Guideline sources The following summarized guidelines for the evaluation and management of eosinophilic granulomatosis with polyangiitis (EGPA) are prepared by our editorial team based on guidelines from the European Expert Group on Eosinophilic Granulomatosis with Polyangiitis (EGPA-EEG 2023), the European League Against Rheumatism (EULAR 2023), the Vasculitis Foundation (VF/ACR 2021), the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2021), and the Single Hub and Access Point for Pediatric Rheumatology in Europe (SHARE initiative 2019). 1 2 3 4 5 Calculator Calculator Calculat ACR/EULAR diagnostic criteria f FFS score for polyarteritis nodos Revised https://web.pathway.md/diseases/reccICvzn3ijJLw0V 1/8 6/29/23, 4:18 AM Eosinophilic granulomatosis with polyangiitis Pathway Guidelines 1. Screening and diagnosis Diagnosis: suspect EGPA in patients with asthma, chronic rhinosinusitis, and eosinophilia developing end-organ involvement, particularly peripheral neuropathy, lung infiltrates, cardiomyopathy, or other complications (such as skin, gastrointestinal, or kidney involvement). B Show 2 more Differential diagnosis: rule out other eosinophilic and vasculitic disorders and investigate the main disease complications, particularly heart, respiratory, skin, renal, and nervous system involvement, in the evaluation of patients with suspected EGPA. B 2. Diagnostic investigations Antineutrophil cytoplasmic antibodies: As per EGPA-EEG 2023 guidelines, obtain ANCA testing in all patients with suspected EGPA. B As per EULAR 2023 guidelines, obtain proteinase 3-ANCA and myeloperoxidase-ANCA testing, with a high-quality antigen-specific assay as the primary method of testing, in patients with signs and/or symptoms raising suspicion of a diagnosis of ANCA-associated vasculitis. A Serum immunoglobulins: measure serum immunoglobulin concentrations before each course of rituximab to detect secondary immunodeficiency in patients with ANCA-associated vasculitis receiving rituximab. B Echocardiography: consider obtaining echocardiography at diagnosis in patients with EGPA. C 3. Diagnostic procedures Biopsy: As per EGPA-EEG 2023 guidelines, perform a biopsy when feasible in the evaluation of patients with suspected EGPA, although it is not essential to make the diagnosis of EGPA. B As per EULAR 2023 guidelines, perform a biopsy to establish a new diagnosis of ANCA- associated vasculitis and for further evaluation of patients suspected of having relapsing vasculitis. B 4. Medical management General principles: https://web.pathway.md/diseases/reccICvzn3ijJLw0V 2/8 6/29/23, 4:18 AM Eosinophilic granulomatosis with polyangiitis Pathway As per EULAR 2023 guidelines: Offer multidisciplinary management in centers with, or with ready access to, expertise in vasculitis in patients with ANCA-associated vasculitis. B Offer the best care based on shared decision-making between the patient and the physician, taking efficacy, safety, and costs into account, in patients with ANCA-associated vasculitis. B As per KDIGO 2021 guidelines: Manage patients with ANCA-associated vasculitis at centers with experience in ANCA- associated vasculitis. B Do not delay immunosuppressive therapy while waiting for a kidney biopsy to be performed or reported in patients with a clinical presentation compatible with small-vessel vasculitis and positive or proteinase 3-ANCA and myeloperoxidase-ANCA serology, especially in patients rapidly deteriorating. D As per ACR 2021 guidelines, consider using the Five-Factor Score to guide the management in patients with EGPA. C Induction of remission: As per EGPA-EEG 2023 guidelines, define EGPA remission as the absence of clinical signs or symptoms attributable to active disease, including asthma and ear-nose-throat manifestations. Consider using the daily dose of corticosteroids for the definition of remission and choosing a maximum daily dose of 7.5 mg of prednisone as the cut-off. B Show 2 more As per EULAR 2023 guidelines: Initiate a combination of high-dose corticosteroids and cyclophosphamide for induction of remission in patients with new-onset EGPA with organ-threatening or life-threatening manifestations. Consider initiating a combination of high-dose corticosteroids and rituximab as an alternative. B Initiate corticosteroids for induction of remission in patients with new-onset EGPA without organ-threatening or life-threatening manifestations. B As per ACR 2021 guidelines, consider initiating the following medications for remission induction in patients with active, non-severe EGPA: mepolizumab and corticosteroids over methotrexate, azathioprine, or mycophenolate mofetil and corticosteroids C methotrexate, azathioprine, or mycophenolate mofetil and corticosteroids over corticosteroids alone C methotrexate, azathioprine, or mycophenolate mofetil and corticosteroids over cyclophosphamide or rituximab and corticosteroids. C Show 3 more Maintenance of remission: As per EGPA-EEG 2023 guidelines: Initiate corticosteroids alone or in combination with mepolizumab in patients with non- severe EGPA. Taper corticosteroids to the minimum effective dose to reduce toxicity. B Initiate rituximab, mepolizumab, or traditional DMARDs in combination with corticosteroids for maintenance of remission in patients with severe EGPA. B https://web.pathway.md/diseases/reccICvzn3ijJLw0V 3/8 6/29/23, 4:18 AM Eosinophilic granulomatosis with polyangiitis Pathway As per EULAR 2023 guidelines: Consider initiating methotrexate, C azathioprine, mepolizumab, or rituximab for maintenance of remission in patients with EGPA after induction of remission for organ- threatening or life-threatening disease. C Initiate mepolizumab for maintenance of remission in patients with relapsing EGPA after induction of remission for non-organ-threatening or life-threatening manifestations at the time of relapse. B As per ACR 2021 guidelines, consider initiating methotrexate, azathioprine, or mycophenolate mofetil over rituximab for remission maintenance in patients with severe EGPA entered remission with cyclophosphamide therapy. C Show 2 more Management of refractory disease: As per EGPA-EEG 2023 guidelines, define refractory EGPA as unchanged or increased disease activity after 4 weeks of appropriate remission-induction therapy. Distinguish the persistence or worsening of systemic manifestations from respiratory manifestations. B Show 2 more As per EULAR 2023 guidelines, initiate mepolizumab for induction of remission in patients with refractory EGPA without active organ-threatening or life-threatening disease. B As per KDIGO 2021 guidelines: Consider increasing the dose of corticosteroids (IV or PO), or adding rituximab if cyclophosphamide induction had been used previously, or vice versa, in patients with refractory disease. Consider performing plasma exchange. C Consider performing plasma exchange, in addition to corticosteroids with either cyclophosphamide or rituximab, in patients with diffuse alveolar bleeding with hypoxemia. C 5. Therapeutic procedures Plasma exchange: Consider performing plasma exchange in patients with serum creatinine > 5.7 mg/dL (500 mmol/l) requiring dialysis or with rapidly increasing serum creatinine, and in patients with diffuse alveolar hemorrhage having hypoxemia. C Perform plasma exchange in patients with an overlap syndrome of ANCA-associated vasculitis and anti-GBM. B Landmark trials: PEXIVAS (plasmapheresis) In patients with severe ANCA-associated vasculitis, plasma exchange was not superior to no plasma exchange with respect to the composite outcome of death from any cause or end-stage kidney disease. Michael Walsh et al. N Engl J Med. 2020 Feb 13. https://web.pathway.md/diseases/reccICvzn3ijJLw0V 4/8 6/29/23, 4:18 AM Eosinophilic granulomatosis with polyangiitis Pathway 6. Surgical interventions Kidney transplantation: delay kidney transplantation until patients are in complete clinical remission for 6 months. Do not delay transplantation because of the persistence of ANCA. B 7. Specific circumstances Pediatric patients: use the Chapel Hill definition (2012) when referring to EGPA in the pediatric population, recognizing that there are no pediatric diagnostic or classification criteria for EGPA. B Show 4 more Patients with renal involvement: insufficient evidence to support the use of rituximab and corticosteroids in patients presenting with markedly reduced or rapidly declining GFR (serum creatinine > 4 mg/dL; > 354 mmol/L). Prefer cyclophosphamide and corticosteroids for induction therapy, or a combination of rituximab and cyclophosphamide as an alternative. I Show 3 more Patients with sinonasal involvement: As per EGPA-EEG 2023 guidelines, optimize topical therapy in patients with EGPA with ear- nose-throat involvement. Involve otolaryngologists in the management of these patients. B As per ACR 2021 guidelines, consider offering nasal rinses and topical therapies (such as antibiotics, lubricants, and corticosteroids) in patients with sinonasal involvement in EGPA. C Patients with respiratory tract involvement: As per EGPA-EEG 2023 guidelines, optimize inhaled therapy in patients with EGPA having active asthma. Involve pulmonologists in the management of these patients. B As per KDIGO 2021 guidelines: Consider performing plasma exchange in patients with diffuse alveolar hemorrhage having hypoxemia. C Perform plasma exchange in patients with an overlap syndrome of ANCA-associated vasculitis and anti-GBM. B Patients on leukotriene inhibitors: Consider continuing leukotriene inhibitors in patients with newly diagnosed EGPA receiving leukotriene inhibitors. C Recognize that leukotriene inhibitors are not contraindicated in patients with EGPA with active asthma and/or sinonasal disease. B 8. Patient education General counseling: provide patients with ANCA-associated vasculitis education focusing on the impact of ANCA-associated vasculitis and its prognosis, key warning symptoms, and treatment (including treatment-related complications). B https://web.pathway.md/diseases/reccICvzn3ijJLw0V 5/8 6/29/23, 4:18 AM Eosinophilic granulomatosis with polyangiitis Pathway 9. Preventative measures Prophylaxis for Pneumocystis jirovecii pneumonia: As per EULAR 2023 guidelines, administer TMP-SMX for prophylaxis against P. jirovecii pneumonia and other infections in patients with ANCA-associated vasculitis receiving rituximab, cyclophosphamide, and/or high doses of corticosteroids. B As per ACR 2021 guidelines, consider administering prophylaxis for the prevention of P. jirovecii pneumonia in patients with EGPA receiving cyclophosphamide or rituximab. C 10. Follow-up and surveillance Serial clinical assessment: As per EGPA-EEG 2023 guidelines: Use validated clinical tools in the assessment of disease activity on follow-up. B Obtain routine monitoring of EGPA-related manifestations, with particular reference to lung function, cardiovascular events, and neurological complications. Obtain long-term monitoring of comorbidities, such as cancer, infections, and osteoporosis. B As per EULAR 2023 guidelines: Obtain periodic assessment for treatment-related adverse effects and comorbidities in patients with ANCA-associated vasculitis. Offer prophylaxis and lifestyle advice to reduce treatment-related complications and other comorbidities. B Obtain structured clinical assessment, rather than ANCA and/or CD19-positive B cell testing alone, to inform decisions on changes in treatment in patients with ANCA- associated vasculitis. B Serial laboratory assessment: do not use the persistence of ANCA positivity, an increase in ANCA levels, or a change in ANCA from negative to positive to guide treatment decisions, as those are only modestly predictive of future disease relapse. D Management of relapse: As per EGPA-EEG 2023 guidelines: Define EGPA relapse as the recurrence of clinical signs or symptoms attributable to active disease following a period of remission. View the need for an increase in the corticosteroid dose or the initiation of or an increase in an immunosuppressant as a relapse. Differentiate the relapse or new onset of systemic vasculitis (systemic relapse) from the isolated exacerbation of asthma and ear-nose-throat manifestations (respiratory relapse). B Treat relapses according to the type (systemic versus respiratory) and severity. Initiate rituximab or cyclophosphamide with corticosteroids in patients with severe systemic relapses. Increase the dose of corticosteroids and/or add mepolizumab in patients with non-severe systemic and respiratory relapses. B As per EULAR 2023 guidelines, initiate a combination of high-dose corticosteroids and cyclophosphamide for induction of remission in patients with relapsing EGPA with organ- threatening or life-threatening manifestations. Consider initiating a combination of high-dose corticosteroids and rituximab as an alternative. B Show 2 more https://web.pathway.md/diseases/reccICvzn3ijJLw0V 6/8 6/29/23, 4:18 AM Eosinophilic granulomatosis with polyangiitis Pathway As per KDIGO 2021 guidelines, reintroduce corticosteroids in combination with cyclophosphamide or rituximab (preferably rituximab) in patients with relapsing disease (life- or organ-threatening). B As per ACR 2021 guidelines, consider initiating rituximab over cyclophosphamide for remission re-induction in patients with EGPA experienced relapse with severe disease manifestations after prior successful remission induction with cyclophosphamide. C Show 4 more Clinical findings Symptoms Past medical history Abdominal pain Allergic rhinitis Arthralgia Asthma Diarrhea Head and neck exam Fever Myalgia Nasal polyps Nausea Lab findings Vomiting Weight loss CRP ESR Neurological exam serum creatinine Mononeuritis multiplex Serological findings Peripheral neuropathy serum IgE Integument exam c-ANCA Livedo reticularis p-ANCA Maculopapular rash Palpable purpura Petechiae Subcutaneous nodules Hematological findings Anemia WBC count blood eosinophils Imaging findings Lung nodule Pulmonary infiltrates Studies 2021 ADVOCATE https://web.pathway.md/diseases/reccICvzn3ijJLw0V 7/8 6/29/23, 4:18 AM Eosinophilic granulomatosis with polyangiitis Pathway In patients with ANCA-associated vasculitis, avacopan was noninferior to prednisone with respect to remission at week 26. David R W Jayne et al. N Engl J Med. 2021 Feb 18. 2020 PEXIVAS (corticosteroids) In patients with severe ANCA-associated vasculitis, a reduced-dose corticosteroid regimen was noninferior to a standard-dose corticosteroid regimen with respect to the composite outcome of death from any cause or end-stage kidney disease. Michael Walsh et al. N Engl J Med. 2020 Feb 13. Show 3 more References 1. Giacomo Emmi, Alessandra Bettiol, Elena Gelain et al. Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis. Nat Rev Rheumatol. 2023 May 9. Open 2. Sharon A Chung, Carol A Langford, Mehrdad Maz et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2021 Aug;73 8 1366 1383. Open 3. Kidney Disease: Improving Global Outcomes KDIGO Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. 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