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Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease associated with vascular inflammation and multisystem organ damage. The literature reporting EGPA incidence or prevalence is limited. We performed a systematic literature review and meta-analysis to describe the incidence, prevalence, and disease burden associated with EGPA. Real-world, observational, English-language studies in MEDLINE, MEDLINE In-Process, and Embase up to 6 June, 2019, were included. A single investigator screened all identified titles/abstracts and extracted data; an additional, independent investigator repeated the screening and validated the extracted data. A random-effects meta-analysis was conducted to generate pooled estimates for EGPA incidence and prevalence. Data from 100 eligible publications were extracted (32 with incidence/prevalence data, 65 with morbidity/healthcare resource data; 3 with both types of data). Significant evidence of between-study heterogeneity for reported incidence (p = 0.0013–0.0016) and prevalence (p = 0.0001–0.0006) estimates was observed. Global and European pooled estimates (95% confidence interval) of EGPA incidence were 1.22 (0.93, 1.60) and 1.07 (0.94, 1.35) cases per million person-years, respectively; global and European pooled estimates (95% confidence interval) for EGPA prevalence were 15.27 (11.89, 19.61) and 12.13 (6.98, 21.06) cases per million individuals, respectively. The proportions of patients experiencing relapses, or who had nasal polyps or severe asthma, varied considerably across studies. EGPA healthcare resource use was high, with inpatient admissions and emergency department visits reported for 17–42% and 25–42% of patients, respectively. Our results indicate that although global and European EGPA incidence and prevalence is low, the associated disease burden is substantial. Key points• We performed a systematic literature review and meta-analysis of real-world, observational studies describing the incidence, prevalence, and disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA).• Based on meta-analysis data from 35 eligible studies reporting incidence and prevalence, the incidence and prevalence of EGPA were low (globally 1.22 cases per million person-years and 15.27 cases per million individuals, respectively).• Among the 49 studies with morbidity and/or healthcare resource data, most reported a large proportion of patients with EGPA relapses and comorbidities of nasal polyps and severe asthma.• Healthcare resource use was also high among patients with EGPA in these studies, with inpatient admissions and emergency department visits reported for 17–42% and 25–42% of patients, respectively. Taken together, these data indicate the substantial disease burden associated with EGPA.

Background The data from cohorts of childhood-onset granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) remain scarce and heterogeneous. We aimed to analyse the features at presentation, therapeutic approaches and the disease course of these rare diseases. Methods Electronic searches of Medline and the Cochrane Central Register of Controlled trials database were conducted. We also checked the reference lists of the studies included and other systematic reviews, to identify additional reports. We included all cohorts, cross-sectional studies or registries reporting features at presentation or outcomes in patients with a diagnosis of childhood-onset GPA or MPA (age <18 years). The pooled prevalence of clinical manifestations at presentation, ANCA and induction therapies for GPA and MPA was calculated. Results We reviewed 570 full texts and identified 14 studies on GPA and 8 on MPA. Childhood-onset GPA and MPA occurred predominantly in female subjects during adolescence. For GPA, ear-nose-throat (ENT) disease (pooled prevalence 82 % [95 % CI 78–87]), constitutional symptoms (73 % [95 % CI 55–88]), renal (65 % [95 % CI 49–79]), and lower respiratory tract (61 % [95 % CI 48–74]) manifestations were the most frequently reported at presentation. Renal disease was a hallmark of MPA (94 % [95 % CI 89–97]). ANCA were detected in >90 % of children with GPA or MPA. Combined corticosteroids and cyclophosphamide was the most frequently used first remission-inducing treatment for GPA (76 % [95 % CI 69–82]) and MPA (62 % [95 % CI 20–96]). Relapses occurred more frequently in GPA (67–100 %) than in MPA (25–50 %). The leading causes of death were the disease itself, and infections. Conclusions Childhood-onset MPA and GPA remain severe diseases with frequent relapses and a high cumulative morbidity. Survival and disease-free survival need to be improved.

ObjectivesThis 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.MethodsThrough 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.ResultsA 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.ConclusionsIn 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.

Objective Severe gastrointestinal lesions are associated with a poor prognosis in eosinophilic granulomatosis with polyangiitis (EGPA). The goal of this study was to develop an effective predictive model for gastrointestinal lesions and to examine clinical patterns, associated factors, treatment, and outcomes of gastrointestinal lesions in EGPA. Methods We retrospectively enrolled 165 EGPA patients. The independent associated factors were analyzed using multivariate logistic regression. A nomogram was conducted to quantify the predictive factors. The correlation between different organ lesions was calculated to explore the clinical patterns. Results A total of 52 patients had gastrointestinal lesions, and 22 developed severe disorders. Common manifestations included abdominal pain (78%), diarrhea (40.4%), and nausea and/or vomiting (32.7%). Severe gastrointestinal lesions included hemorrhage (26.9%), ulcers (17.3%), obstruction (9.6%), and pancreatitis (5.8%). Eosinophilic tissue infiltration, weight loss, and myalgia were independently associated with gastrointestinal involvement. Patients with severe gastrointestinal lesions had a shorter duration from initial symptoms to EGPA diagnosis, less frequent asthma, and ear-nose-throat involvement, and were more likely to receive methylprednisolone pulse. Weight loss, central nervous system involvement, myalgia, and eosinophilic tissue infiltration were retained in the nomogram. An eosinophil ratio of over 19.2% identified gastrointestinal lesions. Significantly more patients with gastrointestinal involvement had a Five Factor Score ≥ 2. Five well-defined clinical models were identified, including the brain-gut pattern. Conclusions Severe gastrointestinal lesions are common in EGPA and early detection is critical. Eosinophils are an important factor associated with gastrointestinal involvement of EGPA. We developed a model to predict the risk of gastrointestinal lesions. The brain-gut pattern might deserve further investigation in EGPA.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by autoimmune-associated inflammation and vessel damage. Based on the clinical manifestations and involvement of immune components, three disease syndromes are distinguished: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we present the current data on the epidemiology, the clinical manifestations of each syndrome, and the most up-to-date classification criteria. The role of the underlying genetic and epigenetic abnormalities, as well as their interplay, is described. The immunological diversification of AAV is also described, with a focus on the immune cell dysfunctions detected in patients. In conclusion, we emphasize the urgent need to unravel the sophisticated mechanisms of this disease, which would enable the development of new, effective therapeutic strategies.

BackgroundAntineutrophil 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.MethodsA 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.ResultsAmong 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).ConclusionsThe 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.

Granulomatosis with polyangiitis (GPA) previously known as Wegener’s granulomatosis (WG) is a rare rheumatic disease affecting subjects of all ages. Prevalence and incidence of this systemic disease greatly varies across different ethnic groups. GPA is the commonest form of ANCA-associated vasculitis (AAV) with PR3 positivity among 85–95% of the cases. Scientific investigations of GPA is warranted because its severity, clinical heterogeneity, fast disease manifestation and end-organ damage. The etiology of GPA is still unknown. Major role of HLA and non-HLA genes with immune functions were identified, however, very limited replication was observed in different ethnic populations. In the present review, we have discussed the updates on the global epidemiology and contribution of HLA and major non-HLA genes/loci in GPA. We have also highlighted the cross disease association of GPA associated genes that may help in better disease management and predictive medicine. We proposed that high-resolution HLA typing and development of genetic risk model would help in early disease diagnosis and understanding the prognosis.

ObjectivesThe aim of this study was to assess the incidence, prevalence and mortality of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Lithuania.DesignRetrospective cohort study.SettingLithuanian National Health Insurance Fund and Causes of Death registries, covering 1 January 2012 through 31 December 2021.ParticipantsPatients were identified from national healthcare registries in Lithuania. The following inclusion criteria were applied: 1) diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) (diagnosis codes M30.1, M31.3 and M31.7, according to International Classification of Diseases 10th version (ICD-10)) recorded between 1 January 2012 and 31 December 2021; 2) diagnosis of AAV was recorded in the database at least twice with at least 1-month period between the two timepoints; 3) a record of at least once prescribed reimbursed medication—glucocorticoids (prednisolone or methylprednisolone), conventional synthetic disease-modifying anti-rheumatic drugs (methotrexate, azathioprine, hydroxychloroquine and cyclophosphamide) or biological disease-modifying anti-rheumatic drug (rituximab or available biosimilars); and 4) age >18 years at the time of diagnosis.Outcome measuresData for the analysis included sex, age, ICD-10 code of AAV, the first date of AAV diagnosis and date of death. The study period was subdivided into periods 1 (2013–2015), 2 (2016–2018) and 3 (2019–2021). Temporal trends of the incidence of AAV were assessed. Point prevalence data were recorded. Sex- and age-standardised mortality ratios (SMRs) were calculated. The life expectancy of patients with AAV was estimated by standard single-decrement life-table analysis.ResultsWe identified 236 patients with AAV (female, 58%) with an annual incidence of 8.22 per 1 000 000 adult inhabitants (period 1, 9.83; period 2, 6.88; period 3, 7.95). Increasing incidence was noted for MPA (period 1, 0.9; period 3, 2.49). The incidence of GPA (4.89 per 1 000 000 inhabitants per year) was three times higher than the total incidence of EGPA and MPA. The prevalence of AAV per 1 000 000 adult population increased from 35.92 in 2015 to 69.14 in 2021. 40 deaths were recorded during the study period, with a mean age at death of 65.2 (±13.03). AAV was associated with reduced life expectancy compared with the general population, especially when diagnosed at a young age. The SMRs for the total AAV cohort revealed a decreasing trend: 1.79 in period 1 and 1.67 in period 3.ConclusionsAAV is associated with increased mortality. During the study period, the incidence of AAV was found to be stable, and the prevalence has increased.

Abstract ObjectivesThis 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.MethodsThis 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.ResultsThe 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.ConclusionThe 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.

ObjectiveTo update the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in a defined geographical area of southern Sweden.MethodsThe 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.ResultsThree 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).ConclusionsThe 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.