Download PDF
Semin Respir Crit Care Med 2004; 25(5): 535-545
DOI: 10.1055/s-2004-836145
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Churg-Strauss Syndrome

Loïc Guillevin1 , Christian Pagnoux1 , Luc Mouthon1
  • 1Department of Internal Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris V, Paris, France
Further Information

Publication History

Publication Date:
09 November 2004 (online)

    Permissions and Reprints

First described in 1951 as an allergic and granulomatous angiitis, Churg-Strauss syndrome (CSS) is a small-vessel vasculitis. Mean age at the time of diagnosis is ∼50 years, with a sex ratio around 1. Asthma is the central feature of CSS and precedes the systemic manifestations in almost all cases, whereas 70% of the patients have maxillary sinusitis, allergic rhinitis, and/or sinus polyposis. General symptoms are frequent, and associated with pulmonary infiltrates in 38 to 77% of the patients; peripheral neuropathy, usually mononeuritis multiplex, in 64 to 75%; skin involvement in 40 to 70%; and gastrointestinal tract symptoms in 37 to 62%. Cardiac involvement is common, with pericarditis in 23% of the patients and myocarditis in 13%, and represents the primary cause of mortality. Hypereosinophilia is the main biological feature of CSS, whereas antineutrophil cytoplasm antibodies (ANCA), especially anti-myeloperoxidase (MPO), are found in one third to one half of the patients. Triggering factors, such as vaccination, desensitization, or exposure to leukotriene-receptor antagonists, have been suspected as contributing to the development of CSS, but its etiology has not yet been fully elucidated. T-helper type 2 (Th2) lymphocytes, by analogy with the pathogenesis of asthma, eosinophils infiltrating tissues, and anti-MPO ANCA are probably implicated in the pathogenesis of vasculitic lesions. CSS usually responds rapidly to corticosteroids. Adjunction of cyclophosphamide is indicated when at least one factor of poor prognosis is present. With treatment, remission is obtained in more than 80% of the patients, but it is often impossible to withdraw corticosteroids completely because of residual asthma. Relapses occur in 25% of the patients, half during the first year. The 10-year survival rate was 79% for our patients, with 73% of them requiring low-dose prednisone maintenance therapy for persistent asthma.

KEYWORDS

Churg-Strauss syndrome - primary systemic necrotizing vasculitis - asthma

REFERENCES

  • 1 Churg J, Strauss L. Allergic granulomatosis, allergic angiitis and periarteritis nodosa.  Am J Pathol. 1951;  27 277-294
    PubMedGoogle Scholar
  • 2 Masi A T, Hunder G G, Lie J T 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
    CrossrefPubMedGoogle Scholar
  • 3 Jennette J C, Falk R J, Andrassy K et al.. Nomenclature of systemic vasculitides: proposal of an international consensus conference.  Arthritis Rheum. 1994;  37 187-192
    CrossrefPubMedGoogle Scholar
  • 4 Fauci A, Haynes B, Katz P. The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic considerations.  Ann Intern Med. 1978;  89 660-676
    PubMedGoogle Scholar
  • 5 Lanham J G, Elkon K B, Pusey C D, Hughes G R. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome.  Medicine (Baltimore). 1984;  63 65-81
    CrossrefPubMedGoogle Scholar
  • 6 Lie J T. Histopathologic specificity of systemic vasculitis.  Rheum Dis Clin North Am. 1995;  21 883-909
    PubMedGoogle Scholar
  • 7 Genereau T, Lortholary O, Pottier M A et al.. Temporal artery biopsy: a diagnostic tool for systemic necrotizing vasculitis. French Vasculitis Study Group.  Arthritis Rheum. 1999;  42 2674-2681
    CrossrefPubMedGoogle Scholar
  • 8 Chumbley L C, Harrison Jr E G, DeRemee R A. Allergic granulomatosis and angiitis (Churg-Strauss syndrome): report and analysis of 30 cases.  Mayo Clin Proc. 1977;  52 477-484
    PubMedGoogle Scholar
  • 9 Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg-Strauss syndrome: clinical study and long-term follow-up of 96 patients.  Medicine (Baltimore). 1999;  78 26-37
    CrossrefPubMedGoogle Scholar
  • 10 Solans R, Bosch J A, Perez-Bocanegra C et al.. Churg-Strauss syndrome: outcome and long-term follow-up of 32 patients.  Rheumatology (Oxford). 2001;  40 763-771
    CrossrefPubMedGoogle Scholar
  • 11 Kurland L, Chuang T, Hunder G. The epidemiology of systemic arteritis. In the Epidemiology of the Rheumatic Disease. New York; Gower 1984: 196-205
    Google Scholar
  • 12 Watts R A, Carruthers D M, Scott D G. Epidemiology of systemic vasculitis: changing incidence or definition?.  Semin Arthritis Rheum. 1995;  25 28-34
    CrossrefPubMedGoogle Scholar
  • 13 Watts R A, Gonzalez-Gay M A, Lane S E, Garcia-Porrua C, Bentham G, Scott D G. Geoepidemiology of systemic vasculitis: comparison of the incidence in two regions of Europe.  Ann Rheum Dis. 2001;  60 170-172
    CrossrefPubMedGoogle Scholar
  • 14 Gonzalez-Gay M A, Garcia-Porrua C, Guerrero J, Rodriguez-Ledo P, Llorca J. The epidemiology of the primary systemic vasculitides in northwest Spain: implications of the Chapel Hill Consensus Conference definitions.  Arthritis Rheum. 2003;  49 388-393
    CrossrefPubMedGoogle Scholar
  • 15 Mahr A, Guillevin L, Poissonnet M, Aymé S. Prevalence of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis and Churg-Strauss syndrome in a french multiethnic population in 2000: a capture-recapture estimate.  Arthritis Rheum. 2004;  51 92-99
    CrossrefPubMedGoogle Scholar
  • 16 Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness.  Annu Rev Immunol. 1999;  17 255-281
    CrossrefPubMedGoogle Scholar
  • 17 Umetsu D, Dekruyff R. TH1 and TH2 CD4+ cells in human allergic diseases.  J Allergy Clin Immunol. 1997;  100 1-6
    PubMedGoogle Scholar
  • 18 Wills-Karp M, Luymbazi J, Xu X et al.. Interleukin-13: central mediator of allergic asthma.  Science. 1998;  282 2258-2261
    CrossrefPubMedGoogle Scholar
  • 19 Grau G E, Roux-Lombard P, Gysler C et al.. Serum cytokine changes in systemic vasculitis.  Immunology. 1989;  68 196-198
    PubMedGoogle Scholar
  • 20 Tsukadaira A, Okubo Y, Kitano K et al.. Eosinophil active cytokines and surface analysis of eosinophils in Churg-Strauss syndrome.  Allergy Asthma Proc. 1999;  20 39-44
    CrossrefPubMedGoogle Scholar
  • 21 Li X, Chopra R, Chou T, Schofield B, Willskarp M, Huang S. Mucosal IFN-gamma gene transfer inhibits pulmonary allergic responses in mice.  J Immunol. 1996;  157 3216-3219
    PubMedGoogle Scholar
  • 22 Hansen G, McIntire J, Yeung V et al.. T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperreactivity and inflammation.  J Clin Invest. 2000;  105 61-70
    PubMedGoogle Scholar
  • 23 Kiene M, Csernok E, Muller A, Metzler C, Trabandt A, Gross W L. Elevated interleukin-4 and interleukin-13 production by T cell lines from patients with Churg-Strauss syndrome.  Arthritis Rheum. 2001;  44 469-473
    CrossrefPubMedGoogle Scholar
  • 24 Gross W L. Churg-Strauss syndrome: update on recent developments.  Curr Opin Rheumatol. 2002;  14 11-14
    CrossrefPubMedGoogle Scholar
  • 25 Schnabel A, Csernok E, Braun J, Gross W L. Inflammatory cells and cellular activation in the lower respiratory tract in Churg-Strauss syndrome.  Thorax. 1999;  54 771-778
    PubMedGoogle Scholar
  • 26 Tai P C, Holt M E, Denny P, Gibbs A R, Williams B D, Spry C J. Deposition of eosinophil cationic protein in granulomas in allergic granulomatosis and vasculitis: the Churg-Strauss syndrome.  Br Med J (Clin Res Ed). 1984;  289 400-402
    CrossrefPubMedGoogle Scholar
  • 27 Peen E, Hahn P, Lauwers G, Williams Jr R C, Gleich G, Kephart G M. Churg-Strauss syndrome: localization of eosinophil major basic protein in damaged tissues.  Arthritis Rheum. 2000;  43 1897-1900
    CrossrefPubMedGoogle Scholar
  • 28 Girard T, Mahr A, Noel L H et al.. Are antineutrophil cytoplasmic antibodies a marker predictive of relapse in Wegener's granulomatosis? A prospective study.  Rheumatology (Oxford). 2001;  40 147-151
    CrossrefPubMedGoogle Scholar
  • 29 Xiao H, Heeringa P, Hu P et al.. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice.  J Clin Invest. 2002;  110 955-963
    CrossrefPubMedGoogle Scholar
  • 30 Porges A J, Redecha P B, Kimberly W T, Csernok E, Gross W L, Kimberly R P. Anti-neutrophil cytoplasmic antibodies engage and activate human neutrophils via Fc gamma RIIa.  J Immunol. 1994;  153 1271-1280
    PubMedGoogle Scholar
  • 31 Falk R, Terrell R, Charles L, Jennette J. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro.  Proc Natl Acad Sci U S A. 1990;  87 4115-4119
    CrossrefPubMedGoogle Scholar
  • 32 Esnault V, Mathieson P, Thiru S, Oliveira D, Lockwood C. Autoantibodies to myeloperoxidase in brown Norway rats treated with mercuric chloride.  Lab Invest. 1992;  67 114-120
    PubMedGoogle Scholar
  • 33 Kinjoh K, Kyogoku M, Good R. Genetic selection for crescent formation yields mouse strain with rapidly progressive glomerulonephritis and small vessel vasculitis.  Proc Natl Acad Sci U S A. 1993;  90 3413-3417
    PubMedGoogle Scholar
  • 34 Heeringa P, Brouwer E, Cohen Tervaert J, Weening J, Kallenberg C. Animal models of anti-neutrophil cytoplasmic antibody associated vasculitis.  Kidney Int. 1998;  53 253-263
    CrossrefPubMedGoogle Scholar
  • 35 Manger B J, Krapf F E, Gramatzki M et al.. IgE-containing circulating immune complexes in Churg-Strauss vasculitis.  Scand J Immunol. 1985;  21 369-373
    CrossrefPubMedGoogle Scholar
  • 36 Guillevin L, Guittard T, Bletry O, Godeau P, Rosenthal P. Systemic necrotizing angiitis with asthma: causes and precipitating factors in 43 cases.  Lung. 1987;  165 165-172
    CrossrefPubMedGoogle Scholar
  • 37 Mathur S, Dooley J, Scheuer P. Quinine induced granulomatous hepatitis and vasculitis.  BMJ. 1990;  300 613
    PubMedGoogle Scholar
  • 38 Imai H, Nakamoto Y, Hirokawa M, Akihama T, Miura A B. Carbamazepine-induced granulomatous necrotizing angiitis with acute renal failure.  Nephron. 1989;  51 405-408
    CrossrefPubMedGoogle Scholar
  • 39 Dietz A, Hubner C, Andrassy K. Macrolide antibiotic-induced vasculitis (Churg-Strauss syndrome) [German].  Laryngorhinootologie. 1998;  77 111-114
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Wechsler M E, Pauwels R, Drazen J M. Leukotriene modifiers and Churg-Strauss syndrome: adverse effect or response to corticosteroid withdrawal?.  Drug Saf. 1999;  21 241-251
    CrossrefPubMedGoogle Scholar
  • 41 Stirling R G, Chung K F. Leukotriene antagonists and Churg-Strauss syndrome: the smoking gun.  Thorax. 1999;  54 865-866
    PubMedGoogle Scholar
  • 42 Solans R, Bosch J A, Selva A, Orriols R, Vilardell M. Montelukast and Churg-Strauss syndrome.  Thorax. 2002;  57 183-185
    CrossrefPubMedGoogle Scholar
  • 43 Weller P F, Plaut M, Taggart V, Trontell A. The relationship of asthma therapy and Churg-Strauss syndrome: NIH workshop summary report.  J Allergy Clin Immunol. 2001;  108 175-183
    CrossrefPubMedGoogle Scholar
  • 44 Wechsler M E, Finn D, Gunawardena D et al.. Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma.  Chest. 2000;  117 708-713
    CrossrefPubMedGoogle Scholar
  • 45 Wechsler M E, Garpestad E, Flier S R et al.. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast.  JAMA. 1998;  279 455-457
    CrossrefPubMedGoogle Scholar
  • 46 Churg J, Churg A. Zafirlukast and Churg-Strauss syndrome.  JAMA. 1998;  279 1949-1950
    CrossrefPubMedGoogle Scholar
  • 47 Churg A, Brallas M, Cronin S R, Churg J. Formes frustes of Churg-Strauss syndrome.  Chest. 1995;  108 320-323
    PubMedGoogle Scholar
  • 48 Hayashi S, Furuya S, Imamura H. Fulminant eosinophilic endomyocarditis in an asthmatic patient treated with pranlukast after corticosteroid withdrawal.  Heart. 2001;  86 E7
    CrossrefPubMedGoogle Scholar
  • 49 Cooper S M, Libman B S, Lazarovich M. Churg-Strauss syndrome in a group of patients receiving fluticasone for asthma.  J Rheumatol. 2002;  29 2651-2652
    PubMedGoogle Scholar
  • 50 Lobel H, Machtey I, Eldror M. Pulmonary infiltrates with eosinophilia in an asthmatic patient treated with disodium cromoglycate.  Lancet. 1972;  2 1032
    PubMedGoogle Scholar
  • 51 Bili A, Condemi J J, Bottone S M, Ryan C K. Seven cases of complete and incomplete forms of Churg-Strauss syndrome not related to leukotriene receptor antagonists.  J Allergy Clin Immunol. 1999;  104 1060-1065
    PubMedGoogle Scholar
  • 52 Le Gall C, Pham S, Vignes S et al.. Inhaled corticosteroids and Churg-Strauss syndrome: a report of five cases.  Eur Respir J. 2000;  15 978-981
    CrossrefPubMedGoogle Scholar
  • 53 Drazen J, Israel E, O'Byrne P. Treatment of asthma with drugs modifying the leukotriene pathway.  N Engl J Med. 1999;  340 197-206
    CrossrefPubMedGoogle Scholar
  • 54 Martin R, Wilton L, Mann R. Prevalence of Churg-Strauss syndrome, vasculitis, eosinophilia and associated conditions: retrospective analysis of 58 prescription-event monitoring cohort studies.  Pharmacoepidemiol Drug Saf. 1999;  8 179-189
    CrossrefPubMedGoogle Scholar
  • 55 Lanham J G. Churg-Strauss syndrome.  Br J Hosp Med. 1992;  47 667-673
    PubMedGoogle Scholar
  • 56 Gaskin G, Clutterbuck E J, Pusey C D. Renal disease in the Churg-Strauss syndrome: diagnosis, management and outcome.  Contrib Nephrol. 1991;  94 58-65
    PubMedGoogle Scholar
  • 57 Haas C, Geneau C, Odinot J M et al.. Angéite granulomateuse de Churg-Strauss: une étude rétrospective de 16 cas.  Ann Med Interne (Paris). 1991;  142 335-342
    PubMedGoogle Scholar
  • 58 Abu-Shakra M, Smythe H, Lewtas J, Badley E, Weber D, Keystone E. Outcome of polyarteritis nodosa and Churg-Strauss syndrome: an analysis of twenty-five patients.  Arthritis Rheum. 1994;  37 1798-1803
    CrossrefPubMedGoogle Scholar
  • 59 Guillevin L, Lhote F, Gayraud M et al.. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome: a prospective study in 342 patients.  Medicine (Baltimore). 1996;  75 17-28
    CrossrefPubMedGoogle Scholar
  • 60 Ramakrishna G, Connolly H M, Tazelaar H D, Mullany C J, Midthun D E. Churg-Strauss syndrome complicated by eosinophilic endomyocarditis.  Mayo Clin Proc. 2000;  75 631-635
    CrossrefPubMedGoogle Scholar
  • 61 Nissim F, von der Valde J, Czernobilsky B. A limited form of Churg-Strauss syndrome: ocular and cutaneous manifestations.  Arch Pathol Lab Med. 1982;  106 305-307
    PubMedGoogle Scholar
  • 62 Gross W L, Schnabel A, Trabandt A. New perspectives in pulmonary angiitis: from pulmonary angiitis and granulomatosis to ANCA associated vasculitis.  Sarcoidosis Vasc Diffuse Lung Dis. 2000;  17 33-52
    PubMedGoogle Scholar
  • 63 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
    CrossrefPubMedGoogle Scholar
  • 64 Luqmani R A, Bacon P A, Moots R J et al.. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis.  QJM. 1994;  87 671-678
    PubMedGoogle Scholar
  • 65 Hoffman G S, Kerr G S, Leavitt R Y et al.. Wegener granulomatosis: an analysis of 158 patients.  Ann Intern Med. 1992;  116 488-498
    CrossrefPubMedGoogle Scholar
  • 66 Généreau T, Lortholary O, Leclerq P et al.. Treatment of systemic vasculitis with cyclophosphamide and steroids: daily oral low-dose cyclophosphamide administration after failure of a pulse intravenous high-dose regimen in four patients.  Br J Rheumatol. 1994;  33 959-962
    PubMedGoogle Scholar
  • 67 Pagnoux C, Cohen P, Mahr A et al.. Treatment of Churg-Strauss syndrome with poor prognosis factors: a prospective, randomized, multicenter trial comparing corticosteroids and 6 vs 12 cyclophosphamide pulses [abstract]. American College of Rheumatology, Orlando, October 23-28, 2003.  Arthritis Rheum. 2003;  49(suppl) 398
    PubMedGoogle Scholar
  • 68 Gaskin G. Plasma exchange of severe glomerulonephritis in ANCA-related vasculitides: a prospective study MEPEX. World Apheresis Association Congress, Paris September 7-10, 2002. 2003 Abstract book, L83
    Google Scholar
  • 69 Jayne D R, Lockwood C M. Intravenous immunoglobulin as sole therapy for systemic vasculitis.  Br J Rheumatol. 1996;  35 1150-1153
    CrossrefPubMedGoogle Scholar
  • 70 Levings M, Sangregorio R, Galbati F, Squadrone S, De Waal Malefyt R, Roncarolo M. IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells.  J Immunol. 2001;  166 5530-5539
    PubMedGoogle Scholar
  • 71 Tatsis E, Schnabel A, Gross W L. Interferon-alpha treatment of four patients with the Churg-Strauss syndrome.  Ann Intern Med. 1998;  129 370-374
    CrossrefPubMedGoogle Scholar
  • 72 Simon H U, Seelbach H, Ehmann R, Schmitz M. Clinical and immunological effects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma.  Allergy. 2003;  58 1250-1255
    CrossrefPubMedGoogle Scholar
  • 73 Termeer C C, Simon J C, Schopf E. Low-dose interferon alfa-2b for the treatment of Churg-Strauss syndrome with prominent skin involvement.  Arch Dermatol. 2001;  137 136-138
    PubMedGoogle Scholar

Loïc GuillevinM.D. 

Department of Internal Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université

Paris V, 27, rue du Faubourg Saint-Jacques

75679 Paris Cedex 14, France

Email: loic.guillevin@cch.ap-hop-paris.fr

      >