Treatment and prognosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
- Section Editors
- Kevin R Flaherty, MD, MS
Kevin R Flaherty, MD, MS
- Section Editor — Interstitial Lung Disease
- Associate Professor of Medicine
- University of Michigan Health System
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Bruce S Bochner, MD
Bruce S Bochner, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Adult Allergy; Asthma
- Samuel M Feinberg Professor of Medicine
- Northwestern University Feinberg School of Medicine
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss), abbreviated EGPA, which was previously called the Churg-Strauss syndrome (CSS) or allergic granulomatosis and angiitis, is a multisystem disorder characterized by allergic rhinitis, asthma, and prominent peripheral blood eosinophilia [1-6]. EGPA is classified as a vasculitis of the small and medium sized arteries, although the vasculitis is often not apparent in the initial phases of the disease.
The most commonly involved organ is the lung, followed by the skin. EGPA, however, can affect any organ system, including the cardiovascular, gastrointestinal, renal, and central nervous systems. Vasculitis of extrapulmonary organs is largely responsible for the morbidity and mortality associated with EGPA.
The diagnosis of EGPA is typically suspected based on the clinical findings (ie, eosinophilia ≥1500/microL, asthma, and allergic rhinitis). A positive antineutrophil cytoplasmic antibody test is present in 40 to 60 percent, but is neither sensitive nor specific. The diagnosis is generally confirmed by a biopsy of an affected tissue, such as lung, skin, or peripheral nerve [1-4] (table 1).
The treatment and prognosis of EGPA will be reviewed here. The epidemiology, pathogenesis, clinical features, and diagnosis of this disorder are discussed separately. (See "Epidemiology, pathogenesis, and pathology of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)" and "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)".)
ASSESSING VASCULITIS SEVERITY
Two scoring systems have been developed to assess vasculitis disease activity in patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) and other vasculitides: the "five-factors score" and the Birmingham Vasculitis Activity Score (BVAS). These scoring systems are used to guide initial therapy.
- Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine (Baltimore) 1984; 63:65.
- Sinico RA, Bottero P. Churg-Strauss angiitis. Best Pract Res Clin Rheumatol 2009; 23:355.
- Pagnoux C, Guilpain P, Guillevin L. Churg-Strauss syndrome. Curr Opin Rheumatol 2007; 19:25.
- 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.
- 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.
- Danieli MG, Cappelli M, Malcangi G, et al. Long term effectiveness of intravenous immunoglobulin in Churg-Strauss syndrome. Ann Rheum Dis 2004; 63:1649.
- 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.
- Stone JH, Hoffman GS, Merkel PA, et al. A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS). Arthritis Rheum 2001; 44:912.
- 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 2008; 26:S35.
- Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA 2007; 298:655.
- Liou HH, Liu HM, Chiang IP, et al. Churg-Strauss syndrome presented as multiple intracerebral hemorrhage. Lupus 1997; 6:279.
- 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.
- Sablé-Fourtassou R, Cohen P, Mahr A, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med 2005; 143:632.
- Cottin V, Khouatra C, Dubost R, et al. Persistent airflow obstruction in asthma of patients with Churg-Strauss syndrome and long-term follow-up. Allergy 2009; 64:589.
- Neumann T, Manger B, Schmid M, et al. Cardiac involvement in Churg-Strauss syndrome: impact of endomyocarditis. Medicine (Baltimore) 2009; 88:236.
- Guillevin L, Jarrousse B, Lok C, et al. Longterm followup after treatment of polyarteritis nodosa and Churg-Strauss angiitis with comparison of steroids, plasma exchange and cyclophosphamide to steroids and plasma exchange. A prospective randomized trial of 71 patients. The Cooperative Study Group for Polyarteritis Nodosa. J Rheumatol 1991; 18:567.
- Hellmich B, Gross WL. Recent progress in the pharmacotherapy of Churg-Strauss syndrome. Expert Opin Pharmacother 2004; 5:25.
- Bourgarit A, Le Toumelin P, Pagnoux C, et al. Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients. Medicine (Baltimore) 2005; 84:323.
- 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.
- 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.
- 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 Rheum 2007; 57:686.
- 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.
- Samson M, Puéchal X, Devilliers H, et al. Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials. J Autoimmun 2013; 43:60.
- De Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005; 52:2461.
- Lhote F, Cohen P, Guilpain P, Guillevin L. [Churg-Strauss syndrome]. Rev Prat 2008; 58:1165.
- Tatsis E, Schnabel A, Gross WL. Interferon-alpha treatment of four patients with the Churg-Strauss syndrome. Ann Intern Med 1998; 129:370.
- Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 2008; 359:2790.
- 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:S52.
- Assaf C, Mewis G, Orfanos CE, Geilen CC. Churg-Strauss syndrome: successful treatment with mycophenolate mofetil. Br J Dermatol 2004; 150:598.
- Lau EM, Cooper W, Bye PT, Yan K. Difficult asthma and Churg-Strauss-like syndrome: a cautionary tale. Respirology 2011; 16:180.
- Demircin G, Baysun S, Bülbül M, et al. Mycophenolate mofetil therapy in a child with Churg-Strauss syndrome. Pediatr Int 2010; 52:e164.
- Hamilos DL, Christensen J. Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin. J Allergy Clin Immunol 1991; 88:823.
- Tsurikisawa N, Taniguchi M, Saito H, et al. Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin. Ann Allergy Asthma Immunol 2004; 92:80.
- Lee RU, Stevenson DD. Hydroxyurea in the treatment of Churg-Strauss syndrome. J Allergy Clin Immunol 2009; 124:1110.
- Saech J, Owczarczyk K, Rösgen S, et al. Successful use of rituximab in a patient with Churg-Strauss syndrome and refractory central nervous system involvement. Ann Rheum Dis 2010; 69:1254.
- Jones RB, Ferraro AJ, Chaudhry AN, et al. A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2009; 60:2156.
- Pepper RJ, Fabre MA, Pavesio C, et al. Rituximab is effective in the treatment of refractory Churg-Strauss syndrome and is associated with diminished T-cell interleukin-5 production. Rheumatology (Oxford) 2008; 47:1104.
- Cartin-Ceba R, Keogh KA, Specks U, et al. Rituximab for the treatment of Churg-Strauss syndrome with renal involvement. Nephrol Dial Transplant 2011; 26:2865.
- Umezawa N, Kohsaka H, Nanki T, et al. Successful treatment of eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) with rituximab in a case refractory to glucocorticoids, cyclophosphamide, and IVIG. Mod Rheumatol 2014; 24:685.
- Grigoriou A, Endean A, Sangle SR, D'Cruz DP. B cell depletion therapy and eosinophilic granulomatosis with polyangiitis with hepatic involvement. Rheumatology (Oxford) 2014; 53:1741.
- Koukoulaki M, Smith KG, Jayne DR. Rituximab in Churg-Strauss syndrome. Ann Rheum Dis 2006; 65:557.
- Dønvik KK, Omdal R. Churg-Strauss syndrome successfully treated with rituximab. Rheumatol Int 2011; 31:89.
- Thiel J, Hässler F, Salzer U, et al. Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Arthritis Res Ther 2013; 15:R133.
- Martínez-Villaescusa M, López-Montes A, López-Rubio E, et al. Treatment-resistant Churg-Strauss syndrome: progression after five years using rituximab. Nefrologia 2013; 33:737.
- Muñoz SA, Gandino IJ, Orden AO, Allievi A. Rituximab in the treatment of eosinophilic granulomatosis with polyangiitis. Reumatol Clin 2015; 11:165.
- Mohammad AJ, Hot A, Arndt F, et al. Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Ann Rheum Dis 2016; 75:396.
- Fanouriakis A, Kougkas N, Vassilopoulos D, et al. Rituximab for eosinophilic granulomatosis with polyangiitis with severe vasculitic neuropathy: Case report and review of current clinical evidence. Semin Arthritis Rheum 2015; 45:60.
- Bouldouyre MA, Cohen P, Guillevin L. Severe bronchospasm associated with rituximab for refractory Churg-Strauss syndrome. Ann Rheum Dis 2009; 68:606.
- 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 2007; 119:1279; author reply 1279.
- Pabst S, Tiyerili V, Grohé C. Apparent response to anti-IgE therapy in two patients with refractory "forme fruste" of Churg-Strauss syndrome. Thorax 2008; 63:747.
- Detoraki A, Di Capua L, Varricchi G, et al. Omalizumab in patients with eosinophilic granulomatosis with polyangiitis: a 36-month follow-up study. J Asthma 2016; 53:201.
- Winchester DE, Jacob A, Murphy T. Omalizumab for asthma. N Engl J Med 2006; 355:1281.
- Moosig F, Gross WL, Herrmann K, et al. Targeting interleukin-5 in refractory and relapsing Churg-Strauss syndrome. Ann Intern Med 2011; 155:341.
- Kim S, Marigowda G, Oren E, et al. Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome. J Allergy Clin Immunol 2010; 125:1336.
- Kahn JE, Grandpeix-Guyodo C, Marroun I, et al. Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J Allergy Clin Immunol 2010; 125:267.
- 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; 148:198.
- 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 1995; 13:193.
- Birck R, Schmitt WH, Kaelsch IA, van der Woude FJ. Serial ANCA determinations for monitoring disease activity in patients with ANCA-associated vasculitis: systematic review. Am J Kidney Dis 2006; 47:15.
- Bacciu A, Bacciu S, Mercante G, et al. Ear, nose and throat manifestations of Churg-Strauss syndrome. Acta Otolaryngol 2006; 126:503.
- Ishiyama A, Canalis RF. Otological manifestations of Churg-Strauss syndrome. Laryngoscope 2001; 111:1619.
- Durel CA, Berthiller J, Caboni S, et al. Long-Term Followup of a Multicenter Cohort of 101 Patients With Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss). Arthritis Care Res (Hoboken) 2016; 68:374.
- Guillevin L, Cohen P, Gayraud M, et al. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999; 78:26.
- Keogh KA, Specks U. Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists. Am J Med 2003; 115:284.
- Baldini C, Della Rossa A, Grossi S, et al. [Churg-Strauss syndrome: outcome and long-term follow-up of 38 patients from a single Italian centre]. Reumatismo 2009; 61:118.
- Sokolowska BM, Szczeklik WK, Wludarczyk AA, et al. ANCA-positive and ANCA-negative phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA): outcome and long-term follow-up of 50 patients from a single Polish center. Clin Exp Rheumatol 2014; 32:S41.
- Groh M, Masciocco G, Kirchner E, et al. Heart transplantation in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). J Heart Lung Transplant 2014; 33:842.
- ASSESSING VASCULITIS SEVERITY
- INITIATING THERAPY
- Systemic glucocorticoids
- MAINTENANCE AND GLUCOCORTICOID SPARING THERAPY
- Inhaled glucocorticoids
- OTHER THERAPIES
- Mycophenolate mofetil
- Intravenous immune globulin
- Anti-IgE therapy
- Anti-IL-5 antibodies
- Plasma exchange
- PREVENTION OF TREATMENT RELATED COMPLICATIONS
- SPECIAL CONSIDERATIONS
- Upper airway involvement
- SUMMARY AND RECOMMENDATIONS