UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Protein-losing gastroenteropathy

Authors
Vladan Milovic, MD, PhD
Richard J Grand, MD
Section Editor
J Thomas Lamont, MD
Deputy Editor
Shilpa Grover, MD, MPH

INTRODUCTION

Protein-losing gastroenteropathies are characterized by an excessive loss of serum proteins into the gastrointestinal tract, resulting in hypoproteinemia (detected as hypoalbuminemia), edema, and, in some cases, pleural and pericardial effusions. The diagnosis of protein-losing gastroenteropathy should be considered in patients with hypoproteinemia in whom other causes, such as malnutrition, heavy proteinuria, and impaired protein synthesis due to liver diseases have been excluded.

This topic will review the pathogenesis, clinical manifestations, diagnosis and treatment of protein-losing gastroenteropathy. Other causes of hypoalbuminemia are discussed elsewhere. (See "Clinical features and diagnosis of malabsorption", section on 'Protein malabsorption' and "Mechanisms of nutrient absorption and malabsorption", section on 'Protein absorption' and "Overview of heavy proteinuria and the nephrotic syndrome" and "Tests of the liver's biosynthetic capacity (eg, albumin, coagulation factors, prothrombin time)", section on 'Albumin'.)

PATHOGENESIS

The normal gastrointestinal tract does not contribute significantly to the catabolism of plasma proteins, accounting for only about 10 percent of the normal turnover of albumin and gamma globulin [1]. Once plasma proteins pass into the gastrointestinal tract, they are degraded rapidly to amino acids and reabsorbed into the portal circulation.

Protein-losing gastroenteropathies can be caused by a diverse group of disorders (table 1). The increase in intestinal leakage of plasma proteins occurs via one of two mechanisms:

Mucosal injury with or without erosions/ulcerations, as in inflammatory bowel disease (IBD) and celiac disease.

                   

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Mon Jun 03 00:00:00 GMT+00:00 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Schmidt PN, Blirup-Jensen S, Svendsen PJ, Wandall JH. Characterization and quantification of plasma proteins excreted in faeces from healthy humans. Scand J Clin Lab Invest 1995; 55:35.
  2. Acciuffi S, Ghosh S, Ferguson A. Strengths and limitations of the Crohn's disease activity index, revealed by an objective gut lavage test of gastrointestinal protein loss. Aliment Pharmacol Ther 1996; 10:321.
  3. Rybolt AH, Bennett RG, Laughon BE, et al. Protein-losing enteropathy associated with Clostridium difficile infection. Lancet 1989; 1:1353.
  4. Dansinger ML, Johnson S, Jansen PC, et al. Protein-losing enteropathy is associated with Clostridium difficile diarrhea but not with asymptomatic colonization: a prospective, case-control study. Clin Infect Dis 1996; 22:932.
  5. Stark ME, Batts KP, Alexander GL. Protein-losing enteropathy with collagenous colitis. Am J Gastroenterol 1992; 87:780.
  6. Ebert EC, Hagspiel KD. Gastrointestinal and hepatic manifestations of systemic lupus erythematosus. J Clin Gastroenterol 2011; 45:436.
  7. Molina JF, Brown RF, Gedalia A, Espinoza LR. Protein losing enteropathy as the initial manifestation of childhood systemic lupus erythematosus. J Rheumatol 1996; 23:1269.
  8. Jaeken J, Vanderschueren-Lodeweyckx M, Casaer P. Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG-deficiency, increased serum arylsulfatase A and increased CSF protein: a new syndrome. Pediatr Res 1980; 14:179.
  9. Hendriksz CJ, McClean P, Henderson MJ, et al. Successful treatment of carbohydrate deficient glycoprotein syndrome type 1b with oral mannose. Arch Dis Child 2001; 85:339.
  10. Kelly DG, Miller LJ, Malagelada JR, et al. Giant hypertrophic gastropathy (Ménétrier's disease): pharmacologic effects on protein leakage and mucosal ultrastructure. Gastroenterology 1982; 83:581.
  11. Sferra TJ, Pawel BR, Qualman SJ, Li BU. Ménétrier disease of childhood: role of cytomegalovirus and transforming growth factor alpha. J Pediatr 1996; 128:213.
  12. Bayerdörffer E, Ritter MM, Hatz R, et al. Healing of protein losing hypertrophic gastropathy by eradication of Helicobacter pylori--is Helicobacter pylori a pathogenic factor in Ménétrier's disease? Gut 1994; 35:701.
  13. Groisman GM, George J, Berman D, Harpaz N. Resolution of protein-losing hypertrophic lymphocytic gastritis with therapeutic eradication of Helicobacter pylori. Am J Gastroenterol 1994; 89:1548.
  14. Yamada M, Sumazaki R, Adachi H, et al. Resolution of protein-losing hypertrophic gastropathy by eradication of Helicobacter pylori. Eur J Pediatr 1997; 156:182.
  15. Farahat K, Hainaut P, Jamar F, et al. Lymphocytic gastritis: an unusual cause of hypoproteinaemia. J Intern Med 1993; 234:95.
  16. Wolber RA, Owen DA, Anderson FH, Freeman HJ. Lymphocytic gastritis and giant gastric folds associated with gastrointestinal protein loss. Mod Pathol 1991; 4:13.
  17. Ladas SD, Tassios PS, Malamou HC, et al. Omeprazole induces a long-term clinical remission of protein-losing gastropathy of Ménétrier's disease. Eur J Gastroenterol Hepatol 1997; 9:811.
  18. Yeaton P, Frierson HF Jr. Octreotide reduces enteral protein losses in Ménétrier's disease. Am J Gastroenterol 1993; 88:95.
  19. 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.
  20. Pratz KW, Dingli D, Smyrk TC, Lust JA. Intestinal lymphangiectasia with protein-losing enteropathy in Waldenstrom macroglobulinemia. Medicine (Baltimore) 2007; 86:210.
  21. Davidson NO. Intestinal lipid absorption. In: Textbook of Gastroenterology, Yamada T, Alpers DH, Kaplowitz N (Eds), JB Lippincott, Philadelphia 2003. p.413.
  22. Umar SB, DiBaise JK. Protein-losing enteropathy: case illustrations and clinical review. Am J Gastroenterol 2010; 105:43.
  23. Malek NP, Ocran K, Tietge UJ, et al. A case of the yellow nail syndrome associated with massive chylous ascites, pleural and pericardial effusions. Z Gastroenterol 1996; 34:763.
  24. Vardy PA, Lebenthal E, Shwachman H. Intestinal lymphagiectasia: a reappraisal. Pediatrics 1975; 55:842.
  25. Freeman HJ, Nimmo M. Intestinal lymphangiectasia in adults. World J Gastrointest Oncol 2011; 3:19.
  26. Abramowsky C, Hupertz V, Kilbridge P, Czinn S. Intestinal lymphangiectasia in children: a study of upper gastrointestinal endoscopic biopsies. Pediatr Pathol 1989; 9:289.
  27. Laor T, Hoffer FA, Burrows PE, Kozakewich HP. MR lymphangiography in infants, children, and young adults. AJR Am J Roentgenol 1998; 171:1111.
  28. Yueh TC, Pui MH, Zeng SQ. Intestinal lymphangiectasia: value of Tc-99m dextran lymphoscintigraphy. Clin Nucl Med 1997; 22:695.
  29. Bhatnagar A, Lahoti D, Singh AK, et al. Scintigraphic diagnosis of protein losing enteropathy using Tc-99m dextran. Clin Nucl Med 1995; 20:1070.
  30. JEFFRIES GH, CHAPMAN A, SLEISENGER MH. LOW-FAT DIET IN INTESTINAL LYMPHANGIECTASIA. ITS EFFECT ON ALBUMIN METABOLISM. N Engl J Med 1964; 270:761.
  31. Tift WL, Lloyd JK. Intestinal lymphangiectasia. Long-term results with MCT diet. Arch Dis Child 1975; 50:269.
  32. Mistilis SP, Skyring AP. Intestinal lymphangiectasia: Therapeutic effect of lymph venous anastomosis. Am J Med 1966; 40:634.
  33. Ballinger AB, Farthing MJ. Octreotide in the treatment of intestinal lymphangiectasia. Eur J Gastroenterol Hepatol 1998; 10:699.
  34. de Koning TJ, Dorland L, van Berge Henegouwen GP. Phosphomannose isomerase deficiency as a cause of congenital hepatic fibrosis and protein-losing enteropathy. J Hepatol 1999; 31:557.
  35. Dousset B, Legmann P, Soubrane O, et al. Protein-losing enteropathy secondary to hepatic venous outflow obstruction after liver transplantation. J Hepatol 1997; 27:206.
  36. Stanley AJ, Gilmour HM, Ghosh S, et al. Transjugular intrahepatic portosystemic shunt as a treatment for protein-losing enteropathy caused by portal hypertension. Gastroenterology 1996; 111:1679.
  37. DAVIDSON JD, WALDMANN TA, GOODMAN DS, GORDON RS Jr. Protein-losing gastroenteropathy in congestive heart-failure. Lancet 1961; 1:899.
  38. Meadows J, Jenkins K. Protein-losing enteropathy: integrating a new disease paradigm into recommendations for prevention and treatment. Cardiol Young 2011; 21:363.
  39. Müller C, Globits S, Glogar D, et al. Constrictive pericarditis without typical haemodynamic changes as a cause of oedema formation due to protein-losing enteropathy. Eur Heart J 1991; 12:1140.
  40. Wilkinson P, Pinto B, Senior JR. Reversible protein-losing enteropathy with intestinal lymphangiectasia secondary to chronic constrictive pericarditis. N Engl J Med 1965; 273:1178.
  41. Feldt RH, Driscoll DJ, Offord KP, et al. Protein-losing enteropathy after the Fontan operation. J Thorac Cardiovasc Surg 1996; 112:672.
  42. Ohuchi H, Yasuda K, Miyazaki A, et al. Haemodynamic characteristics before and after the onset of protein losing enteropathy in patients after the Fontan operation. Eur J Cardiothorac Surg 2013; 43:e49.
  43. Jacobs ML, Rychik J, Byrum CJ, Norwood WI Jr. Protein-losing enteropathy after Fontan operation: resolution after baffle fenestration. Ann Thorac Surg 1996; 61:206.
  44. Donnelly JP, Rosenthal A, Castle VP, Holmes RD. Reversal of protein-losing enteropathy with heparin therapy in three patients with univentricular hearts and Fontan palliation. J Pediatr 1997; 130:474.
  45. Masetti P, Marianeschi SM, Cipriani A, et al. Reversal of protein-losing enteropathy after ligation of systemic-pulmonary shunt. Ann Thorac Surg 1999; 67:235.
  46. Bernier JJ, Florent C, Desmazures C, et al. Diagnosis of protein-losing enteropathy by gastrointestinal clearance of alpha1-antitrypsin. Lancet 1978; 2:763.
  47. Florent C, L'Hirondel C, Desmazures C, et al. Intestinal clearance of alpha 1-antitrypsin. A sensitive method for the detection of protein-losing enteropathy. Gastroenterology 1981; 81:777.
  48. Strygler B, Nicar MJ, Santangelo WC, et al. Alpha 1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders. Gastroenterology 1990; 99:1380.
  49. Florent C, Vidon N, Flourié B, et al. Gastric clearance of alpha-1-antitrypsin under cimetidine perfusion. New test to detect protein-losing gastropathy? Dig Dis Sci 1986; 31:12.
  50. Heimburger DC, Weinsier RL. Therapeutic diets. In: Handbook of Clinical Nutrition, 3rd ed, Heimburger DC, Weinsier RL (Eds), Mosby, St. Louis 1997. p.235.
  51. Alpers DH, Stenson WF, Bier DM. Nutritional planning for patients with protein and calorie deficiency. In: Manual of Nutritional Therapeutics, 3rd ed, Alpers DH, Stenson WF, Bier DM (Eds), Little, Brown, and Co., Boston, MA 1995. p.265.
  52. Kim SJ, Park IS, Song JY, et al. Reversal of protein-losing enteropathy with calcium replacement in a patient after Fontan operation. Ann Thorac Surg 2004; 77:1456.
  53. Thacker D, Patel A, Dodds K, et al. Use of oral budesonide in the management of protein-losing enteropathy after the Fontan operation. Ann Thorac Surg 2010; 89:837.
  54. Kelly AM, Feldt RH, Driscoll DJ, Danielson GK. Use of heparin in the treatment of protein-losing enteropathy after fontan operation for complex congenital heart disease. Mayo Clin Proc 1998; 73:777.
  55. Warnes CA, Feldt RH, Hagler DJ. Protein-losing enteropathy after the Fontan operation: successful treatment by percutaneous fenestration of the atrial septum. Mayo Clin Proc 1996; 71:378.
  56. Sunagawa T, Kinjo F, Gakiya I, et al. Successful long-term treatment with cyclosporin A in protein losing gastroenteropathy. Intern Med 2004; 43:397.
  57. Chehade M, Magid MS, Mofidi S, et al. Allergic eosinophilic gastroenteritis with protein-losing enteropathy: intestinal pathology, clinical course, and long-term follow-up. J Pediatr Gastroenterol Nutr 2006; 42:516.