Inflammatory Bowel Disease and Lymphoproliferative Disorders

Byong Duk Ye

doi:10.4166/kjg.2011.58.4.171

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Ye: Inflammatory Bowel Disease and Lymphoproliferative Disorders

Review Article

Korean J Gastroenterol 2011;58(4):171-177.

Published online: 4 October 2011

DOI: https://doi.org/10.4166/kjg.2011.58.4.171

Inflammatory Bowel Disease and Lymphoproliferative Disorders

Byong Duk Ye

Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

Correspondence to: Byong Duk Ye, Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3181, Fax: +82-2-476-0824, E-mail: bdye@amc.seoul.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The risk of lymphoproliferative disorders (LPDs) has been reported to be increased in autoimmune diseases and chronic inflammatory diseases. Similar with other chronic inflammatory diseases such as rheumatoid arthritis, there is a concern about the risk of LPDs in patients with inflammatory bowel disease (IBD). Generally, in IBD patients, the risk of LPDs appears to be similar with or very slightly higher, compared to the general population. The association of therapeutic agents with the risk of LPDs is difficult to evaluate due to multiple other potentially involved factors and co-treatment with other agents. To date, data show that thiopurine is associated with a moderately increased risk of LPDs in patients with IBD. Evidence regarding the risk of LPDs in IBD patients using methotrexate is not sufficient, but the risk of LPDs seems low. The responsibility of anti-TNF-α agents on the risk of LPDs is difficult to determine, because most of IBD patients receiving anti-TNF-α agents are co-treated with thiopurines. Attention should be given to the high risk of hepatosplenic T-cell lymphoma in young male patients treated with anti-TNF-α agents together with thiopurines. The risk and benefit of immunosuppressive therapy for IBD should be carefully evaluated and individualized considering the risk of LPDs.

Keywords: Inflammatory bowel diseases, Lymphoproliferative disorders, Azathioprine, 6-Mercaptopurine, Tumor necrosis factor alpha

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Table 1.

Risk of Lymphoproliferative Disorders in Patients with Inflammatory Bowel Disease: Population-based Studies (adapted and modified from reference 1 with permission)

Study (reference)	Study area Y	Year of publication	Patients	SIR (95% CI)
Ekbom, et al.²¹	Uppsala, Sweden	1991	CD: 1,665	0.4 (0.0–2.4)
			UC: 3,121	1.2 (0.5–2.4)
			IBD: 4,786	1.0 (0.5–1.9)
Persson, et al.²²	Stockholm, Sweden	1994	CD: 2,151	1.4 (0.4–3.5)
Karlén, et al.²³	Stockholm, Sweden	1999	UC: 1,547	1.2 (0.3–3.5)
Loftus, et al.²⁴	Olmsted County, USA	2000	CD: 216	2.4 (0.1–13.1)
			UC: 238	0.0 (0.0–6.4)
Palli, et al.²⁵	Florence, Italy	2000	CD: 231	NA
			UC: 689	HL: 9.3 (2.5–23.8)
				NHL: 1.8 (0.2–6.5)
			IBD: 920	HL: 8.6 (2.8–20.1)
				NHL: 1.4 (0.2–5.2)
Bernstein, et al.²⁶	Manitoba, Canada	2001	CD: 2,857	2.4 ^a (1.2–5.0)
			UC: 2,672	1.03 ^a (0.5–2.2)
			IBD: 5,529	1.52 ^a (0.9–2.6)
Lewis, et al.²⁷	United Kingdom	2001	CD: 6,605	1.59 (0.6–3.3)
			UC: 10,391	1.2 (0.6–2.2)
Winther, et al.²⁸	Copenhagen County, Denmark	2004	UC: 1,160	0.5 (0.1–1.8)
Jess, et al.²⁹	Copenhagen County, Denmark	2004	CD: 374	LPDs not observed
Askling, et al.³⁰	Multiple Swedish cohorts	2005	CD: 20,120	1.3 (1.0–1.6)
			UC: 27,759	1.0 (0.8–1.3)
			IBD: 47,679	NA

CD, Crohn's disease; UC, ulcerative colitis; IBD, inflammatory bowel disease; NA, not applicable; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma; LPD, lymphoproliferative disorder; SIR, standardised incidence ratio.

^a Incidence rate ratio (IRR).

Table 2.

Risk of Lymphoproliferative Disorders in Patients with Inflammatory Bowel Disease Treated with Thiopurines: Single-center Studies, Population-based Studies and Meta-analyses (adapted and modified from reference 1 with permission)

Study (reference)	Study area	Year of publication	Study setting	Number of patients	RR (95% CI)	SIR (95% CI)
Kinlen³⁴	UK	1985	Single center study	321	NA	12.5 (1.2–46.0)
Connell, et al.³⁵	London, UK	1994	Single center study	755	NA	LPDs not observed
Korelitz, et al.³⁶	New York, USA	1999	Single center study	486	NA	4.9 (0.9–14.5)
Farrell, et al.³⁷	Dublin, Ireland	2000	Single center study	238	NA	37.5 (3.5–138)
Lewis, et al.²⁷	UK	2001	Population-based study	1,465	1.3 (0.03–8.2)	1.6 (0.001–9.0)
Fraser, et al.³⁸	Oxford, UK	2002	Single center study	626	NS (p=0.5)	4.6 (0.9–13.7)
Kandiel, et al.³⁹		2005	Meta-analysis	3,891	2.9 (1.1–8.1)	4.2 (2.1–7.5)
Masunaga, et al.⁴⁰		2007	Meta-analysis	3,791	NS ^a	NA

SIR, standardized incidence ratio; NA, not applicable; LPD, lymphoproliferative disorder.

^a Weighted mean difference=0.0; 95% CI, −0.8–0.7.

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