Abstract
Epstein–Barr virus (EBV)-positive mucocutaneous ulcer is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. We report a 27-year-old male patient with Crohn’s disease (CD) who developed immunomodulator-associated lymphoproliferative disorder. The patient was diagnosed with CD at the age of 17 and was treated with maintenance therapy including high-dose infliximab and azathioprine. When he was admitted to our hospital with a diagnosis of intestinal obstruction, his abdominal computed tomography findings showed not only colonic wall thickening and narrowing of the descending colon but also multiple liver tumor lesions. His ileus symptom improved with conservative therapy, and a pathological evaluation of the tissue biopsy specimens from the descending colon and liver lesions indicated a morphological diagnosis of EBV-positive diffuse large B-cell lymphoma. This was a case of iatrogenic immunodeficiency-associated lymphoproliferative disorder due to an immunomodulator. The treatment was initiated with chemotherapy, but he died of disease progression 10 months after the diagnosis of lymphoma. Although cases of lymphoproliferative disorder due to treatment modalities used for CD are rare in Japan, an increase in the risk of lymphoproliferative diseases should be considered in patients with CD treated with immunomodulatory agents.
Similar content being viewed by others
References
Fukata N, Okazaki K, Omiya M, et al. Hematologic malignancies in the Japanese patients with inflammatory bowel disease. J Gastroenterol. 2014;49:1299–306.
Swerdlow SH, Campo E, Harris NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.
Kamdar KY, Rooney CM, Heslop HE. Posttransplant lymphoproliferative disease following liver transplantation. Curr Opin Organ Transplant. 2011;16:274–80.
Kanegane H, Wakiguchi H, Kanegane C, et al. Viral interleukin-10 in chronic active Epstein–Barr virus infection. J Infect Dis. 1997;176:254–7.
Kutok JL, Wang F. Spectrum of Epstein–Barr virus-associated diseases. Annu Rev Pathol. 2006;1:375–404.
Dojcinov SD, Venkataraman G, Raffeld M, et al. EBV positive mucocutaneous ulcer—a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol. 2010;34:405–17.
Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet. 2009;374:1617–25.
Kotlyar DS, Lewis JD, Beaugerie L, et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis. Clin Gastroenterol Hepatol. 2015;13:847–58.
Askling J, Brandt L, Lapidus A, et al. Risk of haematopoietic cancer in patients with inflammatory bowel disease. Gut. 2005;54:617–22.
Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–95.
Kappelman MD, Farkas DK, Long MD, et al. Risk of cancer in patients with inflammatory bowel diseases: a nationwide population-based cohort study with 30 years of follow-up evaluation. Clin Gastroenterol Hepatol. 2014;12:265–73.
Park SK, Ye BD, Lee C, et al. Risk and clinical characteristics of lymphoma in Korean patients with inflammatory bowel diseases: a multicenter study. J Clin Gastroenterol. 2015;49:e11–6.
Jung YS, Han M, Kim WH, et al. Cancer risk in the early stages of inflammatory bowel disease in Korean patients: a nationwide population-based study. J Crohns Colitis. 2017;11:954–62.
Lewis JD, Bilker WB, Brensinger C, et al. Inflammatory bowel disease is not associated with an increased risk of lymphoma. Gastroenterology. 2001;121:1080–7.
Winther KV, Jess T, Langholz E, et al. Long-term risk of cancer in ulcerative colitis: a population-based cohort study from Copenhagen County. Clin Gastroenterol Hepatol. 2004;2(12):1088–95.
Aozasa K. Pyothorax-associated lymphoma. J Clin Exp Hematop. 2006;46:5–10.
Ok CY, Papathomas TG, Medeiros LJ, et al. EBV-positive diffuse large B-cell lymphoma of the elderly. Blood. 2013;122:328–40.
Cohen M, Narbaitz M, Metrebian F, et al. Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients. Int J Cancer. 2014;135:2816–24.
Ok CY, Ye Q, Li L, et al. Age cutoff for Epstein–Barr virus-positive diffuse large B-cell lymphoma—is it necessary? Oncotarget. 2015;6:13933–45.
Beltran BE, Morales D, Quiñones P, et al. EBV-positive diffuse large b-cell lymphoma in young immunocompetent individuals. Clin Lymphoma Myeloma Leuk. 2011;11:512–6.
Acknowledgements
Guarantor of the article: Tomoo Nakagawa, MD. The authors would like to thank Enago (http://www.enago.jp) for the English language review.
Funding
Tomoo Nakagawa received unrestricted research Grants from AbbVie, Otsuka, EA pharma, Mochida, JIMRO, Asahikasei-Medical, and Nihonkayaku. Makoto Arai received unrestricted research Grants from MSD, Daiishi-Sankyo, and Takeda. Naoya Kato received unrestricted research Grants from AbbVie. The remaining authors disclose no conflicts.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interest.
Ethical approval
This report was reviewed and approved by the Chiba University Ethical Committee.
Human and animal rights
This article does not contain any studies directly involving human participants, as it is a review of data already collected in a hospital database.
Informed consent
For this type of study, formal consent was not necessary.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Hamanaka, S., Nakagawa, T., Ota, S. et al. Immunomodulator-associated Epstein–Barr virus-positive mucocutaneous ulcer in a patient with refractory Crohn’s disease. Clin J Gastroenterol 12, 330–335 (2019). https://doi.org/10.1007/s12328-019-00952-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12328-019-00952-4