Clinical Endoscopy

The Korean Society of Gastrointestinal Endoscopy (대한소화기내시경학회)
권호 표지

Gastrointestinal Complication in Transplant Patients

장기이식 환자에서 발생하는 위장관 합병증

  • Kim, Gun-Min (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Cheung, Dae-Young (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Jin-Il (Department of Internal Medicine, The Catholic University of Korea College of Medicine)
  • 김건민 (가톨릭대학교 의과대학 내과학교실) ;
  • 정대영 (가톨릭대학교 의과대학 내과학교실) ;
  • 김진일 (가톨릭대학교 의과대학 내과학교실)
  • Received : 2010.07.21
  • Accepted : 2010.08.17
  • Published : 2010.08.30
⟨ Previous Next ⟩

Abstract

The gastrointestinal tract is one of the major sites for complications after solid organ and hematopoietic stem cell transplantation, and gastrointestinal complications are the principle cause of morbidity and death. The major gastrointestinal complications after transplantation include mucositis, typhlitis, infectious enterocolitis by virus, bacteria or fungus, pseudomembranous colitis, gastric ulcer, graftversus-host disease, pneumatosis cystoides intestinalis, thrombotic microangiopathy and post-transplantation lymphoproliferative disease. Symptoms and signs of gastrointestinal complications following transplantation are often non-specific and present with varying severity. Moreover, the suppressed immune state often prohibits invasive studies including endoscopy and blurs the serologic and hematologic results. Therefore, it is hard to reach accurate diagnoses even after thorough investigations. Almost all immunosuppressive drugs can lead to gastrointestinal complications and we need proper strategies to minimize their side effects. On the one hand, we can expect better organ and patient survival through the judicious use of a broad range of immunosuppressive drugs; on the other hand, we should try to not ruin survival through proper precautions and early treatment of gastrointestinal complications following successful transplantation.

장기 이식이나 조혈모세포 이식 후 위장관 합병증은 비교적 흔히 발병하며 삶의 질을 감소시키고, 치명적인 경우가 있어 사망률을 증가시킨다. 조혈모세포 이식 후 면역이 저하되는 과정은 생착 전 단계, 조기 생착 단계, 후기 생착 단계로 분류할 수 있으며 각 단계 별로 빈번히 발생하는 합병증이 있다. 장기이식 후 흔히 발생하는 위장관 합병증으로는 점막염, 구토, 복통 등이 있고, 또한 설사, 혈변, 맹장염 등이 관찰된다. 이중 중요한 합병증으로는 이식편대숙주병이 가장 많고, 거대세포 바이러스를 비롯한 바이러스 감염, C. difficile에 의한 위막성결장염이 등이 나타날 수 있다. 이외에도 위장관 궤양성 질환, 낭성장기종, 혈전미세혈관병증, 이식후림프세포증식질환 등이 발생할 수 있다. 장기 이식 후 발생하는 위장관 합병증의 증상은 비 특이적이어서 진단이 어려우며 또한 면역 기능이 억제된 상태여서 내시경 등의 적극적인 검사를 하기도 어렵다. 또한 항암제나 항생제 뿐만 아니라 대부분의 면역억제제가 위장관 합병증을 일으키므로 감별 진단을 하여야 한다. 이식 후 정확한 조기 진단 및 조기 치료가 이환율 및 사망률을 낮출 수 있으므로 환자의 증상을 중심으로 내시경 검사와 조직 검사, 혈청학적인 검사, 방사선 검사 등의 적극적인 검사를 이용하여 조기에 진단하는 것이 이식 후 위장관 합병증을 치료하는 데에 매우 중요하다.

Keywords

References

  1. Armitage JO. Bone marrow transplantation. N Engl J Med 1994;330:827-838. https://doi.org/10.1056/NEJM199403243301206
  2. Barker CC, Anderson RA, Sauve RS, Butzner JD. GI complications in pediatric patients post-BMT. Bone Marrow Transplant 2005;36:51-58. https://doi.org/10.1038/sj.bmt.1705004
  3. Myers JD, Flournoy N, Thomas ED. Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis 1986;153:478-488. https://doi.org/10.1093/infdis/153.3.478
  4. Sakr M, Hassanein T, Gavaler J, et al. Cytomegalovirus infection of the upper GI tract following liver transplantation-- incidence, location, and severity in cyclosporine- and FK506- treated patients. Transplantation 1992;53:786-791. https://doi.org/10.1097/00007890-199204000-00016
  5. Mori T, Mori S, Kanda Y, et al. Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2004;33:431-434. https://doi.org/10.1038/sj.bmt.1704369
  6. Patel R, Snydman DR, Rubin RH, et al. Cytomegalovirus prophylaxis in solid organ transplant recipients. Transplantation 1996;61:1279-1289. https://doi.org/10.1097/00007890-199605150-00001
  7. Gavalda J, de Otero J, Murio E, et al. Two grams daily of oral acyclovir reduces the incidence of cytomegalovirus disease in CMV-seropositive liver transplant recipients. Transpl Int 1997;10:462-465. https://doi.org/10.1111/j.1432-2277.1997.tb00725.x
  8. Badley AD, Seaberg EC, Porayko MK, et al. Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database. Transplantation 1997;64:66-73. https://doi.org/10.1097/00007890-199707150-00013
  9. Lowance D, Neumayer HH, Legendre CM, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med 1999; 340:1462-1470. https://doi.org/10.1056/NEJM199905133401903
  10. Mosimann F, Cuenoud PF, Steinhauslin F, Wauters JP. Herpes simplex esophagitis after renal transplantation. Transpl Int 1994;7:79-82. https://doi.org/10.1111/j.1432-2277.1994.tb01224.x
  11. Helderman JH, Goral S. Gastrointestinal complications of transplant immunosuppression. J Am Soc Nephrol 2002;13: 277-287.
  12. Winston DJ, Pakrasi A, Busuttil RW. Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;131:729-737.
  13. Patel R. Prophylactic fluconazole in liver transplant recipients: a randomized, double-blind, placebo-controlled trial. Liver Transpl 2000;6:376-379. https://doi.org/10.1016/S1527-6465(05)80022-X
  14. Urbach DR, Rotstein OD. Typhlitis. Can J Surg 1999;42: 415-419.
  15. Merine DS, Fishman EK, Jones B, Nussbaum AR, Simmons T. Right lower quadrant pain in the immunocompromised patient: CT findings in 10 cases. AJR Am J Roentgenol 1987; 149:1177-1179. https://doi.org/10.2214/ajr.149.6.1177
  16. West M, Pirenne J, Chavers B, et al. Clostridium difficile colitis after kidney and kidney-pancreas transplantation. Clin Transplant 1999;13:318-323. https://doi.org/10.1034/j.1399-0012.1999.130407.x
  17. Lee JK, Cho JY, Kim YS, et al. Comparative value of sigmoidoscopy and stool cytotoxin-A assay for diagnosis of pseudomembranous colitis. Intest Res 2005;3:61-67.
  18. Steger AC, Timmoney AS, Griffen S, Salem RR, Williams G. The influence of immunosuppression on peptic ulceration following renal transplantation and the role of endoscopy. Nephrol Dial Transplant 1990;5:289-292. https://doi.org/10.1093/ndt/5.4.289
  19. Skala I, Mareckova O, Vitko S, Matl I, Lacha J. Prophylaxis of acute gastroduodenal bleeding after renal transplantation. Transpl Int 1997;10:375-378. https://doi.org/10.1111/j.1432-2277.1997.tb00932.x
  20. Yang CW, Lee SH, Kim YS, et al. Prevention of posttransplant peptic ulcer by misoprostol. Nephron 1996;74:131-135. https://doi.org/10.1159/000189292
  21. Troppmann C, Papalois BE, Chiou A, et al. Incidence, complications, treatment, and outcome of ulcers of the upper GI tract after renal transplantation during the cyclosporine era. J Am Coll Surg 1995;180:433-443.
  22. Ferrara JL, Deeg HJ. Graft-versus-host disease. N Engl J Med 1991;324:667-674. https://doi.org/10.1056/NEJM199103073241005
  23. Welch DC, Wirth PS, Goldenring JR, Ness E, Jagasia M, Washington K. Gastric graft-versus-host disease revisited: does proton pump inhibitor therapy affect endoscopic gastric biopsy interpretation? Am J Surg Pathol 2006;30:444-449. https://doi.org/10.1097/00000478-200604000-00003
  24. Appleton AL, Sviland L, Pearson AD, Green MA, Eastham EJ, Malcolm AJ. The need for endoscopic biopsy in the diagnosis of upper gastrointestinal graft-versus-host disease. J Pediatr Gastroenterol Nutr 1993;16:183-185. https://doi.org/10.1097/00005176-199302000-00015
  25. Iqbal N, Salzman D, Lazenby AJ, Wilcox CM. Diagnosis of gastrointestinal graft-versus-host disease. Am J Gastroenterol 2000;95:3034-3038. https://doi.org/10.1111/j.1572-0241.2000.03250.x
  26. Schulenburg A, Kalhs P, Rabitsch W. Recommendations for diagnosis of acute gastrointestinal graft-versus-host disease in the small intestine. Transplantation 2005;79:1767.
  27. Xu CF, Zhu LX, Xu XM, Chen WC, Wu DP. Endoscopic diagnosis of gastrointestinal graft-versus-host disease. World J Gastroenterol 2008;14:2262-2267. https://doi.org/10.3748/wjg.14.2262
  28. Oomori S, Takagi S, Kikuchi T, et al. Significance of colonoscopy in patients with intestinal graft-versus-host disease after hematopoietic stem cell transplantation. Endoscopy 2005;37:346-350. https://doi.org/10.1055/s-2005-861049
  29. Cheung DY, Kim JI, Kim SS, et al. Endoscopic evaluation in gastrointestinal graft-versus-host disease: comparisons with histological findings. Dig Dis Sci 2008;53:2947-2954. https://doi.org/10.1007/s10620-008-0262-6
  30. Cox GJ, Matsui SM, Lo RS, et al. Etiology and outcome of diarrhea after marrow transplantation: a prospective study. Gastroenterology 1994;107:1398-1407. https://doi.org/10.1016/0016-5085(94)90542-8
  31. Roy J, Snover D, Weisdorf S, Mulvahill A, Filipovich A, Weisdorf D. Simultaneous upper and lower endoscopic biopsy in the diagnosis of intestinal graft-versus-host disease. Transplantation 1991;51:642-646. https://doi.org/10.1097/00007890-199103000-00019
  32. Thompson B, Salzman D, Steinhauer J, Lazenby AJ, Wilcox CM. Prospective endoscopic evaluation for gastrointestinal graft-versus-host disease: determination of the best diagnostic approach. Bone Marrow Transplant 2006;38:371-376. https://doi.org/10.1038/sj.bmt.1705453
  33. Cruz-Correa M, Poonawala A, Abraham SC, et al. Endoscopic findings predict the histologic diagnosis in gastrointestinal graft-versus-host disease. Endoscopy 2002;34:808-813. https://doi.org/10.1055/s-2002-34257
  34. Nishida T, Hamaguchi M, Hirabayashi N, et al. Intestinal thrombotic microangiopathy after allogeneic bone marrow trasplanatation: a clinical imitator of acute enteric graft-versushost disease. Bone Marrow Transplant 2004;33:1143-1150. https://doi.org/10.1038/sj.bmt.1704512
  35. Narimatsu H, Kami M, Hara S, et al. Intestinal thrombotic microangiopathy following reduced-intensity umbilical cord blood transplantation. Bone Marrow Transplant 2005;36: 517-523. https://doi.org/10.1038/sj.bmt.1705099
  36. Loren AW, Tsai DE. Post-transplant lymphoproliferative disorder. Clin Chest Med 2005;26:631-645. https://doi.org/10.1016/j.ccm.2005.06.014
  37. Cohen JI. Epstein-Barr virus infection. N Engl J Med 2000;343:481-492. https://doi.org/10.1056/NEJM200008173430707
  38. Taylor AL, Marcus R, Bradley JA. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit Rev Oncol Hematol 2005;56:155-167. https://doi.org/10.1016/j.critrevonc.2005.03.015
  39. Cockfield SM. Identifying the patient at risk for posttransplant lymphoproliferative disorder. Transpl Infect Dis 2001;3:70-78. https://doi.org/10.1034/j.1399-3062.2001.003002070.x
  40. Nalesnik MA. Posttransplantation lymphoproliferative disorders (PTLD): current perspectives. Semin Thorac Cardiovasc Surg 1996;8:139-148.
  41. Lones MA, Kirov I, Said JW, Shintaku IP, Neudorf S. Posttransplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient. Bone Marrow Transplant 2000;26:1021-1024. https://doi.org/10.1038/sj.bmt.1702593
  42. Allen U, Hebert D, Moore D, Dror Y, Wasfy S; Canadian PTLD Survey Group--1998. Epstein-Barr virus-related posttransplant lymphoproliferative disease in solid organ transplant recipients, 1988-97: a Canadian multi-centre experience. Pediatr Transplant 2001;5:198-203. https://doi.org/10.1034/j.1399-3046.2001.00059.x
  43. Lim GY, Newman B, Kurland G, Webber SA. Post transplantation lymphoproliferative disorder: manifestations in pediatric thoracic organ recipients. Radiology 2002;222:699-708. https://doi.org/10.1148/radiol.2223010456
  44. Tsai DE, Hardy CL, Tomaszewski JE, et al. Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients. Transplantation 2001;71:1076-1088. https://doi.org/10.1097/00007890-200104270-00012
  45. Harris NL, Ferry JA, Swerdlow SH. Posttransplant lymphoproliferative disorders: summary of Society for Hematopathology Workshop. Semin Diagn Pathol 1997;14:8-14.