Gastrointestinal amyloidosis: Clinical manifestations, diagnosis, and management
- Michael Camilleri, MD
Michael Camilleri, MD
- Professor of Medicine, Pharmacology, and Physiology
- Mayo Clinic College of Medicine
Amyloidosis is a generic term that refers to the extracellular tissue deposition of fibrils composed of low molecular weight subunits (5 to 25 kD) of a variety of serum proteins, many of which circulate as constituents of plasma . The subunit proteins forming amyloid deposits are derived from soluble precursors which have undergone conformational changes that lead to the adoption of a predominantly antiparallel beta-pleated sheet configuration. These fibrils can be identified on biopsy specimens both by their characteristic appearance on electron microscopy and by their ability to bind Congo red (leading to green birefringence under polarized light) and thioflavine T (producing an intense yellow-green fluorescence). These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition.
This topic will review the clinical manifestations, diagnosis, and management of gastrointestinal amyloidosis. A general overview of the genetics, pathogenesis, clinical manifestations, diagnosis, and treatment of the different amyloid disorders is discussed in detail, separately. (See "Genetic factors in the amyloid diseases" and "Overview of amyloidosis" and "Renal amyloidosis" and "Clinical manifestations and diagnosis of amyloid cardiomyopathy" and "Treatment of amyloid cardiomyopathy" and "Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)" and "Dialysis-related amyloidosis" and "Musculoskeletal manifestations of amyloidosis".)
TYPES OF AMYLOID
There are several major forms of amyloidosis. Nomenclature for amyloid subunit proteins includes the letter "A," followed by the abbreviation of the name of the precursor protein . (See "Overview of amyloidosis", section on 'Types of amyloidosis'.)
The most common causes of systemic amyloid deposition are as follows:
●AL amyloid, caused by a plasma cell dyscrasia, is due to deposition of protein derived from immunoglobulin light chain fragments.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Nordling E, Abraham-Nordling M. Colonic amyloidosis, computational analysis of the major amyloidogenic species, Serum Amyloid A. Comput Biol Chem 2012; 39:29.
- Glenner GG. Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts). N Engl J Med 1980; 302:1283.
- Cowan AJ, Skinner M, Seldin DC, et al. Amyloidosis of the gastrointestinal tract: a 13-year, single-center, referral experience. Haematologica 2013; 98:141.
- Freudenthaler S, Hegenbart U, Schönland S, et al. Amyloid in biopsies of the gastrointestinal tract-a retrospective observational study on 542 patients. Virchows Arch 2016; 468:569.
- Okuda Y, Takasugi K, Oyama T, et al. [Amyloidosis in rheumatoid arthritis--clinical study of 124 histologically proven cases]. Ryumachi 1994; 34:939.
- Menke DM, Kyle RA, Fleming CR, et al. Symptomatic gastric amyloidosis in patients with primary systemic amyloidosis. Mayo Clin Proc 1993; 68:763.
- LEVINE RA. Amyloid disease of the liver. Correlation of clinical, functional and morphologic features in forty-seven patients. Am J Med 1962; 33:349.
- Iwata T, Hoshii Y, Kawano H, et al. Hepatic amyloidosis in Japan: histological and morphometric analysis based on amyloid proteins. Hum Pathol 1995; 26:1148.
- Jimenez RE, Price DA, Pinkus GS, et al. Development of gastrointestinal beta2-microglobulin amyloidosis correlates with time on dialysis. Am J Surg Pathol 1998; 22:729.
- Ueda M, Horibata Y, Shono M, et al. Clinicopathological features of senile systemic amyloidosis: an ante- and post-mortem study. Mod Pathol 2011; 24:1533.
- Tada S, Iida M, Iwashita A, et al. Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis. Gastrointest Endosc 1990; 36:10.
- Tada S, Iida M, Yao T, et al. Endoscopic features in amyloidosis of the small intestine: clinical and morphologic differences between chemical types of amyloid protein. Gastrointest Endosc 1994; 40:45.
- Battle WM, Rubin MR, Cohen S, Snape WJ Jr. Gastrointestinal-motility dysfunction in amyloidosis. N Engl J Med 1979; 301:24.
- Camilleri M, Malagelada JR, Stanghellini V, et al. Gastrointestinal motility disturbances in patients with orthostatic hypotension. Gastroenterology 1985; 88:1852.
- Malagelada JR, Camilleri M, Stanghellini V. Manometric Diagnosis of Gastrointestinal Motility Disorders, Thieme Medical Publishers, New York 1986.
- Tada S, Iida M, Yao T, et al. Intestinal pseudo-obstruction in patients with amyloidosis: clinicopathologic differences between chemical types of amyloid protein. Gut 1993; 34:1412.
- Tada S, Iida M, Yao T, et al. Gastrointestinal amyloidosis: radiologic features by chemical types. Radiology 1994; 190:37.
- Ebert EC, Nagar M. Gastrointestinal manifestations of amyloidosis. Am J Gastroenterol 2008; 103:776.
- Petre S, Shah IA, Gilani N. Review article: gastrointestinal amyloidosis - clinical features, diagnosis and therapy. Aliment Pharmacol Ther 2008; 27:1006.
- Reddy MB, Poppers DM, Uram-Tuculescu C. Recurrent obscure gastrointestinal bleeding in a patient with gastric amyloid. Clin Gastroenterol Hepatol 2009; 7:e1.
- Kim SH, Kang EJ, Park JW, et al. Gastrointestinal amyloidosis presenting with multiple episodes of gastrointestinal bleeding. Cardiovasc Intervent Radiol 2009; 32:577.
- Baldewijns M, Ectors N, Verbeeck G, et al. Intermittent subobstruction and cholestasis as complications of duodenal amyloid tumours. Gastroenterol Clin Biol 1995; 19:218.
- Hemmer PR, Topazian MD, Gertz MA, Abraham SC. Globular amyloid deposits isolated to the small bowel: a rare association with AL amyloidosis. Am J Surg Pathol 2007; 31:141.
- Brandt K, Cathcart ES, Cohen AS. A clinical analysis of the course and prognosis of forty-two patients with amyloidosis. Am J Med 1968; 44:955.
- Levy DJ, Franklin GO, Rosenthal WS. Gastrointestinal bleeding and amyloidosis. Am J Gastroenterol 1982; 77:422.
- Chang HS, Myung SJ, Yang SK, et al. Massive small bowel bleeding in a patient with amyloidosis. Gastrointest Endosc 2004; 59:126.
- James DG, Zuckerman GR, Sayuk GS, et al. Clinical recognition of Al type amyloidosis of the luminal gastrointestinal tract. Clin Gastroenterol Hepatol 2007; 5:582.
- Hayman SR, Lacy MQ, Kyle RA, Gertz MA. Primary systemic amyloidosis: a cause of malabsorption syndrome. Am J Med 2001; 111:535.
- Madsen LG, Gimsing P, Schiødt FV. Primary (AL) amyloidosis with gastrointestinal involvement. Scand J Gastroenterol 2009; 44:708.
- Suzuki C, Higaki S, Nishiaki M, et al. 99mTc-HSA-D scintigraphy in the diagnosis of protein-losing gastroenteropathy due to secondary amyloidosis. J Gastroenterol 1997; 32:78.
- Guirl MJ, Högenauer C, Santa Ana CA, et al. Rapid intestinal transit as a primary cause of severe chronic diarrhea in patients with amyloidosis. Am J Gastroenterol 2003; 98:2219.
- Yoshiki Y, Yamamoto G, Takazawa Y, et al. AL amyloidosis with severe gastrointestinal invasion and acute obstructive suppurative cholangitis. Ann Hematol 2012; 91:467.
- Jones J, VanRosendaal G, Cleary C, et al. Primary amyloidosis presenting as small bowel encapsulation. Can J Gastroenterol 2004; 18:169.
- Willson TD, Bird J, Azizi R, et al. Extraluminal amyloidoma of the pelvic cavity causing large bowel obstruction. Case Rep Gastroenterol 2011; 5:315.
- Gertz MA, Kyle RA. Hepatic amyloidosis (primary [AL], immunoglobulin light chain): the natural history in 80 patients. Am J Med 1988; 85:73.
- Kyle RA, Bayrd ED. Amyloidosis: review of 236 cases. Medicine (Baltimore) 1975; 54:271.
- Park MA, Mueller PS, Kyle RA, et al. Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. Medicine (Baltimore) 2003; 82:291.
- Buck FS, Koss MN. Hepatic amyloidosis: morphologic differences between systemic AL and AA types. Hum Pathol 1991; 22:904.
- Chopra S, Rubinow A, Koff RS, Cohen AS. Hepatic amyloidosis. A histopathologic analysis of primary (AL) and secondary (AA) forms. Am J Pathol 1984; 115:186.
- Looi LM, Sumithran E. Morphologic differences in the pattern of liver infiltration between systemic AL and AA amyloidosis. Hum Pathol 1988; 19:732.
- Kim SH, Han JK, Lee KH, et al. Abdominal amyloidosis: spectrum of radiological findings. Clin Radiol 2003; 58:610.
- Araoz PA, Batts KP, MacCarty RL. Amyloidosis of the alimentary canal: radiologic-pathologic correlation of CT findings. Abdom Imaging 2000; 25:38.
- Bighi S, Trevisani L, Lupi L, et al. Amyloidosis of the gastric stump: radiographic and CT findings. Gastrointest Radiol 1990; 15:197.
- Kahi CJ, Vakili S, Liepnieks JJ, Benson M. Amyloidoma of the esophagus. Am J Gastroenterol 2007; 102:910.
- Saindane AM, Losada M, Macari M. Focal amyloidoma of the small bowel mimicking adenocarcinoma on CT. AJR Am J Roentgenol 2005; 185:1187.
- Peny MO, Debongnie JC, Haot J, Van Gossum A. Localized amyloid tumor in small bowel. Dig Dis Sci 2000; 45:1850.
- Swerdlow SH, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Fushimi T, Takahashi Y, Kashima Y, et al. Severe protein losing enteropathy with intractable diarrhea due to systemic AA amyloidosis, successfully treated with corticosteroid and octreotide. Amyloid 2005; 12:48.
- Shin JK, Jung YH, Bae MN, et al. Successful treatment of protein-losing enteropathy due to AA amyloidosis with octreotide in a patient with rheumatoid arthritis. Mod Rheumatol 2013; 23:406.
- Okuda Y, Takasugi K. Successful use of a humanized anti-interleukin-6 receptor antibody, tocilizumab, to treat amyloid A amyloidosis complicating juvenile idiopathic arthritis. Arthritis Rheum 2006; 54:2997.
- Sato H, Sakai T, Sugaya T, et al. Tocilizumab dramatically ameliorated life-threatening diarrhea due to secondary amyloidosis associated with rheumatoid arthritis. Clin Rheumatol 2009; 28:1113.
- Dainaka K, Isozaki Y, Kunieda K, et al. [A case of gastrointestinal amyloidosis and hypoproteinemia improved by tocilizumab]. Nihon Shokakibyo Gakkai Zasshi 2016; 113:245.
- Inoue D, Arima H, Kawanami C, et al. Excellent therapeutic effect of tocilizumab on intestinal amyloid a deposition secondary to active rheumatoid arthritis. Clin Rheumatol 2010; 29:1195.
- Kuroda T, Otaki Y, Sato H, et al. A case of AA amyloidosis associated with rheumatoid arthritis effectively treated with Infliximab. Rheumatol Int 2008; 28:1155.
- Wixner J, Mundayat R, Karayal ON, et al. THAOS: gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease. Orphanet J Rare Dis 2014; 9:61.
- Dhodapkar MV, Jagannath S, Vesole D, et al. Treatment of AL-amyloidosis with dexamethasone plus alpha interferon. Leuk Lymphoma 1997; 27:351.
- Gertz MA, Lacy MQ, Dispenzieri A. Myeloablative chemotherapy with stem cell rescue for the treatment of primary systemic amyloidosis: a status report. Bone Marrow Transplant 2000; 25:465.
- Gertz MA, Lacy MQ, Dispenzieri A, et al. Transplantation for amyloidosis. Curr Opin Oncol 2007; 19:136.
- Suhr OB, Holmgren G, Steen L, et al. Liver transplantation in familial amyloidotic polyneuropathy. Follow-up of the first 20 Swedish patients. Transplantation 1995; 60:933.
- Mejhert M, Hast R, Sandstedt B, Janczewska I. Ten-year follow-up after autologous stem cell transplantation of a patient with immunoglobulin light-chain (AL) amyloidosis with deposits in the heart, liver and gastrointestinal tract. BMJ Case Rep 2011; 2011.
- Landau H, Hassoun H, Rosenzweig MA, et al. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia 2013; 27:823.
- Gottenberg JE, Merle-Vincent F, Bentaberry F, et al. Anti-tumor necrosis factor alpha therapy in fifteen patients with AA amyloidosis secondary to inflammatory arthritides: a followup report of tolerability and efficacy. Arthritis Rheum 2003; 48:2019.
- Levy M, Fryd CH, Eliakim M. Intrahepatic obstructive jaundice due to amyloidosis of the liver. A case report and review of the literature. Gastroenterology 1971; 61:234.
- TYPES OF AMYLOID
- CLINICAL MANIFESTATIONS
- Clinical presentation
- - Gastrointestinal tract amyloidosis
- - Hepatic amyloidosis
- Imaging findings
- DIFFERENTIAL DIAGNOSIS
- Symptomatic treatment
- Treatment of the underlying disorder
- SUMMARY AND RECOMMENDATIONS