Characteristics and Disease Burden of Patients With Eosinophilic Granulomatosis With Polyangiitis Initiating Mepolizumab in the United States.

BACKGROUND/OBJECTIVE: Although the high disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA) has been established, the disease burden in patients initiating mepolizumab in real-world practice is poorly understood. This study aimed to assess characteristics and burden of real-world patients with EGPA initiating mepolizumab. METHODS: This was a database study (GSK study ID: 214156) of US patients (≥12 years old) with EGPA and ≥1 mepolizumab claim (index date) identified from the Merative MarketScan Commercial and Medicare Supplemental Databases (November 1, 2015, to March 31, 2020). Outcomes assessed in the 12-month baseline period before index (inclusive) included patient characteristics, treatment use, EGPA relapses, asthma exacerbations, health care resource utilization, and costs. RESULTS: In the 103 patients included (mean age, 51.1 years; 63.1% female), the most common manifestations were asthma (89.3%), chronic sinusitis (57.3%), and allergic rhinitis (43.7%). In total, 91.3% of patients had ≥1 oral corticosteroid (OCS) claim (median dose, 7.4 mg/d prednisone-equivalent), 45.6% were chronic OCS users (≥10 mg/d during the 90 days preindex), 99.0% had ≥1 EGPA-related relapse, and 62.1% ≥1 asthma exacerbation. During the baseline period, 26.2% and 97.1% of patients had EGPA-related inpatient admissions and office visits, respectively. Median all-cause total health care costs per patient were $33,298, with total outpatient costs ($16,452) representing the largest driver. CONCLUSIONS: Before initiating mepolizumab, a substantial real-world EGPA disease burden is evident for patients, with resulting impact on health care systems, and indicative of unmet medical needs. Mepolizumab treatment, with a demonstrated positive clinical benefit-risk profile may represent a useful treatment option for reducing EGPA disease burden.

Mepolizumab: Therapeutic strategy for a pediatric patient with eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis. It is a multisystem disorder and can affect every organ system. EGPA is a rare disease, with an estimated prevalence of 1/70,000-100,000 in Europe. As its onset usually occurs in adulthood, data from pediatric patients are limited. We present here a very rare practical EGPA clinical case involving a pediatric patient. Presently, data on mepolizumab usage in pediatric patients are limited, with only a few case reports published.

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.

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.

The prevalence, burden of disease, and healthcare utilization of patients with eosinophilic granulomatosis with polyangiitis in Japan: a retrospective, descriptive cohort claims database study.

OBJECTIVES: To estimate eosinophilic granulomatosis with polyangiitis (EGPA) prevalence and disease burden in patients with newly diagnosed EGPA in Japan. METHODS: This retrospective descriptive cohort study (GSK ID: 209751, HO-18-19652) used administrative claim data from patients (aged ≤74 years) with EGPA (study period: January 1, 2005-December 31, 2017), identified from their first ICD-10 code for EGPA (index). Data were examined during the 12 months before (baseline) and 12 months following the index date (follow-up). EGPA prevalence, respiratory comorbidities, all-cause healthcare utilization, and oral corticosteroid (OCS) use were assessed. RESULTS: EGPA prevalence (95%CI) increased from 4.2 (0,23.7)/million people (2005) to 38.0 (31.8,45.1)/million people (2017), was generally more common in females versus males, and increased with age. Of the 45 patients with newly diagnosed EGPA, 57.8% had acute bronchitis and 42.2% had upper respiratory tract infections during baseline. During follow-up, 60.0% of patients were hospitalized at least once and 77.8% used OCS (OCS dependent [≥80% of days]: 73.1%). CONCLUSIONS: In Japan, EGPA prevalence increased over time, was generally more common in females, and increased with patient age. EGPA burden was high; respiratory comorbidities were common, and most patients required hospitalization and OCS use. Our data suggest additional EGPA treatment options are needed.

Hypothyroidism in vasculitis.

OBJECTIVE: To study the prevalence, risk and clinical associations of hypothyroidism among several forms of vasculitis. METHODS: Patients with GCA, Takayasu's arteritis (TAK), PAN and the three forms of ANCA-associated vasculitis [AAV; granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA)] enrolled in a prospective, multicentre, longitudinal study were included. RESULTS: The study included data on 2085 patients [63% female, 90% White] with a mean age of 54.6 years (s.d. 17.2). Diagnoses were GCA (20%), TAK (11%), PAN (5%), GPA (42%), microscopic polyangiitis (8%) and EGPA (14%). Hypothyroidism was present in 217 patients (10%) (83% female), with a mean age 59.8 years (s.d. 14.5). Age- and sex-adjusted risk of hypothyroidism was GCA, odds ratio (OR) 0.61 (95% CI 0.41, 0.90); TAK, OR 0.57 (95% CI 0.31, 1.03); PAN, OR 0.59 (95% CI 0.25, 1.38); GPA, OR 1.51 (95% CI 1.12, 2.05); microscopic polyangiitis, OR 1.81 (95% CI 1.18, 2.80) and EGPA, OR 0.82 (95% CI 0.52, 1.30). Among patients with AAV, age- and sex-adjusted risk of hypothyroidism was higher with positive MPO-ANCA [OR 1.89 (95% CI 1.39, 2.76)]. The clinical manifestations of vasculitis were similar in patients with and without hypothyroidism, except transient ischaemic attacks, which were more frequently observed in patients with GCA and hypothyroidism (12% vs 2%; P = 0.001). CONCLUSIONS: Differences in the risk of hypothyroidism among vasculitides may be due to genetic susceptibilities or immune responses. This study confirms an association of hypothyroidism with MPO-ANCA.

Mortality predictors in ANCA-associated vasculitis: Experience of a Brazilian monocentric cohort of a rheumatology center.

ABSTRACT: The mortality rate of patients with anti-neutrophil cytoplasm antibody -associated vasculitis (AAV) is higher than the general population. To date, no studies have evaluated the factors associated with unfavorable outcomes in Brazilian patients, who represent a miscegenated population. Our objective was to identify clinical and laboratory features associated with mortality in Brazilian patients with AAV.One hundred twenty eight patients fulfilling the American College of Rheumatology and Chapel Hill Classification Criteria followed between 2000 and 2018 in our Rheumatology Outpatient Clinics were included. Data were obtained from an ongoing electronic database. Patients were divided into 2 groups (dead or alive in 2018), and disease activity (Birmingham vasculitis activity score [BVAS]), vasculitis-related damage (VDI), and laboratory parameters were compared at the most recent attendance and at the last attendance before death.Of the 128 patients followed, 78.9% had granulomatosis with polyangiitis, 16.4% had eosinophilic granulomatosis with polyangiitis, and 4.6% had microscopic polyangiitis. In 2018, 78 patients were alive, 25 had died, and 25 had lost contact. The main cause of death was infection. According to the univariate analysis, the Birmingham vasculitis activity score, VDI, and glucocorticoid dose were higher in the group of patients who died. Laboratorial features related to mortality were creatinine, hemoglobin, erythrocyte sedimentation ratio, and C-reactive protein (CRP). Logistic regression analysis showed that high VDI, creatinine levels, and CRP levels were independent factors associated with mortality. Survival was significantly decreased in patients with renal impairment.This is the first study to use this approach performed in a Brazilian population and it showed that damage index, renal impairment, and CRP levels were associated with mortality in a miscegenated population with AAV.

Burden of illness associated with eosinophilic granulomatosis with polyangiitis: a systematic literature review and meta-analysis.

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.

Clinical characteristics and prognostic factors in an argentinian cohort with ANCA-associated vasculitis / Características clínicas y factores pronósticos en una cohorte argentina de vasculitis asociada a ANCA

Abstract ANCA-associated vasculitis is a heterogeneous group of rare autoimmune conditions of unknown cause. Clinical characteristics and prognostic factors were analyzed in 47 patients: 20 (42.5%) with granulomatosis with polyangiitis, 17 (36.2%) with microscopic polyangiitis, 6 (12.8%) with renal-limited vasculitis, and 4 (8.5%) with eosinophilic granulomatosis with polyangiitis. Mean age at diagnosis was 53.5 ± 16.5 years and the median of BVAS (Birmingham Vasculitis Activity Score) was 14 (4-42). The most frequent clinical manifesta tions were: general in 44 (93.6%), renal in 30 (63.8%) and respiratory in 28 (59.6%). All received corticosteroids at the beginning of treatment. Intravenous cyclophosphamide was associated in 20 (42.5%) and oral route in 14 (29.8%); azathioprine in 3 (6.4%) and rituximab in 2 (4.2%). At a median follow-up of 35.5 months (range 0.14- 234), 21 relapses were recorded in 14 patients. Overall mortality was 3.5 deaths per 100 patient-year in the whole group. Those over 55 years old, the presence of alveolar hemorrhage, those with FFS (Five Factor Score) of 2, and patients with MPA had poor prognosis. Renal involvement, ANCA pattern and BVAS were not associated to a poorer prognosis.

Resumen Las vasculitis asociadas a ANCA son un grupo heterogéneo de entidades autoinmunes, poco frecuentes, de etiología desconocida. Analizamos las características clínicas y factores pronóstico en 47 pacientes: 20 (42.5%) granulomatosis con poliangeítis, 17 (36.2%) poliangeítis microscópica, 6 (12.8%) vasculitis limitada al riñón y 4 (8.5%) granulomatosis eosinofílica con poliangeítis. La edad promedio al diagnóstico fue 53.5 ± 16.5 años y la mediana de BVAS (Birmingham Vasculitis Activity Score) 14 (4-42). Las manifestaciones clínicas más frecuentes fueron: generales en 44 (93.6%), renales 30 (63.8%) y respiratorias en 28 (59.6%). Todos recibieron corticoides al inicio del tratamiento. Se asoció ciclofosfamida endovenosa en 20 (42.5%) y oral en 14 (29.8%); azatioprina en 3 (6.4%) y rituximab en 2 (4.2%). En una mediana de seguimiento de 35.5 meses (rango 0.14-234), se registraron 21 recaídas en 14 pacientes. La mortalidad fue 3.5 por cien pacientes-año en todo el grupo. Los mayores de 55 años, con presencia de hemorragia alveolar, FFS (Five Factor Score) de 2, y los casos con poliangeítis microscópica tuvieron peor pronóstico. El compromiso renal, el patrón de ANCA y el BVAS no se asociaron a peor pronóstico.

Clinical characteristics and prognostic factors in an Argentinian cohort with ANCA-associated vasculitis.

ANCA-associated vasculitis is a heterogeneous group of rare autoimmune conditions of unknown cause. Clinical characteristics and prognostic factors were analyzed in 47 patients: 20 (42.5%) with granulomatosis with polyangiitis, 17 (36.2%) with microscopic polyangiitis, 6 (12.8%) with renal-limited vasculitis, and 4 (8.5%) with eosinophilic granulomatosis with polyangiitis. Mean age at diagnosis was 53.5 ± 16.5 years and the median of BVAS (Birmingham Vasculitis Activity Score) was 14 (4-42). The most frequent clinical manifestations were: general in 44 (93.6%), renal in 30 (63.8%) and respiratory in 28 (59.6%). All received corticosteroids at the beginning of treatment. Intravenous cyclophosphamide was associated in 20 (42.5%) and oral route in 14 (29.8%); azathioprine in 3 (6.4%) and rituximab in 2 (4.2%). At a median follow-up of 35.5 months (range 0.14-234), 21 relapses were recorded in 14 patients. Overall mortality was 3.5 deaths per 100 patient-year in the whole group. Those over 55 years old, the presence of alveolar hemorrhage, those with FFS (Five Factor Score) of 2, and patients with MPA had poor prognosis. Renal involvement, ANCA pattern and BVAS were not associated to a poorer prognosis.

Las vasculitis asociadas a ANCA son un grupo heterogéneo de entidades autoinmunes, poco frecuentes, de etiología desconocida. Analizamos las características clínicas y factores pronóstico en 47 pacientes: 20 (42.5%) granulomatosis con poliangeítis, 17 (36.2%) poliangeítis microscópica, 6 (12.8%) vasculitis limitada al riñón y 4 (8.5%) granulomatosis eosinofílica con poliangeítis. La edad promedio al diagnóstico fue 53.5 ± 16.5 años y la mediana de BVAS (Birmingham Vasculitis Activity Score) 14 (4-42). Las manifestaciones clínicas más frecuentes fueron: generales en 44 (93.6%), renales 30 (63.8%) y respiratorias en 28 (59.6%). Todos recibieron corticoides al inicio del tratamiento. Se asoció ciclofosfamida endovenosa en 20 (42.5%) y oral en 14 (29.8%); azatioprina en 3 (6.4%) y rituximab en 2 (4.2%). En una mediana de seguimiento de 35.5 meses (rango 0.14-234), se registraron 21 recaídas en 14 pacientes. La mortalidad fue 3.5 por cien pacientes-año en todo el grupo. Los mayores de 55 años, con presencia de hemorragia alveolar, FFS (Five Factor Score) de 2, y los casos con poliangeítis microscópica tuvieron peor pronóstico. El compromiso renal, el patrón de ANCA y el BVAS no se asociaron a peor pronóstico.

Venous thrombosis and predictors of relapse in eosinophil-related diseases.

Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6-7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10-62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94-29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.

Pleuritis and Pericarditis in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

BACKGROUND: Pleural and pericardial involvements are well recognized in eosinophilic granulomatosis with polyangiitis (EGPA) but considered rare manifestations of the other forms of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). RESEARCH QUESTION: What are the frequency and clinical characteristics of pleuritis and pericarditis in AAV? STUDY DESIGN: and Methods: Using an institutional database of 1,830 patients with AAV, we analyzed clinical notes and diagnosis codes for key words related to pleuritis and pericarditis. Chart review to confirm these findings was performed. RESULTS: Eighty-eight of 1,058 patients (8.3%) with granulomatosis with polyangiitis (GPA), 27 of 267 (10.1%) with microscopic polyangiitis (MPA), and 35 of 201 (17.4%) with EGPA had a manifestation of pleuritis and/or pericarditis attributable to vasculitis. There was a higher frequency of pericarditis in EGPA compared with that in the other AAVs (P < .01). There was no difference in the frequency of pleuritis in GPA, MPA, or EGPA. In the 156 patients with AAV with pleuritis and/or pericarditis, this was a presenting feature in 127 (81.4%). Overall, it was a presenting feature in 6.9% of all patients with AAV, including 6.5% with GPA, 8.6% with MPA, and 15.9% with EGPA. INTERPRETATION: Pleuritis and pericarditis occur across all the AAVs and, when present, are commonly presenting features of these diseases. Patients with EGPA have a higher proportion of pericardial involvement compared with pleural involvement, whereas this distribution is more equal in patients with GPA and MPA. Pleuritis and pericarditis are underrecognized features of AAV. All forms of AAV should be considered in the differential diagnosis when evaluating a patient with pleuritis or pericarditis.

Demographic and Clinical Features of ANCA-Associated Vasculitides in a Peruvian Tertiary Center.

AIM: The aim of this study was to identify the demographic and clinical features of patients with ANCA-associated vasculitides (AAVs) in a Peruvian tertiary referral hospital. METHODS: Medical records of patients with AAV according to classification criteria or diagnosed by an experienced rheumatologist, and covering the period between January 1990 and December 2019, were reviewed. Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal-limited vasculitis (RLV) were included. Demographic factors (age at diagnosis, sex), disease duration, clinical manifestations (per organ involvement), creatinine level at diagnosis (milligram per deciliter), ANCA status, diagnosis, 2009 Five Factor Score, disease categorization, and treatment were recorded. RESULTS: Two hundred twelve patients were included. Their female-to-male ratio was 1.9:1 (139 [65.6%]/73 [34.4%]), and their mean (SD) age at diagnosis was 59.2 (12.5) years. One hundred fifty-eight patients (74.5%) had MPA, 42 (19.8%) GPA, 7 (3.3%) RLV, and 5 (2.4%) EGPA. Neurological, lung, and renal involvements were the most frequently affected systems. Myeloperoxidase preferentially occurred in MPA (82.5%), whereas proteinase 3 did occur in GPA (79.5%). Microscopic polyangiitis patients were older (61.1 [11.5] years). Female sex predominated in MPA and RLV (2.4:1 and 6:1, respectively), but the opposite was the case for EGPA (1:4). Ear-nose-throat and ocular involvement were more frequent in GPA (both p's < 0.001), and neurological and cardiovascular involvement were more frequent in EGPA (p < 0.001 and p = 0.002, respectively). CONCLUSIONS: This is one of the largest series of AAV patients in Latin America. Overall, female sex predominated. Microscopic polyangiitis was the most frequent AAV, and myeloperoxidase-ANCA was the most frequent antibody in Peruvian AAV population.

Prevalence of Eosinophilic Granulomatosis With Polyangiitis and Associated Health Care Utilization Among Patients With Concomitant Asthma in US Commercial Claims Database.

OBJECTIVE: To estimate the prevalence and associated disease burden of eosinophilic granulomatosis with polyangiitis (EGPA) in patients with asthma from a US claims database. METHODS: Two cohorts were defined using enrollees (aged ≥18 years) from the Optum deidentified Clinformatics Datamart claims database 2010-2014, based on validated EGPA case definitions with varying specificity: EGPA 1 (main cohort; more specific; patients with 2 codes [in any combination] within 12 months of each other for eosinophilia, vasculitis, or mononeuritis multiplex) and EGPA 2 (sensitivity analysis cohort; less specific; patients with 2 codes of above conditions and/or neurologic symptoms within 12 months of each other). Patients had 3 or more asthma medications in the 12-month baseline before index date (date of the second code). Eosinophilic granulomatosis with polyangiitis prevalence, asthma severity during the baseline period, oral corticosteroid (OCS) use, and health care utilization during the 12-month follow-up period were determined. RESULTS: Overall, 88 and 604 patients were included in main cohort EGPA 1 and sensitivity analysis cohort EGPA 2, respectively; corresponding annual EGPA prevalence rates were 3.2 to 5.9 and 23.4 to 30.7 cases/million patients. Approximately 75% of patients were prescribed OCS and ~30% experienced 1 or more hospitalization; 75% in EGPA 1 and 52% in EGPA 2 with 1 or more non-OCS prescription in the 90 days before index date had severe asthma. CONCLUSIONS: Eosinophilic granulomatosis with polyangiitis prevalence estimates varied based on specificity of the case definition but were generally consistent with previous country-specific estimates. Despite differences in prevalence, both cohorts displayed a generally similar, high burden of OCS use and health care utilization, highlighting the substantial disease burden among patients with EGPA and the need for specific treatments.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): Prospective evaluation at a tertiary referral centre.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population. METHODS: Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses. RESULTS: 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /µl vs CSI-: 3000 /µl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy. CONCLUSIONS: CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.

Serum Mannose-Binding Lectin Levels Are Correlated with the Disease Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Center Study.

Mannose-binding lectin (MBL) is a soluble pattern-recognition molecule, which plays a crucial role in the innate immune system and the activation of lectin complement pathway. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease affecting the small vasculatures and is characterized by the alteration of innate and adaptive immunity and complement activation. In this study, we investigated whether serum MBL is associated with disease activity of AAV, which was measured by ELISA. Associations between serum MBL and AAV-specific indices, as well as clinical and laboratory data were assessed using Kendall's tau. Among the 80 patients, 42 (52.5%), 21 (26.3), and 17 (21.3%) patients were classified as microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), respectively. The median values of erythrocyte sedimentation rate, C-reactive protein, and serum MBL were 36.5 (normal range < 20) mm/h, 2.4 (normal range < 8) mg/dL, and 8.6 ng/mL, respectively. The median serum levels of MBL in MPA, GPA, and EGPA patients were 8.4, 9.3, and 8.2 ng/mL. Correlation analysis showed that serum MBL was associated with Birmingham Vasculitis Activity Score (BVAS) (R = 0.169, p = 0.027), but not with other AAV-specific indices and clinical and laboratory data. In addition, serum MBL was significantly associated with the pulmonary manifestation score based on BVAS (R = 0.247, p = 0.001). In summary, among the AAV-specific indices and clinical and laboratory variables analyzed, serum MBL is correlated with BVAS and pulmonary manifestation score based on the BVAS.

Increasing incidence and prevalence of ANCA-associated vasculitis in Northern Norway.

OBJECTIVE: ANCA-associated vasculitides (AAV) have increased in prevalence since the 1980s. We aimed to investigate the incidence and prevalence of AAV during a 15-year period from 1999 to 2013 in Northern Norway, looking for variations during this period. METHODS: Patient records were retrieved from The Northern Norwegian Vasculitis Registry; in addition we searched all regional hospital databases. Patients diagnosed with AAV from 1999 through to 2013 were included. For prevalence data, patients residing in the area, but with AAV diagnosis prior to 1999, were also included. The diagnosis of AAV was based on the European Medicines Agency algorithm. RESULTS: We identified 140 cases; 88 were classified as granulomatosis with polyangiitis (GPA), 37 as microscopic polyangiitis (MPA) and 15 as eosinophilic granulomatosis with polyangiitis (EGPA). Adult (age ≥15 years) annual incidence rates per million were as follows: for GPA 15.6 (95% CI: 12.5, 19.2), MPA 6.5 (95% CI: 4.6, 9.0), EGPA 2.7 (95% CI: 1.5, 4.5) and overall AAV 24.7 (95% CI: 20.8, 29.2). Incidences of MPA and overall AAV showed an increasing trend (P < 0.05). Adult point prevalence rates per million in 2013 were 261 (95% CI: 213, 316) for GPA, 58.2 (95% CI: 36.9, 87.3) for MPA, 32.9 (95% CI: 17.5, 56.3) for EGPA and 351 (95% CI: 296, 416) for overall AAV. CONCLUSION: The incidence rate of GPA and the prevalence rates of GPA and EGPA are currently the highest reported. MPA increased significantly from a prior low incidence. The overall AAV annual incidence and prevalence are still increasing.

"Idiopathic Eosinophilic Vasculitis": Another Side of Hypereosinophilic Syndrome? A Comprehensive Analysis of 117 Cases in Asthma-Free Patients.

BACKGROUND: The absence of asthma may rule out a diagnosis of eosinophilic granulomatosis with polyangiitis in patients with hypereosinophilic syndrome (HES) and features of vasculitis. OBJECTIVE: To describe eosinophilic vasculitis (EoV) as a possible manifestation of HES in asthma-free patients. METHODS: We screened our hospital database and the literature for patients with HES who met the following 4 criteria: (1) histopathological or clinical features of EoV (biopsy-proven vasculitis with predominant eosinophilic infiltration of the vessel wall and/or features of vasculitis with tissue and/or blood hypereosinophilia [absolute eosinophil count >1.5 G/L]); (2) no other obvious causes of reactive eosinophilia, organ damage, and vasculitis; (3) the absence of antineutrophil cytoplasmic antibodies; and (4) the absence of current asthma. RESULTS: Ten of our 83 (12%) asthma-free patients with HES and 107 additional cases in the literature met the criteria for EoV. After a critical analysis of the patients' clinical and laboratory characteristics and outcomes, we identified 41 cases of single-organ EoV (coronary arteritis, n = 29; temporal arteritis, n = 8; cerebral vasculitis, n = 4). Of the remaining 76 patients with EoV, the most frequent manifestations (>10%) were cutaneous vasculitis (56%), peripheral neuropathy (24%), thromboangiitis obliterans-like disease (16%), fever (13%), central nervous system involvement (13%), deep venous thrombosis (12%), and nonasthma lung manifestations (12%). Blood hypereosinophilia more than 1.5 G/L was observed in 79% of patients, and necrotizing vasculitis was observed in 44%. CONCLUSIONS: Our results suggest that idiopathic EoV (HES-associated vasculitis) can be classified as an eosinophilic-rich, necrotizing, systemic form of vasculitis that affects vessels of various sizes in asthma-free patients.

Peripheral neuropathy in antineutrophil cytoplasmic antibody-associated vasculitides: Insights from the DCVAS study.

OBJECTIVE: Reported prevalence of vasculitic neuropathy (VN) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is highly variable, and associations with other organ manifestations have not been studied systematically while accounting for diagnostic certainty of VN. METHODS: Data of all patients with AAV within the Diagnostic and Classification criteria for primary systemic VASculitis study were analyzed cross-sectionally. VN was categorized as definite (histology proven), probable (multiple mononeuropathy or nerve biopsy consistent with vasculitis), or possible (all others). Associations with other organ manifestations were compared in patients with and without VN. RESULTS: Nine hundred fifty-five patients (mean age 57 years, range 18-91 years, 51% female) were identified. Of these, 572 had granulomatosis with polyangiitis (GPA), 218 microscopic polyangiitis (MPA), and 165 eosinophilic granulomatosis with polyangiitis (EGPA). The prevalence of VN was 65% in EGPA, 23% in MPA, and 19% in GPA. Nerve biopsy was performed in 32/269 (12%) patients, demonstrating definite vasculitis in 17/32 (53%) of patients. VN was associated with myeloperoxidase-ANCA positivity (p = 0.004) and skin (p < 0.001), musculoskeletal, (p < 0.001) and cardiovascular (p = 0.005) involvement. Patients with VN were less likely to have renal (p < 0.001), eye (p < 0.001), and gastrointestinal (p = 0.023) involvement. CONCLUSIONS: Our study provides comprehensive insights into the prevalence and organ associations of VN in a large, systematically collected AAV cohort. VN is most commonly associated with skin, musculoskeletal, and cardiovascular manifestations. In routine clinical practice, diagnosis of VN is infrequently confirmed by the gold standard of nerve biopsy but rather supported by the clinical setting of active systemic AAV.

Epidemiology of primary systemic vasculitis in children: a population-based study from southern Sweden.

OBJECTIVES: To estimate the annual incidence rate of paediatric primary systemic vasculitis (PSV) in a defined geographical area in southern Sweden. METHODS: Potential cases of PSV [IgA vasculitis (IgAV, Henoch-Schönlein purpura), Kawasaki disease (KD), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), polyarteritis nodosa (PAN), and Takayasu's arteritis (TAK)] were identified in a comprehensive regional healthcare register. The study area is Skåne, the southernmost county of Sweden (population 1.29 million; 21.4% aged <18 years). Case records for children (0-17 years) assigned a diagnosis code between M300 and M319 and/or D690 were reviewed to ascertain diagnosis. Only patients diagnosed between 2004 and 2014 were included. RESULTS: In total, 556 patients with PSV were identified. The annual incidence rate per million children (95% confidence interval) was estimated to be 200 (183-217) for all PSV, 175.5 for IgAV (160-191), 20.1 for KD (14.9-25.4), 1.4 (0-2.8) for each of GPA and MPA, 0.7 (0-1.7) for PAN, and 0.4 (0-1.1) for each of EGPA and TAK. Among children aged <10 years, 99.5% of cases were either IgAV or KD, both exhibiting a seasonal pattern paralleling infections. There were no deaths, but three cases of end-stage renal disease were noted, all in MPA. CONCLUSIONS: Vasculitis is relatively common during childhood. Mild cases associated with the infection season are most common in the youngest age groups, while during adolescence a substantial proportion has more severe forms of vasculitis.