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Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after rituximab for refractory nephrotic syndrome

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Abstract

Background

Rituximab, an anti-CD20 antibody that targets B cells, is a promising agent against steroid-dependent and steroid-resistant nephrotic syndrome in children.

Case-Diagnosis/Treatment

We report a 3-year-old boy who presented with atypical Pneumocystis jiroveci pneumonia (PCP) following administration of rituximab for refractory nephrotic syndrome. He had received cyclosporine and daily prednisolone for over 1 year. Following rituximab therapy, a hazy shadow was observed on his chest X-ray. Chest-computed tomography revealed multiple nodular lesions in bilateral lungs, although his clinical symptoms were subtle. PCR analysis demonstrated the presence of Pneumocystis DNA in his bronchoalveolar lavage. Lung wedge resection of the nodular lesion exhibited granulomas containing a few cysts of P. jiroveci that primarily consisted of T cells and histiocytes and lacked B cells. A deficiency of B cells following rituximab treatment suggests a dramatic effect on the immune response and, therefore, could result in granulomatous PCP. Nodular granulomatous lesions of PCP comprise an emerging concept previously reported in adults with hematological disease, bone marrow transplant, or treatment with rituximab. We report the first pediatric case of nodular PCP. Granulomatous PCP can be life-threatening. Moreover, bronchoalveolar lavage often fails to demonstrate the presence of P. jiroveci DNA. Wedge biopsy is warranted for definitive diagnosis. Our patient fully recovered with sulfamethoxazole/trimethoprim treatment because of early detection.

Conclusions

The indication of rituximab for refractory nephrotic syndrome has increased recently. Therefore, recognition of the risk of atypical PCP is important. Our findings suggest that PCP prophylaxis should be considered following rituximab therapy.

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Fig. 1
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Abbreviations

PCP:

Pneumocystis jiroveci pneumonia

RTX:

Rituximab

NS:

Nephrotic syndrome

FRNS:

Frequently relapsing nephrotic syndrome

SDNS:

Steroid-dependent nephrotic syndrome

SRNS:

Steroid-resistant nephrotic syndrome

References

  1. Bagga A, Sinha A, Moudgil A (2007) Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med 356:2751–2752

    Article  PubMed  CAS  Google Scholar 

  2. Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas E, 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 23:1269–1279

    Article  PubMed  Google Scholar 

  3. 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 24:1321–1328

    Article  PubMed  Google Scholar 

  4. Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, Laubach J, Bawn SD, Gordon LI, Winter JN, Furmann RR, Vose JM, Zelenets AD, Mamtani R, Raisch DW, Dorshimer GW, Rosen ST, Muro K, Gottardi-Litell NR, Talley RL, Sartot O, Green D, Major EO, Cl B (2009) Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the research on adverse drug events and reports project. Blood 113:4834–4840

    Article  PubMed  CAS  Google Scholar 

  5. Burton C, Kaczmarski R, Jan-Mohamed R (2003) Interstitial pneumonitis related to rituximab therapy. N Engl J Med 348:2690–2691

    Article  PubMed  Google Scholar 

  6. 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–e246

    Article  PubMed  Google Scholar 

  7. Brusamolino E, Rusconi C, Montalbetti L, Gargantini L, Uziel L, Pinotti G, Fava S, Rigacci L, Pagnucco G, Pascutto C, Morra E, Lazzarino M (2006) Dose-dense R-CHOP-14 supported by pegfilgrastim in patients with diffuse large B-cell lymphoma: a phase II study of feasibility and toxicity. Haematologica 91:496–502

    PubMed  CAS  Google Scholar 

  8. Ennishi D, Terui Y, Yokoyama M, Mishima Y, Takahashi S, Takeuchi K, Ikeda K, Tanimoto M, Hatake K (2008) Increased incidence of interstitial pneumonia by CHOP combined with rituximab. Int J Hematol 87:393–397

    Article  PubMed  CAS  Google Scholar 

  9. Katsuya H, Suzumiya J, Sasaki H, Ishitsuka K, Takamatsu Y, Tamura K (2009) Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma. Leuk Lymphoma 50:1818–1823

    Article  PubMed  CAS  Google Scholar 

  10. Teichmann LL, Woenckhaus M, Vogel C, Salzberger B, Scholmerich J, Fleck M (2008) Fatal Pneumocystis pneumonia following rituximab administration for rheumatoid arthritis. Rheumatology 47:1256–1257

    Article  PubMed  CAS  Google Scholar 

  11. Hugle B, Solomon M, Harvey E, James A, Wadhwa A, Amin R, Bell-Peter A, Benseler S (2010) Pneumocystis jiroveci pneumonia following rituximab treatment in Wegener’s granulomatosis. Arthritis Care Res (Hoboken) 62(11):1661–1664

    Article  Google Scholar 

  12. Motto DG, Williams JA, Boxer LA (2002) Rituximab for refractory childhood autoimmune hemolytic anemia. Isr Med Assoc J 4:1006–1008

    PubMed  CAS  Google Scholar 

  13. Bussone G, Ribeiro E, Dechartres A, Viallard JF, Bonnotte B, Fain O, Godeau B, Michel M (2009) Efficacy and safety of rituximab in adult’s warm antibody autoimmune haemolytic anemia: retrospective analysis of 27 cases. Am J Hematol 84:153–157

    Article  PubMed  CAS  Google Scholar 

  14. Dungarwalla M, Marsh JC, Tooze JA, Lucas G, Ouwehand W, Pettengell R, Dearden CE, Gordon Smith EC, Elebute MO (2007) Lack of clinical efficacy of rituximab in the treatment of autoimmune neutropenia and pure red cell aplasia: implications for their pathophysiology. Ann Hematol 86:191–197

    Article  PubMed  CAS  Google Scholar 

  15. Morrison LH (2004) Therapy of refractory pemphigus vulgaris with monoclonal anti-CD20 antibody (rituximab). J Am Acad Dermatol 51:817–819

    Article  PubMed  Google Scholar 

  16. Kumar D, Gourishankar S, Mueller T, Cockfield S, Weinkauf J, Vethanayagam D, Humar A (2009) Pneumocystis jirovecii pneumonia after rituximab therapy for antibody-mediated rejection in a renal transplant recipient. Transpl Infect Dis 11:167–170

    Article  PubMed  CAS  Google Scholar 

  17. Shelton E, Yong M, Cohney S (2009) Late onset Pneumocystis pneumonia in patients receiving rituximab for humoral renal transplant rejection. Nephrology 14:696–699

    Article  PubMed  Google Scholar 

  18. Hartel PH, Shilo K, Klassen-Fischer M, Neafie RC, Ozbudak IH, Galvin JR, Franks TJ (2010) Granulomatous reaction to Pneumocystis jirovecii: clinicopathologic review of 20 cases. Am J Surg Pathol 34:730–734

    PubMed  Google Scholar 

  19. Chang H, Shih LY, Wang CW, Chuang WY, Chen CC (2010) Granulomatous Pneumocystis jiroveci pneumonia in a patient with diffuse large B-cell lymphoma: case report and review of the literature. Acta Haematol 123:30–33

    Article  PubMed  Google Scholar 

  20. Kumar N, Bazari F, Rhodes A, Chua F, Tinwell B (2011) Chronic Pneumocystis jiroveci presenting as asymptomatic granulomatous pulmonary nodules in lymphoma. J Infect 62:484–486

    Article  PubMed  Google Scholar 

  21. Lund FE, Hollifield M, Schuer K, Lines JL, Randall TD, Garvy BA (2006) B cells are required for generation of protective effector and memory CD4 cells in response to Pneumocystis lung infection. J Immunol 176:6147–6154

    PubMed  CAS  Google Scholar 

  22. Totet A, Duwat H, Magois E, Jounieaux V, Roux P, Raccurt C, Nevez G (2004) Similar genotypes of Pneumocystis jirovecii in different forms of Pneumocystis infection. Microbiology 150:1173–1178

    Article  PubMed  CAS  Google Scholar 

  23. Totet A, Duwat H, Daste G, Berry A, Escamilla R, Nevez G (2006) Pneumocystis jirovecii genotypes and granulomatous pneumocystosis. Med Mal Infect 36:229–231

    Article  PubMed  CAS  Google Scholar 

  24. Kovacs JA, Hiemenz JW, Macher AM, Stover D, Murray HW, Shelhamer J, Lane HC, Urmacher C, Honig C, Longo DL (1984) Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med 100:663–671

    PubMed  CAS  Google Scholar 

  25. Mansharamani NG, Garland R, Delaney D, Koiziel H (2000) Management and outcome patterns for adult Pneumocystis carinii pneumonia, 1985 to 1995: comparison of HIV-associated cases to other immunocompromised state. Chest 118:704–711

    Article  PubMed  CAS  Google Scholar 

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Financial disclosure

The authors have no financial relationships relevant to this article to disclose. None of the authors have any conflict of interests to declare.

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Authors and Affiliations

  1. Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Mai Sato, Shuichi Ito, Masao Ogura & Koichi Kamei

  2. Division of Infectious Diseases, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Isao Miyairi & Ippei Miyata

  3. Division of Pulmonology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Masataka Higuchi

  4. Division of Pathology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Kentaro Matsuoka

Authors
  1. Mai Sato
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  2. Shuichi Ito
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  3. Masao Ogura
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  4. Koichi Kamei
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Correspondence to Shuichi Ito.

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Sato, M., Ito, S., Ogura, M. et al. Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after rituximab for refractory nephrotic syndrome. Pediatr Nephrol 28, 145–149 (2013). https://doi.org/10.1007/s00467-012-2286-6

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  • DOI: https://doi.org/10.1007/s00467-012-2286-6

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