Exfoliative bowel rejection – a dangerous loss of integrity

The varied ramifications of acute rejection (AR) in solid organ transplantation identify its importance and warrant the formidable effort placed by the transplant community in preventing and controlling this host derived process. In general, the effects of AR are limited to mild graft dysfunction (following therapy) with the understanding that even mild rejection episodes may be predisposing the graft to a higher risk of chronic allograft failure (rejection). However, AR is occasionally not well controlled and progresses, causing severe (sometimes irreversible) injury, placing the allograft at risk for an acute loss. This latter scenario takes place in small bowel allografts in relatively common fashion. The initial stages of acute rejection of the small bowel allograft are typically displayed by mixed inflammatory infiltrates within the lamina propria and mucosal interstitium as well as immune cell mediated injury to epithelial crypt cells. As this process progresses, there is shortening and eventual flattening of villi with the destruction of glandular structures. The culmination of poorly controlled acute allograft rejection is the extensive destruction of bowel mucosa and loss of surface epithelium, also known as exfoliation . At this point the histologic change is obvious and dramatic, with the bowel mucosa appearing severely inflamed and denuded with early formation of granulation tissue. As the loss of surface epithelium, or mucosal exfoliation, is such a distinct clinicopathological feature, we believe this exfoliative process is synonymouswith the severe stage of acute bowel allograft rejection. Among other things, this loss of the mucosal barrier integrity hampers bowel absorptive capacity and predisposes the host to bacterial translocation. In the June 2003 issue of Pediatric Transplantation, Ishii et al. (1) report their analysis of 92 pediatric intestinal transplant cases and find a 15% incidence of exfoliative (severe) rejection that is associated with an extremely high rate of graft loss and mortality. This reported high rate of graft failure after exfoliative rejection solidifies the general impression held by bowel transplant centers who find this entitiy so difficult to contend with (2). Even if histological recovery occurs (regenerating mucosa), there is a low likelihood of clinical recovery. The patient often develops infectious complications during the course of aggressive immunosuppressive therapy and may necessitate graft removal. In this regard, Ishii et al. reported a graft loss rate of 93% (14/15) and patient loss of 69% (9/13) when exfoliative rejection took place. The rate of graft failure after severe rejection is similar in our own series in patients who developed severe rejection during the early post-operative period. However, we find that recipients who develop exfoliative (or severe) rejection later than 6 months tend to respond better to therapy (100% graft loss in early phase vs. 40% graft loss in later phase) (presented at the First Joint Meeting of the American Society of Transplant Surgeons and the American Society of Transplant Physicians (Transplant 2000), May13–17, 2000, Chicago, IL, USA). This late onset of severe exfoliative rejection is often associated with intentional or unintentional decreased levels of immunosuppression (e.g. following the therapy of PTLD or patient s poor-compliance with immunosuppressive drugs). Ishii et al. likewise showed that patients who had histological recovery had a later onset of exfoliative rejection. On the other hand, early onset of severe rejection did not correlate with the level of immunosuppression in our experience. Perhaps these are the patients who have stronger and /or humoral component (3) in their immune response to the allograft, although positive cytotoxic crossmatch was not associated with increased incidence of exfoliative rejection by Ishii et al. Ishii et al. also report that the inclusion of the liver has a protective effect on occurrence of Pediatr Transplantation 2004: 8: 426–427