we conducted a matched cohort study of all patients with incident GPA with up to ten age-, sex-, and entry time-matched individuals randomly selected from the general population. We compared incidence rates of VTE, PE, and DVT between the two groups, and calculated hazard ratios (HR), adjusting for relevant confounders. Among 549 individuals with incident GPA (57.6% female, mean age 55.4 years), the incidence rates for VTE, PE, and DVT were 7.22, 2.73, and 6.32 per 1,000 person-years, respectively; the corresponding rates were 1.36, 0.74, and 0.81 per 1,000 person-years among the 5,490 non-GPA individuals. Compared with the non-GPA cohort, the fully adjusted HRs among GPA patients were 2.90 (95% CI, 1.10-7.64), 4.70 (95% CI, 1.74-12.69), and 1.66 (95% CI, 0.52-5.27) for VTE, PE, and DVT, respectively. The risks of VTE, PE, and DVT were highest during the first year after GPA diagnosis with HR (95% CI) of 11.04 (1.37-88.72), 26.94 (4.56-159.24), and 2.68 (0.23-31.21), respectively. GPA patients are at significantly increased risk of PE, but not DVT. Monitoring for these complications is particularly warranted in this patient population, especially early after diagnosis.

Respiratory involvement in antineutrophil cytoplasmic antibody-associated vasculitides: a retrospective study based on POLVAS registry.

OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.

Infection is associated with increased risk of MPO- but not PR3-ANCA-associated vasculitis.

OBJECTIVES: To determine whether development of ANCA-associated vasculitis (AAV) shows a relationship with a prior infection and if prior infection affects disease characteristics and outcome. METHODS: All incident cases of AAV diagnosed in a defined region of Sweden from 2000 through 2016 were identified. For each case, 10 individuals from the general population, matched for age, sex and area of residence, were selected. Infections occurring in AAV patients and controls prior to the date of AAV diagnosis (index date for respective controls) were identified using an administrative database. Conditional logistic regression models were used to calculate odds ratios (OR) of developing AAV. Occurrence, clinical characteristics and outcome of AAV were analysed with respect to prior infection. RESULTS: Two-hundred and seventy patients with AAV (48% female) and 2687 controls were included. Prior to diagnosis/index date, 146 (54%) AAV patients had been diagnosed with infection vs 1282 (48%) controls, with OR for AAV 1.57 (95% CI 1.18, 2.19) in those with infections of the upper respiratory tract and 1.68 (1.02, 2.77) in those with pneumonia. Difference from controls was significant in patients with MPO-ANCA 1.99 (95% CI 1.25, 3.1) but not in those with PR3-ANCA 1.0 (0.61, 1.52). Patients with prior infection showed higher disease activity at AAV diagnosis. No differences in disease characteristics, comorbidities or outcome in those with and without prior infections were observed. CONCLUSIONS: Respiratory tract infections are positively associated with development of MPO- but not PR3-ANCA vasculitis. Prior infection is associated with higher disease activity at AAV diagnosis.