Eosinophile Granulomatose mit Polyangiitis – ein Übersichtsartikel

 

 Permissions and Reprints

Zusammenfassung

Die eosinophile Granulomatose mit Polyangiitis (EGPA) ist eine seltene Form der ANCA-assoziierten Vaskulitiden (AAV) aus der Gruppe der Kleingefäßvaskulitiden. Sie ist definiert als eine Vaskulitis kleiner und mittelgroßer Gefäße mit granulomatöser Entzündung sowie Blut- und Gewebseosinophilie. Fast alle Patienten haben allergische Symptome mit Asthma bronchiale und rhinosinusitischen Beschwerden. Das sonstige klinische Spektrum variiert je nach Lokalisation, Schweregrad und Art der Krankheitsmanifestation. Durch die eosinophile Infiltration und Inflammation kann es zu Rhinosinusitis, Pneumonitis, gastrointestinaler Beteiligung und Kardiomyopathie kommen. Insbesondere Letztere ist mit einer schlechteren Prognose assoziiert. Als nekrotisierende pauci-immune Kleingefäßvaskulitis kann die EGPA, ähnlich wie die anderen AAV, pulmonale Infiltrate mit alveolärer Hämorrhagie, eine Glomerulonephritis, kutane Vaskulitis mit Purpura, sowie zentrale und periphere neurologische Schädigungen verursachen. Das Auftreten perinukleärer ANCA (pANCA), mit Spezifität gegen die Myeloperoxidase (MPO) wird in etwa einem Drittel der Fälle beobachtet, ist allerdings nicht spezifisch für die EGPA. MPO-ANCA-positive Patienten haben häufiger eine periphere neurologische Beteiligung und eine Glomerulonephritis, während ANCA-negative Patienten häufiger eine kardiale und pulmonale Beteiligung aufweisen. Eine differentialdiagnostische Herausforderung im klinischen Alltag stellt die Abgrenzung zum hypereosinophilen Syndrom (HES) dar. Das Therapiekonzept der EGPA hängt davon ab, ob der Schweregrad der Erkrankung potentiell Organ- oder lebensbedrohlich ist. Bei schweren Formen der EGPA werden in der Akuttherapie hauptsächlich Glukokortikoide in Kombination mit Cyclophosphamid eingesetzt. Rituximab wird mittlerweile als alternative Behandlungsoption in den Leitlinien genannt. Zur Remissionserhaltung stehen verschiedene immunsuppressive Therapien zur Verfügung. Bei EGPA ohne schwere Organbeteiligung ist die IL-5 Blockade mit Mepolizumab zugelassen.

Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of ANCA-associated vasculitis (AAV) within the group of small vessel vasculitides. It is defined by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia. Almost all patients have allergic symptoms with bronchial asthma and rhinosinusitis symptoms. Further clinical manifestations vary depending on the localisation, severity, and type of disease manifestation. Eosinophilic infiltration and inflammation may result in rhinosinusitis, pneumonitis, gastrointestinal involvement, and cardiomyopathy. The latter, in particular, is associated with a worse prognosis. As a necrotising pauci-immune small-vessel vasculitis, EGPA, similar to the other AAVs, can cause pulmonary infiltrates with alveolar haemorrhage, glomerulonephritis, cutaneous vasculitis with purpura as well as central and peripheral neurologic injuries. The presence of perinuclear ANCA (pANCA) with specificity against myeloperoxidase (MPO) is observed in approximately one-third of patients but is not specific to EGPA. MPO-ANCA-positive patients are more likely to have peripheral neurologic involvement and glomerulonephritis, whereas ANCA-negative patients are more likely to have cardiac and pulmonary involvement. What is frequently challenging in the clinical routine is to differentiate EGPA from the hypereosinophilic syndrome (HES). The therapeutic approach to EGPA depends on whether the severity of the disease is potentially organ or life-threatening. For severe forms of EGPA, acute therapy mainly includes glucocorticoids in combination with cyclophosphamide. Rituximab has come to be mentioned as an alternative treatment option in the guidelines. Various immunosuppressive therapies are available for remission maintenance. In EGPA without severe organ involvement, IL-5 blockade with mepolizumab is an approved treatment.

Publication History

Article published online:
14 November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

• Literatur

• 1 Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: A unifying view of disease spectrum. Rheumatol (United Kingdom) 2019; 58: 1707-1709
  PubMedGoogle Scholar
• 2 Jennette JC, Falk RJ, Bacon PA. et al. 2012 Revised International Chapel Hill consensus conference nomenclature of vasculitides. In: Arthritis and Rheumatism 2013; 1-11
  PubMed
• 3 Furuta S, Iwamoto T, Nakajima H. Update on eosinophilic granulomatosis with polyangiitis. Allergol Int 2019; 68: 430-436
  CrossrefPubMedGoogle Scholar
• 4 Fagni F, Bello F, Emmi G. Eosinophilic Granulomatosis With Polyangiitis: Dissecting the Pathophysiology. Front Med 2021; 8: 627776
  CrossrefPubMedGoogle Scholar
• 5 Dejaco C, Oppl B, Monach P. et al. Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss). PLoS One 2015; 10: e0121737 DOI: 10.1371/journal.pone.0121737.
  CrossrefPubMedGoogle Scholar
• 6 Gleich GJ, Adolphson CR. The Eosinophilic Leukocyte: Structure and Function. Adv Immunol 1986; 39: 177-253 DOI: 10.1016/S0065-2776(08)60351-X.
  CrossrefPubMedGoogle Scholar
• 7 Clottu AS, Humbel M, Fluder N. et al. Innate Lymphoid Cells in Autoimmune Diseases. Front Immunol 2022; 12: 5271
  CrossrefPubMedGoogle Scholar
• 8 Sinico RA, Di Toma L, Maggiore U. et al. Renal Involvement in Churg-Strauss Syndrome. Am J Kidney Dis 2006; 47: 770-779 DOI: 10.1053/j.ajkd.2006.01.026.
  CrossrefPubMedGoogle Scholar
• 9 Cui Z, Zhao MH, Segelmark M. et al. Natural autoantibodies to myeloperoxidase, proteinase 3, and the glomerular basement membrane are present in normal individuals. Kidney Int 2010; 78: 590-597 DOI: 10.1038/ki.2010.198.
  CrossrefPubMedGoogle Scholar
• 10 Tomasson G, Grayson PC, Mahr AD. et al. Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis-a meta-analysis. Rheumatology 2012; 51: 100-109 DOI: 10.1093/rheumatology/ker280.
  CrossrefPubMedGoogle Scholar
• 11 Moiseev S, Bossuyt X, Arimura Y. et al. International consensus on antineutrophil cytoplasm antibodies testing in eosinophilic granulomatosis with polyangiitis. Am J Respir Crit Care Med 2020; 202: 1360-1372 DOI: 10.1164/rccm.202005-1628SO.
  CrossrefPubMedGoogle Scholar
• 12 Lyons PA, Peters JE, Alberici F. et al. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat Commun 2019; 10: 5120 DOI: 10.1038/s41467-019-12515-9.
  CrossrefPubMedGoogle Scholar
• 13 Pagnoux C, Guillevin L. Churg-Strauss syndrome: Evidence for disease subtypes?. Curr Opin Rheumatol 2010; 22: 21-28
  CrossrefPubMedGoogle Scholar
• 14 Berti A, Cornec D, Casal Moura M. et al. Eosinophilic Granulomatosis With Polyangiitis: Clinical Predictors of Long-term Asthma Severity. Chest 2020; 157: 1086-1099 DOI: 10.1016/j.chest.2019.11.045.
  CrossrefPubMedGoogle Scholar
• 15 Low CM, Keogh KA, Saba ES. et al. Chronic rhinosinusitis in eosinophilic granulomatosis with polyangiitis: clinical presentation and antineutrophil cytoplasmic antibodies. Int Forum Allergy Rhinol 2020; 10: 217-222 DOI: 10.1002/alr.22503.
  CrossrefPubMedGoogle Scholar
• 16 Szczeklik W, Sokołowska B, Mastalerz L. et al. Pulmonary findings in Churg-Strauss syndrome in chest X-rays and high resolution computed tomography at the time of initial diagnosis. Clin Rheumatol 2010; 29: 1127-1134 DOI: 10.1007/s10067-010-1530-3.
  CrossrefPubMedGoogle Scholar
• 17 Cottin V, Bel E, Bottero P. et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Eur Respir J 2016; 48: 1429-1441 DOI: 10.1183/13993003.00097-2016.
  CrossrefPubMedGoogle Scholar
• 18 Sehgal M, Swanson JW, DeRemee RA. et al. Neurologic Manifestations of Churg-Strauss Syndrome. Mayo Clin Proc 1995; 70: 337-341 DOI: 10.4065/70.4.337.
  CrossrefPubMedGoogle Scholar
• 19 Comarmond C, Pagnoux C, Khellaf M. et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum 2013; 65: 270-281 DOI: 10.1002/art.37721.
  CrossrefPubMedGoogle Scholar
• 20 Neumann T, Manger B, Schmid M. et al. Cardiac Involvement in Churg-Strauss Syndrome. Medicine (Baltimore) 2009; 88: 236-243 DOI: 10.1097/MD.0b013e3181af35a5.
  CrossrefPubMedGoogle Scholar
• 21 Davis MDP, Daoud MS, McEvoy MT. et al. Cutaneous manifestations of Churg-Strauss syndrome: A clinicopathologic correlation. J Am Acad Dermatol 1997; 37: 199-203 DOI: 10.1016/S0190-9622(97)80125-9.
  CrossrefPubMedGoogle Scholar
• 22 Dejaco C, Oppl B, Monach P. et al. Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss). PLoS One 2015; 10: e0121737 DOI: 10.1371/journal.pone.0121737.
  CrossrefPubMedGoogle Scholar
• 23 Schirmer J, Sanchez-Alamo B, Monti S. et al. Pos0830 Systematic Literature Review Informing The 2022 Update Of The Eular Recommendations For The Management Of Anca-Associated Vasculitis: Focus On Treatment Strategies. Ann Rheum Dis 2022; 81: 1-706 DOI: 10.1136/annrheumdis-2022-eular.3156.
  CrossrefPubMedGoogle Scholar
• 24 Vaglio A, Casazza I, Grasselli C. et al. Churg-Strauss syndrome. Kidney Int 2009; 76: 1006-1011 DOI: 10.1038/ki.2009.210.
  CrossrefPubMedGoogle Scholar
• 25 Durel CA, Sinico RA, Teixeira V. et al. Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA): A multicentric retrospective study of 63 biopsy-proven cases. Rheumatol (United Kingdom) 2021; 60: 359-365 DOI: 10.1093/rheumatology/keaa416.
  CrossrefPubMedGoogle Scholar
• 26 Lanham JG, Elkon KB, Pusey CD. et al. Systemic vasculitis with asthma and eosinophilia: A clinical approach to the churg-strauss syndrome. Med (United States) 1984; 63: 65-81 DOI: 10.1097/00005792-198403000-00001.
  CrossrefPubMedGoogle Scholar
• 27 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: 1094-1100 DOI: 10.1002/art.1780330806.
  CrossrefPubMedGoogle Scholar
• 28 Grayson PC, Ponte C, Suppiah R. et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis 2022; 81: 309-314 DOI: 10.1136/annrheumdis-2021-221794.
  CrossrefPubMedGoogle Scholar
• 29 Henes JC, Wirths S, Hellmich B. Differential diagnosis of hypereosinophilia. Z Rheumatol 2019; 78: 313-321
  CrossrefPubMedGoogle Scholar
• 30 Yates M, Watts RA, Bajema IM. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75: 1583-1594
  CrossrefPubMedGoogle Scholar
• 31 Schirmer JH, Aries PM, de Groot K. et al. S1-Leitlinie Diagnostik und Therapie der ANCA-assoziierten Vaskulitiden. Z Rheumatol 2017; 76: 77-104
  CrossrefPubMedGoogle Scholar
• 32 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; 73: 1366-1383 DOI: 10.1002/art.41773.
  CrossrefPubMedGoogle Scholar
• 33 Hauser T, Mahr A, Metzler C. et al. The leucotriene receptor antagonist montelukast and the risk of Churg-Strauss syndrome: A case-crossover study. Thorax 2008; 63: 677-682 DOI: 10.1136/thx.2007.087825.
  CrossrefPubMedGoogle Scholar
• 34 Guillevin L, Pagnoux C, Seror R. et al. The five-factor score revisited: Assessment of prognoses of systemic necrotizing vasculitides based on the french vasculitis study group (FVSG) cohort. Medicine (Baltimore) 2011; 90: 19-27 DOI: 10.1097/MD.0b013e318205a4c6.
  CrossrefPubMedGoogle Scholar
• 35 Pagnoux C, Quéméneur T, Ninet J. et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: Results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. In: Arthritis and Rheumatology. 2015: 1117-1127
  Google Scholar
• 36 Cohen P, Pagnoux C, Mahr A. et al. Churg-Strauss syndrome with poor-prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Care Res 2007; 57: 686-693 DOI: 10.1002/art.22679.
  CrossrefPubMedGoogle Scholar
• 37 Gayraud M, Guillevin L, le Toumelin P. et al. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: Analysis of four prospective trials including 278 patients. Arthritis Rheum 2001; 44: 666-675 DOI: 10.1002/1529-0131(200103)44:3<666::AID-ANR116>3.0.CO;2-A.
  CrossrefPubMedGoogle Scholar
• 38 Cohen P, Pagnoux C, Mahr A. et al. Churg-Strauss syndrome with poor-prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Care Res 2007; 57: 686-693 DOI: 10.1002/art.22679.
  CrossrefPubMedGoogle Scholar
• 39 Moosig F, Bremer JP, Hellmich B. et al. A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): Monocentric experiences in 150 patients. Ann Rheum Dis 2013; 72: 1011-1017 DOI: 10.1136/annrheumdis-2012-201531.
  CrossrefPubMedGoogle Scholar
• 40 Terrier B, Pugnet G, de Moreuil C. et al. Rituximab versus Conventional Therapeutic Strategy for Remission Induction in Eosinophilic Granulomatosis with Polyangiitis: A Double-blind, Randomized, Controlled Trial [abstract]. Arthritis Rheumatol. 2021 73. (suppl. Im Internet: https://acrabstracts.org/abstract/rituximab-versus-conventional-therapeutic-strategy-for-remission-induction-in-eosinophilic-granulomatosis-with-polyangiitis-a-double-blind-randomized-controlled-trial/
  PubMedGoogle Scholar
• 41 Stone JH, Merkel PA, Spiera R. et al. Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis A BS TR AC T. 2010
  PubMed
• 42 Puéchal X, Pagnoux C, Baron G. et al. Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial. Arthritis Rheumatol 2017; 69: 2175-2186 DOI: 10.1002/art.40205.
  CrossrefPubMedGoogle Scholar
• 43 Puéchal X, Pagnoux C, Baron G. et al. Non-severe eosinophilic granulomatosis with polyangiitis: Long-term outcomes after remission-induction trial. Rheumatol (United Kingdom) 2019; 58: 2107-2116 DOI: 10.1093/rheumatology/kez139.
  CrossrefPubMedGoogle Scholar
• 44 Wechsler ME, Akuthota P, Jayne D. et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med 2017; 376: 1921-1932 DOI: 10.1056/nejmoa1702079.
  Google Scholar
• 45 Bettiol A, Urban ML, Dagna L. et al. Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study. Arthritis Rheumatol 2022; 74: 295-306 DOI: 10.1002/art.41943.
  CrossrefPubMedGoogle Scholar
• 46 Ribi C, Cohen P, Pagnoux C. et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: A multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheum 2008; 58: 586-594 DOI: 10.1002/art.23198.
  CrossrefPubMedGoogle Scholar
• 47 Metzler C, Hellmich B, Gause A. et al. Churg Strauss syndrome - Successful induction of remission with methotrexate and unexpected high cardiac and pulmonary relapse ratio during maintenance treatment. Clin Exp Rheumatol 2004; 22
  PubMedGoogle Scholar
• 48 Maritati F, Alberici F, Oliva E. et al. Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial. PLoS One 2017; 12: e0185880 DOI: 10.1371/journal.pone.0185880.
  CrossrefPubMedGoogle Scholar
• 49 Bellos I, Boletis I, Lionaki S. A Meta-Analysis of the Safety and Efficacy of Maintenance Therapies for Antineutrophil Cytoplasmic Antibody Small-Vessel Vasculitis. Kidney Int Reports 2022; 7: 1074-1083 DOI: 10.1016/j.ekir.2022.02.020.
  CrossrefPubMedGoogle Scholar
• 50 Guillevin L, Pagnoux C, Karras A. et al. Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis. N Engl J Med 2014; 371: 1771-1780 DOI: 10.1056/nejmoa1404231.
  CrossrefPubMedGoogle Scholar
• 51 Bettiol A, Urban ML, Bello F. et al. Pos0246 Sequential Rituximab And Mepolizumab In Eosinophilic Granulomatosis With Polyangiitis. Ann Rheum Dis 2022; 81: 362-363 DOI: 10.1136/annrheumdis-2022-eular.4320.
  CrossrefPubMedGoogle Scholar
• 52 Hellmich B, Holle J, Moosig F. Eosinophilic granulomatosis with polyangiitis: Update on classification and management. Z Rheumatol 2022; 81: 286-299 DOI: 10.1007/s00393-021-01153-6.
  CrossrefPubMedGoogle Scholar