Involvement In Eosinophilic Granulomatosis With Polyangiitis Research Articles

Severe heart failure and intracardiac thrombosis: going beyond the appearance for diagnosis and treatments.

We describe the case of a 45-year-old female affected by asthma and nasal polyposis who presented to the emergency department because of worsening dyspnea and paresthesia of the left lower limb. Comprehensive instrumental examinations revealed the presence of severe left ventricle dysfunction, intra-cardiac thrombus, deep vein thrombosis, pulmonary embolism, lung infiltrates, polyserositis, and neurological involvements. Finally, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, a rare vasculitis of small-medium blood vessels with several organ involvements. Treatment with anticoagulants, corticosteroids, and cyclophosphamide led to a significant clinical improvement. However, a subcutaneous cardiac defibrillator was implanted because of the persistence of severe left ventricular dysfunction and the high cardiovascular risk phenotype. Indeed, several cardiac manifestations may occur in EGPA, particularly in patients with anti-neutrophil cytoplasmic antibody-negative disease. Therefore, clinicians should have high clinical suspicion because cardiac involvement in EGPA results in a poor prognosis if not diagnosed and adequately treated.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis: acute eosinophilic myocarditis and chronic inflammatory cardiomyopathy

Abstract Objectives Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify the high-risk population. Methods We included EGPA patients hospitalized in our centre from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac MRI and endomyocardial biopsy results, the patients were divided into three groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. Results A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-Control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, P < 0.01), ANCA positivity decreased (41.33/31.82/14.86%, P < 0.01) and lung involvement was reduced (73.33/72.73/43.24%, P = 0.02). In EGPA-EM, cardiac troponin was further elevated (0.27 vs 6.00 ng/ml, P < 0.01), ejection fractions decreased (57.79 vs 33.20%, P < 0.01) while more ST-T abnormality was observed (41.89 vs 20.45%, P = 0.02). The prognosis of EGPA-EM was significantly worse, with a 14.86% death rate and 2-year event-free survival rate below 50%. Furthermore, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [area under the receiver operating characteristic curve 0.85 (95% CI 0.78–0.92), sensitivity 0.78, specificity 0.86]. Conclusions We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given in a timely manner and anti-IL-5 antibodies should be be tested in trials.

Renal involvement in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis, which typically affects small-to medium-sized blood vessels. It is characterized by the presence of tissue infiltrates rich in eosinophils, along with the formation of granulomatous lesions. About 40% of cases have positive anti-neutrophil cytoplasm antibodies (ANCA), with predominant perinuclear staining, and anti-myeloperoxidase (anti-MPO) specificity in about 65% of cases. Typical manifestations of EGPA include the late onset of asthma, nasal and sinus-related symptoms, peripheral neuropathy, and significant eosinophilia observed in the peripheral blood. In contrast to granulomatosis with polyangiitis and microscopic polyangiitis, renal involvement in EGPA is less frequent (about 25%) and poorly studied. Necrotizing pauci-immune crescentic glomerulonephritis is the most common renal presentation in patients with ANCA-positive EGPA. Although rarely, other forms of renal involvement may also be observed, such as eosinophilic interstitial nephritis, mesangial glomerulonephritis, membranous nephropathy, or focal sclerosis. A standardized treatment for EGPA with renal involvement has not been defined, however the survival and the renal outcomes are usually better than in the other ANCA-associated vasculitides. Nonetheless, kidney disease is an adverse prognostic factor for EGPA patients. Larger studies are required to better describe the renal involvement, in particular for patterns different from crescentic glomerulonephritis, and to favor the development of a consensual therapeutic approach. In this article, in addition to personal data, we will review recent findings on patient clinical phenotypes based on ANCA, genetics and the impact of biological drugs on disease management.

At the Heart of Eosinophilic Granulomatosis with Polyangiitis: into Cardiac and Vascular Involvement.

To provide an overview of existing literature on pathogenetic and clinical aspects of cardiac and vascular involvement in eosinophilic granulomatosis with polyangiitis (EGPA). In EGPA, cardiac and vascular involvement are more common than previously thought. However, no international recommendations on the topic are available yet. Herein, we summarize the existing evidence on the topic and propose a diagnostic approach for cardiac involvement in EGPA. The prevalence of cardiovascular involvement in patients with EGPA varies greatly among published studies, ranging between 3.1-18.7% for occlusive arterial disease, 5.8-30% for venous thrombosis and 17-92% for heart involvement. Cardiac involvement in EGPA is associated with high mortality even though manifestations are heterogeneous. In principle, every anatomical structure of the heart can be involved, and EGPA-related heart disease may be completely asymptomatic at first. A careful diagnostic work-up for early detection and prompt treatment initiation is therefore required. While cardiac manifestations are more common in anti-neutrophil cytoplasmic antibodies (ANCA)-negative patients, arterial and venous thrombotic events are not linked to ANCA status but correlate closely with disease activity and accumulate at disease onset. Thrombotic events (mainly venous) are considerably more frequent in EGPA than in the general population contributing substantially to morbidity and highlighting the importance of developing specific prevention strategies for patients who are diagnosed with EGPA.

Hepatic Involvement in Eosinophilic Granulomatosis with Polyangiitis

We presented a case report of Eosinophilic Granulomatosis with Polyangiitis (EGPA) with hepatic involvement which presented itself as multiple nodules in the liver. This confirmed Hprevious literature results, which have reported hepatic involvement in EGPA. The results of the study showed a 45-year-old female with asthma, presented with polyarthralgia, hypostasis in both hands and skin lesions on the body. Lab tests revealed elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP). The total Leukocyte count was 11900 (/ul) with 22% Eosinophil. Computed Tomography (CT) scan of both lungs and liver showed multiple irregular nodules. In the biopsy of the skin lesions, Eosinophilic Vasculitis was reported. Electromyography and Nerve Conduction Velocity (EMG-NCV) was compatible to C8-T11 radiculopathy and Axonal Sensory Motor Polyneuropathy. According to the tests and biopsies the patient was diagnosed with EGPA. Although EGPA is characterized by asthma, hypereosinophilia and vasculitis, it can be presented with atypical manifestations as well.

Novel Targets for Drug Use in Eosinophilic Granulomatosis With Polyangiitis.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare autoimmune disease characterized by medium and small vessels inflammation. Cardiac vasculitic involvement is one of the most severe manifestations with a significant impact on patients' long-term prognosis: anyway, a specific therapeutic approach for heart involvement in EGPA has not been explored yet. Current regimen consists of a long-term therapy with high dose of glucocorticoids, causing the well-known related-adverse events; immunosuppressive drugs are used in patients with severe manifestations, with some limitations. New therapeutic approaches are needed for patients with refractory disease or contraindications to conventional therapies. The quest for the ideal therapy is going toward a more and more personalized approach: on the one hand, efforts are made to use already existing therapies in the most appropriate way; on the other hand, new insights into EGPA pathogenesis allow the discovery of new targets, as demonstrated by mepolizumab and rituximab, targeting eosinophils, and B-cell compartments. This review summarizes the emerging therapies used in EGPA, focusing on the most recent studies on biologics and analyzing their efficacy and safety.

Clinical features of central nervous system involvement in patients with eosinophilic granulomatosis with polyangiitis: a retrospective cohort study in China

BackgroundCentral nervous system (CNS) involvement is extremely rare in eosinophilic granulomatosis with polyangiitis (EGPA), but is associated with a poor prognosis in the five-factor score. This study aims to elucidate the clinical features and independently associated factors of EGPA with CNS involvement.ResultsCNS involvement was observed in 17.3% (19/110) of EGPA patients from Peking Union Medical College Hospital between 2007 and 2019. We retrospectively reviewed their clinical data and analyzed the independently associated factors. Their mean age was 51.7 ± 11.56 years with no male/female predominance. Ischemic lesions were the most common manifestations, accounting for 63.2% of the 19 cases, followed by posterior reversible encephalopathy syndrome (36.8%), spinal cord involvement (15.8%), medulla oblongata involvement (15.8%), and intracranial hemorrhages (15.8%). Compared to the control group, patients with CNS involvement were of older age (51.7 ± 11.56 vs. 43.7 ± 13.78 years, p = 0.019) and had a higher ratio in the digestive tract involvement (52.6% vs. 28.6%, p = 0.042). Further multivariate analysis revealed that age, disease duration, and fever were the potential independent risk factors for CNS involvement of EGPA. Glucocorticoids combined with cyclophosphamide were the strategic therapy (94.7%). Intrathecal injections of dexamethasone and methotrexate were administered to 21.1% of the patients. Although seven patients relapsed during glucocorticoid reduction, seventeen patients finally achieved clinical remission. One patient died of acute intracerebral hemorrhage within one month, and another died of gastrointestinal perforation. Outcomes and cumulative survival show no significant differences between the two groups.ConclusionsCNS involvement is uncommon in EGPA with various manifestations, and ischemic lesions are the most frequent. Age, disease duration, and fever are independent factors associated with CNS involvement in EGPA. The therapy of glucocorticoids combined with cyclophosphamide and intrathecal injections yields favorable responses. Acute intracranial hemorrhage and gastrointestinal perforation may be the principal causes of death.

Isolated CNS involvement in eosinophilic granulomatosis with polyangiitis treated with mepolizumab: A case report

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis disease involving small-sized vessels. The literature has reported involvement of the central nervous system (CNS) in 5% cases, and isolated CNS involvement is extremely rare. Due to its rarity and scarcity of clinical data, standardized treatment of isolated CNS involvement in EGPA is unclear. Mepolizumab, an anti-interleukin-5 monoclonal antibody, was previously introduced to treat EGPA with longer remission period, more patients showing remission, and reduction in prednisolone dose of those who already taking prednisolone compared to placebo. We describe a case of isolated CNS involvement in EGPA, confirmed by brain biopsy and treated with mepolizumab, which was refractory to conventional immunotherapy.

Cardiac Involvement in Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Study in the Chinese Population.

Introduction: Cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA) is associated with a poor prognosis and high mortality; however, few studies about cardiac involvement in EGPA in the Chinese population are available. We conducted this study to determine the clinical characteristics and overall outcomes of Chinese EGPA patients with cardiac involvement.Materials and Methods: We retrospectively collected the clinical data of 83 patients diagnosed with EGPA and analyzed the differences between the patients with and without cardiac involvement.Results: The prevalence of cardiac involvement in EGPA in this cohort was 27.7%. Compared with those without cardiac involvement, EGPA patients with cardiac involvement tended to have a younger age at onset (mean ± SD: 38.4 ± 10.5 vs. 42.1 ± 15.9 years, respectively, p = 0.039), higher eosinophil count (median [IQR]: 5810 [4020–11090] vs. 2880 [1530–6570] n/μL, respectively, p = 0.004), higher disease activity assessed using the Birmingham vasculitis activity score (BVAS) (median [IQR]: 20 [16–28] vs. 15 [12–18], respectively, p = 0.001), and poorer prognosis (Five Factor Score [FFS] ≥ 1: 100% vs. 38.3%, respectively, p = 0.001). In the cardiac involvement group, 43.5% of patients were asymptomatic, but cardiac abnormalities could be detected by cardiac examinations. With appropriate treatment, the overall outcomes of EGPA patients with cardiac involvement in our cohort were good, with only 3 (13.0%) patients dying in the acute phase and no patients dying during follow-up.Conclusions: Cardiac involvement in EGPA was associated with a younger age at onset, higher eosinophil count, higher disease activity, and a poorer prognosis. Comprehensive cardiac examinations and appropriate treatment are essential to improve the prognosis of those with cardiac involvement.

The Critical Role of Cardiac Magnetic Resonance Imaging in Evaluating Patients With Eosinophilic Granulomatosis With Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare autoimmune systemic necrotizing vasculitis of blood vessels that often presents with hypereosinophilia. Cardiac involvement in EGPA directly correlates with the mortality of patients with the disease and is a central part of the disease process. The evaluation and treatment of cardiac anomalies are vital in patients with EGPA. The frequency with which cardiac involvement is seen in the disease process makes early diagnosis crucial in all patients with EGPA. Early treatment has been proven to reverse or cause the disease to go into remission. Several studies have shown that cardiac magnetic resonance (CMR) imaging is the most sensitive and best early indicator of cardiovascular involvement in EGPA. CMR routinely outperforms other diagnostic techniques such as ECG (echocardiography) and CTA (computed tomography angiography) in the detection of cardiac anomalies and should be a part of the standardized assessment of all patients with EGPA. CMR is also a non-invasive diagnostic tool that can also outperform biopsy in the detection of EGPA cardiac involvement. CMR is also a valuable technique that can be used to monitor disease progression while treatment is being performed. Although long-term research studies have yet to show these benefits, the studies that are available today provide ample evidence that shows CMR imaging could ultimately help bring down mortality rates currently seen in EGPA patients if it is used as an evaluation tool from initial diagnosis and throughout the entire course of disease management.

Multi-modality Imaging in a Hypereosinophilic Syndrome with Cardiac Involvement

Introduction Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare, multi-system auto-immune vasculitic disorder characterized by allergic rhinitis, asthma, and prominent peripheral blood eosinophilia. Cardiac involvement is the primary contributor to mortality. Case Report Mr. W is a 53-year-old man with a history of asthma and environmental allergies presented to the emergency department with sudden onset of blurred vision in his left eye and evidence of optic neuritis. He endorsed a 2-week history of night sweats, arthralgias, anorexia, transient ankle edema, and a recent rash. His exam was notable for purpuric lesions in extremities and left visual field deficits. Laboratory data showed a WBC's of 36,000 cells/mm3 with 69% eosinophils, CRP of 63 mg/dl, ESR of 122 mm/min, IgE of 1,741 IU/ml, and troponin of 11 ng/ml. An Electrocardiogram showed low voltage and q waves in anteroseptal leads. An infectious work-up was negative.A brain MRI revealed acute punctate infarcts. A transthoracic echocardiogram (TTE) revealed a severely dilated left ventricle with an ejection fraction of 25%. Cardiac catheterization showed normal coronary arteries, elevated filling pressures, and normal cardiac output. Cardiac Magnetic Resonance (CMR) showed moderate to severe biventricular dysfunction, a moderate pericardial effusion, and patchy bi-ventricular subendocardial enhancement ( Figure 1 A). So he underwent endomyocardial biopsy, which showed increased perivascular eosinophils/eosinophilic degranulation and fibrin ( Figure 1 B). The differential diagnosis was EGPA, hypersensitivity myocarditis or a myeloproliferative variant of hypereosinophilic syndrome. A bone marrow biopsy was performed which showed hypereosinophilia ( Figure 1 C), without evidence of malignancy, confirming EGPA. He was treated with high dose steroids with a prolonged taper and cyclophosphamide, which rapidly resolved his eosinophilia. A repeat TTE 7 weeks later showed near normalization of cardiac function and resolution of pericardial fluid. Conclusion Cardiac involvement in EGPA is up to 60% and early development of myocardial fibrosis. Prompt recognition via multi-modality imaging and endomyocardial biopsy and rapid treatment with high dose steroids or other immunotherapies, may prevent early progression to dilated or restrictive cardiomyopathy.

A Rare Presentation of Eosinophilic Granulomatosis with Polyangiitis with Diffuse Lymphadenopathy

A Rare Presentation of Eosinophilic Granulomatosis with Polyangiitis with Diffuse Lymphadenopathy

Focus on audiologic impairment in eosinophilic granulomatosis with polyangiitis.

To evaluate the clinical features of audiologic impairment and its relationship with the nasal, vestibular, and rheumatologic profile in a cohort of patients with eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg-Strauss syndrome. Prospective cross-sectional study. Thirty-nine patients with EGPA, considered controlled according to the Birmingham Vasculitis Activity Score and the Vasculitis Damage Index, underwent a complete audiologic evalutaion with otomicroscopy, impedance audiometry, speech audiometry, and auditory brainstem responses; rhinologic evaluation was made by means of fiberoptic endoscopy and nasal cytology; the clinical evaluation was completed with analysis of the facial function and, in patients with referred vertigo, with videonystagmography (VNG). Data were compared to the rheumatologic profile (eosinophil count, antineutrophil cytoplasmic antibodies status). Thirty-four of 39 patients fulfilled the inclusion criteria. Of those, 18 (52, 8%) were affected by variable degrees of hearing loss (sensorineural hearing loss [SNHL]) in four cases (11, 8%), mixed sensorineural and conductive hearing loss in two (5, 9%), presbycusis in six (17, 6%), and otitis media with effusion (OME) in six (17, 6%). Vestibular impairment was represented by benign paroxysmal positional vertigo and unspecific dizziness in three (8, 8%) and four cases (11, 8%), respectively, all with normal VNG. Ear involvement was statistically related to the EGPA vasculitic pattern and independent from the nasal impairment, cytology, and duration of nasal symptoms. No facial palsy was registered. In our experience, the largest in the existing literature, the otological involvement in EGPA is common and may occur variably as SNHL or OME. Otological involvement occurs early in the course of the disease process, but is nonspecific in making the diagnosis of EGPA. Its recognition is therefore fundamental. 4. Laryngoscope, 126:2792-2797, 2016.

Asthma Control and Airway Inflammation in Patients with Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis that occurs in patients with asthma, nasal disease, blood and tissue eosinophilia, and extrapulmonary manifestations. The aim of our study was to assess the clinical, functional, and inflammatory status of upper and lower airways in 37 patients with EGPA, examined 6.4 ± 4.7 years after diagnosis, when they were in partial or complete remission from systemic involvement while on treatment with low-dose oral corticosteroids as maintenance therapy. All patients performed spirometry and were assessed for bronchial hyperreactivity, sputum eosinophilia, and fractional exhaled nitric oxide; asthma control was evaluated according to the Global Initiative for Asthma (GINA) guidelines and the Asthma Control Test. Markers of systemic disease were compared with the data available at diagnosis. Nasal involvement was evaluated by using the Sino-Nasal Outcome Test, nasal endoscopy, and nasal cytology. The impact on the quality of life was evaluated by using generic (36-item short form health survey) and organ-specific questionnaires. At the time of the study visit, almost all patients were receiving low-dose oral corticosteroids and immunomodulating drugs, but only 50% were being treated with inhaled corticosteroids. Although low systemic disease activity was documented in the large majority of patients, poorly controlled asthma and rhinosinusitis with eosinophilic airway inflammation were demonstrated in almost all patients. A significant correlation was found between sputum and blood eosinophilia and between fractional exhaled nitric oxide and asthma control. The 36-item short form health survey questionnaire results significantly correlated with the Sino-Nasal Outcome Test but not with the Asthma Control Test. Systemic treatment controls systemic involvement in EGPA, but not asthma and nasal diseases, which negatively affects patients' quality of life.

Cholestatic Hepatitis in a Patient With Eosinophilic Granulomatosis and Polyangiitis

Introduction: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a multisystem disorder, commonly treated with chronic steroid therapy, characterized by asthma, chronic rhinosinusitis, and prominent eosinophilia. EGPA can involve any organ system, lungs being most common. Eosinophilic gastroenteritis is the most common gastrointestinal involvement, typically presenting with abdominal pain and diarrhea. Liver/biliary involvement in EGPA is reported but rare. The case below is a patient with EGPA who has had a several year history of RUQ abdominal pain, intermittent elevated LFTs, and jaundice and further evaluation revealed EGPA-related cholestatic hepatitis by liver biopsy. Case Description: The patient is a 57 y/o male with a history of EGPA on chronic steroids, GERD, and gallstone pancreatitis that has had several admissions since 2009 for chronic RUQ pain, nausea, elevated LFTs and jaundice. He underwent cholecystectomy in 2009 with liver biopsy at that time which revealed portal and periportal hepatitis as well as centrilobular cholestasis. On his most recent presentation, it was thought he had choledocholithiasis and possible cholangitis. His bilirubin remained elevated despite an ERCP that was done with extraction of small stones and sludge. He underwent a second ERCP with sludge extraction and common bile duct stent placement but his bilirubin remained elevated. Chronic liver disease markers were negative. Given his previous biopsy results, another liver biopsy was obtained and demonstrated liver parenchyma with cholestasis, predominantly in pericentral zones and accompanying mild to moderate mixed acute and chronic lobular inflammation with evidence of hepatocyte damage. This is consistent with a cholestatic hepatitis seen in patients with Churg-Strauss Syndrome/EGPA. His steroids were increased to 60mg daily for 1 month. Weekly labs were obtained and his liver chemistries normalized over two months. His prednisone was tapered down to his original dose of 20mg daily. Discussion: Liver involvement in EGPA is rare but should be considered in patients with a history of EGPA who present with cholestasis. Better control of EGPA with immunosuppression has shown significant improvement in these cases.Figure 1Table 1: Liver Function Tests Before and After Treatment Course

Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis

BackgroundTo investigate the prevalence and prognostic relevance of cardiac involvement in an ANCA-associated vasculitis (AAV) population of eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis (GPA) patients. MethodsProspective cohort study of fifty EGPA and forty-one GPA patients in sustained remission without previous in-depth cardiac screening attending our clinical immunology outpatient department. Cardiac screening included clinical evaluation, ECG, 24-hour Holter registration, echocardiography and cardiac magnetic resonance imaging (CMR) with coronary angiography and endomyocardial biopsy upon indication. Fifty age-, sex- and cardiovascular risk factor-matched control subjects were randomly selected from a population study. Long-term outcome was assessed using all-cause and cardiovascular mortality. ResultsA total of 91 AAV-patients (age 60±11, range 63–87years) were compared to 50-matched control subjects (age 60±9years, range 46–78years). ECG and echocardiography demonstrated cardiac abnormalities in 62% EGPA and 46% GPA patients vs 20% controls (P<0.001 and P=0.014, respectively). A total of 69 AAV-patients underwent additional CMR, slightly increasing the prevalence of cardiac involvement to 66% in EGPA and 61% in GPA patients. After a mean follow-up of 53±18months, presence of cardiac involvement using ECG and echocardiography in AAV-patients showed increased all-cause and cardiovascular mortality (Log-rank P=0.015 and Log-rank P=0.021, respectively). ConclusionCardiac involvement in EGPA and GPA patients with sustained remission is high, even if symptoms are absent and ECG is normal. Moreover, cardiac involvement is a strong predictor of (cardiovascular) mortality. Therefore, risk stratification using cardiac imaging is recommended in all AAV-patients, irrespective of symptoms or ECG abnormalities.