Lymphoma in a Crohn’s Disease Patient Treated with Azathioprine and Infliximab

Fatma F. Elmijbri ¹, Sahar H. Summad *²

1,2. Benghazi Medical Center.

*Correspondence to: Sahar H. Summad, Benghazi Medical Center.

Copyright

© 2023 Sahar H. Summad. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 07 August 2023

Published: 01 September 2023

Abstract

In patients with inflammatory bowel disease, malignancies rank second behind cardiovascular diseases as the leading cause of death (IBD). In fact, people with IBD are more likely to develop a variety of extraintestinal malignancies, particularly lymphomas, the majority of which are non-Hodgkin lymphomas. Hodgkin lymphoma-type is a rather uncommon lymphoproliferative condition; to date, there have been just a few incidences of Hodgkin lymphoma (HL) in IBD patients. Here we report a case of Hodgkin lymphoma developing in a patient with Crohn’s disease being treated with both azathioprine and infliximab.

Case Summary

A 52 years old lady with Crohn's disease on azathioprine treatment has presented with a history of gradually progressive exertional dyspnoea. A physical examination confirmed the presence of fixed lymph nodes of hard consistency in the left cervical area and left axilla without evidence of any other superficial lymphadenopathy or organomegaly.

The biochemical results showed increased ESR and CRP as well as a neutrophilic leukocytosis of approximately 13,000 leukocytes per microliter. The chest X-ray showed a left mediastinal enlargement (Figure 1).

Chest Computed Tomography (Figure 2) was consistent with thoracoabdominal lymphadenopathies.

Histopathology and immunohistochemistry tests were positive for CD30 in RS-Burg- like cells giving rise to a diagnosis of atypical lymphoproliferative disease; mimicking Hodgkin’s lymphoma.

PET scan demonstrated nodal assessment of glucose avid multiple pathologically enlarged variable-sized LNs

Infliximab was, then, put on hold, but the patient continued on oral pentasa and azathioprine, and was referred to Oncology.

Discussion

The majority of infliximab-associated lymphomas are hepatosplenic T-cell or B-cell non-Hodgkin types. The risk of lymphoma development increases regardless of the underlying condition when infliximab is used with another immunosuppressive.

Our patient was also on azathioprine, However, a multi-center study did not show an increase in the incidence of neoplasia when compared to those who did not receive it. but the combined risk should further be explored.

Ulcerative colitis is more likely to be involved as a possible predisposing factor in the pathogenesis of HL. however; given its occurrence in literature, Crohn’s Disease can infrequently be associated with extra-intestinal HL, even without immunosuppressive therapy.

Another distinguishing aspect of immunosuppression-associated lymphomas is the well-established link between many of these malignancies and EBV and CMV infections. However, both were negative in our patient. Moreover, EBV-associated HL usually involves the colorectal region, and the small bowel, but our patient’s HL was extra-intestinal.

Azathioprine is used in patients with CD to maintain remission and as a steroid- sparing medication. Long-term azathioprine usage has previously been connected to the development of reversible lymphoma in IBD patients. However, its advantages clearly outweigh the risk of lymphoma, justifying its use in our case and others. It has to be determined whether this risk increases with concomitant and long-term usage of infliximab.

Conclusions

In conclusion, if patients are kept on long-term infliximab along with other immunosuppressive therapy, a higher index of suspicion and closer monitoring are needed. This potential uncommon complication needs to be acknowledged by both physicians and patients.

Reference

1. Beral V, Newton R. Overview of the epidemiology of immunodeficiency-associated cancers. J Natl Cancer Inst Monogr. 1998;(23):1-6. doi:10.1093/OXFORDJOURNALS.JNCIMONOGRAPHS.A024164

2. Lo B, Zhao M, Vind I, Burisch J. The Risk of Extraintestinal Cancer in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis of Population-based Cohort Studies. Clin Gastroenterol Hepatol. 2021;19(6):1117-1138.e19.   doi:10.1016/j.cgh.2020.08.015

3. Zeidan A, Sham R, Shapiro J, Baratta A, Kouides P. Hepatosplenic T-cell lymphoma in a patient with Crohn’s disease who received infliximab therapy. Leuk Lymphoma. 2007;48(7):1410-1413. doi:10.1080/10428190701345433

4. Bucher C, Degen L, Dirnhofer S, et al. Biologics in inflammatory disease: infliximab associated risk of lymphoma development. Gut. 2005;54(5):732. doi:10.1136/gut.2004.059352

5. Mahé E, Descamps V, Grossin M, Fraitag S, Crickx B. CD30+ T-cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab. Br J Dermatol. 2003;149(1):170-173. doi:10.1046/J.1365-2133.2003.05384.X

6. Biancone L, Orlando A, Kohn A, et al. Infliximab and newly diagnosed neoplasia in Crohn’s disease: a multicentre matched pair study. Gut. 2006;55(2):228. doi:10.1136/GUT.2005.075937

7. Nakashima C, Tanioka M, Takahashi K, Miyachi Y. Diffuse large B-cell lymphoma in a patient with rheumatoid arthritis treated with infliximab and methotrexate. Clin Exp Dermatol. 2008;33(4):437-439. doi:10.1111/J.1365-2230.2007.02683.X

8. Bickston SJ, Lichtenstein GR, Arseneau KO, Cohen RB, Cominelli F. The relationship between infliximab treatment and lymphoma in Crohn’s disease. Gastroenterology. 1999;117(6):1433-1437. doi:10.1016/S0016-5085(99)70294-5

9. Musso M, Porretto F, Crescimanno A, BondÌ F, Polizzi V, Polizzi R. Crohn’s disease complicated by relapsed extranodal Hodgkin’s lymphoma: prolonged complete remission after unmanipulated PBPC autotransplant. Bone Marrow Transplant. 2000;26(8):921-923. doi:10.1038/SJ.BMT.1702621
10. Palli D, Trallori G, Bagnoli S, et al. Hodgkin’s disease risk is increased in patients with ulcerative colitis. Gastroenterology. 2000;119(3):647-653. doi:10.1053/gast.2000.16487.