Pediatric Nephrology

, Volume 28, Issue 9, pp 1875–1879 | Cite as

Fulminant viral myocarditis after rituximab therapy in pediatric nephrotic syndrome

  • Anne-Laure Sellier-Leclerc
  • Emre Belli
  • Valérie Guérin
  • Peter Dorfmüller
  • Georges Deschênes
Brief Report



We report a 7-year-old boy with high-degree steroid-dependent idiopathic nephrotic syndrome (SDNS) who went into remission with rituximab (RTX) maintenance therapy.


Four months after this patient received his first RTX infusion, there was a progressive and sustained decrease of immunoglobulin (Ig)G and IgM levels. Thirteen months after the initiation of RTX therapy he was in sustained remission without any steroid or oral immunosuppressive therapy; however, B cell depletion was still present. At this time he developed a fulminant myocarditis due to enterovirus. Despite aggressive treatment and the administration of intravenous polyvalent immunoglobulins there was no clinical improvement. He successfully underwent heart transplant surgery.


We conclude that B cell depletion with RTX is efficacious in the treatment of paediatric SDNS but that it may be associated with severe infectious complications. Therefore, we recommend a close monitoring of Ig levels in children who have received RTX therapy and a supplementation with intravenous Ig as soon as the Ig levels fall below the lower limit of the normal range


Idiopathic nephrotic syndrome Rituximab B cell depletion Hypogammaglobulinemia Fulminant myocarditis 


  1. 1.
    Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F (2008) Rituximab treatment for severe steroid-or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:1269–1279PubMedCrossRefGoogle Scholar
  2. 2.
    Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, Saito M, Yoneko M, Iijima K (2009) Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol 24:1321–1328PubMedCrossRefGoogle Scholar
  3. 3.
    Sellier-Leclerc AL, Macher MA, Loirat C, Guérin V, Watier H, Peuchmaur M, Baudouin V, Deschênes G (2010) Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 25:1109–1115PubMedCrossRefGoogle Scholar
  4. 4.
    Gulati A, Sinha A, Jordan SC, Hari P, Dinda AK, Sharma S, Srivastava RN, Moudgil A, Bagga A (2010) Efficacy and safety of treatment with rituximab for difficult steroid-resistant and-dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol 5:2207–2212PubMedCrossRefGoogle Scholar
  5. 5.
    Prytula A, Iijima K, Kamei K, Geary D, Gottlich E, Majeed A, Taylor M, Marks SD, Tuchman S, Camilla R, Ognjanovic M, Filler G, Smith G, Tullus K (2010) Rituximab in refractory nephrotic syndrome. Pediatr Nephrol 25:461–468PubMedCrossRefGoogle Scholar
  6. 6.
    Sellier-Leclerc AL, Baudouin V, Kwon T, Macher MA, Guérin V, Lapillonne H, Deschênes G, Ulinski T (2012) Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood–follow-up after CD19 recovery. Nephrol Dial Transplant 27(3):1083–1089PubMedCrossRefGoogle Scholar
  7. 7.
    Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, Pape L, Patzer L, Billing H, Weber L, Pohl M, Rosenthal K, Rosahl A, Mueller-Wiefel DE, Dötsch J (2012) Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant 27(5):1910–1915PubMedCrossRefGoogle Scholar
  8. 8.
    Keystone E, Fleischmann R, Emery P, Furst DE, van Vollenhoven R, Bathon J, Dougados M, Baldassare A, Ferraccioli G, Chubick A, Udell J, Cravets MW, Agarwal S, Cooper S, Magrini F (2007) Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: an open-label extension analysis. Arthritis Rheum 56(12):3896–3908PubMedCrossRefGoogle Scholar
  9. 9.
    Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschenes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755PubMedCrossRefGoogle Scholar
  10. 10.
    Kamei K, Ito S, Iijima K (2010) Severe respiratory adverse events associated with rituximab infusion. Pediatr Nephrol 5(6):1193CrossRefGoogle Scholar
  11. 11.
    Carson KR, Focosi D, Major EO, Petrini M, Richey EA, West DP, Bennett CL (2009) Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) project. Lancet Oncol 10:816–824PubMedCrossRefGoogle Scholar
  12. 12.
    Sato M, Ito S, Ogura M, Kamei K, Miyairi I, Miyata I, Higuchi M, Matsuoka K (2013) Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after rituximab for refractory nephrotic syndrome. Pediatr Nephrol 28:145–149PubMedCrossRefGoogle Scholar
  13. 13.
    Bhatt GC, Sankar J, Kushwaha KP (2012) Use of intravenous immunoglobulin compared with standard therapy is associated with improved clinical outcomes in children with acute encephalitis syndrome complicated by myocarditis. Pediatr Cardiol 33:1370–1376PubMedCrossRefGoogle Scholar
  14. 14.
    Ardelean DS, Gonska T, Wires S, Cutz E, Griffiths A, Harvey E, Tse SM, Benseler SM (2010) Severe ulcerative colitis after rituximab therapy. Pediatrics 126:e243–246PubMedCrossRefGoogle Scholar
  15. 15.
    Sailler L (2008) Rituximab off label use for difficult-to-treat auto-immune diseases: Reappraisal of benefits and risks. Clinic Rev Allerg Immunol 34:103–110CrossRefGoogle Scholar
  16. 16.
    Marotte H, Paintaud G, Watier H, Miossec P (2008) Rituximab related late-onset neutropenia in a patient with severe rheumatoid athritis. Ann Rheum Dis 67:893–894PubMedCrossRefGoogle Scholar
  17. 17.
    Cooper N, Arnold DM (2010) The effect of rituximab on humoral and cell mediated immunity and infection in the treatment of autoimmune diseases. Br J Haematol 149:3–13PubMedCrossRefGoogle Scholar
  18. 18.
    Venhoff N, Effelsberg NM, Salzer U, Warnatz K, Peter HH, Lebrecht D, Schlesier M, Voll RE, Thiel J (2012) Impact of rituximab on immunoglobulin concentrations and B cell numbers after cyclophosphamide treatment in patients with ANCA-associated vasculitides. PLoS One 7(5):e37626PubMedCrossRefGoogle Scholar
  19. 19.
    De La Torre I, Leandro MJ, Valor L, Becerra E, Edwards JC, Cambridge G (2012) Total serum immunoglobulin levels in patients with RA after multiple B-cell depletion cycles based on rituximab: relationship with B-cell kinetics. Rheumatology (Oxford) 51(5):833–840CrossRefGoogle Scholar
  20. 20.
    Nishio M, Endo T, Fujimoto K, Sato N, Sakai T, Obara M, Kumano K, Minauchi K, Koike T (2005) Persistent pan-hypogammaglobulinemia with selected loss of memory B cells and impaired isotype expression after rituximab therapy for post-transplant EBV-associated autoimmune hemolytic anemia. Eur J Haematol 75:527–529PubMedCrossRefGoogle Scholar
  21. 21.
    Walker AR, Kleiner A, Rich L, Conners C, Fisher RI, Anolik J, Friedberg JW (2008) Profound hypogammaglobulinemia 7 years after treatment for indolent lymphoma. Cancer Invest 26:431–433PubMedCrossRefGoogle Scholar
  22. 22.
    Kimby E (2005) Tolerability and safety of rituximab (MabThera). Cancer Treat Rev 31:456–473PubMedCrossRefGoogle Scholar
  23. 23.
    Cambridge G, Stohl W, Leandro MJ, Migone TS, Hilbert DM, Edwards JC (2006) Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum 54:723–732PubMedCrossRefGoogle Scholar
  24. 24.
    Cooper N, Davies EG, Thrasher AJ (2009) Repeated courses of rituximab for autoimmune cytopenias may precipitate profound hypogammaglobulinaemia requiring replacement intravenous immunoglobulin. Br J Haematol 146:120–122PubMedCrossRefGoogle Scholar
  25. 25.
    Besada E, Bader L, Nossent H (2011) Sustained hypogammaglobulinemia under rituximab maintenance therapy could increase the risk for serious infections: a report of two cases. Rheumatol Int. doi: 10.1007/s00296-011-2353-5 PubMedGoogle Scholar
  26. 26.
    Otremba MD, Adam SI, Price CC, Hohuan D, Kveton JF (2012) Use of intravenous immunoglobulin to treat chronic bilateral otomastoiditis in the setting of rituximab induced hypogammaglobulinemia. Am J Otolaryngol 33(5):619–622PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2013

Authors and Affiliations

  • Anne-Laure Sellier-Leclerc
    • 1
  • Emre Belli
    • 2
  • Valérie Guérin
    • 3
  • Peter Dorfmüller
    • 4
  • Georges Deschênes
    • 5
    • 6
  1. 1.Department of Pediatric Nephrology, Hôpital Femme-Mère-Enfants Hospices Civils de LyonBronFrance
  2. 2.Department of Pediatric CardiologyCentre Chirurgical Marie LannelongueLe Plessis-Robinson, ParisFrance
  3. 3.Laboratory of Immunology, Robert Debré HospitalAssistance Publique Hôpitaux de ParisParisFrance
  4. 4.Department of Anathomo-pathologyCentre Chirurgical Marie LannelongueLe Plessis-Robinson, ParisFrance
  5. 5.Department of Pediatric Nephrology, Robert Debré HospitalAssistance Publique Hôpitaux de ParisParisFrance
  6. 6.University Denis DiderotParis 7France

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