Diagnosis Of Eosinophilic Granulomatosis With Polyangiitis Research Articles

Eosinophilic Granulomatosis with Polyangiitis with ophthalmic involvement: A Case report and Literature Review

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic necrotizing vasculitis primarily affecting small blood vessels. It is characterized by extravascular eosinophilic granulomas, peripheral eosinophilia, and often coexists with asthma. This rare condition can affect individuals of any gender and age, presenting with a variety of multisystemic symptoms. Prognosis is largely influenced by cardiac involvement, evaluated using the Five-Factor Score (FFS) to guide treatment decisions. Respiratory manifestations, particularly severe and corticosteroid-dependent asthma, are common in EGPA and may aid in its early diagnosis. In this case report, we describe a patient with an uncontrolled asthma admitted for moderate asthma exacerbation. Clinical examination revealed ocular redness and skin lesions, along with hypereosinophilia on assessment and reticulo-micronodular infiltrates on chest CT scan. EGPA diagnosis was confirmed based on the ACR 1990 criteria, wich have been updated and substituted with more objective criteria in 2022. According to the FFS score, the patient underwent systemic corticosteroid therapy in conjunction with azathioprine, leading to an overall favorable outcome over a 3-year follow-up period.

Burden of Eosinophilic Granulomatosis with Polyangiitis in Europe

BackgroundReal-world evidence characterising the burden of eosinophilic granulomatosis with polyangiitis (EGPA) in Europe is limited.ObjectiveTo characterise patients in a large European EGPA cohort.MethodsThis retrospective, non-interventional, longitudinal study recruited cross-specialty physicians from France, Germany, Italy, Spain, and the United Kingdom to conduct medical chart reviews for patients with a physician-confirmed diagnosis of EGPA. Patients were ≥12 years of age at diagnosis with ≥1 year of follow-up data from the first clinical visit with the physician (index date). Outcome measures collected from index date to end of follow-up included clinical manifestations and healthcare resource utilisation (HCRU).ResultsIn total, 407 patient medical charts were reviewed by 204 physicians; median (interquartile range) duration of follow-up from index date was 2.2 (1.7, 3.5) years. Most patients (73.5%) had asthma. Patients underwent multiple diagnostic assessments, and 74.9% received ≥3 different therapies between diagnosis and end of follow-up (98.8% oral corticosteroids, 63.9% immunosuppressive therapies, 45.5% biologics). During follow-up, 84.5% of patients experienced EGPA clinical manifestations; most were considered moderate or severe and commonly affected the lungs (55.8%; including lung infiltrates: 25.8% and severe asthma: 24.8%), ear, nose, and throat (53.3%), and skin (41.8%). HCRU was substantial: 26.0% of patients made emergency department visits, 36.6% were hospitalised and 84.8% had outpatient visits.ConclusionsThese real-world data show that EGPA presents a substantial burden to patients and the healthcare system. Earlier and better differential diagnosis and appropriate treatment may help reduce incidence of clinical manifestations and HCRU.

SERPINA3, FGA, AGP1, ITIH3 and SAA1 as novel biomarkers for eosinophilic granulomatosis with polyangiitis diagnosis and activity assessment.

To identify novel biomarkers for diagnosis and prediction of active eosinophilic granulomatosis with polyangiitis (EGPA) through data-independent acquisition (DIA) analysis. Plasma from 11 EGPA patients and 10 healthy controls (HCs) were analyzed through DIA to identify potential biomarkers. The results were validated in 32 EGPA patients, 24 disease controls (DCs), and 20 HCs using enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of candidate biomarkers. Thirty-five differentially expressed proteins (DEPs) (24 upregulated and 11 downregulated) were screened between EGPA and HC groups. Five proteins, including serine proteinase inhibitor A3 (SERPINA3), alpha-fibrinogen (FGA), alpha-1 acid glycoprotein 1(AGP1), inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3), and serum amyloid A1 (SAA1), were significantly upregulated in EGPA compared with HCs. Apart from SAA1, all proteins were also higher in EGPA patients compared with DCs. Furthermore, a panel of SERPINA3 and SAA1 exhibited potential diagnostic value for EGPA with an area under the curve (AUC) of 0.953, while a panel of SERPINA3, FGA, AGP1, and ITIH3 showed good discriminative power to differentiate EGPA from DCs with AUC of 0.926. Moreover, SERPINA3, FGA, and AGP levels were significantly higher in active EGPA and correlated well with disease activity. A combination of SERPINA3 and AGP1 exhibited an excellent AUC of 0.918 for disease activity assessment. SERPINA3, FGA, AGP1, ITIH3 and SAA1 were identified as potential biomarkers for EGPA diagnosis and disease activity assessment. Among them, as a single biomarker, SERPINA3 has the best diagnostic performance.

Sudden Visual Loss due to Arteritic Anterior Ischaemic Optic Neuropathy: A Rare Manifestation of Eosinophilic Granulomatosis with Polyangiitis.

eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multisystem inflammatory disease characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of various organs. While the eye is uncommonly affected in patients with EGPA, multiple ophthalmic manifestations have been reported, which can result in serious visual impairment without timely treatment. we report the case of a 79-year-old woman with a history of asthma and nasal polyps who presented with low-grade fever, mild alteration of mental status, and fatigue. Chest X-ray revealed bilateral interstitial infiltrates. Lab tests showed elevated C-reactive protein level and eosinophilia (eosinophil count, 4.6 x109 cells/l); blood cultures and parasitological examination of stools tested negative. Four days after presentation, the patient reported sudden and severe blurring of vision in her left eye. Ophthalmological examination revealed bilateral swollen optic disc and visual field loss, more severe in the left eye. A diagnosis of EGPA complicated by arteritic anterior ischaemic optic neuropathy (A-AION) was proposed, while an alternative or concurrent diagnosis of giant cell arteritis was ruled out based on clinical picture. Immunosuppressive treatment with high-dose intravenous glucocorticoids was promptly started. The patient's visual defect did not improve; however, two months later, no worsening was registered on ophthalmic reassessment. A-AION is an infrequent but severe manifestation of EGPA, requiring prompt diagnosis and emergency-level glucocorticoid therapy to prevent any further vision loss. Disease awareness and a multidisciplinary approach are crucial to expedite diagnostic work-up and effective management of EGPA-related ocular complications. Arteritic ischaemic optical neuropathy is a potential cause of sudden and severe visual loss in eosinophilic granulomatosis with polyangiitis (EGPA) patients.Visual loss due to arteritic ischaemic optical neuropathy is rarely reversible; however, a timely glucocorticoid treatment may prevent further progression of visual impairment.Multidisciplinary approach is crucial to expedite diagnostic work-up and effective management of EGPA patients with ocular complications.

Benralizumab Reduces Respiratory Exacerbations and Oral Glucocorticosteroid Dose in Patients with Severe Asthma and Eosinophilic Granulomatosis with Polyangiitis.

Benralizumab reduces exacerbations and long-term oral glucocorticosteroid (OCS) exposure in patients with severe eosinophilic asthma. In patients with eosinophilic granulomatosis with polyangiitis (EGPA), uncontrolled symptoms and exacerbations of asthma and chronic rhinosinusitis (CRS) are important reasons for continued OCS therapies. We aimed to describe outcomes of patients with severe asthma and EGPA treated with benralizumab in real-life. We retrospectively analyzed adult patients from the Severe Asthma Unit at LMU Munich diagnosed with severe asthma and EGPA treated with benralizumab, differentiating two groups: Group A, patients with a stable daily OCS dose and diagnosis of EGPA >6 months ago; and Group B, patients treated with high-dose daily OCS due to recent diagnosis of EGPA <6 months ago. We compared outcome parameters at baseline and 12 months after initiation of benralizumab, including respiratory exacerbations, daily OCS dose, and lung function. Group A included 17 patients, all receiving OCS therapy and additional immunosuppressants; 15 patients (88%) continued benralizumab for more than 12 months, demonstrating a significant reduction in daily OCS dose and exacerbations while FEV1 increased. Group B included 9 patients, all with high-dose daily OCS and some receiving cyclophosphamide pulse therapy for life-threatening disease. Benralizumab addition during induction was well tolerated. A total of 7/9 (78%) continued benralizumab for more than 12 months and preserved EGPA remission at the 12-month timepoint. In this real-life cohort of patients with severe asthma and EGPA, benralizumab initiation during remission maintenance reduced respiratory exacerbations and daily OCS dose. Benralizumab initiation during remission induction was associated with a high rate of clinical EGPA remission.

Трудности диагностики эозинофильного гранулематоза с полиангиитом в клинической практике

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multisystem immune-mediated vasculitis with damage to medium and small vessels (including capillaries, venules and veins), first described in 1951. The etiology and pathogenesis of this disease associated with a combination of immunocomplex and allergic mechanisms have not been fully studied, and there are no generally accepted techniques to initial therapy. The diversity of the clinical picture at the disease onset, the gradual manifestation of signs, the need to take into account not only clinical but also laboratory parameters, makes it difficult to make a correct diagnosis in the early stages. This article describes a clinical case of a relatively late diagnosis of EGPA, which may be due to a lack of practitioner awareness about such a rare disease and a late referral to a rheumatologist. Not only morphological verification and immunological tests of patients can speed up diagnosis, but also discussion of such clinical cases in the medical community. Currently, the EGPA therapy possibilities have been expanded by including the disease in indications for biological treatments aimed at interleukin 5, which will improve the disease prognosis and reduce the burden of long-term hormonal therapy. KEYWORDS: eosinophilic granulomatosis with polyangiitis, vasculitis, eosinophilia, differential diagnosis, bronchial asthma, clinical case. FOR CITATION: Karoli N.A., Kanaeva T.V., Nikitina N.M. Difficulties in diagnosing eosinophilic granulomatosis with polyangiitis in clinical practice. Russian Medical Inquiry. 2024;8(3):171–175 (in Russ.). DOI: 10.32364/2587-6821-2024-8-3-8.

Cardiac Mass and Cerebrovascular Accident as Primary Manifestations of Churg-Strauss Syndrome.

Churg-Strauss syndrome (CSS), recently named eosinophilic granulomatosis with polyangiitis (EGPA), is a rare form of systemic vasculitis with extravascular granulomas occurring in patients with asthma and tissue eosinophilia. We represent a large left ventricular granuloma, confirmed by histopathologic evaluation, detected as a ventricular mass by echocardiography in a 45-year-old asthmatic male who was admitted for a cerebrovascular accident. Paraclinical and histopathologic findings confirmed the diagnosis of EGPA. As cardiac involvement in patients with EGPA is associated with poor prognosis, routine echocardiographic evaluation of these patients is suggested.

CPC03 Triad of generalized rash, peripheral eosinophilia and coexisting obstructive airway disease

Abstract An 87-year-old woman was referred to the acute dermatology service with a 1-week history of a generalized painful rash. She was under the care of the medical team for treatment of pneumonia with symptoms of a cough, fevers and shortness of breath. Her past medical history included adult-onset asthma, hyponatraemia and hypertension. She had never smoked. On examination, she had erythematous smooth papules and plaques on her limbs and torso with palmoplantar involvement, alongside purple macules and patches where older lesions were present. There was no lymphadenopathy and no mucosal involvement. She had an oxygen requirement of 2 L per minute via nasal cannula. Initial blood tests showed eosinophils of 2.8 × 109 cells L−1 and a C-reactive protein (CRP) of 77 mg L−1. A chest radiograph showed bilateral ill-defined shadowing. Two skin punch biopsies were performed for histology and immunofluorescence. Vasculitis screen identified positive antinuclear antibodies (anti-Ro) and reduced complement C4 with negative antineutrophil cytoplasmic antibody (ANCA). The patient remained unwell with increasing CRP and peripheral eosinophilia (up to 9.2 × 109 cells L−1) with rash progressing to exhibit a reticular pattern. Alongside bilateral patchy ground glass opacification on chest computed tomography, a clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was made. Differential diagnoses included viral exanthem, erythema multiforme and urticarial vasculitis. Screening for cardiac, renal and sinus involvement was undertaken. The patient improved clinically following the initiation of systemic steroids and the peripheral eosinophilia returned to baseline. Skin histology reinforced the clinical diagnosis of EGPA, demonstrating a dermal and perivascular eosinophilic infiltrate with focal extension into vessel walls. EGPA is a rare small- to medium-sized vessel vasculitis with an annual incidence of 0.9–2.4 per million and a median age at diagnosis of 49–59 years. The clinicopathological hallmarks, as in this case, are asthma with peripheral eosinophilia and pulmonary eosinophilic infiltrates. Median time from onset of asthma to presentation with EGPA is 5–9 years. EGPA remains a clinical diagnosis, reinforced by serological and histological findings, although ANCA is reported to be negative in 60–70% of cases. Systemic steroids are the first-line therapy, with a role for second-line immunosuppressants such as methotrexate and rituximab. The key learning points from this case are to keep an open mind in considering a systemic cause for cutaneous manifestations, especially when the patient does not fulfil the usual demographic picture.

Eosinophilic granulomatosis with polyangiitis: etiopathogenesis, classification and clinical phenotypes

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic disease that can be classified as both a hypereosinophilic condition and an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and is characterized by granulomatous inflammation. The pathogenesis of EGPA is not completely understood. It is likely that this disease is Th2-mediated, and blood and tissue eosinophilia serves as the main diagnostic criterion. The hallmarks and main effectors of organ damage in EGPA include asthma-associated necrotizing vasculitis of small-to-medium vessels and eosinophilic proliferation. Endothelial injury and vascular inflammation in EGPA is caused by ANCA via activation of circulating neutrophils. Two clinical phenotypes of the disease have been described based on the detection of ANCA: ANCA-negative with manifestations of hypereosinophilia (for example, pulmonary infiltrates and cardiomyopathy) and ANCA-positive with clinical signs of vasculitis (for example, glomerulonephritis, purpura, and mononeuritis multiplex). Both phenotypes were confirmed by histological and genomic research. However, these two coexisting mechanisms cannot be separated in clinical practice.The aim of the article is to present current knowledge of eosinophilic and ANCA-mediated aspects of the pathogenesis, classification and clinical phenotypes of EGPA, and consider prospects for future research.Conclusion. The development of EGPA is based on eosinophilic dysfunction. This dysfunction means that patients with a genetically determined predisposition to recognize the ANCA antigen and with HLA-DQ (human leukocyte antigen DQ) alleles produce anti-myeloperoxidase autoantibodies and later develop an aberrant autoimmune process. Further comprehensive post-genomic studies are needed to identify the pathogenetic mechanisms and characterize molecular features of EGPA clinical phenotypes. The elaboration of molecular endotypes will lead to the identification of new activity biomarkers and therapeutic targets that can improve the diagnosis of EGPA and the treatment outcomes.

Anti-IL5 Monoclonal Antibodies Reduce Asthma Exacerbations and Corticosteroids Dose in Three Eosinophilic Granulomatosis with Polyangiitis Case Reports.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystem necrotizing small and medium-sized vessel vasculitis with eosinophilic adult-onset asthma as part of its spectrum. Therapeutic choices include corticosteroids, immunosuppressive agents, and novel immunomodulators. Mepolizumab and benralizumab are monoclonal antibodies targeting Interleukin-5 (IL-5), which plays a leading role in every stage of production and maturation of eosinophils and are recently undergoing evaluation and administered in steroid-dependent, relapsing and/or refractory EGPA. Herein we describe the cases of three patients with a prior EGPA diagnosis, experiencing frequent asthmatic exacerbations despite oral and inhaled corticosteroid treatment (two patients) and adverse effects of corticosteroids (one patient). Two patients are under treatment with mepolizumab and one patient with benralizumab as an add-on supplemental regimen. In our case series anti-IL5 monoclonal antibodies proved efficient asthma-controlling and corticosteroid-sparing agents.

ЭОЗИНОФИЛЬНЫЙ ГРАНУЛЕМАТОЗ С ПОЛИАНГИИТОМ

Introduction. Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as allergic granulomatosis (Churg-Stross syndrome), in the modern sense is a necrotizing multisystem vasculitis of predominantly small vessels associated with hyperproduction of antineutrophil cytoplasmic antibodies (ANCA), peripheral blood hypereosinophilia. Although the most frequently involved are the respiratory organs (rhinosinusitis, bronchial asthma, pulmonary infiltrates), EGPA affects any organs and systems (heart, kidneys, gastrointestinal tract, nervous system, skin, joints, etc.) which makes its diagnosis difficult. Aim. To present an observation of a difficult-to-diagnose clinical case of eosinophilic granulomatosis with polyangiitis. Materials and methods. The analysis of clinical, laboratory, special testing of the patient was carried out. Results. Diagnosis of EGPA in this patient was difficult. Fever up to 40°C, papulo-necrotic skin eruptions on upper and lower extremities, trunk; weight loss; multiple organ involvement of heart, lungs, kidneys, liver; positive hemoculture with isolation of Staph. haemoliticus, and from skin lesions of Staph. epidermidis – all these served as a reason to suspect staphylococcal sepsis with possible infectious endocarditis and prescribe antimicrobial therapy which was ineffective. Progression of the disease with worsening clinical manifestations, detection of blood eosinophilia (18%), positive ANCA on immunological examination, eosinophilic and lymphohistiocytic infiltration around microvessels on histological examination of the musculocutaneous flap allowed the diagnosis of EGPA to be verified. Pulse chemotherapy with cyclophosphamide and medium doses of methylprednisolone led to regression of the disease manifestations in the patient. Conclusion. The course of EGPA can include life-threatening conditions (acute myocardial infarction and pulmonary hemorrhage). Timely diagnosis and standards of active chemotherapy expand possibilities of managing this severe group of patients.

Testicular vasculitis in eosinophilic granulomatosis with polyangiitis: a case-based review.

Testicular vasculitis (TV) develops when an organ is involved in systemic vasculitis. A 47-year-old man with eosinophilic granulomatosis with polyangiitis (EGPA) developed TV as the first clinical episode. The patient had bronchial asthma for 8years and developed left testicular pain before developing arthralgia, abdominal involvement, and sensory polyneuropathy, which led to the diagnosis of EGPA. The induration of the affected testicle persisted even after initiating immunosuppressive therapy with corticosteroids and cyclophosphamide, raising concern for testicular neoplasm, while testicular pain and other symptoms resolved. The patient underwent inguinal orchiectomy, and a histology examination of the resected testicle revealed fibrinoid necrotizing vasculitis. Only three cases of biopsy-proven TV in patients with EGPA have been reported in our review of published English-language articles. Two of the three patients in the reviewed cases developed TV before being diagnosed with EGPA. Moreover, all patients underwent extirpation of the affected testicle, leading to a pathological diagnosis of TV. This report suggests that TV may develop and be the presenting condition in EGPA, although urogenital involvement is rare.

A NEAR MISS IS AS GOOD AS A MILE: RECOGNIZING HYPEREOSINOPHILIC SYNDROME

<h3>Introduction</h3> We discuss a case of hypereosinophilic syndrome (HES) misdiagnosed as acute chest syndrome (ACS). Learning objectives include recognizing premature closure as a cognitive bias and review of diagnostic criteria for Eosinophilic Granulomatosis with Polyangiitis (EGPA). <h3>Case Description</h3> A 46-year-old woman with asthma and sickle-cell disease (SCD) complained of worsening nasal congestion, productive cough, and shortness of breath persisting despite multiple courses of antibiotics. She underwent sinus surgery, and microscopy of ethmoid sinus contents revealed eosinophilic inflammation. She developed worsening cough and shortness of breath and was treated with antibiotics for presumed pneumonia. Her respiratory status deteriorated, requiring intubation. CXR revealed patchy opacification concerning for ACS. AEC was 4320 cells/µL. She was started on methylprednisolone and successfully extubated. The diagnosis of EGPA was established, and she was transitioned to mepolizumab. Symptoms have improved on this treatment. <h3>Discussion</h3> ACS is diagnosed in a patient with SCD when a new pulmonary infiltrate is present on chest imaging. This is frequently attributed to complications of a vaso-occlusive crisis or infection, as it was initially in this case. However, given her history of asthma, peripheral eosinophilia and recent pansinusitis with eosinophilic infiltration, a diagnosis of EGPA should be considered. In diagnostic reasoning, physicians aim to quickly develop a working diagnosis based on history and objective data in attempt to treat the presenting condition. However, one must be careful to avoid premature closure, a type of cognitive error, which occurs when physicians accept an initial diagnosis and fail to contemplate other alternatives, leading to misdiagnosis and ultimate delay in treatment.

ANSWERS LIE IN THE COMPLETE BLOOD COUNT: A CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS PRESENTING WITH ACUTE ST-WAVE ELEVATION MYOCARDIAL INFARCTION

ANSWERS LIE IN THE COMPLETE BLOOD COUNT: A CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS PRESENTING WITH ACUTE ST-WAVE ELEVATION MYOCARDIAL INFARCTION

Mechanisms and Neuroimaging Patterns of Hypereosinophilia-Related Ischemic Stroke: A Narrative Review through Three Cases.

Background: Hypereosinophilic syndromes (HES) are a group of relatively rare disorders in which neurological manifestations, including ischemic stroke, are common. The hypothesized pathophysiological mechanisms are hypercoagulability, cardioembolism (mainly mediated by myocardial involvement) and damage to the endothelium. A variable ischemic pattern has been described, including an association of territorial and border zone ischemic stroke. Methods: Three patients who presented to our department with acute stroke were selected aiming to show these three different mechanisms inferred from the stroke pattern on brain Magnetic Resonance Imaging (MRI) and to simultaneously illustrate the three main causes of HES. Results and Discussion: The first patient is a 55-year-old man with an abrupt onset of aphasia due to an acute ischemic stroke involving the left parietal lobule and the angular gyrus; recent lab test had shown hypereosinophilia. An extensive workup excluded primary and secondary causes of hypereosinophilia so a diagnosis of idiopathic hypereosinophilia was done and he was treated with high doses of steroids. The second patient had severe hypereosinophilia and developed multiple small, scattered ischemic lesions, mainly in border zone zones. The history of severe asthma and recurrent sinusitis supported the diagnosis of EGPA (Eosinophilic Granulomatosis with Polyangiitis); considering the severe clinical conditions and the presumptive role of hypereosinophilia in determining her symptoms, steroid treatment was promptly started, with good clinical response. The third patient also presented with multiple metachronous ischemic lesions, both in cortical and border zone distribution and marked eosinophilia; the diagnostic work-up found an ovarian cancer. She was treated with steroids and then underwent surgery and adjuvant chemotherapy. Conclusions: HES should be considered in stroke etiological evaluation, although it is a rare disorder, and border zones pattern without large artery steno-occlusion on neuroimaging may help to raise the suspicion in the neurovascular diagnostic pathway. A thorough research of the sources of hypereosinophilia should be performed to select the appropriate therapy.

Eosinophilic granulomatosis with polyangiitis: diagnosis and treatment-related issues

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic necrotizing vasculitis of small to medium-sized vessels associated with antineutrophil cytoplasmic antibodies (ANCA). EGPA is usually diagnosed in patients with bronchial asthma (BA) and is characterized by a predominant lesion of the lungs, skin, and peripheral nervous system. ANCAs to myeloperoxidase are detected in 1/3 of patients with EGPA. Presence or absence of ANCAs differentiates 2 disease phenotypes with different clinical characteristics and prognosis. New opportunities for the treatment of EGPA appeared after identification of the key role of eosinophils in EGPA and development of targeted drugs for the treatment of eosinophilic BA that are being studied now. Aim of the review is to highlight modern approaches to the diagnosis and treatment of patients with EGPA, primarily through the use of targeted biological therapy. Conclusion. EGPA is a multisystem disease with ambivalent manifestations associated with eosinophilic or ANCA-mediated small vessel injuries. Currently, there is no “gold standard” for the diagnosis of EGPA, although the efficacy of pharmacological therapy is directly related to early detection and timely initiation of treatment. Monoclonal antibodies targeting interleukin-5 (IL-5) are an effective alternative to conventional systemic corticosteroids used alone or in combination with immunosuppressants (cyclophosphamide for induction and azathioprine for maintenance therapy) in patients with severe/refractory disease and unfavorable prognosis. The clinical benefits of the targeted anti-IL-5 drug mepolizumab were confirmed in a randomized controlled trial, and this drug was approved for the treatment of patients with EGPA. Currently, new drugs, including targeted ones, are being tested for induction and maintenance therapy. Pulmonologists and rheumatologists should coordinate patient management to improve the results of treatment and the prognosis of the disease.

Self-Reported Data and Physician-Reported Data in Patients With Eosinophilic Granulomatosis With Polyangiitis: Comparative Analysis.

BackgroundPatient-based registries can help advance research on rare diseases such as eosinophilic granulomatosis with polyangiitis (EGPA), a complex multiorgan form of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.ObjectiveThe aim of this study is to compare patient-reported and physician-reported data on manifestations, treatments, and outcomes for patients with EGPA.MethodsWe completed a comparative analysis of patients ≥18 years with EGPA in Canada and the United States from the following 2 cohorts: (1) The Vasculitis Patient-Powered Research Network (VPPRN), a self-enrolled secure portal with patient-entered data updated quarterly (2014-2019) and (2) the Vasculitis Clinical Research Consortium (VCRC) observational studies, a physician-entered database (2003-2019) of patients who fulfilled the 1990 American College of Rheumatology classification criteria for EGPA. The studied parameters included demographic characteristics, clinical manifestations, ANCA status, treatments, and relapses.ResultsData from 195 patients with a validated diagnosis of EGPA in the VPPRN and 354 patients enrolled in the VCRC were analyzed. Compared to the VCRC cohort, the patients in the VPPRN cohort were more likely to be female (135/195, 69.2% compared to 209/354, 59%; P=.02) and younger at diagnosis (47.3 compared to 50.0 years; P=.03); both cohorts reported similar frequencies of asthma (177/184, 96.2% in the VPPRN cohort compared to 329/354, 92.9% in the VCRC cohort; P=.13) and cardiac manifestations (44/153, 28.8% compared to 75/354, 21.2%; P=.06), but the VPPRN cohort reported less frequent lung manifestations other than asthma and more frequent disease manifestations in all other organ systems. The ANCA positivity was 48.9% (64/131) in the VPPRN patients compared to 38.9% (123/316; P=.05) in the VCRC cohort. Relapsing disease after study enrollment was reported in 32.3% (63/195) of patients in the VPPRN compared to 35.7% (99/277) of patients in the VCRC. Most therapies (GC, cyclophosphamide, mepolizumab) were used at similar frequencies in both groups, except for rituximab with VPPRN patients reporting more use than the VCRC cohort (47/195, 24.1% compared to 29/277, 10.5%; P<.001).ConclusionsOverall, patients and physicians report manifestations of EGPA at similar frequencies. However, observed differences between patient and physician reports imply the potential occurrence of selection biases. These results support the use of patient-reported data in EGPA but also the need for careful consideration of disease-specific definitions for the study of EGPA and how patient- and physician-reported data are collected.Trial RegistrationClinicalTrials.gov NCT00315380, https://clinicaltrials.gov/ct2/show/NCT00315380; ClinicalTrials.gov NCT01241305, https://clinicaltrials.gov/ct2/show/NCT01241305

ATYPICAL CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a multi-organ vasculitis. However, the hallmarks of the disease are eosinophilia, chronic sinusitis, and asthma. Vasculitic organ involvement might be absent early on, making the diagnosis challenging1. We present the case of a patient with atypical presentation and serology for EGPA. CASE PRESENTATION: A 71-year-old male with a history of non-asthmatic eosinophilic bronchitis, chronic sinusitis, and peripheral eosinophilia (peak 936 cells/uL; 17.6%) was admitted to the hospital with dyspnea and rapidly progressive acute hypoxemic respiratory failure requiring transfer to the intensive care unit. He was started on high flow nasal cannula (60LPM; FiO2 90%-100%). Bilateral crackles noted with no pitting edema. Chest CT showed bilateral airspace disease and ground glass opacities. He tested negative twice for SARS-CoV-2. White blood cell count, kidney function, and brain natriuretic peptide were normal. Autoimmune workup was ordered. He was started on empiric broad-spectrum antibiotic, and gently diuresed. As his presentation was suggestive of eosinophilic lung disease, and in light of significant oxygen requirement, the decision was made to hold on bronchoscopy and start solumedrol at 125mg/day. On ICU Day 3, autoimmune workup showed elevated anti-nuclear antibody titer of 1:160 with a speckled pattern, elevated anti-myeloperoxidase (MPO) antibody titer of 49.4 (p-ANCA), and elevated anti-proteinase-3 (anti-PR3) antibody titers of 18.8 (c-ANCA). Infectious workup was negative. The patient was diagnosed with possible EGPA. He was started on cyclophosphamide in addition to steroids. Oxygen requirement continued to improve. He was discharged home on oxygen at 4LPM and oral steroid with a plan for monthly cyclophosphamide infusion. Follow-up in 2 months with repeat chest CT showed marked improvement. DISCUSSION: The manifestations of EGPA are dynamic, with a few manifestations presenting earlier than others2. With the temporal spacing of signs and symptoms, it is often diagnosed late when more clues are evident. In 1990, the American College of Rheumatology (ACR) established a set of 6 criteria: asthma, peripheral eosinophilia >10%, mononeuropathy or polyneuropathy, migratory pulmonary infiltrates, paranasal sinus abnormality, and biopsy containing blood vessel with extravascular eosinophils2. At least 4 out of six of these criteria must be met to have a diagnosis of EGPA with a specificity of 99.7%. p-ANCA (anti-MPO) is present in around 70% of patients with active EGPA, whereas c-ANCA (anti-PR3) is nearly absent3. Our patient met 3 out of the 6 criteria, and his serology was atypical, showing high titers for both p-ANCA and c-ANCA. CONCLUSIONS: EGPA diagnosis in our patient was not a robust one. However, establishing a presumed diagnosis early and starting immunosuppressive therapy likely saved his life. REFERENCE #1: Guillevin L, Cohen P, Gayraud M, et al. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999; 78:26. REFERENCE #2: Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990; 33:1094. REFERENCE #3: Sablé-Fourtassou R, Cohen P, Mahr A, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med 2005; 143:632 DISCLOSURES: No relevant relationships by Tony Abdo, source=Web Response No relevant relationships by Ahel El Haj Chehade, source=Web Response No relevant relationships by Ahmad Hassan, source=Web Response

COVID-19 and eosinophilic granulomatosis with polyangiitis or COVID-19 mimicking eosinophilic granulomatosis with polyangiitis?

Coronavirus disease 2019 (COVID-19) and eosinophilic granulomatosis with polyangiitis (EGPA) share similarities in clinical, imaging findings and may present with respiratory distress. Differentiating a new-onset EGPA from COVID-19 during the current pandemic is a diagnostic challenge, particularly if other EGPA symptoms are overlooked. Here in this study we reviewed the literature regarding EGPA patients with COVID-19 and patients who diagnosed with EGPA or suffered an EGPA flare mimicking COVID-19. We conducted a literature survey in PUBMED database using meshed keywords “COVID-19” and “EGPA”, “COVID-19” and “eosinophilic granulomatosis with polyangiitis”, “COVID-19” and “Churg Strauss Syndrome”, to reveal previously reported cases involving EGPA patients who had COVID-19 infection, patients who suspected to have COVID-19 but eventually diagnosed with EGPA and patients with a known diagnosis of EGPA who suffered a flare but a COVID-19 infection was suspected initially. A total of 11 cases (6 literature cases, 5 cases from our clinic) were included in our study. Seven (63.6%) of the cases were defined as COVID-19 mimicker and 4 (36.4%) were EGPA with COVID-19. All of the cases in EGPA with COVID-19 group had a history of asthma. All of them had a positive PCR result and ground-glass opacities in thorax CT. In COVID-19 mimicker group, six (85.7%) patients had a history of asthma and other EGPA features that were observed were eosinophilia in 6 (85.7%). Our study provided clues regarding the EGPA/COVID-19 diagnostic challenge which may be useful in the current pandemic. Since none of the findings in COVID-19 are disease-specific, other conditions like EGPA should not be overlooked particularly in PCR negative patients and clinical, laboratory and imaging findings should be interpreted carefully. Furthermore, we did not observe poor outcomes in EGPA patients who had COVID-19.

Neurological impact of eosinophilic granulomatosis with polyangiitis.

Nervous system (NS)affectionmay occur in Eosinophilic Granulomatosis with Polyangiitis (EGPA), butitsclinical manifestations and pathophysiologyare rarely described. Our aims are to characterizecentralandperipheralNS (CNS/PNS) involvement and comparebiologicalmarkers inEGPApatients with and without neurological manifestations. Retrospective observational study, including EGPA patients with and without neurological manifestations. Demographics, clinical data, andimmunological markers were analyzed. Descriptive and inferential statistics were performed. Sixteenpatientswereincluded;11 (68.8%) ofwhom were male, with a mean age of 63.38years;8 with (Group 1) and 8 without (Group 2) neurologicalfindings.Neurological impairment preceded EGPA diagnosis in 5 patients, and occurred during follow-up in 3 patients after a median of 4.0years.CNS manifestations observed were stroke (n = 2), bilateralcentral retinal artery occlusion(n = 1), and compressive dorsal myelopathy due to extradural granulation tissue (n = 1). PNSmanifestationswere axonal polyneuropathy (n = 3), sensorineural hearing loss (n = 3), and multiplex mononeuropathy (n = 1). Two patients had both PNS and CNS involvement. There were no statistical differences regarding biological markers [eosinophil count, myeloperoxidase (MPO) antibodies titers] between the 2 groups.One patient from Group 1 wasunresponsive to treatmentandpermanent neurological sequelaewere observed in 7 cases. EGPA-related NS involvement can be heterogeneousandisresponsible for long-term sequelae. In our sample,themainneurological scenarios wereperipheral neuropathy, VIIIcranial nerve neuropathy,ischemic lesions and compressivemyelopathy.Patientswith andwithoutneurological manifestations did notdiffer ineosinophilic count and MPO titer.