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Crohn’s ileitis after liver transplantation from a living related donor with Crohn’s disease
  1. K A Papadakis,
  2. R Matuk,
  3. M T Abreu,
  4. E A Vasiliauskas,
  5. P R Fleshner,
  6. J Lechago,
  7. T Tran,
  8. F F Poordad,
  9. P Martin,
  10. J Vierling,
  11. S R Targan
  1. Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA
  1. Correspondence to:
    Dr K A Papadakis
    Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd, D-4063 Los Angeles, California 90048, USA; Papadakiskcshs.org

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We read with interest the case described by Sonwalkar et al of a patient who developed fulminant Crohn’s colitis after allogeneic stem cell transplantation (ASCT) (Gut 2003;52:1518–21). Although the donor had no known Crohn’s disease (CD) and did not carry the IBD3 or IBD5 haplotypes associated with CD, HLA class III mismatches at IBD3 and a CD associated polymorphism of the 5′UTR of NOD2/CARD15 were present in the donor and in the reconstituted immune cell population of the recipient post ASCT. The authors hypothesised that adoptive transfer of CD susceptibility may have occurred between ACST donor and recipient.

Herein, we report a case of a patient who developed CD after receiving a living related liver transplant from a donor with known CD. A 24 year old female received a liver transplant from a living related donor for decompensated cirrhosis secondary to vertically transmitted chronic hepatitis C infection. The family history was significant for a maternal aunt diagnosed with CD, who served as the liver donor, and a maternal uncle and grandfather with colon cancer. Following liver transplantation, the patient was maintained on an immunosuppressive regimen consisting of tacrolimus 3 mg twice daily, sirolimus 5 mg daily, as well as TMP-SMZ prophylaxis. Her initial post-transplant course was uneventful but she later developed recurrent hepatitis C infection, treated with pegylated interferon and ribavirin. She presented with symptoms consistent with intermittent small bowel obstruction 11 months post-transplant. She was also receiving prednisone 15 mg daily at that time. A computed tomography scan of the abdomen and pelvis (see fig 1A on the Gutwebsite: www.gutjnl.com) and an upper gastrointestinal with small bowel follow through study (see fig 1B on the Gutwebsite: www.gutjnl.com) demonstrated marked fold thickening of the distal ileum. An enteroscopy demonstrated patchy ulcerations in the jejunum and Roux-en-Y limb of the small bowel. Biopsies showed focal ulceration and mild active inflammation without evidence of granuloma or viral inclusions. Wireless capsule endoscopy demonstrated multiple erosive and ulcerative changes in the distal small intestine (see fig 1C, 1D on the Gutwebsite: www.gutjnl.com).

Figure 1

 Histopathological examination of a resected ileal specimen demonstrated focal villous blunting, expansion of the lamina propria with acute and chronic inflammatory cells, reactive crypt changes, and occasional crypt abscesses and focal gastric metaplasia (arrow and insert). SM, submucosa.

Because of persistent symptoms and concern for possible lymphoproliferative disorder, the patient underwent an open laparoscopy which revealed nodularity of the terminal ileum. Intraoperative colonoscopy demonstrated nodularity and three ulcers in the distal ileum. Histopathological examination of the resected ileal specimen demonstrated focal villous blunting, expansion of the lamina propria with acute and chronic inflammatory cells, reactive crypt changes, and occasional crypt abscesses and focal gastric metaplasia (see fig 1E, arrow and insert below). Mucosal ulcerations were underlined by inflamed granulation tissue containing occasional histiocytes and multinucleated giant cells. The submucosa also showed intense fibrosis and hyperplasia of the nerve bundles (not shown).

Few cases of de novo IBD developing after liver transplantation for chronic liver disease other than primary sclerosing cholangitis have been described.1–4 We present a case of CD developing in the recipient of a liver transplant from a living related donor with a known history of CD. The recipient tested negative for any of the three common CD associated NOD2/CARD15 variants (R702W, G908R, 1007fsinsC) but unfortunately we were unable to screen the liver donor for these polymorphisms. Our case, similar to that described by Sonwalkar et al, raises the intriguing possibility that CD susceptibility may have been transferred to the recipient with liver transplantation as well. Collins et al have reported complete and stable replacement of recipient haematopoiesis and B lymphopoiesis with donor derived cells approximately six weeks following orthotopic liver transplantation for haemochromatosis.5 T lineage reconstitution also occurred and derived almost exclusively from expansion of mature memory/effector T cells from the transplanted liver. One possibility is that the expanded immune cells have become tolerant to the graft but not to the intestinal luminal antigens leading to the development of CD.4 Whether liver donor selection should exclude those with a known diagnosis of CD is unclear and is still premature to answer.

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