Guideline sources The following summarized guidelines for the evaluation and management of microscopic polyangiitis (MPA) are prepared by our editorial team based on guidelines from the European League Against Rheumatism (EULAR 2023), the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2021), the Vasculitis Foundation (VF/ACR 2021), and the Single Hub and Access Point for Pediatric Rheumatology in Europe (SHARE initiative 2019). 1 2 3 4 Calculator Calculator ACR/EULAR diagnostic criteria f Revised Five Factor Score for pr https://web.pathway.md/diseases/recbx4dLyPXNH5gZq 1/8 6/30/23, 1:02 AM Microscopic polyangiitis Pathway Guidelines 1. Diagnostic investigations Antineutrophil cytoplasmic antibodies: obtain both 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 2. Diagnostic procedures Biopsy: perform biopsies to assist in establishing a new diagnosis of ANCA-associated vasculitis and for further evaluation of patients suspected of having relapsing vasculitis. B 3. Medical management General principles: 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 Induction of remission: As per EULAR 2023 guidelines, initiate a combination of corticosteroids and either rituximab or cyclophosphamide for induction of remission in patients with new-onset MPA with organ- threatening or life-threatening disease. A Show 3 more Landmark trials: ADVOCATE https://web.pathway.md/diseases/recbx4dLyPXNH5gZq 2/8 6/30/23, 1:02 AM Microscopic 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. As per KDIGO 2021 guidelines, initiate corticosteroids in combination with cyclophosphamide or rituximab as initial therapy in patients with new-onset ANCA-associated vasculitis. B As per ACR 2021 guidelines, consider initiating rituximab over cyclophosphamide for remission induction in patients with active, severe MPA. C Show 4 more Maintenance of remission: As per EULAR 2023 guidelines: Initiate rituximab for maintenance of remission after induction of remission with either rituximab or cyclophosphamide in patients with MPA. Consider initiating azathioprine or methotrexate as alternatives. B Continue therapy to maintain remission for 24-48 months following induction of remission in patients with new-onset MPA. B Consider continuing therapy for a longer duration in patients with relapse or with an increased risk of relapse, balanced against patient preferences and risks of continuing immunosuppression. B As per KDIGO 2021 guidelines, initiate low-dose corticosteroids and either rituximab or azathioprine as maintenance therapy after induction of remission in patients with MPA. B Show 6 more As per ACR 2021 guidelines, consider initiating rituximab over methotrexate or azathioprine for remission maintenance in patients with severe MPA entered remission after treatment with cyclophosphamide or rituximab. C Show 6 more Anticoagulant therapy: insufficient evidence to recommend an optimal duration of anticoagulation in patients with MPA experiencing venous thrombotic events. I 4. Therapeutic procedures Plasma exchange: As per EULAR 2023 guidelines: Consider performing plasma exchange as part of therapy to induce remission in patients with MPA with a serum creatinine > 300 mcmol/L due to active glomerulonephritis. B Do not perform plasma exchange routinely for the treatment of alveolar hemorrhage in patients with MPA. D As per KDIGO 2021 guidelines: 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 https://web.pathway.md/diseases/recbx4dLyPXNH5gZq 3/8 6/30/23, 1:02 AM Microscopic polyangiitis Pathway Perform plasma exchange in patients with an overlap syndrome of ANCA-associated vasculitis and anti-GBM. B As per ACR 2021 guidelines: Consider avoiding routine plasma exchange in addition to remission induction therapy in patients with MPA and active glomerulonephritis. D Consider avoiding plasma exchange in addition to remission induction therapy in patients with active, severe MPA and alveolar hemorrhage. D 5. Surgical interventions Kidney transplantation: As per KDIGO 2021 guidelines, delay kidney transplantation until patients are in complete clinical remission for 6 months. Do not delay transplantation because of the persistence of ANCA. B As per ACR 2021 guidelines, consider evaluating patients with MPA in remission and stage 5 CKD for renal transplantation. C 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. 6. Specific circumstances Pediatric patients (diagnosis and classification): Recognize that there are no validated diagnostic criteria for MPA. B Use the Chapel Hill 2012 criteria for MPA in epidemiological and/or clinical studies. B Pediatric patients (ANCA testing): obtain ANCA for the diagnosis of ANCA-associated vasculitis. B Show 2 more Pediatric patients (diagnostic imaging): Obtain CXR in all patients with ANCA-associated vasculitis, followed by chest CT in case of abnormal findings or if the clinical concern of lung involvement remains despite a normal CXR. B Obtain pulmonary function tests, including diffusing capacity/transfer factor of the lung for CO, in patients with suspected lung involvement. B https://web.pathway.md/diseases/recbx4dLyPXNH5gZq 4/8 6/30/23, 1:02 AM Microscopic polyangiitis Pathway Pediatric patients (biopsy): attempt histopathological confirmation of the diagnosis of ANCA- associated vasculitis while not delaying treatment in patients with organ- or life-threatening disease. B Show 2 more Pediatric patients (treatment): consider initiating a biological agent in patients with ANCA- associated vasculitis with critical organ- or life-threatening disease failed standard vasculitis therapy or if concerns exist regarding cyclophosphamide toxicity. Administer B-cell depleting therapy as first-line therapy. C 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 respiratory tract involvement: 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 7. 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 8. Preventative measures Prophylaxis for Pneumocystis jirovecii pneumonia: 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 9. Follow-up and surveillance Serial clinical assessment: 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. https://web.pathway.md/diseases/recbx4dLyPXNH5gZq 5/8 6/30/23, 1:02 AM Microscopic polyangiitis Pathway 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 refractory disease: As per EULAR 2023 guidelines, obtain a thorough reassessment of disease status and comorbidities and consider offering additional or different treatment in patients with MPA refractory to therapy to induce remission. Manage patients with refractory disease in close conjunction with, or refer to, a center with expertise in vasculitis. 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 As per ACR 2021 guidelines: Consider switching to other therapy over combining two therapies in patients with severe MPA refractory to rituximab or cyclophosphamide for remission induction. C Consider administering IVIG in addition to current therapy in patients with MPA refractory to remission induction therapy. C Management of relapse: As per EULAR 2023 guidelines, initiate a combination of corticosteroids and either rituximab or cyclophosphamide, preferably rituximab, B for induction of remission in patients with relapsing MPA. A 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 MPA experienced relapse with severe disease manifestations and not receiving rituximab for remission maintenance. C Consider switching from rituximab to cyclophosphamide over administering additional rituximab for remission re-induction in patients with MPA experienced relapse with severe disease manifestations while receiving rituximab for remission maintenance. C Clinical findings Symptoms Past medical history Abdominal pain Meningitis https://web.pathway.md/diseases/recbx4dLyPXNH5gZq 6/8 6/30/23, 1:02 AM Microscopic polyangiitis Pathway Anorexia Ocular exam Arthralgia Cough Episcleritis Diarrhea Hypopyon Fatigue Scleritis Fever Lab findings Hematemesis Hematuria Urine RBC casts Hemoptysis ESR Limb numbness serum CRP Melena serum creatinine Myalgia serum urea Nausea urine protein Pleuritic chest pain Shortness of breath Imaging findings Vomiting Alveolar filling pattern Weight loss Ground-glass opacities Neurological exam Intracerebral hemorrhage Mononeuritis multiplex Peripheral neuropathy Integument exam Livedo reticularis Palpable purpura Skin nodules Skin ulceration Urticaria Serological findings anti-MPO antibodies anti-PR3 antibodies c-ANCA p-ANCA Studies 2021 ADVOCATE 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. https://web.pathway.md/diseases/recbx4dLyPXNH5gZq 7/8 6/30/23, 1:02 AM Microscopic polyangiitis Pathway 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 4 more References 1. Kidney Disease: Improving Global Outcomes KDIGO Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100 4S S1 S276. Open 2. Bernhard Hellmich, Beatriz Sanchez-Alamo, Jan H Schirmer et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2023 Mar 16;ard-2022 223764. Open 3. Nienke de Graeff, Noortje Groot, Paul Brogan et al. European consensus-based recommendations for the diagnosis and treatment of rare paediatric vasculitides - the SHARE initiative. Rheumatology Oxford). 2019 Apr 1;58 4 656 671. Open 4. 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 5. Michael Walsh, Peter A Merkel, Chen-Au Peh et al. Plasma Exchange and Glucocorticoids in Severe ANCA Associated Vasculitis. N Engl J Med. 2020 Feb 13;382 7 622 631. Open 6. Anand Padmanabhan, Laura Connelly-Smith, Nicole Aqui et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019 Jun;34 3 171 354. Open 7. Ravi Suppiah, Joanna C Robson, Peter C Grayson et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Ann Rheum Dis. 2022 Mar;81 3 321 326. Open 8. Eleana Ntatsaki, David Carruthers, Kuntal Chakravarty et al. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology Oxford). 2014 Dec;53 12 2306 9. Open https://web.pathway.md/diseases/recbx4dLyPXNH5gZq 8/8