Thrombotic microangiopathy in a patient with eosinophilic granulomatosis with polyangiitis: case-based review

  • Jon BadiolaEmail author
  • Nuria Navarrete-Navarrete
  • José Mario Sabio
Cases with a Message


The correct diagnosis, classification and therapeutic management of thrombotic microangiopathies (TMA) continue to be a challenge for the clinician. We report a rare case of eosinophilic granulomatosis with polyangiitis (EGPA) as a trigger for complement-mediated TMA in a 57-year-old man who was successfully treated with corticoids, cyclophosphamide and therapeutic plasma exchange. Additionally, we review few other cases reported in the literature and the pathophysiological pathway of association between TMA and EGPA. We found that the mutual relationships between the inflammation triggered by vasculitis, the exacerbated complement activation, together with hypereosinophilia and endothelial damage seem to be the key in explaining the connection between both entities. We suggest that an understanding of the multi-causal nature of TMAs is crucial for the correct diagnosis and treatment of these patients.


Thrombotic microangiopathy Eosinophilic granulomatosis with polyangiitis Complement-mediated diseases Atypical haemolytic uremic syndrome ANCA-associated vasculitis 


Author contributions

All the authors have contributed to patient management and clinical procedures, have drafted and revised the manuscript and have approved the final version.

Compliance with ethical standards

Conflict of interest

JB, NNN and JMS declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from the patient to publish this case report.


  1. 1.
    Greco A, Rizzo MI, De Virgilio A et al (2015) Churg-Strauss syndrome. Autoimmun Rev 14:341–348CrossRefGoogle Scholar
  2. 2.
    George JN, Nester CM (2014) Syndromes of thrombotic microangiopathy. N Engl J Med 371:654–666. CrossRefPubMedGoogle Scholar
  3. 3.
    Masias C, Vasu S, Cataland SR (2017) None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood 129:2857–2863. CrossRefPubMedGoogle Scholar
  4. 4.
    Scully M, Cataland S, Coppo P et al (2017) Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost 15:312–322. CrossRefPubMedGoogle Scholar
  5. 5.
    Åkesson A, Zetterberg E, Klintman J (2017) At the cross section of thrombotic microangiopathy and atypical hemolytic uremic syndrome: a narrative review of differential diagnostics and a problematization of nomenclature. Ther Apher Dial 21:304–319. CrossRefPubMedGoogle Scholar
  6. 6.
    Masi AT, Hunder GG, Lie JT et al (1990) The American College of Rheumatology 1990 criteria for the classification of Churg–Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 33:1094–1100CrossRefGoogle Scholar
  7. 7.
    Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD (2011) Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int 31:1409–1417. CrossRefPubMedGoogle Scholar
  8. 8.
    Fukui S, Iwamoto N, Tsuji S et al (2015) Eosinophilic granulomatosis with polyangiitis with thrombotic microangiopathy: is simultaneous systemic lupus erythematosus associated with clinical manifestations?: A case report and review of the literature. Medicine (Baltimore) 94:e1943. CrossRefGoogle Scholar
  9. 9.
    Cao M, Ferreiro T, Leite BN et al (2017) Two cases of atypical hemolytic uremic syndrome (aHUS) and eosinophilic granulomatosis with polyangiitis (EGPA): a possible relationship. CEN Case Rep 6:91–97. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Song D, Wu L, Wang F et al (2013) The spectrum of renal thrombotic microangiopathy in lupus nephritis. Arthritis Res Ther 15:R12. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mathew RO, Nayer A, Asif A (2016) The endothelium as the common denominator in malignant hypertension and thrombotic microangiopathy. J Am Soc Hypertens 10:352–359. CrossRefPubMedGoogle Scholar
  12. 12.
    Fujimura Y, Matsumoto M (2010) Registry of 919 patients with thrombotic microangiopathies across Japan: database of Nara Medical University during 1998–2008. Intern Med 49:7–15CrossRefGoogle Scholar
  13. 13.
    Chen S-F, Wang H, Huang Y-M et al (2015) Clinicopathologic characteristics and outcomes of renal thrombotic microangiopathy in anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis. Clin J Am Soc Nephrol 10:750–758. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Rosove MH (2014) Thrombotic microangiopathies. Semin Arthritis Rheum 43:797–805. CrossRefPubMedGoogle Scholar
  15. 15.
    van Timmeren MM, Heeringa P (2012) Pathogenesis of ANCA-associated vasculitis: recent insights from animal models. Curr Opin Rheumatol 24:8–14. CrossRefPubMedGoogle Scholar
  16. 16.
    Blanchard C, Rothenberg ME (2009) Biology of the eosinophil. Adv Immunol 101:81–121. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Maino A, Rossio R, Cugno M et al (2012) Hypereosinophilic syndrome, Churg–Strauss syndrome and parasitic diseases: possible links between eosinophilia and thrombosis. Curr Vasc Pharmacol 10:670–675CrossRefGoogle Scholar
  18. 18.
    Akuthota P, Weller PF (2015) Spectrum of eosinophilic end-organ manifestations. Immunol Allergy Clin N Am 35:403–411. CrossRefGoogle Scholar
  19. 19.
    Ames PRJ, Margaglione M, Mackie S, Alves JD (2010) Eosinophilia and thrombophilia in churg strauss syndrome: a clinical and pathogenetic overview. Clin Appl Thromb Hemost 16:628–636. CrossRefPubMedGoogle Scholar
  20. 20.
    Liapis H, Ho AK, Brown D et al (2005) Thrombotic microangiopathy associated with the hypereosinophilic syndrome. Kidney Int 67:1806–1811. CrossRefPubMedGoogle Scholar
  21. 21.
    Yuste C, Quiroga B, Verde E et al (2012) The non-casual relation between eosinophilia and thrombotic microangiopathy. Transfus Apher Sci 47:365–367. CrossRefPubMedGoogle Scholar
  22. 22.
    Ohguchi H, Sugawara T, Harigae H (2009) Thrombotic thrombocytopenic purpura complicated with hypereosinophilic syndrome. Intern Med 48:1687–1690CrossRefGoogle Scholar
  23. 23.
    Le Quintrec M, Roumenina L, Noris M, Frémeaux-Bacchi V (2010) Atypical hemolytic uremic syndrome associated with mutations in complement regulator genes. Semin Thromb Hemost 36:641–652. CrossRefPubMedGoogle Scholar
  24. 24.
    Kavanagh D, Goodship T (2010) Genetics and complement in atypical HUS. Pediatr Nephrol 25:2431–2442. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Loirat C, Noris M, Fremeaux-Bacchi V (2008) Complement and the atypical hemolytic uremic syndrome in children. Pediatr Nephrol 23:1957–1972. CrossRefPubMedGoogle Scholar
  26. 26.
    Noris M, Galbusera M, Gastoldi S et al (2014) Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood 124:1715–1726. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Xiao H, Schreiber A, Heeringa P et al (2007) Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol 170:52–64. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Xing G, Chen M, Liu G et al (2009) Complement activation is involved in renal damage in human antineutrophil cytoplasmic autoantibody associated pauci-immune vasculitis. J Clin Immunol 29:282–291. CrossRefPubMedGoogle Scholar
  29. 29.
    Gou S-J, Yuan J, Chen M et al (2013) Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int 83:129–137. CrossRefPubMedGoogle Scholar
  30. 30.
    Manenti L, Vaglio A, Gnappi E et al (2015) Association of serum C3 concentration and histologic signs of thrombotic microangiopathy with outcomes among patients with ANCA-associated renal vasculitis. Clin J Am Soc Nephrol 10:2143–2151. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Bresin E, Rurali E, Caprioli J et al (2013) Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol 24:475–486. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Kavanagh D, Goodship THJ (2011) Atypical hemolytic uremic syndrome, genetic basis, and clinical manifestations. Hematol Am Soc Hematol Educ Progr 2011:15–20. CrossRefGoogle Scholar
  33. 33.
    Noris M, Caprioli J, Bresin E et al (2010) Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5:1844–1859. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Vieira-Martins P, El Sissy C, Bordereau P et al (2016) Defining the genetics of thrombotic microangiopathies. Transfus Apher Sci 54:212–219. CrossRefPubMedGoogle Scholar
  35. 35.
    Pickering MC, de Jorge EG, Martinez-Barricarte R et al (2007) Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains. J Exp Med 204:1249–1256. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Fremeaux-Bacchi V, Fakhouri F, Garnier A et al (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554–562. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Servais A, Noël L-H, Roumenina LT et al (2012) Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int 82:454–464. CrossRefPubMedGoogle Scholar
  38. 38.
    Manenti L, Gnappi E, Vaglio A et al (2013) Atypical haemolytic uraemic syndrome with underlying glomerulopathies. A case series and a review of the literature. Nephrol Dial Transplant 28:2246–2259. CrossRefPubMedGoogle Scholar
  39. 39.
    Monteferrante G, Brioschi S, Caprioli J et al (2007) Genetic analysis of the complement factor H related 5 gene in haemolytic uraemic syndrome. Mol Immunol 44:1704–1708. CrossRefPubMedGoogle Scholar
  40. 40.
    Westra D, Vernon KA, Volokhina EB et al (2012) Atypical hemolytic uremic syndrome and genetic aberrations in the complement factor H-related 5 gene. J Hum Genet 57:459–464. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Li A, Makar RS, Hurwitz S et al (2016) Treatment with or without plasma exchange for patients with acquired thrombotic microangiopathy not associated with severe ADAMTS13 deficiency: a propensity score-matched study. Transfusion 56:2069–2077. CrossRefPubMedGoogle Scholar
  42. 42.
    Cataland SR, Wu HM (2014) How I treat: the clinical differentiation and initial treatment of adult patients with atypical hemolytic uremic syndrome. Blood 123:2478–2484. CrossRefPubMedGoogle Scholar
  43. 43.
    Mache CJ, Acham-Roschitz B, Frémeaux-Bacchi V et al (2009) Complement inhibitor eculizumab in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 4:1312–1316. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Legendre CM, Licht C, Muus P et al (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2169–2181. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Hematology and HemotherapyVirgen de las Nieves University HospitalGranadaSpain
  2. 2.Systemic Autoimmune Diseases Unit, Department of Internal MedicineVirgen de las Nieves University HospitalGranadaSpain

Personalised recommendations