An Association Between Hodgkin’s Lymphoma and Crohn’s Disease: A Case Series

Background:

Although rare, there is an association between non-Hodgkin’s lymphomas (NHL) and Crohn’s disease (CD). The etiology of NHL in CD has been traditionally been attributed to the use of immunosuppressive agents: TNF blockers and thiopurines. An association between CD and Hodgkin’s lymphoma (HL), however, is less well established. We present a case series of 4 patients (pts), the largest reported thus far.

Case 1:

An 18 YO M with CD presented in 12/2003 with pruritis, fevers, myalgias, fatigue, and cervical and axillary adenopathy. Diagnosed with CD as a child, he had received multiple prior therapies: corticosteroids, 6-MP, asacol, as well as infliximab for 3 months prior to presentation. Cervical node biopsy indicated classical HL, nodular sclerosis. Infliximab was discontinued, and he received 5 cycles of bleomycin, doxorubicin, vincristine, etoposide, cytoxan, prednisone followed by involved field XRT to the mediastinum. He completed therapy in 5/2004, achieving a complete remission (CR). In regards to his CD, he underwent cecal and ileal resections in 2007 and 2009. He has been managed successfully with adalimumab since 2010 and has not experienced a recurrence of HL.

Case 2:

A 32 YO F with CD presented in 9/2012 with fatigue, night sweats, weight loss, and fevers. She was diagnosed with CD at age 11, initially receiving balsalazide and sulfasalazine. She received infliximab from Feb-June 2014, but switched to certolizumab and 6- MP in 8/2012 due to infusion-related reactions. Her symptoms were initially attributed to CD; however, CT scans showed a peri-colonic mass and retroperitoneal lymphadenopathy. Biopsy of the mass revealed classical HL, EBV-associated, nodular sclerosis. PET/CT indicated involvement of thoracic and abdominal nodes, liver, spleen, and marrow as well. She discontinued therapy for CD and received 6 cycles of adriamycin, vinblastine, and dacarbazine (AVD). Bleomycin was omitted as PFTs indicated a mild defect. She achieved a CR which she has maintained for a year and a half. She did not resume treatment for CD as she remains asymptomatic.

Case 3:

A 33 YO F with CD presented in 6/2014 with pruritis and weight loss. CT imaging revealed a mediastinal mass and diffuse lymphadenopathy, biopsy-proven to be classical HL. She was diagnosed with CD in 4/2013, for which she had been receiving adalimumab since 9/2013. It was discontinued subsequently. She had Stage IV disease by PET/CT and is receiving ABVD.

Case 4:

A 49 YO M presented with a persistent rash for several months, followed by an episode of fever, nausea, vomiting, diarrhea, and abdominal pain in 1/2009. CT imaging indicated an 8 cm cecal mass with mesenteric and para-aortic lymphadenopathy. Biopsy of the mass revealed EBV- associated classical HL. PET/CT imaging indicated involvement of the cecal mass and abdominal nodes as well as bone marrow. He received 6 cycles of AVD. Bleomycin was held early on due to pneumonitis. Post-treatment scans indicated a residual FDG-avid cecal mass; however, biopsies were negative for HL. Laparoscopic resection of the mass in 12/2009 revealed CD, but no HL. As he had no CD-related symptoms, he was not placed on immunosuppression. Restaging scans in 12/2010 indicated an ongoing CR.

Conclusion:

While HL has been reported with various immunodeficiencies, this is the largest case series in CD disease. The presence of EBV in 2 pts suggests that immune dysregulation may have contributed to its pathogenesis. However, whether the etiology is the immunosuppressive therapy and/or the autoimmune disease remains unclear. Post-marketing surveillance has found a few cases of HL in pts with autoimmune diseases receiving TNF blockers, often with concomitant immunosuppressants. Furthermore, the withdrawal of immunosuppression resulting in a spontaneous regression of HL has also been reported. One of our pts, however, did not receive immunosuppression prior to HL, implying that CD and associated immune dysregulation may be the precipitating factor. This is conceivable given the location of HL in this patient (colon). It is also possible that the occurrence of HL and CD may have been mutually exclusive in pts 1 and 3, who were of the typical age for HL and had the characteristic mediastinal mass. Limited data are available regarding these pts; it appears that cytotoxic chemotherapy and withdrawal of the immunosuppression are appropriate management. Once identified, pts should be followed in a prospective fashion.