Churg-Strauss Syndrome

ABSTRACT

Churg-Strauss syndrome was originally called “allergic granulomatosis and angiitis,” describing the combination of eosinophilic inflammation, extravascular granulomas, and necrotizing vasculitis occurring in patients with severe asthma. It is now classified as a small-vessel vasculitis and, together with Wegener's granulomatosis and microscopic polyangiitis, as one of the vasculitides associated with antineutrophil cytoplasmic autoantibodies (ANCA). Glucocorticoid-sparing agents used in the treatment of asthma, such as leukotriene receptor antagonists, may unmask this particular form of vasculitis as oral glucocorticoids are withdrawn. ANCA occur in 40-75% of patients with active disease and typically react with myeloperoxidase. Patients' symptoms are defined by various degrees of eosinophilic inflammation and necrotizing vasculitis, which may affect any organ. On presentation, Churg-Strauss syndrome needs to be differentiated from other eosinophilic pneumonias, idiopathic hypereosinophilic syndrome, and Wegener's granulomatosis and microscopic polyangiitis. Churg-Strauss syndrome remains a rare disease with a poorly understood pathogenesis. Treatment consists primarily of glucocortoids. Patients who have ANCA at the time of presentation should be treated according to the treatment principles for ANCA-associated vasculitides. However, the exact role of glucocorticoid-sparing immunosuppressive agents and treatment options for refractory disease remain poorly studied.

Churg-Strauss syndrome - vasculitis - asthma - eosinophilia - ANCA - leukotriene receptor antagonists

REFERENCES

• 1 Churg J, Strauss L. Allergic granulomatosis, allergic angiitis and periarteritis nodosa.  Am J Pathol. 1951;  27 277-301
• 2 Jennette J C, Falk R J, Andrassy K et al.. Nomenclature of systemic vasculitides: The proposal of an international consensus conference.  Arthritis Rheum. 1994;  37 187-192
• 3 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. 1984;  63 65-81
• 4 Sorensen S F, Slot O, Tvede N, Petersen J. A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature.  Ann Rheum Dis. 2000;  59 478-482
• 5 Keogh K A, Specks U. Churg-Strauss syndrome. Clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists.  Am J Med. 2003;  115 284-290
• 6 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
• 7 Chumbley L C, Harrison E G, DeRemee R A. Allergic granulomatosis and angiitis (Churg-Strauss syndrome).  Mayo Clin Proc. 1977;  52 477-484
• 8 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. 1999;  78 26-37
• 9 Lie J T. Limited forms of Churg-Strauss syndrome.  Pathol Annu. 1993;  28(Pt 2) 199-220
• 10 Churg A, Brallas M, Cronin S R, Churg J. Formes frustes of Churg-Strauss syndrome.  Chest. 1995;  108 320-323
• 11 Churg A. Recent advances in the diagnosis of Churg-Strauss syndrome.  Mod Pathol. 2001;  14 1284-1293
• 12 Watts R A, Carruthers D M, Scott D GI. Epidemiology of systemic vasculitis: changing incidence or definition?.  Semin Arthritis Rheum. 1995;  25 28-34
• 13 Watts R A, Lane S E, Bentham G, Scott D G. Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom.  Arthritis Rheum. 2000;  43 414-419
• 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
• 15 Mahr A, Guillevin L, Poissonnet M, Ayme S. Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate.  Arthritis Rheum. 2004;  51 92-99
• 16 Reinhold-Keller E, Herlyn K, Wagner-Bastmeyer R, Gross W L. Stable incidence of primary systemic vasculitides over five years: results from the German vasculitis register.  Arthritis Rheum. 2005;  53 93-99
• 17 Loughlin J E, Cole J A, Rothman K J, Johnson E S. Prevalence of serious eosinophilia and incidence of Churg-Strauss syndrome in a cohort of asthma patients.  Ann Allergy Asthma Immunol. 2002;  88 319-325
• 18 Harrold L R, Andrade S E, Go A S et al.. Incidence of Churg-Strauss syndrome in asthma drug users: a population-based perspective.  J Rheumatol. 2005;  32 1076-1080
• 19 Reid A J, Harrison B DW, Watts R A, Watkin S W, McCann B G, Scott D GI. Churg-Strauss syndrome in a district hospital.  QJM. 1998;  91 219-229
• 20 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
• 21 Sable-Fourtassou R, Cohen P, Mahr A et al.. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome.  Ann Intern Med. 2005;  143 632-638
• 22 Worthy S A, Muller N L, Hansell D M, Flower C D. Churg-Strauss syndrome: the spectrum of pulmonary CT findings in 17 patients.  AJR Am J Roentgenol. 1998;  170 297-300
• 23 Silva C I, Muller N L, Fujimoto K, Johkoh T, Ajzen S A, Churg A. Churg-Strauss syndrome: high resolution CT and pathologic findings.  J Thorac Imaging. 2005;  20 74-80
• 24 Choi Y H, Im J G, Han B K, Kim J H, Lee K Y, Myoung N H. Thoracic manifestation of Churg-Strauss syndrome: radiologic and clinical findings.  Chest. 2000;  117 117-124
• 25 Sinico R A, Di Toma L, Maggiore U et al.. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome.  Arthritis Rheum. 2005;  52 2926-2935
• 26 Lesens O, Hansmann Y, Nerson J et al.. Severe Churg-Strauss syndrome with mediastinal lymphadenopathy treated with interferon therapy.  Eur J Intern Med. 2002;  13 458
• 27 Sehgal M, Swanson J W, DeRemee R A, Colby T V. Neurologic manifestations of Churg-Strauss syndrome.  Mayo Clin Proc. 1995;  70 337-341
• 28 Davis M D, Daoud M S, McEvoy M T, Su W P. Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic correlation.  J Am Acad Dermatol. 1997;  37 199-203
• 29 Finan M C, Winkelmann R K. The cutaneous extravascular necrotizing granuloma (Churg-Strauss granuloma) and systemic disease: a review of 27 cases.  Medicine (Baltimore). 1983;  62 142-158
• 30 Guillevin L, Lhote F, Gayraud M et al.. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome.  Medicine. 1996;  75 17-28
• 31 Morgan J M, Raposo L, Gibson D G. Cardiac involvement in Churg-Strauss syndrome shown by echocardiography.  Br Heart J. 1989;  62 462-466
• 32 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
• 33 Val-Bernal J F, Mayorga M, Garcia-Alberdi E, Pozueta J A. Churg-Strauss syndrome and sudden cardiac death.  Cardiovasc Pathol. 2003;  12 94-97
• 34 Stollberger C, Finsterer J, Winkler W B. Eosinophilic pericardial effusion in Churg-Strauss syndrome.  Respir Med. 2005;  99 377-379
• 35 Hasley P B, Follansbee W P, Coulehan J L. Cardiac manifestations of Churg-Strauss syndrome: report of a case and review of the literature.  Am Heart J. 1990;  120 996-999
• 36 Hellemans S, Dens J, Knockaert D. Coronary involvement in the Churg-Strauss syndrome.  Heart. 1997;  77 576-578
• 37 Kozak M, Gill E A, Green L S. The Churg-Strauss syndrome. A case report with angiographically documented coronary involvement and a review of the literature.  Chest. 1995;  107 578-580
• 38 Roufosse F, Cogan E, Goldman M. The hypereosinophilic syndrome revisited.  Annu Rev Med. 2003;  54 169-184
• 39 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
• 40 Memain N, De B M, Guillevin L, Wechsler B, Meyer O. Delayed relapse of Churg-Strauss syndrome manifesting as colon ulcers with mucosal granulomas: 3 cases.  J Rheumatol. 2002;  29 388-391
• 41 Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis.  Medicine (Baltimore). 2005;  84 115-128
• 42 Clutterbuck E J, Evans D J, Pusey C D. Renal involvement in Churg-Strauss syndrome.  Nephrol Dial Transplant. 1990;  5 161-167
• 43 Kikuchi Y, Ikehata N, Tajima O, Yoshizawa N, Miura S. Glomerular lesions in patients with Churg-Strauss syndrome and the anti- myeloperoxidase antibody.  Clin Nephrol. 2001;  55 429-435
• 44 Ames P R, Roes L, Lupoli S, Brancaccio V, Khamashta M A, Hughes G R. Thrombosis in Churg-Strauss syndrome. Beyond vasculitis?.  Br J Rheumatol. 1996;  35 1181-1183
• 45 Garcia G, Achouh L, Cobarzan D, Fichet D, Humbert M. Severe venous thromboembolic disease in Churg-Strauss syndrome.  Allergy. 2005;  60 409-410
• 46 Merkel P A, Lo G H, Holbrook J T et al.. High incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study.  Ann Intern Med. 2005;  142 620-626
• 47 Wallaert B, Gosset P, Prin L, Bart F, Marquette C H, Tonnel A B. Bronchoalveolar lavage in allergic granulomatosis and angiitis.  Eur Respir J. 1993;  6 413-417
• 48 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
• 49 Kallenberg C G. Churg-Strauss syndrome: just one disease entity?.  Arthritis Rheum. 2005;  52 2589-2593
• 50 Schmitt W H, Csernok E, Kobayashi S, Klinkenborg A, Reinhold-Keller E, Gross W L. Churg-Strauss syndrome. Serum markers of lymphocyte activation and endothelial damage.  Arthritis Rheum. 1998;  41 445-452
• 51 Hurst S, Chizzolini C, Dayer J M, Olivieri J, Roux-Lombard P. Usefulness of serum eosinophil cationic protein (ECP) in predicting relapse of Churg and Strauss vasculitis.  Clin Exp Rheumatol. 2000;  18 784-785
• 52 Cottin V, Tardy F, Gindre D, Vernet G, Deviller P, Cordier J F. Urinary eosinophil-derived neurotoxin in Churg-Strauss syndrome.  J Allergy Clin Immunol. 1995;  96 261-264
• 53 Kurosawa M, Nakagami R, Morioka J et al.. Interleukins in Churg-Strauss syndrome.  Allergy. 2000;  55 785-787
• 54 Drage L A, Davis M D, De Castro F et al.. Evidence for pathogenic involvement of eosinophils and neutrophilsin Churg-Strauss syndrome.  J Am Acad Dermatol. 2002;  47 209-216
• 55 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
• 56 Schonermarck U, Csernok E, Trabandt A, Hansen H, Gross W L. Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA- associated vasculitides.  Clin Exp Rheumatol. 2000;  18 457-463
• 57 Muschen M, Warskulat U, Perniok A et al.. Involvement of soluble CD95 in Churg-Strauss syndrome.  Am J Pathol. 1999;  155 915-925
• 58 Guillevin L, Amouroux J, Arbeille B, Boura R. Churg-Strauss angiitis. Arguments favoring the responsibility of inhaled antigens.  Chest. 1991;  100 1472-1473
• 59 Cohen Tervaert J W, Kallenberg C GM. Anti-myeloperoxidase antibodies in Churg-Strauss syndrome.  J Neurol. 1993;  240 449-452
• 60 Savage C O, Harper L, Holland M. New findings in pathogenesis of antineutrophil cytoplasm antibody-associated vasculitis.  Curr Opin Rheumatol. 2002;  14 15-22
• 61 Specks U. Antineutrophil cytoplasmic antibodies: are they pathogenic?.  Clin Exp Rheumatol. 2004;  22 S7-12
• 62 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
• 63 Pfister H, Ollert M, Frohlich L F et al.. Antineutrophil cytoplasmic autoantibodies against the murine homolog of proteinase 3 (Wegener autoantigen) are pathogenic in vivo.  Blood. 2004;  104 1411-1418
• 64 Little M A, Smyth C L, Yadav R et al.. Anti-neutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo.  Blood. 2005;  106 2050-2058
• 65 Knoell D L, Lucas J, Allen J N. Churg-Strauss syndrome associated with Zafirlukast.  Chest. 1998;  114 332-334
• 66 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
• 67 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
• 68 Tuggey J M, Hosker H S. Churg-Strauss syndrome associated with montelukast therapy.  Thorax. 2000;  55 805-806
• 69 Hashimoto M, Fujishima T, Tanaka H et al.. Churg-Strauss syndrome after reduction of inhaled corticosteroid in a patient treated with pranlukast for asthma.  Intern Med. 2001;  40 432-434
• 70 Guilpain P, Viallard J F, Lagarde P et al.. Churg-Strauss syndrome in two patients receiving montelukast.  Rheumatology (Oxford). 2002;  41 535-539
• 71 Solans R, Bosch J A, Selva A, Orriols R, Vilardell M. Montelukast and Churg-Strauss syndrome.  Thorax. 2002;  57 183-185
• 72 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
• 73 Masuzawa A, Moriguchi M, Tsuda T et al.. Churg-Strauss syndrome associated with hypersensitivity to acetaminophen.  Intern Med. 2005;  44 496-498
• 74 Hübner C, Dietz A, Stremmel W, Stiehl A, Andrassy K. Macrolide-induced Churg-Strauss syndrome in a patient with atopy.  Lancet. 1997;  350 563
• 75 Orriols R, Munoz X, Ferrer J, Huget P, Morell F. Cocaine-induced Churg-Strauss vasculitis.  Eur Respir J. 1996;  9 175-177
• 76 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
• 77 Sheffer A L, Rocklin R E, Goetzl E J. Immunologic components of hypersensitivity reactions to cromolyn sodium.  N Engl J Med. 1975;  293 1220-1224
• 78 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
• 79 Lilly C M, Churg A, Lazarovich M et al.. Asthma therapies and Churg-Strauss syndrome.  J Allergy Clin Immunol. 2002;  109 S1-19
• 80 Langford C A, Klippel J H, Balow J E, James S P, Sneller M C. Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 2: inflammatory bowel disease, systemic vasculitis, and therapeutic toxicity.  Ann Intern Med. 1998;  129 49-58
• 81 Gayraud M, Guillevin L, Cohen P et al.. Treatment of good-prognosis polyarteritis nodosa and Churg-Strauss syndrome: comparison of steroids and oral or pulse cyclophosphamide in 25 patients. French Cooperative Study Group for Vasculitides.  Br J Rheumatol. 1997;  36 1290-1297
• 82 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
• 83 Metzler C, Hellmich B, Gause A, Gross W L, de Groot K. 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 S52-S61
• 84 Della Rossa A, Baldini C, Tavoni A et al.. Churg-Strauss syndrome: clinical and serological features of 19 patients from a single Italian centre.  Rheumatology (Oxford). 2002;  41 1286-1294
• 85 Assaf C, Mewis G, Orfanos C E, Geilen C C. Churg-Strauss syndrome: successful treatment with mycophenolate mofetil.  Br J Dermatol. 2004;  150 598-600
• 86 Tatsis E, Schnabel A, Gross W L. Interferon-a treatment of four patients with the Churg-Strauss syndrome.  Ann Intern Med. 1998;  129 370-374
• 87 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
• 88 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
• 89 Gordon A C, Edgar J D, Finch R G. Acute exacerbation of vasculitis during interferon-alpha therapy for hepatitis C-associated cryoglobulinaemia.  J Infect. 1998;  36 229-230
• 90 Metzler C, Lamprecht P, Hellmich B, Reuter M, Arlt A C, Gross W L. Leucoencephalopathy after treatment of Churg-Strauss syndrome with interferon {alpha}.  Ann Rheum Dis. 2005;  64 1242-1243
• 91 Lane S E, Watts R A, Shepstone L, Scott D G. Primary systemic vasculitis: clinical features and mortality.  QJM. 2005;  98 97-111