Epstein-Barr virus in inflammatory bowel disease: the spectrum of intestinal lymphoproliferative disorders.
BACKGROUND
Inflammatory bowel disease (IBD) patients on thiopurine therapy are at increased risk of Epstein-Barr virus (EBV)-associated lymphomas. This virus is frequently detected in the intestinal mucosa of IBD patients and may cause a wide spectrum of lymphoproliferations similar to post-transplantation lymphoproliferative disorders (PTLDs). We aimed to assess whether histological aberrations aid in predicting EBV presence and to correlate histological assessment and EBV load with disease outcome in IBD.


METHODS
We included all IBD patients from our centre who underwent EBV testing of intestinal biopsies between January 2004 and October 2013. All biopsies were classified according to the WHO PTLD classification and the EBV load was scored per high-power field (HPF). Clinical data were collected from patient charts. Reported clinical outcomes included colectomy, need for chemotherapy and mortality.


RESULTS
Our cohort included 58 patients: 28 were EBV-positive and 30 EBV-negative. An atypical infiltrate was seen more frequently in EBV-positive than in EBV-negative patients (57.1 versus 3.3%; p < 0.001). A high EBV load occurred more frequently in EBV-positive patients undergoing colectomy than in EBV-positive patients without colectomy (50.0 versus 10.0%; p = 0.048). Monomorphic lymphoproliferative disorders, including two overt lymphomas, were present in 10 patients. Reduction of immunosuppression resulted in histological normalization and loss of EBV expression in seven of eight non-lymphoma patients.


CONCLUSIONS
The presence of atypical infiltrate in the intestinal mucosa of IBD patients warrants EBV testing. Reduction of immunosuppression is an effective strategy to achieve morphological normalization and loss of EBV. Lymphoproliferation related to IBD appears to have less aggressive clinical behaviour than PTLDs.
Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands Loes.Nissen@radboudumc.nl.
Loes H C
LH
Nissen
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
Iris D
ID
Nagtegaal
Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Dirk J
DJ
de Jong
Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
Wietske
W
Kievit
Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Lauranne A A P
LA
Derikx
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
Patricia J T A
PJ
Groenen
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
J Han J M
JH
van Krieken
Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Frank
F
Hoentjen
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000473:pathology; D002648:Child; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000150:complications / Q000473:pathology* / Q000628:therapy; D003424:Crohn Disease / Q000150:complications / Q000473:pathology* / Q000628:therapy; D004279:DNA, Viral / Q000097:blood*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000473:pathology* / Q000821:virology; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D019562:Viral Load; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha
Epstein–Barr virus; Inflammatory bowel diseases; lymphoma