Inflammatory Bowel Disease and Hodgkin's Lymphoma: Two New Observations

Introduction :

Malignancies are the second most common cause of death after cardiovascular diseases in patients with inflammatory bowel disease (IBD). Indeed, patients with IBD have an increased risk for developing a variety of extraintestinal malignancies, in particular, lymphomas and mostly non-Hodgkin lymphomas. In the spectrum of lymphoproliferative disorders, Hodgkin lymphoma-type is rare, only a few cases with Hodgkin's lymphoma (HL) in IBD patients have so far been reported. We report two new cases.

Case 1 :

A 44 year old male presented in 2010 with a history of abdominal pain, intermittent diarrhea, and rectal bleeding. The clinical, endoscopic, and pathologic findings were consistent with ulcerative colitis. Initial medical treatment was Azathioprine (50 mg, three times a day), Prednisolone (50 mg, one time a day), and 5-aminosalicylic acid (800 mg, three times a day). He was also diagnosed as having type 2 diabetes, treated with insulin. The patient was continually treated with Azathioprine through 5 years, with reduced dose (100 mg/d) because of hematological toxicity. In 2016, the patient was readmitted with severe pneumonia. He reported having abdominal pain, weight loss, night sweat, and intermittent fever for three to four months before admission. A computed tomography was performed, showed retroperitoneal, peri-aortic and iliac bilateral lymphadenopathy. Needle biopsy was performed out and histology revealed large cells of Hodgkin's type, and intense staining for CD30 and CD15 all in favor of the diagnosis of HL.

Case 2 :

The second patient is a 30-year-old man with ileocecal Crohn disease diagnosed at age 23 years. Remission was induced with corticosteroids and maintained by Azathioprine (150 mg/d). Three month before his admission to our unit, he complains from intermittent fever, decline in general condition. Cervical and axillary lymphadenopathy were noted. The lymph node biopsy revealed mixed-cellularity Hodgkin lymphoma. Computed tomography scan revealed stade IIIB disease for both patients. They received 6 cycles of adriamycin, bleomycin, vincristine, and dacarbazine. A complete regression of lymphadenopathy was confirmed by CT and positron emission tomography scan. Presently, the patients remain in remission and without any signs of lymphoproliferative disorder or IBD (on sulfasalazine).

Discussion :

IBD patients show a trend toward higher risks of developing hematological malignancies. Compared with the general population, there is an increased risk for lymphoma, especially non-Hodgkin lymphoma, with a standardized incidence rate of 1.42 (95% CI, 1.16-1.73). HL is a known rare comorbidity that can emerge in IBD patients. Thiopurines were shown to increase the incidence of lymphoma after kidney transplantation and similar observations have been reported in patients with IBD. In observational cohort, the risk of acquiring lymphomas was significantly higher (4- to 5- fold) in patients with thiopurine exposure; this risk appears to rise with longer duration of therapy and to decrease after drug withdrawal. Most of the thiopurine promoted lymphomas are attributed to the cytotoxic effects of thiopurines on EBV-specific immune cells that prevent the proliferation of EBV-infected B lymphocytes.

IBD itself may contribute to the development of lymphoproliferative disorders, particularly primary intestinal HL. Indeed, recent population-based study showed an association between lymphomas and IBD, regardless of the use of thiopurines. In fact, inflammation itself plays a role in lymphomagenesis. Local sites of inflammation may be particularly at risk of lymphoproliferation, due to chronic B-cell stimulation, may also explain the frequency of gastrointestinal lymphoproliferative disorders involving the gastrointestinal tract (26% of cases). The duration of the disease appears also as an independent risk factor for lymphoma.

Conclusion :

HL can emerge in IBD patients on immunosuppressive therapy and physicians must be aware of this possibility. EBV infection might have an intermediate role between immunosuppressive treatment and lymphoma. Those data should alert clinicians that, not only thiopurine use but also the disease itself could contribute to a higher occurrence of lymphoproliferative disorders.