Background
Churg-Strauss syndrome (CSS), or allergic granulomatous angiitis, is a rare syndrome that affects small- to medium-sized arteries and veins. Wegener granulomatosis, Churg-Strauss syndrome, and the microscopic form of periarteritis (ie, microscopic polyangiitis) are three closely related vasculitic syndromes that affect medium- and small-sized vessels and are associated with antibodies to neutrophil cytoplasmic antigens (ANCAs).[1, 2, 3, 4]
In 1951, Churg and Strauss first described the syndrome in 13 patients who had asthma, eosinophilia, granulomatous inflammation, necrotizing systemic vasculitis, and necrotizing glomerulonephritis.[2]
The American College of Rheumatology (ACR) has proposed 6 criteria for the diagnosis of Churg-Strauss syndrome.[5] The presence of 4 or more criteria yields a sensitivity of 85% and a specificity of 99.7%. These criteria include (1) asthma (wheezing, expiratory rhonchi), (2) eosinophilia of more than 10% in peripheral blood, (3) paranasal sinusitis, (4) pulmonary infiltrates (may be transient), (5) histological proof of vasculitis with extravascular eosinophils, and (6) mononeuritis multiplex or polyneuropathy.
The 1994 Chapel Hill consensus conference on the classification of vasculitides did not modify the ACR criteria.[6]
Pathophysiology
Churg-Strauss syndrome is a granulomatous small-vessel vasculitis. The cause of this allergic angiitis and granulomatosis is unknown.[7] No data have been reported regarding the role of immune complexes or cell-mediated mechanisms in this disease, although autoimmunity is evident with the presence of hypergammaglobulinemia, increased levels of immunoglobulin E (IgE), rheumatoid factor, and ANCA.
A Churg-Strauss syndrome–like syndrome develops as a rare complication in people with asthma who are steroid-dependent and who are treated with leukotriene receptor antagonists (eg, montelukast, zafirlukast) upon reduction in their oral steroid dose.[8] The Churg-Strauss syndrome–like complication is reported in people whose withdrawal of oral steroids is also facilitated by inhaled steroids. This complication is probably related to steroid withdrawal, which unmasks underlying Churg-Strauss syndrome,[9, 10, 11] rather than to the drugs themselves. However, in rare cases, this syndrome has developed when a leukotriene receptor antagonist has been substituted for inhaled steroids without a history of oral steroid withdrawal.
HLA-DRB4 positivity may be a genetic risk factor for the development of Churg-Strauss syndrome and may increase the likelihood of vasculitic manifestations of the disease.[12]
Epidemiology
Frequency
United States
The incidence of Churg-Strauss syndrome in the United States is 1-3 cases per 100,000 adults per year.[13]
International
The international incidence of Churg-Strauss syndrome is approximately 2.5 cases per 100,000 adults per year.
Mortality/Morbidity
- The principal causes of morbidity and mortality in Churg-Strauss syndrome are myocarditis and myocardial infarction secondary to coronary arteritis.[14]
- With treatment, the 1-year survival rate is 90% and the 5-year survival rate is 62%.[1, 15]
Sex
Churg-Strauss syndrome is slightly more common in males than in females.
Age
The age at onset varies from 15-70 years, with a mean age of approximately 38 years. Churg-Strauss syndrome in pediatric patients is well described, but mostly as case reports. The mean age at diagnosis is around 50 years.
Guillevin L, Cohen P, Gayraud M, et al. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore). Jan 1999;78(1):26-37. [Medline].
Churg J, Strauss L. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol. Mar-Apr 1951;27(2):277-301. [Medline].
Churg A. Pulmonary angiitis and granulomatosis revisited. Hum Pathol. Oct 1983;14(10):868-83. [Medline].
Keogh KA, Specks U. Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists. Am J Med. Sep 2003;115(4):284-90. [Medline].
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. Aug 1990;33(8):1094-100. [Medline].
Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. Feb 1994;37(2):187-92. [Medline].
Hellmich B, Ehlers S, Csernok E, Gross WL. Update on the pathogenesis of Churg-Strauss syndrome. Clin Exp Rheumatol. Nov-Dec 2003;21(6 Suppl 32):S69-77. [Medline].
Franco J, Artes MJ. Pulmonary eosinophilia associated with montelukast. Thorax. Jun 1999;54(6):558-60. [Medline].
Wechsler ME, Finn D, Gunawardena D, et al. Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma. Chest. Mar 2000;117(3):708-13. [Medline].
Hauser T, Mahr A, Metzler C, Coste J, Sommerstein R, Gross WL, et al. The leucotriene receptor antagonist montelukast and the risk of Churg-Strauss syndrome: a case-crossover study. Thorax. Aug 2008;63(8):677-82. [Medline].
Wechsler ME, Garpestad E, Flier SR, et al. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast. JAMA. Feb 11 1998;279(6):455-7. [Medline].
Vaglio A, Martorana D, Maggiore U, Grasselli C, Zanetti A, Pesci A, et al. HLA-DRB4 as a genetic risk factor for Churg-Strauss syndrome. Arthritis Rheum. Sep 2007;56(9):3159-66. [Medline].
Eustace JA, Nadasdy T, Choi M. Disease of the month. The Churg Strauss Syndrome. J Am Soc Nephrol. Sep 1999;10(9):2048-55. [Medline].
Hasley PB, Follansbee WP, Coulehan JL. Cardiac manifestations of Churg-Strauss syndrome: report of a case and review of the literature. Am Heart J. Oct 1990;120(4):996-9. [Medline].
Keogh KA, Specks U. Churg-Strauss syndrome: update on clinical, laboratory and therapeutic aspects. Sarcoidosis Vasc Diffuse Lung Dis. Mar 2006;23(1):3-12. [Medline].
Sinico RA, Sabadini E, Maresca AM. Mesalazine-induced Churg-Strauss syndrome in a patient with Crohn's disease and sclerosing cholangitis. Clin Exp Rheumatol. Mar-Apr 2006;24(2 Suppl 41):S104. [Medline].
Orriols R, Munoz X, Ferrer J, Huget P, Morell F. Cocaine-induced Churg-Strauss vasculitis. Eur Respir J. Jan 1996;9(1):175-7. [Medline].
Sablé-Fourtassou R, Cohen P, Mahr A, Pagnoux C, Mouthon L, Jayne D, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med. Nov 1 2005;143(9):632-8. [Medline].
Choi YH, Im JG, Han BK, Kim JH, Lee KY, Myoung NH. Thoracic manifestation of Churg-Strauss syndrome: radiologic and clinical findings. Chest. Jan 2000;117(1):117-24. [Medline].
Kim Y, Lee KS, Choi DC, et al. The spectrum of eosinophilic lung disease: radiologic findings. J Comput Assist Tomogr. Nov-Dec 1997;21(6):920-30. [Medline].
Buschman DL, Waldron JA Jr, King TE Jr. Churg-Strauss pulmonary vasculitis. High-resolution computed tomography scanning and pathologic findings. Am Rev Respir Dis. Aug 1990;142(2):458-61. [Medline].
Worthy SA, Müller NL, Hansell DM, Flower CD. Churg-Strauss syndrome: the spectrum of pulmonary CT findings in 17 patients. AJR Am J Roentgenol. Feb 1998;170(2):297-300. [Medline].
Hervier B, Durant C, Masseau A, Ponge T, Hamidou M, Mussini JM. Use of muscle biopsies for diagnosis of systemic vasculitides. J Rheumatol. Mar 2011;38(3):470-4. [Medline].
Lie JT. Histopathologic specificity of systemic vasculitis. Rheum Dis Clin North Am. Nov 1995;21(4):883-909. [Medline].
Katzenstein AL. Diagnostic features and differential diagnosis of Churg-Strauss syndrome in the lung. A review. Am J Clin Pathol. Nov 2000;114(5):767-72. [Medline].
Chemmalakuzhy AJ, Zhou XJ, Hedayati SS. ANCA-negative glomerulonephritis associated with nonasthmatic Churg-Strauss syndrome. Nat Clin Pract Nephrol. Oct 2008;4(10):568-74. [Medline].
Lhote F, Cohen P, Guilpain P, Guillevin L. [Churg-Strauss syndrome]. Rev Prat. Jun 15 2008;58(11):1165-74. [Medline].
Grau RG. Churg-Strauss syndrome: 2005-2008 update. Curr Rheumatol Rep. Dec 2008;10(6):453-8. [Medline].
Mukhtyar C, Flossmann O, Hellmich B, Bacon P, Cid M, Cohen-Tervaert JW, et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force. Ann Rheum Dis. Jul 2008;67(7):1004-10. [Medline].
Casian A, Jayne D. Plasma exchange in the treatment of Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and renal limited vasculitis. Curr Opin Rheumatol. Jan 2011;23(1):12-7. [Medline].
Bonaci-Nikolic B, Nikolic MM, Andrejevic S, Zoric S, Bukilica M. Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides. Arthritis Res Ther. 2005;7(5):R1072-81. [Medline].
Cohen P, Guillevin L, Baril L, et al. Persistence of antineutrophil cytoplasmic antibodies (ANCA) in asymptomatic patients with systemic polyarteritis nodosa or Churg-Strauss syndrome: follow-up of 53 patients. Clin Exp Rheumatol. Mar-Apr 1995;13(2):193-8. [Medline].
Espinoza LR. Combination therapy to treat churg-strauss syndrome: corticosteroids with short- or long-term cyclophosphamide pulses. Curr Rheumatol Rep. Dec 2008;10(6):427-9. [Medline].
Yamasaki A, Tomita K, Fujii Y, Hasegawa Y, Watanabe M, Sano H, et al. Repressed ileal artery aneurysms in Churg-Strauss syndrome following combination treatment with glucocorticoid and cyclophosphamide. Rheumatol Int. Aug 8 2008;[Medline].
Ribi C, Cohen P, Pagnoux C, Mahr A, Arène JP, Lauque D, et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheum. Feb 2008;58(2):586-94. [Medline].
Guillevin L, Cevallos R, Durand-Gasselin B, et al. Treatment of glomerulonephritis in microscopic polyangiitis and Churg-Strauss syndrome. Indications of plasma exchanges, Meta-analysis of 2 randomized studies on 140 patients, 32 with glomerulonephritis. Ann Med Interne (Paris). 1997;148(3):198-204. [Medline].
Tatsis E, Schnabel A, Gross WL. Interferon-alpha treatment of four patients with the Churg-Strauss syndrome. Ann Intern Med. Sep 1 1998;129(5):370-4. [Medline].
Metzler C, Schnabel A, Gross WL, Hellmich B. A phase II study of interferon-alpha for the treatment of refractory Churg-Strauss syndrome. Clin Exp Rheumatol. May-Jun 2008;26(3 Suppl 49):S35-40. [Medline].
Beasley R, Bibby S, Weatherall M. Leukotriene receptor antagonist therapy and Churg-Strauss syndrome: culprit or innocent bystander?. Thorax. Oct 2008;63(10):847-9. [Medline].
Boyer D, Vargas SO, Slattery D, Rivera-Sanchez YM, Colin AA. Churg-Strauss syndrome in children: a clinical and pathologic review. Pediatrics. Sep 2006;118(3):e914-20. [Medline].
Chumbley LC, Harrison EG, DeRemee RA. Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Report and analysis of 30 cases. Mayo Clin Proc. Aug 1977;52(8):477-84. [Medline].
Giavina-Bianchi P, Giavina-Bianchi M, Agondi R, Kalil J. Omalizumab and Churg-Strauss syndrome. J Allergy Clin Immunol. Jul 2008;122(1):217; author reply 217-8. [Medline].
Giavina-Bianchi P, Giavina-Bianchi M, Agondi R, Kalil J. Three months' administration of anti-IgE to a patient with Churg-Strauss syndrome. J Allergy Clin Immunol. May 2007;119(5):1279; author reply 1279-80. [Medline].
Green RL, Vayonis AG. Churg-Strauss syndrome after zafirlukast in two patients not receiving systemic steroid treatment. Lancet. Feb 27 1999;353(9154):725-6. [Medline].
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). Jan 1999;78(1):26-37. [Medline].
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). Jan 1996;75(1):17-28. [Medline].
Kaushik VV, Reddy HV, Bucknall RC. Successful use of rituximab in a patient with recalcitrant Churg-Strauss syndrome. Ann Rheum Dis. Aug 2006;65(8):1116-7. [Medline].
Kümpers P, Erdbrügger U, Grossheim M, Meyer GP, Hiss M, Gwinner W, et al. Endothelial microparticles as a diagnostic aid in Churg-Strauss vasculitis-induced cardiomyopathy. Clin Exp Rheumatol. May-Jun 2008;26(3 Suppl 49):S86-9. [Medline].
Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine (Baltimore). Mar 1984;63(2):65-81. [Medline].
Lhote F, Guillevin L. Polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical aspects and treatment. Rheum Dis Clin North Am. Nov 1995;21(4):911-47. [Medline].
Lie JT. Illustrated histopathologic classification criteria for selected vasculitis syndromes. American College of Rheumatology Subcommittee on Classification of Vasculitis. Arthritis Rheum. Aug 1990;33(8):1074-87. [Medline].
Lightfoot RW Jr. Churg-Strauss syndrome and polyarteritis nodosa. Curr Opin Rheumatol. Feb 1991;3(1):3-7. [Medline].
Noth I, Strek ME, Leff AR. Churg-Strauss syndrome. Lancet. Feb 15 2003;361(9357):587-94. [Medline].
Pabst S, Tiyerili V, Grohé C. Apparent response to anti-IgE therapy in two patients with refractory "forme fruste" of Churg-Strauss syndrome. Thorax. Aug 2008;63(8):747-8. [Medline].
Roccatello D, Baldovino S, Alpa M, Rossi D, Napoli F, Naretto C, et al. Effects of anti-CD20 monoclonal antibody as a rescue treatment for ANCA-associated idiopathic systemic vasculitis with or without overt renal involvement. Clin Exp Rheumatol. May-Jun 2008;26(3 Suppl 49):S67-71. [Medline].
Schmitt WH, Csernok E, Kobayashi S, et al. Churg-Strauss syndrome: serum markers of lymphocyte activation and endothelial damage. Arthritis Rheum. Mar 1998;41(3):445-52. [Medline].
Specks U, DeRemee RA. Granulomatous vasculitis. Wegener's granulomatosis and Churg-Strauss syndrome. Rheum Dis Clin North Am. May 1990;16(2):377-97. [Medline].
Tidman M, Olander R, Svalander C, Danielsson D. Patients hospitalized because of small vessel vasculitides with renal involvement in the period 1975-95: organ involvement, anti-neutrophil cytoplasmic antibodies patterns, seasonal attack rates and fluctuation of annual frequencies. J Intern Med. Aug 1998;244(2):133-41. [Medline].
Tiliakos A 4th, Shaia S, Hostoffer R, Kent L. The use of infliximab in a patient with steroid-dependent churg-strauss syndrome. J Clin Rheumatol. Apr 2004;10(2):96-7. [Medline].
Todd DC, Cockcroft DW. Prolonged survival in Churg-Strauss syndrome. Ann Allergy Asthma Immunol. Jan 2004;92(1):92-3. [Medline].
Tuggey JM, Hosker HS. Churg-Strauss syndrome associated with montelukast therapy. Thorax. Sep 2000;55(9):805-6. [Medline].
Wechsler ME, Finn D, Gunawardena D, Westlake R, Barker A, Haranath SP, et al. Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma. Chest. Mar 2000;117(3):708-13. [Medline].
Weyand CM, Goronzy JJ. Multisystem interactions in the pathogenesis of vasculitis. Curr Opin Rheumatol. Jan 1997;9(1):3-11. [Medline].
Winchester DE, Jacob A, Murphy T. Omalizumab for asthma. N Engl J Med. Sep 21 2006;355(12):1281-2. [Medline].

