Current Treatment Options in Gastroenterology

, Volume 4, Issue 1, pp 39–49 | Cite as

Protein-losing enteropathy and gastropathy

  • Brian R. Landzberg
  • Mark B. Pochapin

Opinion statement

  • The diagnosis of protein-losing enteropathy (PLE) should be considered in all patients with hypoalbuminemia and edema without other known causes, and established by plasma alpha1-antitrypsin (a1-AT) clearance or nuclear studies.

  • The therapy for PLE should focus principally on the treatment of the underlying disease after it has been identified. Therapeutic goals should include improvement of hypoalbuminemia, edema, and lymphopenia.

  • The existing primary literature for therapy of PLE syndromes consists mainly of case reports and expert opinions, subject to substantial reporting bias and unknown rates of spontaneous remission; the rarity of and the diversity among this set of diseases make future large randomized trials unlikely. Therapeutic choices, therefore, must involve clinical acumen, empiricism, and understanding of the pathophysiology of the underlying disease process, and must be tailored to each individual patient’s syndrome.

  • Dietary interventions including hypolipidic, high-protein regimens, supplemented by medium-chain triglycerides (MCTs), are extremely useful, particularly in protein loss due to increased lymphatic pressure.

  • Corticosteroids can be very useful in certain cases of PLE (though not without substantial long-term toxicity) when clinical serologic or histologic markers of inflammatory disease are present. Octreotide is a well tolerated drug that has been demonstrated to improve PLE in some patients, and is worth consideration.

  • Octreotide is a well tolerated drug that has been demonstrated to improve PLE in some patients, and is worth consideration.

  • Surgery finds its best role in treating gastrointestinal protein loss from neoplasia, inflammatory bowel disease, and hypertrophic gastritis. Most other PLEs are distributed too widely for surgical intervention.

  • Protein-losing gastropathy (PLG) behaves somewhat differently from the general group of PLE, marked by excellent responses to elimination of Helicobacter pylori, antisecretory therapy, and surgical resection.

  • Protein-losing enteropathy stemming from cardiovascular disease is best treated by medical or surgical cardiovascular interventions; however, some patients may respond to mucosa-directed therapy.


Octreotide Constrictive Pericarditis Protein Loss Fontan Operation Small Bowel Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Pochapin MB: Protein-losing disorders of the gastrointestinal tract. In Clinical Practice of Gastroenterology. Edited by Brandt LJ. Philadelphia: Churchill Livingstone; 1999:476–483. Reviews the pathology, pathophysiology and clinical features of PLE with discussion of the most common underlying disease entities.Google Scholar
  2. 2.
    Albright F, Forbes AP, Barterr FC, et al.: Studies on fate of intravenously administered plasma proteins in idiopathic hypoproteinemia and osteoporosis. In Symposia on Nutrition. Edited by Youmans YB. Cincinnati: Robert Gould Research Foundation, 1950:352.Google Scholar
  3. 3.
    Waldmann TA, Wochner RD, Strober W: The role of the gastrointestinal tract in plasma protein metabolism. Am J Med 1969, 46:275–284.PubMedCrossRefGoogle Scholar
  4. 4.
    Hess J, Kruizinga K, Bijleveld CMA, et al.: Protein-losing enteropathy after the Fontan operation. J Thorac Cardiovasc Surg 1984, 88:606–609.PubMedGoogle Scholar
  5. 5.
    Mertens L, Hagler DJ, Sauer U, et al.: Protein-losing enteropathy after the Fontan operation: an international multicenter study. J Thorac Cardiovasc Surg 1998, 115:1063–1073. Large review of 114 patients with PLE occurring after the Fontan procedure for congenital heart disease with interesting perspectives on the pathophysiology of PLE and the success of various treatment approaches tried in this specialized subset of PLE.PubMedCrossRefGoogle Scholar
  6. 6.
    Lemes V, Murphy AM, Osterman FA, et al.: Fenestration of extracardiac Fontan and reversal of protein-losing enteropathy: case report. Pediatr Cardiol 1998, 19:355–357.PubMedCrossRefGoogle Scholar
  7. 7.
    Warnes CA, Feldt RH, Hagler DJ: Protein-losing enteropathy after the Fontan operation: successful treatment by percutaneous fenestration of the atrial septum. Mayo Clin Proceed 1996, 71:378–379.CrossRefGoogle Scholar
  8. 8.
    Rychik J, Rome JJ, Jacobs ML: Late surgical fenestration for complications after the Fontan operation. Circulation 1997, 96:33–36.PubMedGoogle Scholar
  9. 9.
    Sierra C, Calleja F, Picazo B, et al.: Protein-losing enteropathy secondary to Fontan procedure resolved after cardiac transplantation. J Pediatr Gastroenterol Nutr 1997, 24:229–230.PubMedCrossRefGoogle Scholar
  10. 10.
    Therrien J, Webb GD, Gatzoulis MA: Reversal of protein losing enteropathy with prednisone in adults with modified Fontan operations: long term palliation or bridge to cardiac transplantation? Heart 1999, 82:241–243.PubMedGoogle Scholar
  11. 11.
    Rychik J, Piccoli DA, Barber G: Usefulness of corticosteroid therapy for protein losing enteropathy after the Fontan procedure. Am J Cardiol 1991, 68:819–821.PubMedCrossRefGoogle Scholar
  12. 12.
    Rothman A, Snyder J: Protein-losing enteropathy following the Fontan operation: resolution with prednisone therapy. Am Heart J 1991, 121:618–619.PubMedCrossRefGoogle Scholar
  13. 13.
    Zellers TM, Brown K: Protein-losing enteropathy after the modified Fontan operation: oral prednisone treatment with biopsy and laboratory proved improvement. Pediatr Cardiol 1996, 17:115–117.PubMedCrossRefGoogle Scholar
  14. 14.
    Bendayan I, Casaldaliga J, Castello F, Miro L: Heparin therapy and reversal of protein losing enteropathy in a case with congential heart disease. Pediatr Cardiol 2000, 21:267–268.PubMedCrossRefGoogle Scholar
  15. 15.
    Kelly AM, Feldt RH, Driscoll DJ, et al.: Use of heparin in the treatment of protein-losing enteropathy after Fontan operation for complex congenital heart disease. Mayo Clin Proc 1998, 73:777–779.PubMedCrossRefGoogle Scholar
  16. 16.
    Bernier JJ, Florent C, Desmazures C, et al.: Diagnosis of protein-losing enteropathy by gastrointestinal clearance of alpha1-antitrypsin. Lancet 1978, 2:763–764.PubMedCrossRefGoogle Scholar
  17. 17.
    Strygler B, Nicor MJ, Santangelo WC, et al.: Alpha1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders. Gastroenterology 1990, 99:1380–1387.PubMedGoogle Scholar
  18. 18.
    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, 81:777–780.PubMedGoogle Scholar
  19. 19.
    Oommen R, Kurien G, Balakrishnan N, Narasimhan S: Tc-99m-albumin scintigraphy in the localization of protein loss in the gut. Clin Nucl Med 1992, 17:787–790.PubMedCrossRefGoogle Scholar
  20. 20.
    Bhatnagar A, Lahoti D, Singh AK, et al.: Scintigraphic diagnosis of protein-losing enteropathy, using Tc-99m dextran. Clin Nucl Med 1993, 20:1070–1073.CrossRefGoogle Scholar
  21. 21.
    Bhatnagar A, Kashyap R, Chauhan UPS, et al.: Diagnosing protein-losing enteropathy: a new approach using Tc-99 human immunoglobulin. Clin Nucl Med 1995, 20:969–972.PubMedCrossRefGoogle Scholar
  22. 22.
    Carpani de Kaski M, Peters AM, Bradley D, et al.: Detection and quantification of protein-losing enteropathy with indium-111 transferrin. Eur J Nucl Med 1996, 23:530–533.CrossRefGoogle Scholar
  23. 23.
    Bloom B, Chaikoff IL, Reinhardt WO: Intestinal lymph as pathway for transport of absorbed fatty acids of different chain lengths. Am J Physiol 1951, 166:451.PubMedGoogle Scholar
  24. 24.
    Tift WL, Lloyd JK: Intestinal lymphangiectasia. Long-term results with MCT diet. Arch Dis Child 1975, 50:269–276.PubMedGoogle Scholar
  25. 25.
    Simmonds WJ: The effect of fluid, electrolyte and food intake on thoracic duct lymph flow in unanaesthetized rats. Austr J Exp Biol Med Sci 1954, 32:285.Google Scholar
  26. 26.
    Holt PR: Dietary treatment of protein loss in intestinal lymphangiectasia. The effect of eliminating dietary long chain triglycerides on albumin metabolism in this condition. Pediatrics 1964, 34:629–635.PubMedGoogle Scholar
  27. 27.
    Jeffries GH, Chapman A, Sleisenger MH: Low-fat diet intestinal lymphangiectasia. N Engl J Med 1964, 270:761–766.PubMedCrossRefGoogle Scholar
  28. 28.
    Stoelinga GBA, VanMunster, EJJ, Slooff JF: Chylous effusions into intestine in patient with protein-losing gastroenteropathy. Pediatrics 1963, 31:1011–1081.PubMedGoogle Scholar
  29. 29.
    Leyland FC, Fosbrooke AS, Lloyd JK, et al.: Use of medium chain triglyceride diets in children with malabsorption. Arch Dis Child 1969, 44:170–179.PubMedGoogle Scholar
  30. 30.
    Alfano V, Tritto G, Alfonsi L, et al.: Stable reversal of pathologic signs of primitive intestinal lymphangiectasia with a hypolipidic, MCT-enriched diet. Nutrition 2000, 16:303–304.PubMedCrossRefGoogle Scholar
  31. 31.
    Clinical Staff Conference: Idiopathic hypoalbuminemia —Clinical staff conference at National Institutes of Health. Ann Intern Med 1959, 51:53–576.Google Scholar
  32. 32.
    Fleischer TA, Strober W, Muchmore AV, et al.: Corticosteroid responsive intestinal lymphangiectasia secondary to an inflammatory process. N Engl J Med 1979, 300:605–606.CrossRefGoogle Scholar
  33. 33.
    Belaiche J, Vesin P, Carlet J, et al.: Entéropathie avec perte de protéines et syndrome inflammatoire: rémission speculaire après flash intraveineux de méthylprednisolone. Gastroenterol Clin Biol 1982, 6:438–442.PubMedGoogle Scholar
  34. 34.
    Lebenthal E, Gaifman M, Nitzan M: Case report: protein-losing gastroenteropathy responding to corticosteroid treatment. Acta Paediatr Scand 1970, 59:217–220.PubMedGoogle Scholar
  35. 35.
    Itoi K, Sasaki T, Sawai T, et al.: Protein-losing gastroenteropathy in association with immune deposits in gastrointestinal mucosal capillaries. Am J Gastroenterol 1989, 84:187–191.PubMedGoogle Scholar
  36. 36.
    Bac DJ, Van Hagen PM, Postema PTE, et al.: Octreotide for protein losing enteropathy with intestinal lymphangiectasia. Lancet 1995, 345:1639.PubMedCrossRefGoogle Scholar
  37. 37.
    Nakabayashi H, Sagara H, Usukura N, et al.: Effect of somatostatin on the flow rate and triglyceride levels of thoracic duct lymph in normal and vagotomized dogs. Diabetes 1981, 30:440–445.PubMedGoogle Scholar
  38. 38.
    Reubi JC, Horisberger U, Waser B, et al.: Preferential location of somatostatin receptors in germinal centers of human gut lymphoid tissue. Gastroenterology 1992, 103:1207–1214.PubMedGoogle Scholar
  39. 39.
    Reubi JC, Waser B, Markusse HM, et al.: Vascular somatostatin receptors in synovium from patients with rheumatoid arthritis. Eur J Pharmacol 1994, 271:371–378.PubMedGoogle Scholar
  40. 40.
    Ballinger AB, Farthing MJG: Octreotide in the treatment of intestinal lymphangiectasia. Eur J Gastroenterol Hepatol 1998, 10:699–702.PubMedGoogle Scholar
  41. 41.
    Ratnoff OD: Increased vascular permeability induced by plasmin. J Exp Med 1965, 122:905–921.CrossRefPubMedGoogle Scholar
  42. 42.
    Kondo M, Bamba T, Hosokawa K, et al.: Tissue plasminogen activator in the pathogenesis of protein-losing gastroenteropathy. Gastroenterology 1976, 70:1045–1047.PubMedGoogle Scholar
  43. 43.
    Mine K, Matsubayashi S, Nakai Y, Nakagawa T: Intestinal lymphangiectasia markedly improved with antiplasmin therapy. Gastroenterology 1989, 96:1596–1599.PubMedGoogle Scholar
  44. 44.
    Heresbach D, Raoul JL, Bretagne JF, Gosselin M: Intestinal lymphangiectasia: lack of efficacy of antiplasmin therapy? Gastroenterology 1991, 100:1152–1153.PubMedGoogle Scholar
  45. 45.
    Cohen SA, Diuguid DL, Whitlock RT, Holt PR: Intestinal lymphangiectasia and antiplasmin therapy [letter]. Gastroenterology 1992, 102:2193.PubMedGoogle Scholar
  46. 46.
    Persic M, Browse NL, Prpic I: Intestinal lymphangiectasia and protein losing enteropathy responding to small bowel resection [letter]. Arch Dis Childh 1998, 78:194.PubMedGoogle Scholar
  47. 47.
    Mistilis SP, Skyring AP: Intestinal lymphangiectasia. Therapeutic effect of lymph venous anastomosis. Am J Med 1966, 40:634–641.CrossRefGoogle Scholar
  48. 48.
    Ivey K, DenBesten L, Kent TH, Clifton JA: Lymphangiectasia of the colon with protein loss and malabsorption. Gastroenterology 1969, 57:709–714.PubMedGoogle Scholar
  49. 49.
    Waldmann TA, Steinfeld JL, Dutcher TF, et al.: The role of the gastrointestinal system in "idiopathic hypoproteinemia." Gastroenterology 1968, 54(suppl):795–796.PubMedGoogle Scholar
  50. 50.
    Ménétrier P: Des polyadenomes gastriques et de leurs rapports avec le cancer de l’estomac. Arch Physiol Norm Pathol 1888, 4:32–35.Google Scholar
  51. 51.
    Citrin Y, Sterling K, Halstead JA: The mechanism of hypoproteinemia associated with giant hypertrophy of the gastric mucosa. N Engl J Med 1957, 257:906–912.PubMedCrossRefGoogle Scholar
  52. 52.
    Crampton JR, Hunter JO, Neale G, et al.: Chronic lymphocytic gastritis and protein losing gastropathy. Gut 1989, 30(suppl):71–74.PubMedGoogle Scholar
  53. 53.
    Schindler R: On hypertrophic glandular gastritis, hypertrophic gastropathy and parietal cell mass. Gastroenterology 1963, 45:77–83.PubMedGoogle Scholar
  54. 54.
    Scharschmidt BF: The natural history of hypertrophic gastropathy. Am J Med 1977, 63:644–652.PubMedCrossRefGoogle Scholar
  55. 55.
    Herskovic T, Spiro HM, Gryboski JD: Acute transient gastrointestinal protein loss. Pediatrics 1968, 41:818–821.PubMedGoogle Scholar
  56. 56.
    Walker F: Spontaneous remission in hypertrophic gastropathy. South Med J 1981, 74:1273–1276.PubMedGoogle Scholar
  57. 57.
    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, 89:1548–1551.PubMedGoogle Scholar
  58. 58.
    Bayerdorffer E, Ritter MM, Hatz R, et al.: Menetrier’s disease and Helicobacter pylori [letter]. N Engl J Med 1993, 329:60.PubMedCrossRefGoogle Scholar
  59. 59.
    Salmeron M, Desplaces N, Lavergne A, et al.: Campylobacter pylori, hypertrophic erosive gastritis and hypoalbuminemia healed by cephalexin therapy. Gastroenterol Clin Biol 1989, 13:109–110.PubMedGoogle Scholar
  60. 60.
    Madsen LG, Taskiran M, Madsen JL, Bytzer P: Ménétrier’s disease and Helicobacter pylori: normalization of gastrointestinal protein loss after eradication therapy. Digest Dis Sci 1999, 44:2307–2312.PubMedCrossRefGoogle Scholar
  61. 61.
    Crampton JR, Hunter JO, Neale G, Wight DGD: Chronic lymphocytic gastritis and protein-losing gastropathy. Gut 1989, 30:71–74.PubMedGoogle Scholar
  62. 62.
    Meuwissen SGM, Ridwan BU, Hasper HJ, Innemee G: Hypertrophic protein-losing gastropathy. A retrospective analysis of 40 cases in the Netherlands. Scand J Gastroenterology Suppl 1992, 194:1–7. Like the article by Searcy and Malagelada [77], a large collection of patients with an uncommon disease, providing a useful broad overview of clinical presentations, prognosis, and therapeutic approaches taken.Google Scholar
  63. 63.
    Kang JY, Tang KF, Goh A, et al.: Remission of Menetrier’s disease associated with ranitidine administration. Austr N Z J Med 1990, 20:716–717.Google Scholar
  64. 64.
    Krol TC, Isenberg, JI Remission in a patient with Menetrier’s disease: spontaneous or induced by treatment? J Clin Gastroenterol 1985, 7:161–168.PubMedCrossRefGoogle Scholar
  65. 65.
    Murata I, Yoshikawa I, Kuroda T, et al.: Varioliform gastritis and duodenitis associated with proteinlosing gastroenteropathy, treated with omeprazole. J Gastroenterol 1996, 31:109–113.PubMedCrossRefGoogle Scholar
  66. 66.
    Bradburn DM, Redwood NF, Venables CW, Gunn A: Medical therapy of Ménétrier’s disease with omeprazole. Digestion 1992, 52:204–208.PubMedGoogle Scholar
  67. 67.
    Ladas SD, Tassios PS, Malamou HC, et al.: Omeprazole induces a long-term clinical remission of proteinlosing gastropathy of Menetrier’s disease. Eur J Gastroenterol Hepatol 1997, 9:811–813.PubMedGoogle Scholar
  68. 68.
    Krag E, Frederiksen HJ, Olsen N, Henriksen JH: Cimetidine treatment of protein-losing gastropathy (Ménétrier’s disease). A clinical and pathophysiological study. Scand J Gastroenterol 1978, 13:636–639.PubMedGoogle Scholar
  69. 69.
    Kenny DG, Miller LJ, Malagelada JR, et al.: Giant hypertrophic gastropathy (Menetrier’s disease): Pharmacologic effects on protein leakage and mucosal ultrastructure. Gastroenterology 1982, 83:581–589.Google Scholar
  70. 70.
    Smith RL, Powell DW: Prolonged treatment of Menetrier’s disease with an anticholinergic drug. Gastroenterology 1978, 74:903–906.PubMedGoogle Scholar
  71. 71.
    Davis GE, O’Rourke MC, Metz JR, et al.: Hypertrophic gastropathy symptoms responsive to prednisone. J Clin Gastroenterol 1991, 13:436–441.PubMedCrossRefGoogle Scholar
  72. 72.
    Winney RJ, Gilmour HM, Matthews JD: Prednisolone in giant hypertrophic gastritis. (Menetrier’s disease) Am J Digest Dis 1976, 21:337–339.PubMedCrossRefGoogle Scholar
  73. 73.
    Yeaton P, Frierson HF Jr: Octreotide reduces enteral protein losses in Ménétrier’s disease. Am J Gastroenterol 1993, 88:95–98.PubMedGoogle Scholar
  74. 74.
    Kondo M, Ikezaki M, Kato H, Masuda M: Anti-fibrinolytic therapy of giant hypertrophic gastritis (Menetrier’s disease). Scand J Gastroenterol 1978, 13:851–856.PubMedCrossRefGoogle Scholar
  75. 75.
    Balfour DC Jr, Hightower NC Jr, Gambill EE, et al.: Giant hypertrophy of the gastric rugae (Menetrier’s disease) associated with severe hypoproteinemia, relieved only by total gastrectomy: report of a case. Gastroenterology 1950, 16:773.PubMedGoogle Scholar
  76. 76.
    Scharschmidt BF: The natural history of hypertrophic gastropathy (Menetrier’s disease). Report of a case with 16 year followup and review of 120 cases from the literature. Am J Med 1977, 63:644–652.PubMedCrossRefGoogle Scholar
  77. 77.
    Searcy RM, Malagelada JR: Ménétrier’s disease and idiopathic hypertrophic gastropathy. Ann Intern Med 1984, 100:565–570.PubMedGoogle Scholar
  78. 78.
    Scott HW, Shull HJ, Law DH, et al.: Surgical management of Ménétrier’s disease with protein-losing gastropathy. Ann Surg 1975, 181:765–777.PubMedCrossRefGoogle Scholar
  79. 79.
    Sundt TM 3rd, Compton CC, Malt RA: Menetrier’s disease, a trivalent gastropathy. Ann Surg 1988, 208:694–701.PubMedCrossRefGoogle Scholar
  80. 80.
    Gold BM, Meyers MA: Progression of Ménétrier’s disease with postoperative gastrojejunal intussusception. Gastroenterology 1977, 73:583–586.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2001

Authors and Affiliations

  • Brian R. Landzberg
    • 1
  • Mark B. Pochapin
    • 1
  1. 1.Division of Gastroenterology and Hepatology, Department of MedicineWeill Medical College of Cornell University and New York-Presbyterian HospitalNew YorkUSA

Personalised recommendations