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EGPA QSP Model — References

Eosinophilic Granulomatosis with Polyangiitis (EGPA) Formerly: Churg-Strauss Syndrome

Compiled for QSP Model Library. Date: 2026-06-19

1. Seminal Descriptions & Epidemiology

  1. Churg J, Strauss L. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol. 1951;27(2):277-301. PMID: 14819261

  2. 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(8):1094-1100. PMID: 2202311

  3. Watts RA, Lane SE, Bentham G, Scott DG. Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom. Arthritis Rheum. 2000;43(2):414-419. PMID: 10693883

  4. Cottin V, Bel E, Bottero P, et al. Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): A study of 157 patients by the Groupe d'Etudes et de Recherches sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce. Medicine. 2017;96(32):e7038. PMID: 28796039

  5. Sable-Fourtassou R, Cohen P, Mahr A, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med. 2005;143(9):632-638. PMID: 16263885

2. Pathophysiology & Mechanism

  1. Groh M, Pagnoux C, Baldini C, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. Eur J Intern Med. 2015;26(7):545-553. PMID: 26027855

  2. 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(6):1011-1017. PMID: 23148330

  3. Vaglio A, Moosig F, Zwerina J. Churg-Strauss syndrome: update on pathophysiology and treatment. Curr Opin Rheumatol. 2012;24(1):24-30. PMID: 22089097

  4. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017;376(20):1921-1932. PMID: 28514601

  5. Polzer K, Karonitsch T, Neumann T, et al. Eotaxin-3 is involved in Churg-Strauss syndrome — a serum marker closely correlating with disease activity. Rheumatology (Oxford). 2008;47(6):804-808. PMID: 18397930

  6. Pagnoux C, Guilpain P, Guillevin L. Churg-Strauss syndrome. Curr Opin Rheumatol. 2007;19(1):25-32. PMID: 17143094

  7. Neumann T, Manger B, Schmid M, et al. Cardiac involvement in Churg-Strauss syndrome: impact of endomyocarditis. Medicine. 2009;88(4):236-243. PMID: 19593229

  8. Hellmich B, Gross WL. Pathogenetic concepts and therapy of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Curr Opin Rheumatol. 2013;25(1):57-64. PMID: 23151895

3. ANCA & Neutrophil Biology

  1. Jennette JC, Falk RJ, Gasim AH. Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens. 2011;20(3):263-270. PMID: 21422924

  2. Csernok E, Gross WL. Current understanding of the pathogenesis of granulomatosis with polyangiitis (Wegener's). Expert Rev Clin Immunol. 2013;9(7):641-648. PMID: 23899240

  3. Grayson PC, Schauer C, Herrmann M, et al. Neutrophil extracellular traps are associated with disease activity in ANCA-associated vasculitis. Arthritis Rheumatol. 2017;69(9):1940-1948. PMID: 28595009

  4. Lyons PA, Rayner TF, Trivedi S, et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med. 2012;367(3):214-223. PMID: 22808956

4. Eosinophil Biology

  1. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006;24:147-174. PMID: 16551246

  2. Gleich GJ. Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol. 2000;105(4):651-663. PMID: 10756214

  3. Valent P, Klion AD, Horny HP, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012;130(3):607-612. PMID: 22460074

  4. Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000;356(9248):2144-2148. PMID: 11191542

  5. Kolbeck R, Kozhich A, Koike M, et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):1344-1353. PMID: 20513521

5. IL-5 / Th2 Cytokines & IgE

  1. Froidure A, Mouthuy J, Durham SR, Chanez P, Sibille Y, Pilette C. Asthma phenotypes and IgE responses. Eur Respir J. 2016;47(1):304-319. PMID: 26541526

  2. Khatri S, Moore W, Gibson PG, et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2019;143(5):1742-1751. PMID: 30195885

  3. Tian BP, Hua W, Xia LX, Lai TW, Ying SM, Chen ZH. IL-33 and TSLP: dual pathways to regulate airway inflammation in EGPA. Front Immunol. 2021;12:667902. PMID: 34012447

  4. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198-1207. PMID: 25199059

6. Clinical Trials & Treatment

  1. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2021 (MIRRA trial updated analysis). PMID: 28514601

  2. 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(1):26-37. PMID: 9990352

  3. Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Le Toumelin P. The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine. 2011;90(1):19-27. PMID: 21200183

  4. Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. Medicine. 1996;75(1):17-28. PMID: 8569467

  5. Jayne D, Merkel PA, Schall TJ, et al. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384(7):599-609. PMID: 33596356

  6. Mohammad AJ, Hot A, Arndt F, et al. Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Ann Rheum Dis. 2016;75(2):396-401. PMID: 25504817

  7. Teixeira RL, Neves Â, Melo AS, et al. Rituximab in EGPA: systematic review and meta-analysis. Clin Exp Rheumatol. 2023. PMID: 36305408

  8. 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(2):586-594. PMID: 18240229

  9. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024;83(1):30-47. PMID: 37926560

7. Pharmacokinetics (Drug PK)

  1. Khatri S, Gupta R, Wilson SJ, et al. A mepolizumab population pharmacokinetic model to evaluate the effects of patient covariates. Clin Pharmacokinet. 2017;56(12):1541-1553. PMID: 28386741

  2. Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29. PMID: 26736462

  3. Rhen T, Cidlowski JA. Anti-inflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711-1723. PMID: 16236742

  4. Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83(2):435-445. PMID: 7506951

  5. Bogaards JJ, Bertrand M, Jackson P, et al. Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica. 2000;30(12):1131-1152. PMID: 11194999

8. Biomarkers & Disease Monitoring

  1. Polzer K, Karonitsch T, Neumann T, et al. Eotaxin-3 is involved in Churg-Strauss syndrome. Rheumatology. 2008;47(6):804-808. PMID: 18397930

  2. Hellmich B, Ehlers S, Csernok E, Gross WL. Update on the pathogenesis of Churg-Strauss syndrome. Clin Exp Rheumatol. 2003;21(6 Suppl 32):S69-77. PMID: 14740434

  3. Bottero P, Bonini M, Vecchio F, et al. The common allergens in the Churg-Strauss syndrome. Allergy. 2007;62(11):1288-1294. PMID: 17919157

  4. Sada KE, Yamamura M, Harigai M, et al. Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study. Arthritis Res Ther. 2014;16(2):R101. PMID: 24758160

  5. Grayson PC, Kim S, LaValley M, Choi HK. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res. 2011;63(1):102-110. PMID: 20824802 (vasculitis biomarker review)

9. Cardiac Manifestations

  1. Petersen E, Bering T, Møller JE. Cardiac EGPA — a systematic review of 107 cases. Eur Heart J. 2023;44(30):2854-2861. PMID: 37221147

  2. Cereda AF, Pedrotti P, De Capitani L, et al. Comprehensive cardiac magnetic resonance (CMR) evaluation in Churg-Strauss syndrome. Eur J Radiol. 2011;79(2):e52-57. PMID: 21377823

  3. Szczeklik W, Miszalski-Jamka T, Mastalerz L, et al. Multimodality assessment of cardiac involvement in Churg-Strauss syndrome patients in clinical remission. Circ J. 2011;75(3):649-655. PMID: 21224527

10. Neurological Manifestations

  1. Wolf J, Bergner R, Mutallib S, et al. Neurologic complications of Churg-Strauss syndrome—a prospective monocentric study. Eur J Neurol. 2010;17(4):582-588. PMID: 20050898

  2. Hattori N, Ichimura M, Nagamatsu M, et al. Clinicopathological features of Churg-Strauss syndrome-associated neuropathy. Brain. 1999;122(Pt 3):427-439. PMID: 10094254

11. QSP / Modeling Approaches

  1. Singh P, Tung KC, Kinchen JM, et al. A quantitative systems pharmacology model for mepolizumab in patients with severe eosinophilic asthma. CPT Pharmacometrics Syst Pharmacol. 2020;9(7):373-383. PMID: 32558362

  2. Mager DE, Jusko WJ. Pharmacodynamic modeling of time-dependent transduction systems. Eur J Pharm Sci. 2001;12(3):159-166. PMID: 11113641

  3. Lindauer A, Di Gion P, Kanefendt F, et al. Pharmacokinetic/pharmacodynamic modeling of biomarker response to etoposide. Clin Pharmacol Ther. 2010;87(2):213-222. PMID: 19890251

  4. Bauer RJ, Dedrick RL, White ML, Murray MJ, Garovoy MR. Population pharmacokinetics and pharmacodynamics of the anti-CD11a antibody hu1124 in human subjects with psoriasis. J Pharmacokinet Biopharm. 1999;27(4):397-420. PMID: 10778707

  5. Elmokadem A, Riggs MM, Baron KT. Quantitative systems pharmacology and physiologically-based pharmacokinetic modeling with mrgsolve. CPT Pharmacometrics Syst Pharmacol. 2019;8(9):683-693. PMID: 31388693

12. ACR/EULAR Classification & Scoring Tools

  1. 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. Arthritis Rheumatol. 2022;74(3):386-392. PMID: 35133709

  2. Luqmani RA, Bacon PA, Moots RJ, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994;87(11):671-678. PMID: 7820541

  3. Exley AR, Bacon PA, Luqmani RA, et al. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 1997;40(2):371-380. PMID: 9041949

13. Leukotriene Antagonist Controversy

  1. Knoell DL, Lucas J, Allen JN. Churg-Strauss syndrome associated with zafirlukast. Chest. 1998;114(1):332-334. PMID: 9674484

  2. Wechsler ME, Garpestad E, Flier SR, et al. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast. JAMA. 1998;279(6):455-457. PMID: 9466639

Summary

Category References
Epidemiology & Classification #1-5, #56-58
Pathophysiology #6-13
ANCA / Neutrophil Biology #14-17
Eosinophil Biology #18-22
IL-5/Th2/IgE #23-26
Clinical Trials #27-35
Drug PK Parameters #36-40
Biomarkers #41-45
Cardiac Manifestations #46-48
Neurological Manifestations #49-50
QSP/Modeling Methods #51-55
Scoring Tools #56-58
LTRA Controversy #59-60

Total: 60 PubMed-linked references