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ANCA-associated vasculitis

Etiology: - Wegener's granulomatosis (granulomatosis with polyangiitis) - microscopic polyangiitis - Churg-Strauss disease (eosinophilic granulomatosis with polyangiitis) Pathology: - see anti-neutophil cytoplasmic antibody (ANCA) Clinical manifestations: - pauci-immune glomerulonephritis - necrotizing pauci-immune rapidly progressive glomerulonephritis [7] - pulmonary hemorrhage, hemoptysis - epistaxis - peripheral neuropathy, mononeuritis multiplex [1] Laboratory: - c or central type cANCA in serum (Wegener's granulomatosis) - p or peripheral type pANCA in serum (Churg-Strauss disease, microscopic polyangiitis, other) - cocaine-associated vasculitis both cANCA in serum & pANCA in serum Radiology: - chest X-ray - pulmonary nodules - CT of thorax - cavitary pulmonary nodules [1] Complications: - incidence of stroke is higher than in the general population (RR 1.8), - RR= 3.2 in patients < 65 years [13] - high platelet count at diagnosis is associated with increased risk [13] Management: 1) combination therapy (Wegener's granulomatosis, microscopic polyangiitis) a) rituximab 375 mg/m2/week (4 doses) in combination with glucocorticoids preferred induction for severe disease [10] - induction & maintenance of remission [4,6] - if cyclophosphamide is contraindicated, not tolerated, or is otherwise unacceptable (NICE) [NGC] - reduced-dose prednisolone (0.5 mg/kg/day) non-inferior to high-dose prednisolone (1.0 mg/kg/day) [9] b) methotrexate in combination with glucocorticoid preferred induction for less severe disease [10] 2) combination therapy (Churg-Strauss syndrome) a) glucocorticoid plus cyclophosphamide or rituximab is recommended to induce remission in severe disease b) glucocorticoid plus mepolizumab or methotrexate, azathioprine of mycophenolate mofetil to induce remission in less severe disease 3) other modalities a) plasmapheresis [5] b) cyclophosphamide - 2 mg/kg/day PO for one year after induction of remission - monthly cyclophosphamide is less toxic, but also less effective c) azathioprine 1-2 mg/kg/day: - useful in maintaining remissions induced by cyclophosphamide - use in conjunction with prednisone as needed [1] d) prednisone 1 mg/kg PO QD for 4 weeks followed by slow taper, subsequent conversion to alternate day therapy for 6-9 months e) daratumumab (Darzalex) inhibits CD38-positive plasma cells that may linger after anti-CD20 (rituximab) treatment [12] 4) prognosis a) Response in 90%, complete remission in 75% of patients b) 50% of patients with relapses 5) rule out infection prior to initiating immunosuppressive therapy 6) immunosuppressive therapy reduces risk of ESRD or death from 51% to 31% [1]

Interactions

disease interactions

Related

anti-neutrophil cytoplasmic antibody (ANCA)

Specific

allergic angiitis & granulomatosis of Churg-Strauss; eosinophilic granulomatosis with polyangiitis (EGPA) ANCA-associated glomerulonephritis cocaine-associated vasculitis granulomatosis with polyangiitis; Wegener's granulomatosis microscopic polyangiitis

General

vasculitis

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 16,17,18 American College of Physicians, Philadelphia 2012,2015,2018.
  2. Jayne DR, Gaskin G, Rasmussen N et al Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007 Jul;18(7):2180-8. PMID: 17582159
  3. Bosch X et al, Antineutrophil cytoplasmic antibodies. Lancet 2006, 368:404 PMID: 16876669
  4. Specks U et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med 2013 Aug 1; 369:417 PMID: 23902481 http://www.nejm.org/doi/full/10.1056/NEJMoa1213277
  5. Gaffo AL. Diagnostic approach to ANCA-associated vasculitides. Rheum Dis Clin North Am. 2010 Aug;36(3):491-506 PMID: 20688246
  6. Stone JH, Merkel PA, Spiera R et al Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32 PMID: 20647199
  7. Rutgers A, Sanders JS, Stegeman CA, Kallenberg CG. Pauci-immune necrotizing glomerulonephritis. Rheum Dis Clin North Am. 2010 Aug;36(3):559-72 PMID: 20688250
  8. Poulton CJ, Nachman PH, Hu Y et al Pathways to renal biopsy and diagnosis among patients with ANCA small-vessel vasculitis. Clin Exp Rheumatol. 2013 Jan-Feb;31(1 Suppl 75):S32-7. PMID: 23343774 Free PMC Article
  9. Furuta S, Nakagomi D, Kobayashi Y et al Effect of Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Associated Vasculitis. A Randomized Clinical Trial. JAMA. 2021;325(21):2178-2187 PMID: 34061144 https://jamanetwork.com/journals/jama/fullarticle/2780489
  10. Chung SA, Langford CA, Maz M et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol 2021 Aug; 73:1366-1383. PMID: 34235894 https://onlinelibrary.wiley.com/doi/10.1002/art.41773
  11. Hunter RW, Welsh N, Farrah TE et al. ANCA associated vasculitis. BMJ. 2020;369:m1070 PMID: 32291255 PMCID: PMC7179255 Free PMC article https://www.bmj.com/content/369/bmj.m1070
  12. Rixecker TM, Leppervpm, Mang S et al Daratumumab for a Patient With Refractory Antineutrophil Cytoplasmatic Antibody- Associated Vasculitis. JAMA Intern Med. Published online April 10, 2023 PMID: 37036724 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2803783
  13. Tabakovic D, Smith R, Jayne D, Mohammad AJ. High Risk of Stroke in ANCA-associated Vasculitis. A Population-Based Study. Rheumatology. 2023;62(8):2806-2812 PMID: 36440920 PMCID: PMC10393431 Free PMC article https://www.medscape.com/s/viewarticle/995641
  14. Wallace ZS, Miloslavsky EM. Management of ANCA associated vasculitis. BMJ. 2020 Mar 18;368:m421. PMID: 32188597 Review.
  15. Nakazawa D, Masuda S, Tomaru U, Ishizu A. Pathogenesis and therapeutic interventions for ANCA-associated vasculitis. Nat Rev Rheumatol. 2019 Feb;15(2):91-101. PMID: 30542206 Free article. Review.
  16. Kallenberg CG. Key advances in the clinical approach to ANCA-associated vasculitis. Nat Rev Rheumatol. 2014 Aug;10(8):484-93. PMID: 24980139 Review.