Genetic and Non-Genetic Contributions to Eosinophilic Granulomatosis with Polyangiitis: Current Knowledge and Future Perspectives.

In this work, we present a comprehensive overview of the genetic and non-genetic complexity of eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a rare complex systemic disease that occurs in people presenting with severe asthma and high eosinophilia. After briefly introducing EGPA and its relationship with the anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAVs), we delve into the complexity of this disease. At first, the two main biological actors, ANCA and eosinophils, are presented. Biological and clinical phenotypes related to ANCA positivity or negativity are explained, as well as the role of eosinophils and their pathological subtypes, pointing out their intricate relations with EGPA. Then, the genetics of EGPA are described, providing an overview of the research effort to unravel them. Candidate gene studies have investigated biologically relevant candidate genes; the more recent genome-wide association studies and meta-analyses, able to analyze the whole genome, have confirmed previous associations and discovered novel risk loci; in the end, family-based studies have dissected the contribution of rare variants and the heritability of EGPA. Then, we briefly present the environmental contribution to EGPA, reporting seasonal events and pollutants as triggering factors. In the end, the latest omic research is discussed and the most recent epigenomic, transcriptomic and microbiome studies are presented, highlighting the current challenges, open questions and suggesting approaches to unraveling this complex disease.

Renal damage and old age: risk factors for thrombosis in patients with ANCA-associated vasculitis.

INTRODUCTION: Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis. METHODS: In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank. RESULTS: 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726-0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035-1.0041, P = 0.009). CONCLUSION: Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE.

Diagnostic and prognostic role of serum interleukin-6 and carotid ultrasonography to detect subclinical atherosclerosis in patients with RA and ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 2: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (eGPA) are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of GPA and eGPA were collected and reported in this review. RESULTS: 467 references were discovered during literature review process. In total, 42 references for GPA and 35 references for eGPA were included in this review. CONCLUSION: GPA and eGPA are vasculitis syndromes which commonly present in the context of multisystem disease. For GPA, pulmonary and renal disease are common; for eGPA a history of asthma is nearly ubiquitous. Sinonasal disease is a very common feature for both disease processes and may precede the development of systemic symptoms in many patients. Clinical work up and diagnosis is complex and generally requires multidisciplinary care. Treatment primarily consists of immunosuppressive agents, and a number of steroids, steroid sparing agents, and biologics have been shown to be effective. The role of sinus surgery includes tissue biopsy for diagnosis, functional surgery for symptom management in select cases, and reconstruction of cosmetic and functional defects.

Eosinophil-associated diseases: the Allergist's and Clinical Immunologist's perspective.

Summary: Eosinophil-associated diseases (EADs) refer to heterogeneous conditions in which eosinophils are believed to play critical pathological roles. They encompass common respiratory conditions, such as asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), less common primary eosinophilic disorders of gastrointestinal tract, and rare conditions including eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). A literature search was carried out in January 2024 in the MEDLINE and Scopus databases using the PubMed search engine (PubMed, National Library of Medicine, Bethesda, MD). We focused on blood eosinophilia and hypereosinophilia. A diagnostic workup is proposed. From allergist's point of view, we focused the review on 4 groups of eosinophilic disorders of specific interest. Our increased understanding of type 2 inflammation and biology has recently led to development of highly effective precision targeted therapies that are now approved for a growing number of eosinophilic disorders. Novel targeted biologics have a major impact on treatment strategies and have resulted in major advances in our understanding of the pathogenesis of these disorders. In the context of EADs, according to the heterogeneity of eosinophilic disorders a multidisciplinary approach should be adopted. Allergists and Clinical Immunologists play an important role as they have a clear understanding of the eosinophilic inflammation and the role of cytokines and are trained to recognize and characterize type 2 (T2) inflammation and its associated pathologies.

Unmet needs and evidence gaps in hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis.

Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are rare systemic inflammatory disorders with overlapping symptoms, elevated eosinophil counts, and heterogenous clinical presentations. Although progress has been made in recent years, there are substantial gaps in our understanding of the pathologic mechanisms involved in these diseases, as well as numerous unmet needs relating to both diagnosis and patient management. For example, in most cases of HES, the underlying cause of hypereosinophilia is unknown, while in EGPA, although a polygenic genetic susceptibility has been found, understanding of the pathogenic mechanisms remains largely elusive. Delineating differences between certain disease variants may be challenging, and there are no reliable predictive markers of disease course. In addition, the current diagnostic criteria for HES and classification criteria for EGPA are not easy to implement in a nonspecialist setting, and specialist referral pathways need to be signposted more clearly. Furthermore, disease-specific activity scores need to be developed to aid the assessment of treatment effects, and improved biomarkers are needed to aid with treatment stratification. In this review, we outline the limitations of our current understanding of HES and EGPA and highlight areas for future work, which ultimately should help improve patient management and outcomes.

[Eosinophilic small vessel vasculites (EGPA) a hidden severe asthma comorbitity].

A 72-year-old woman presented to the emergency department due to worsening dyspnea. She had been diagnosed with asthma a year earlier. At arrival, her oxygen saturation was only 84%. During lung auscultation, wheezing was noted over all lung fields. A blood test showed a significant increase in eosinophils in peripheral blood, highest value of 1.4 x 10E9/L. Further investigations in the respiratory ward showed a positive MPO-ANCA, which, together with clinical features of asthma, chronic rhinosinusitis with polyps, mononeuritis multiplex and eosinophilia, led to the diagnosis of eosinophilic granulomatosis with polyangiitis, or what used to be called Churg-Strauss syndrome. Corticosteroid treatment was initiated and subsequently tapered down when treatment with mepolizumab was started, which is an IL-5 inhibitor. Her symptoms quickly became much better. Frequent exacerbations and pulmonary symptoms became things of the past.

Sinonasal and respiratory outcomes of eosinophilic granulomatosis with polyangiitis patients receiving 100 mg mepolizumab in real-life clinical practice: 1-year follow up study.

Background: Mepolizumab 300 mg is an approved treatment option for patients with eosinophilic granulomatosis with polyangiitis (EGPA), yet, the adequacy of 100 mg of mepolizumab in disease control is controversial.Objective: To evaluate the sinonasal and respiratory outcomes of EGPA patients treated with 100 mg mepolizumab for one year.Methods: Evaluations of 11 patients were made of the sinonasal outcome test (SNOT-22) (nasal, otologic, sleep, and emotional domains), asthma control test (ACT), forced expiratory volume in 1 s (FEV1), blood eosinophil counts and oral steroid doses before mepolizumab treatment (T0) and at the 6th (T6) and 12th (T12) months.Results: A significant decrease was observed in the total SNOT-22 scores in the 6th month, after which the scores continued to be stable until the 12th month. (SNOT-22 median (IQR); T0: 70(53-82); T6: 19(4-35); T12: 11(6-40); T0-T6, p = 0.02; T6-T12, p = 0.85). In the subdomains of SNOT-22, nasal and sleep-related domains improved significantly in the first 6 months, and the otologic and emotional domains only improved from baseline in the 12th month. There was a significant decrease in blood eosinophil counts in the 6th month and oral steroid dose in the 12th month (eosinophils, median(IQR), T0: 1000(700-1800), T6: 100(0-200), p = 0.02; OCS dose, median(IQR), T0: 16(8-16); T6: 4(0-4); T12: 0(0-4); T0-T12, p = 0.002). A significant improvement was observed in ACT values in the 6th month (ACT median (IQR); T0:16(8-18); T6: 22(21-25); p = 0.01).Conclusion: Mepolizumab 100 mg provided a significant decrease in SNOT-22 values, especially in nasal and sleep domains, eosinophil counts and OCS dose in the 6th month.

The role of anti-eosinophilic therapies in eosinophilic granulomatosis with polyangiitis: a systematic review.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, mostly affecting small-sized arteries and usually occurring in patients with an allergic background. Eosinophils seem to play a significant role in the pathogenesis of the disease and, therefore, biologics targeting interleukin 5 (IL5), a cytokine tightly linked to eosinophils, have emerged as a promising therapeutic tool. A systematic review of Medline was conducted from 2007 to 2022 to search for data regarding the use of anti-IL5 therapies in patients with EGPA. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. The efficacy and safety of mepolizumab, an anti-IL5 monoclonal antibody (mAb), was confirmed by a randomized controlled trial (RCT), although a significant proportion of patients did not respond to this treatment. Other studies showed that both doses of 100 mg and 300 mg of mepolizumab are almost equally effective in EGPA. Benralizumab, an anti-IL5 receptor mAb has preliminary promising results and an RCT is planned to be conducted. Apart from their clinical efficacy in EGPA, anti-IL5 therapies may have steroid-sparing properties. Anti-IL5 therapies seem to be effective and safe in patients with refractory/relapsing EGPA and can be used as a steroid-sparing treatment. Nevertheless, more research is needed to clarify the pathophysiology of the disease; this may potentially lead to the identification of biomarkers to pinpoint patients most likely to respond to anti-IL5-blockade.

Polyangiitis overlap syndrome: a rare clinical entity.

Polyangiitis overlap syndrome is a rare clinical entity comprising patients with overlapping features of more than one vasculitis, usually eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis (GPA). Few cases of polyangiitis overlap syndrome have been described in the literature, mostly associated with c-ANCA, anti-proteinase (PR)-3 positivity, a protean clinical picture characterized by vasculitis, eosinophilia and eosinophilic infiltrates in tissues and a favorable response to steroids and immunosuppressant treatments. Herein, we present a case of a 66-year-old woman with nasal obstruction, external nose deformity, sensorineural hearing loss, peripheral blood eosinophilia, high titer anti-PR3 antibodies and lung involvement. Nasal septum biopsies showed inflammatory infiltrate with eosinophilic component; histopathology of the lung demonstrated necrotizing granulomas associated with inflammatory infiltrate composed of numerous neutrophils and some eosinophils. The patient was diagnosed with polyangiitis overlap syndrome and successfully treated with cyclophosphamide. Recognizing this entity is fundamental given the distinct clinical phenotype and outcomes to therapy in the complex scenario of ANCA-associated vasculitides.

Benralizumab: A novel treatment for the cutaneous features of paediatric eosinophilic granulomatosis with polyangiitis (pEGPA).

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis presenting primarily with pulmonary and cutaneous features. The disease is typically seen in the fifth or sixth decade of life (1, 2). We report a case of EGPA in an adolescent who was successfully treated with the interleukin-5 (IL-5) receptor inhibitor, benralizumab.

Structured histopathology and laboratory evidence in nasal polyposis with different pathogenesis.

PURPOSE: Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD), intrinsic asthma, eosinophilic granulomatosis with polyangiitis (EGPA) and odontogenic sinusitis may be associated with nasal polyps. The aim of the study was to compare circulating inflammatory cells and structural histopathology of these groups of nasal polyposis. METHODS: We retrospectively evaluated 71 patients with nasal polyps stratified according to the above-mentioned pathogenesis. All patients underwent preoperative laboratory investigations and primary endoscopic sinus surgery. Surgical specimens were submitted to structured histopathological evaluation. RESULTS: The median tissue eosinophil count (cells/HPF) was significantly different between the considered groups of nasal polyposis (p=0.0004). The median of NERD sub-cohort was significantly higher than intrinsic asthma (p=0.0030), odontogenic CRS (p=0.0001) and EGPA ones (p=0.0094). Eosinophilic aggregates positive rate was significantly higher in NERD sub-cohort than in odontogenic CRS (p=0.0072), EGPA (p=0.0497) and asthma (p=0.0188) ones. EGPA sub-cohort had a higher neutrophil infiltrate positive rate than NERD (p=0.0105) and intrinsic asthma ones (p=0.0040). Odontogenic CRS sub-cohort had a higher neutrophil infiltrate positive rate than NERD (p=0.0140) and asthma ones (p=0.0096). EGPA sub-cohort had a higher presence of fibrosis than NERD (p=0.0237) and odontogenic CRS sub-cohort (p=0.0107). Odontogenic sub-cohort had a lower sub-epithelial edema positive rate than NERD (p=0.0028) and asthma (p=0.0149) ones. CONCLUSIONS: Structural histopathology may identify nasal polyps histotypes with different morphological patterns. The identified histopathological features can facilitate the recognition of rational therapeutic and follow-up approaches that consider the tissue modifications associated with the response to drugs and surgery.

[A CASE OF EOSINOPHILIC GRANULOMATOUS WITH POLYANGIITIS WITH SKIN LESIONS ASSOCIATED WITH PSORIASIS].

A 72-year-old woman who was undergoing treatment for bronchial asthma and psoriasis vulgaris experienced malaise three months earlier and visited our hospital on account of abnormal lung shadows. Chest computed tomography revealed ground-glass opacities in the peripheral lung fields and eosinophilia in the bronchoalveolar lavage fluid, which suggested eosinophilic pneumonia. Antineutrophil cytoplasmic antibody was negative. Her lower limbs had multiple palpable papules mixed with well-treated psoriasis and the histopathology of the skin biopsy revealed eosinophil infiltration around small vessels, suggesting the occurrence of eosinophilic granulomatosis with polyangiitis (EGPA). We were able to evaluate minor skin lesions mixed with psoriasis through collaboration between the pulmonologist and the dermatologist. In the diagnosis of EGPA, it is important to carefully examine the whole body and not overlook minor findings before starting steroids.

Pharmacological profile of mepolizumab.

An elevated number of eosinophils have been implicated in several type 2 inflammatory chronic diseases that occur at various sites in the body. Over the past 20 years, our knowledge of diseases associated with increased numbers of eosinophils has advanced thanks to the development of drugs that can reduce or even eliminate eosinophils. One such agent is mepolizumab, a humanized monoclonal antibody that binds to interleukin -5 (IL-5). This article briefly and clearly summarizes the pharmacological profile of mepolizumab and its current indications for a number of chronic eosinophilic diseases.

Added value of Joint ENT-Rheumatology clinic in the management of ANCA-associated vasculitis: One year's experience.

PURPOSE: ANCA-associated vasculitides (AAV) represent a group of diagnoses, including granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). Most commonly, they present initially with ENT-associated symptomatology, and therefore they often pose a diagnostic challenge. We aim to present our one-year experience in the joint management of AAV in a multi-disciplinary setting. METHODS: We performed a retrospective analysis based on the records of 39 patients who were seen in the joint clinic, during a period of one year. RESULTS: After clinical assessment, 13 patients had changes made to their ENT treatment, 2 had some changes in their immunosuppression, while 11 had changes in both ENT and Rheumatology treatment. Six patients did not require any alterations to their therapeutic scheme. On average three separate appointments were reduced to a single appointment in the joint clinic where definitive treatment decisions were made. This led to significant cost reductions. CONCLUSIONS: Cost-effectiveness, patient satisfaction, rapid multi-disciplinary evaluation, avoidance of unnecessary immunosuppression, patient education and medical training are only a few of the many advantages of this proposed joint service.

Rare presentation of eosinophilic granulomatosis polyangiitis with left ventricular endomyocardial fibrosis in a child.

Eosinophilic granulomatosis polyangiitis represents less than 2% of vasculitis cases in childhood. Children have worse long-term outcomes and higher mortality. Cardiac involvement portends a worse prognosis. We describe here an adolescent girl who presented with heart failure and stroke. Her blood investigations showed eosinophilia and high IgE levels. Cardiac evaluation revealed myocarditis, intracardiac thrombus, and endomyocardial fibrosis, a rare presentation of this disease in childhood.

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.

Benralizumab in eosinophilic granulomatosis with polyangiitis complicated by Staphylococcus aureus sepsis.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is an ANCA-associated small-vessels vasculitis characterized by hypereosinophilia and eosinophilic asthma. EGPA with life-threatening organ involvement, particularly cardiac and central nervous system (CNS), is a medical emergency requiring immediate immunosuppression. We describe a 58-year-old patient with a history of chronic rhinosinusitis and eosinophilic asthma, who presented with fever, hypereosinophilia and systemic inflammation. Diagnostic workup identified a cardiac mass, CNS vasculitis, CNS embolization and Staphylococcus aureus in blood cultures. Due to rapid normalization of blood cultures, the intracardiac mass was not considered as primarily infective. Active EGPA with cardiac and CNS involvement complicated by a secondary S. aureus sepsis was diagnosed. In order to not negatively impact antibacterial immunity in active EGPA, antibiotic therapy was combined with Benralizumab, which was well tolerated and EGPA resolved rapidly. Benralizumab could serve as a therapeutic option for eosinophil-mediated pathologies in severely ill patients where immunosuppressives are initially contraindicated.

The causes of a peripheral blood eosinophilia in a secondary care setting.

BACKGROUND: A peripheral blood eosinophilia of greater than 1.0 × 109 /L is relatively unusual and offers a clue to the underlying diagnosis. In 2003, we established a specialist service to diagnose unexplained eosinophilia. OBJECTIVE: To describe the causes of an eosinophilia in our service and the diagnostic algorithm we developed. METHODS: Subjects were referred by physician colleagues across a range of specialties and undertook standard investigations following a semi-structured protocol. Data were extracted from a bespoke database. RESULTS: Three hundred and eighty two subjects were referred over a 17-year period. Average age was 54 years and 183 (48%) of subjects were female, with 21 of 25 (84%) females in the idiopathic eosinophilic pneumonia group (p < 0001), 22 of 30 (73%) females in the gastrointestinal disease group (p < .008), but 11 of 37 (30%) females in the eosinophilic granulomatosis with polyangiitis group (p < .04). A diagnosis was assigned after systematic evaluation using a pre-defined algorithm in 361 (94.5%) of cases. Fungal allergy (82 subjects: 21%), parasitic infection (61 subjects: 16%) and severe eosinophilic asthma (50 subjects: 13%) were the three commonest individual diagnoses. Hypereosinophilic syndrome (HES) disease including eosinophilic granulomatosis with polyangiitis (EGPA) accounted for 85 subjects (20%) of which seven subjects (2%) had myeloproliferative disease (M-HES). A high IgE was common, and 79 (91%) of subjects with complete data who had an IgE of ≥1000 IU/L had fungal allergy or parasite infection. The serum tryptase was raised in 44 of 302 (14.5%) of individuals across all diagnostic groups, though none had mastocytosis. CONCLUSION: A diagnosis of an unexplained eosinophilia can usually be determined using as semi-structured algorithm. Parasitic infection and fungal allergy often with severe eosinophilic asthma were common causes, whereas HES, particularly myeloproliferative, disease was relatively rare.

Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA): a multicentric retrospective study of 63 biopsy-proven cases.

OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort. METHODS: We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy. RESULTS: Sixty-three patients [27 women, median age 60 years (18-83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1-296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation. CONCLUSION: Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases.