Abstract
Cryptogenic organizing pneumonia (COP, formerly bronchiolitis obliterans organizing pneumonia) is rare in children. We describe an 11-year-old girl with Epstein–Barr virus (EBV) reactivation/presumed post-transplant lymphoproliferative disease (PTLD) 15 months after undergoing a deceased donor kidney transplantation. Treatment with reduced immunosuppression, ganciclovir, and cytomegalovirus immunoglobulin was complicated by severe graft rejection, prompting therapy with methylprednisolone, anti-thymocyte globulin and four weekly doses of rituximab (total 1500 mg/m2). Tacrolimus- and prednisone-based anti-rejection prophylaxis was complemented with low-dose sirolimus. When the lactate dehydrogenase and uric acid levels rose 10 weeks after the first rituximab infusion and bilateral pulmonary nodules were detected by computerized tomography, recurrence of PTLD was suspected. Open lung biopsy of the clinically asymptomatic patient identified the nodules as COP, characterized by abundant CD3+ T-cells, few B-cells, and the absence of EBV, cytomegalovirus, or adenovirus antigens. With normalization of the peripheral B-cell count, EB viremia reappeared and persisted, despite minimal immunosuppression. Four years later, the patient was diagnosed with classical Hodgkin lymphoma-type PTLD with multiple pulmonary and abdominal nodes. This first report of rituximab-associated, pediatric COP highlights the risk of pulmonary complications after treatment with B-cell depleting agents in solid organ transplant recipients, and the importance of a histopathologic diagnosis and vigilant follow-up of such lesions.
Notes
For conversion of SI units (μM) to conventional units (mg/dl) divide by 88.4.
References
Epler GR, Colby TV, McLoud TC, Carrington CB, Gaensler EA (1985) Bronchiolitis obliterans organizing pneumonia. N Engl J Med 312:152–158
Schlesinger C, Koss MN (2005) The organizing pneumonias: an update and review. Curr Opin Pulm Med 11:422–430
Inoue T, Toyoshima K, Kikui M (1996) Idiopathic bronchiolitis obliterans organizing pneumonia (idiopathic BOOP) in childhood. Pediatr Pulmonol 22:67–72
Epler GR (2001) Bronchiolitis obliterans organizing pneumonia. Arch Intern Med 161:158–164
Kim R, Meyer KC (2008) Therapies for interstitial lung disease: past, present and future. Ther Adv Respir Dis 2:319–338
Dharnidharka VR, Araya CE (2009) Post-transplant lymphoproliferative disease. Pediatr Nephrol 24:731–736
Choquet S, Leblond V, Herbrecht R, Socie G, Stoppa AM, Vandenberghe P, Fischer A, Morschhauser F, Salles G, Feremans W, Vilmer E, Peraldi MN, Lang P, Lebranchu Y, Oksenhendler E, Garnier JL, Lamy T, Jaccard A, Ferrant A, Offner F, Hermine O, Moreau A, Fafi-Kremer S, Morand P, Chatenoud L, Berriot-Varoqueaux N, Bergougnoux L, Milpied N (2006) Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood 107:3053–3057
Wagner SA, Mehta AC, Laber DA (2007) Rituximab-induced interstitial lung disease. Am J Hematol 82:916–919
Heresi GA, Farver CF, Stoller JK (2008) Interstitial pneumonitis and alveolar hemorrhage complicating use of rituximab: case report and review of the literature. Respiration 76:449–453
Bitzan M, Anselmo M, Carpineta L (2009) Rituximab (B-cell depleting antibody) associated lung injury (RALI): A pediatric case and systematic review of the literature. Pediatr Pulmonol 44:922–934
Lioté H, Lioté F, Seroussi B, Mayaud C, Cadranel J (2010) Rituximab-induced lung disease: a systematic literature review. Eur Respir J doi:10.1183/09031936.00080209
Fan LL, Deterding RR, Langston C (2004) Pediatric interstitial lung disease revisited. Pediatr Pulmonol 38:369–378
Fazekas T, Wiesbauer P, Kronberger M, Wank H, Gadner H, Dworzak M (2008) Nodular pulmonary lesions in children after autologous stem cell transplantation: a source of misinterpretation. Br J Haematol 140:429–432
Soubrier M, Jeannin G, Kemeny JL, Tournadre A, Caillot N, Caillaud D, Dubost JJ (2008) Organizing pneumonia after rituximab therapy: two cases. Joint Bone Spine 75:362–365
Presas JL, Piriz J, Serra SL, Paz ED, Allievi A, Kartin D, Olmedo G (1998) Bronchiolitis obliterans with organizing pneumonia associated with idiopathic thrombocytopenic purpura. Medicina (B Aires) 58:58–60
Morelon E, Stern M, Israel-Biet D, Correas JM, Danel C, Mamzer-Bruneel MF, Peraldi MN, Kreis H (2001) Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. Transplantation 72:787–790
Lindenfeld JA, Simon SF, Zamora MR, Cool CD, Wolfel EE, Lowes BD, Ireland N, Keller K, Frisk R, Stepien L, Cleveland JC Jr, Zolty R (2005) BOOP is common in cardiac transplant recipients switched from a calcineurin inhibitor to sirolimus. Am J Transplant 5:1392–1396
Ditschkowski M, Elmaagacli AH, Trenschel R, Peceny R, Koldehoff M, Schulte C, Beelen DW (2007) T-cell depletion prevents from bronchiolitis obliterans and bronchiolitis obliterans with organizing pneumonia after allogeneic hematopoietic stem cell transplantation with related donors. Haematologica 92:558–561
Acknowledgments
The authors wish to thank all members of the Division of Nephrology, including our nurses, trainees, nephrologists, and allied health professionals involved in the patient’s dedicated care over the years, as well as members of the Departments/Divisions of Surgery, Hematology/Oncology and Respirology. The EBV PCR was carried out in the Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh. The remaining studies were performed in the laboratories of the Montreal Children’s Hospital and McGill University Health Centre.
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The author(s) declare that they have no competing interests.
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Bitzan, M., Ouahed, J.D., Carpineta, L. et al. Cryptogenic organizing pneumonia after rituximab therapy for presumed post-kidney transplant lymphoproliferative disease. Pediatr Nephrol 25, 1163–1167 (2010). https://doi.org/10.1007/s00467-010-1447-8
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DOI: https://doi.org/10.1007/s00467-010-1447-8