Small Bowel Amyloidosis

  • Raghav Bansal
  • Umer Syed
  • Jacob Walfish
  • Joshua Aron
  • Aaron Walfish
Small Intestine (D Sachar, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Small Intestine

Abstract

Purpose of Review

The goal of this paper is to review the literature on small bowel amyloidosis. Our review focuses on the underlying etiology, histopathology, clinical features, endoscopic and radiologic findings, and the mainstay of management.

Recent Findings

The latest research shows changing epidemiological trends of different types of amyloidosis. It also reveals a better understanding of its pathophysiology and shows improvement in treatment outcomes.

Summary

Amyloidosis is a group of diseases of multiple etiologies and clinical presentations. It is characterized by pathological deposition of insoluble fibrillar proteins within various organs leading to disruption of their structure and function. The classification of amyloidosis includes primary, secondary, dialysis-related, senile, and hereditary. Amyloidosis can be systemic or localized. The incidence of AA amyloidosis is declining in frequency. If the gastrointestinal (GI) tract is involved, the small intestine is the most commonly affected site. Overall, outcomes among patients with newly diagnosed amyloidosis have improved. This article focuses on small bowel amyloidosis.

Keywords

Small bowel Amyloidosis Gastrointestinal 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349(6):583–96.  https://doi.org/10.1056/NEJMra023144.CrossRefPubMedGoogle Scholar
  2. 2.
    Sattianayagam PT, Hawkins PN, Gillmore JD. Systemic amyloidosis and the gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 2009;6(10):608–17.  https://doi.org/10.1038/nrgastro.2009.147.CrossRefPubMedGoogle Scholar
  3. 3.
    Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJ, et al. Nomenclature 2014: amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid. 2014;21(4):221–4.  https://doi.org/10.3109/13506129.2014.964858.CrossRefPubMedGoogle Scholar
  4. 4.
    • Cowan AJ, Skinner M, Seldin DC, Berk JL, Lichtenstein DR, O'Hara CJ, et al. Amyloidosis of the gastrointestinal tract: a 13-year, single-center, referral experience. Haematologica. 2013;98(1):141–6.  https://doi.org/10.3324/haematol.2012.068155. This retrospective study details the clinical characteristics, treatment regimens, and survival rates of amyloidosis involving the gastrointestinal tract. CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    • Freudenthaler S, Hegenbart U, Schonland S, Behrens HM, Kruger S, Rocken C. Amyloid in biopsies of the gastrointestinal tract—a retrospective observational study on 542 patients. Virchows Arch. 2016;468(5):569–77. This study is the largest series investigating the histopathological and demographic characteristics of amyloidosis in gastrointestinal biopsies.  https://doi.org/10.1007/s00428-016-1916-y.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    • Lane T, Pinney JH, Gilbertson JA, Hutt DF, Rowczenio DM, Mahmood S, et al. Changing epidemiology of AA amyloidosis: clinical observations over 25 years at a single national referral centre. Amyloid. 2017;24(3):162–6. This large single center retrospective study investigates the changing epidemiology of patients diagnosed with AA amyloidosis over a 25-year period.  https://doi.org/10.1080/13506129.2017.1342235.CrossRefPubMedGoogle Scholar
  7. 7.
    • Tosca Cuquerella J, Bosca-Watts MM, Anton Ausejo R, Tejedor Alonso S, Mora De Miguel F, Minguez Perez M. Amyloidosis in inflammatory bowel disease: a systematic review of epidemiology, clinical features, and treatment. J Crohns Colitis. 2016;10(10):1245–53.  https://doi.org/10.1093/ecco-jcc/jjw080. This is an observational study and a systematic review of the prevalence of amyloidosis in IBD patients. CrossRefPubMedGoogle Scholar
  8. 8.
    Sharma P, Aguilar R, Siddiqui OA, Nader MA. Secondary systemic amyloidosis in inflammatory bowel disease: a nationwide analysis. Ann Gastroenterol. 2017;30(5):504–11.  https://doi.org/10.20524/aog.2017.0168.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Werther JL, Schapira A, Rubinstein O, Janowitz HD. Amyloidosis in regional enteritis. A report of five cases. Am J Med. 1960;29(3):416–23.  https://doi.org/10.1016/0002-9343(60)90037-1.CrossRefPubMedGoogle Scholar
  10. 10.
    • Greenstein AJ, Sachar DB, Panday AK, Dikman SH, Meyers S, Heimann T, et al. Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients. Medicine (Baltimore). 1992;71(5):261–70. This landmark single center study is the largest case series of patients with secondary amyloidosis from underlying inflammatory bowel disease.  https://doi.org/10.1097/00005792-199209000-00001.CrossRefGoogle Scholar
  11. 11.
    Menke DM, Kyle RA, Fleming CR, Wolfe JT 3rd, Kurtin PJ, Oldenburg WA. Symptomatic gastric amyloidosis in patients with primary systemic amyloidosis. Mayo Clin Proc. 1993;68(8):763–7.  https://doi.org/10.1016/S0025-6196(12)60634-X.CrossRefPubMedGoogle Scholar
  12. 12.
    • Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med. 2007;356(23):2361–71. This is a comprehensive single center study on the long-term course of 374 patients with AA amyloidosis.  https://doi.org/10.1056/NEJMoa070265.CrossRefPubMedGoogle Scholar
  13. 13.
    Gillmore JD, Wechalekar A, Bird J, Cavenagh J, Hawkins S, Kazmi M, et al. BCSH committee guidelines on the diagnosis and investigation of AL amyloidosis. Br J Haematol. 2015;168(2):207–18.  https://doi.org/10.1111/bjh.13156.CrossRefPubMedGoogle Scholar
  14. 14.
    Saindane AM, Losada M, Macari M. Focal amyloidoma of the small bowel mimicking adenocarcinoma on CT. AJR Am J Roentgenol. 2005;185(5):1187–9.  https://doi.org/10.2214/AJR.04.1134.CrossRefPubMedGoogle Scholar
  15. 15.
    • Katoh N, Matsuda M, Ikeda S. Clinical, endoscopic, and histopathological features of localized immunoglobulin light chain (AL) amyloidosis in the gastrointestinal tract. Amyloid. 2015;22(4):254–6.  https://doi.org/10.3109/13506129.2015.1075972. This study focuses on the endoscopic and histological findings in patients with localized AL amyloidosis of the gastrointestinal tract. CrossRefPubMedGoogle Scholar
  16. 16.
    • Mahmood S, Bridoux F, Venner CP, Sachchithanantham S, Gilbertson JA, Rowczenio D, et al. Natural history and outcomes in localized immunoglobulin light-chain amyloidosis: a long-term observational study. Lancet Haematol. 2015;2(6):e241–50.  https://doi.org/10.1016/S2352-3026(15)00068-X. This large retrospective study reports the clinical features and long-term outcomes in patients with localized amyloidosis affecting the gastrointestinal tract. CrossRefPubMedGoogle Scholar
  17. 17.
    Tada S, Iida M, Yao T, Kawakubo K, Yao T, Okada M, et al. Endoscopic features in amyloidosis of the small intestine: clinical and morphologic differences between chemical types of amyloid protein. Gastrointest Endosc. 1994;40(1):45–50.  https://doi.org/10.1016/S0016-5107(94)70008-7.CrossRefPubMedGoogle Scholar
  18. 18.
    • Iida T, Yamano H, Nakase H Systemic amyloidosis with gastrointestinal involvement: diagnosis from endoscopic and histological views. J Gastroenterol Hepatol 2017.  https://doi.org/10.1111/jgh.13996. This recent literature review concentrates on the endoscopic and histological findings in patients with systemic amyloidosis with GI involvement.
  19. 19.
    Jimenez RE, Price DA, Pinkus GS, Owen WF Jr, Lazarus JM, Kay J, et al. Development of gastrointestinal beta2microglobulin amyloidosis correlates with time on dialysis. Am J Surg Pathol. 1998;22(6):729–35.  https://doi.org/10.1097/00000478-199806000-00010.CrossRefPubMedGoogle Scholar
  20. 20.
    Yoshimatsu S, Ando Y, Terazaki H, Sakashita N, Tada S, Yamashita T, et al. Endoscopic and pathological manifestations of the gastrointestinal tract in familial amyloidotic polyneuropathy type I (Met30). J Intern Med. 1998;243(1):65–72.  https://doi.org/10.1046/j.1365-2796.1998.00247.x.CrossRefPubMedGoogle Scholar
  21. 21.
    Tada S, Iida M, Iwashita A, Matsui T, Fuchigami T, Yamamoto T, et al. Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis. Gastrointest Endosc. 1990;36(1):10–4.  https://doi.org/10.1016/S0016-5107(90)70913-3.CrossRefPubMedGoogle Scholar
  22. 22.
    • Alcalde-Vargas A, Leo-Carnerero E, Rojas-Mercedes N, Trigo-Salado C, Herrera-Justiniano JM, Márquez-Galán JL. Correlation between location of amyloid deposits and endoscopic and clinical manifestations in symptomatic gastrointestinal amyloidosis. Rev Esp Enferm Dig. 2015;107(1):49–51. This retrospective study correlates the location of amyloid deposits and its endoscopic appearance. PubMedGoogle Scholar
  23. 23.
    Asakura K, Yanai S, Nakamura S, Kawaski K, Eizuka M, Ishida K, et al. Endoscopic findings of small-bowel lesions in familial amyloid polyneuropathy: a case report. Medicine (Baltimore). 2016;95(11):e2896.  https://doi.org/10.1097/MD.0000000000002896.CrossRefGoogle Scholar
  24. 24.
    James DG, Zuckerman GR, Sayuk GS, Wang HL, Prakash C. Clinical recognition of Al type amyloidosis of the luminal gastrointestinal tract. Clin Gastroenterol Hepatol. 2007;5(5):582–8.  https://doi.org/10.1016/j.cgh.2007.02.038.CrossRefPubMedGoogle Scholar
  25. 25.
    Wang Z, Huang C, Ji F. Primary amyloidosis mimicking Crohn’s disease: a case report. Int J Clin Exp Med. 2015;8(9):16137–9.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Lim AY, Lee JH, Jung KS, Gwag HB, Kim DH, Kim SJ, et al. Clinical features and outcomes of systemic amyloidosis with gastrointestinal involvement: a single-center experience. Korean J Intern Med. 2015;30(4):496–505.  https://doi.org/10.3904/kjim.2015.30.4.496.CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Mumford AD, O'Donnell J, Gillmore JD, Manning RA, Hawkins PN, Laffan M. Bleeding symptoms and coagulation abnormalities in 337 patients with AL-amyloidosis. Br J Haematol. 2000;110(2):454–60.  https://doi.org/10.1046/j.1365-2141.2000.02183.x.CrossRefPubMedGoogle Scholar
  28. 28.
    Sucker C, Hetzel GR, Grabensee B, Stockschlaeder M, Scharf RE. Amyloidosis and bleeding: pathophysiology, diagnosis, and therapy. Am J Kidney Dis. 2006;47(6):947–55.  https://doi.org/10.1053/j.ajkd.2006.03.036.CrossRefPubMedGoogle Scholar
  29. 29.
    Tada S, Iida M, Yao T, Kitamoto T, Yao T, Fujishima M. Intestinal pseudo-obstruction in patients with amyloidosis: clinicopathologic differences between chemical types of amyloid protein. Gut. 1993;34(10):1412–7.  https://doi.org/10.1136/gut.34.10.1412.CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Siau K, Elzubeir A, Cooper SC, Iqbal T. Amyloidosis: an unusual cause of upper gastrointestinal bleeding. BMJ Case Rep 2016.  https://doi.org/10.1136/bcr-2016-217653.
  31. 31.
    Pearson DC, Price LM, Urbanski S. Pneumatosis cystoides intestinalis: an unusual complication of systemic amyloidosis. J Clin Gastroenterol. 1996;22(1):74–6.  https://doi.org/10.1097/00004836-199601000-00022.CrossRefPubMedGoogle Scholar
  32. 32.
    Inayat F, Hurairah A. Duodenal amyloidosis masquerading as iron deficiency anemia. Cureus. 2016;8(8):e725.  https://doi.org/10.7759/cureus.725.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Hurlsone DP. Iron-deficiency anemia complicating AL amyloidosis with recurrent small bowel pseudo-obstruction and hindgut sparing. J Gastroenterol Hepatol. 2002;17(5):623–4.  https://doi.org/10.1046/j.1440-1746.2002.02719.x.CrossRefGoogle Scholar
  34. 34.
    Groisman G, Cohen HI. Small intestinal amyloidosis: a rare cause of diverticular disease. Case Reports in Pathol. 2014;2014:1–4.Google Scholar
  35. 35.
    Tian L, Tang A, Zhang X, Mei Z, Liu F, Li J, et al. Incomplete ileus and hemafecia as the presenting features of multi-organ involved primary systemic AL amyloidosis: a rare case report. BMC Gastroenterol. 2017;17(1):72.  https://doi.org/10.1186/s12876-017-0628-3.CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Nishimura N, Mizuno M, Miyake M, Matsueda K. Primary light chain amyloidosis featuring worm-like small bowel polyposis. Intern Med. 2017;56(18):2529–30.  https://doi.org/10.2169/internalmedicine.8812-17.CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Von Rosenvinge EC, Forman JS, Goldberg EM. Electronic clinical challenges and images in GI: image 1. Amyloidomas of the small bowel. Gastroenterology. 2008;135(3):e1–2.  https://doi.org/10.1053/j.gastro.2008.07.052.CrossRefGoogle Scholar
  38. 38.
    Choi JH, Ko BM, Kim C, Kim HK, Han JP, Hong SJ, et al. A case of localized amyloid light-chain amyloidosis in the small intestine. Intest Res. 2014;12(3):245–50.  https://doi.org/10.5217/ir.2014.12.3.245.CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Michael H, Brandt LJ, Tanaka KE, Berkowitz D, Cardillo M, Weidenheim K. Congo-red negative colonic amyloid with scalloping of the valvulae conniventes. Gastrointest Endosc. 2001;53(6):653–5.  https://doi.org/10.1067/mge.2001.113581.CrossRefPubMedGoogle Scholar
  40. 40.
    Kim SH, Han JK, Lee KH, Won HJ, Kim KW, Kim JS, et al. Abdominal amyloidosis: spectrum of radiological findings. Clin Radiol. 2003;58(8):610–20.  https://doi.org/10.1016/S0009-9260(03)00142-9.CrossRefPubMedGoogle Scholar
  41. 41.
    Araoz PA, Batts KP, MacCarty RL. Amyloidosis of the alimentary canal: radiologic-pathologic correlation of CT findings. Abdom Imaging. 2000;25(1):38–44.  https://doi.org/10.1007/s002619910007.CrossRefPubMedGoogle Scholar
  42. 42.
    Georgiades CS, Neyman EG, Barish MA, Fishman EK. Amyloidosis: review and CT manifestations. Radiographics. 2004;24(2):405–16.  https://doi.org/10.1148/rg.242035114.CrossRefPubMedGoogle Scholar
  43. 43.
    Schroeder FM, Miller FJ Jr, Nelson JA, Rankin RS. Gastrointestinal angiographic findings in systemic amyloidosis. AJR Am J Roentgenol. 1978;131(1):143–6.  https://doi.org/10.2214/ajr.131.1.143.CrossRefPubMedGoogle Scholar
  44. 44.
    Real de Asúa D, Costa R, Galván JM, Filigheddu MT, Trujillo D, Cadiñanos J. Systemic AA amyloidosis: epidemiology, diagnosis, and management. Clin Epidemiol. 2014;6:369–77.  https://doi.org/10.2147/CLEP.S39981. eCollection 2014CrossRefPubMedCentralPubMedGoogle Scholar
  45. 45.
    Yilmaz M, Unsal A, Sokmen M, Harmankaya O, Alkim C, Kabukcuoglu F, et al. Duodenal biopsy for diagnosis of renal involvement in amyloidosis. Clin Nephrol. 2012;77(2):114–8.  https://doi.org/10.5414/CN107139.CrossRefPubMedGoogle Scholar
  46. 46.
    • Sanchorawala V, Sun F, Quillen K, Sloan JM, Berk JL, Seldin DC. Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation: 20-year experience. Blood. 2015;126(20):2345–7.  https://doi.org/10.1182/blood-2015-08-662726. This study looks at remission, durability, and long-term results in AL amyloidosis patients treated with HDM/SCT. CrossRefPubMedGoogle Scholar
  47. 47.
    • Muchtar E, Gertz MA, Kumar SK, Lacy MQ, Dingli D, Buadi FK, et al. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood. 2017;129(15):2111–9.  https://doi.org/10.1182/blood-2016-11-751628. This study is a large single center retrospective analysis outlining trends in patient management and patient outcomes in patients newly diagnosed AL amyloidosis. CrossRefPubMedGoogle Scholar
  48. 48.
    • Okuda Y, Ohnishi M, Matoba K, Jouyama K, Yamada A, Sawada N, et al. Comparison of the clinical utility of tocilizumab and anti-TNF therapy in AA amyloidosis complicating rheumatic diseases. Mod Rheumatol. 2014;24(1):137–43.  https://doi.org/10.3109/14397595.2013.854048. This study is a retrospective comparative study in patients with secondary amyloidosis due to rheumatic diseases receiving anti cytokine therapy. CrossRefPubMedGoogle Scholar
  49. 49.
    Courties A, Grateau G, Philippe P, Flipo RM, Astudillo L, Aubry-Rozier B, et al. AA amyloidosis treated with tocilizumab: case series and updated literature review. Amyloid. 2015;22(2):84–92.  https://doi.org/10.3109/13506129.2014.1002031.CrossRefPubMedGoogle Scholar
  50. 50.
    • Esatoglu SN, Hatemi G, Ugurlu S, Gokturk A, Tascilar K, Ozdogan H. Long-term follow-up of secondary amyloidosis patients treated with tumor necrosis factor inhibitor therapy: a STROBE-compliant observational study. Medicine (Baltimore). 2017;96(34):e7859.  https://doi.org/10.1097/MD.0000000000007859. This is a single center long-term observational study reporting efficacy, safety, and outcomes of anti-TNF therapy in patients with secondary amyloidosis diverse underlying etiologies. CrossRefGoogle Scholar
  51. 51.
    Okumura K, Yamashita T, Masuda T, Misumi Y, Ueda A, Ueda M, et al. Long-term outcome of patients with hereditary transthyretin V30M amyloidosis with polyneuropathy after liver transplantation. Amyloid. 2016;23(1):39–45.  https://doi.org/10.3109/13506129.2015.1123149.CrossRefPubMedGoogle Scholar
  52. 52.
    • Banerjee D, Roeker LE, Grogan M, Swiecicki P, Poterucha J, Heimbach J, et al. Outcomes of patients with familial transthyretin amyloidosis after liver transplantation. Prog Transplant. 2017;27(3):246–50.  https://doi.org/10.1177/1526924817715463. This study looks at transplant outcomes in patients with familial transthyretin amyloidosis. CrossRefPubMedGoogle Scholar
  53. 53.
    Reddy AB, Wright RA, Wheeler GE, Nazer H. Nonobstructive gastroparesis in amyloidosis improved with metoclopramide. Arch Intern Med. 1983;143(2):247–8.  https://doi.org/10.1001/archinte.1983.00350020069014.CrossRefPubMedGoogle Scholar
  54. 54.
    Gil R, Debiais F, Lefevre JP, Pouget-Abadie JF, Marechaud R, Simmat G. Boissonnot amyloidosis with gastroparesis. Improvement with domperidone. Presse Médicale Presse Med. 1984;13(9):564.Google Scholar
  55. 55.
    Fushimi T, Takahashi Y, Kashima Y, Fukushima K, Ishii W, Kaneko K, et al. Severe protein losing enteropathy with intractable diarrhea due to systemic AA amyloidosis, successfully treated with corticosteroid and octreotide. Amyloid. 2005;12(1):48–53.  https://doi.org/10.1080/13506120500032725.CrossRefPubMedGoogle Scholar
  56. 56.
    Poullos PD, Stollman N. Gastrointestinal amyloidosis: approach to treatment. Curr Treat Options Gastroenterol. 2003;6(1):17–25.  https://doi.org/10.1007/s11938-003-0029-2.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Raghav Bansal
    • 1
  • Umer Syed
    • 1
  • Jacob Walfish
    • 2
  • Joshua Aron
    • 1
  • Aaron Walfish
    • 1
  1. 1.Division of Gastroenterology and Hepatology, Elmhurst Hospital CenterIcahn School of Medicine at Mount SinaiElmhurstUSA
  2. 2.Department of Medicine, NYU School of MedicineNYU Langone HealthBrooklynUSA

Personalised recommendations