AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Background

Protein-losing enteropathy (PLE) is a pathophysiologic process that results in the loss of serum proteins into the gastrointestinal (GI) tract. It may result as either a primary manifestation or a subclinical component of various disease processes. Historically, patients with hypoalbuminemia of unknown cause were referred to as having idiopathic hypoproteinemia, edema disease, or nephrosis without nephrosis. These patients had neither a decrease in the production of albumin (ie, no signs of malnutrition or hepatic disease) nor an increase in albumin losses from the respiratory tract, kidneys, or skin.

In 1949, Albright et al demonstrated an increase in protein turnover in patients with PLE. In 1958, Citrin et al were the first to use radiolabeled tracers to demonstrate the actual loss of a protein-containing fluid into the GI tract. Several additional diagnostic techniques using radiolabeled substrates were developed, but a major advance was made when Crossley and Elliot demonstrated that measurement of alpha1-antitrypsin (A1-AT) levels in the stool was a reliable and simple test for PLE. This approach has identified a variety of conditions that have subclinical PLE as a component of the disease process.

Pathophysiology

No single explanation accounts for the protein loss into the GI tract that can occur with many different conditions. Recent experimental work has focused on the loss of heparan sulfate proteoglycans from the basolateral surface of the intestinal epithelial cell. While not yet conclusive, damage to this epithelial matrix component, either by increased pressure in lymphatics or inflammation, offers an intriguing and unifying hypothesis for the many causes of PLE.

For practical purposes, the disease processes that cause PLE can be grouped into 2 major categories: (1) PLE secondary to lymphatic obstruction and (2) PLE secondary to mucosal erosion or ulceration. Obstruction of lymphatics from any cause can produce increased pressure throughout the lymphatic system of the GI tract. This results in the stasis of lymph and, if the pressure is high enough, the loss of lymphatic fluid rich in albumin and other proteins from the lacteals in intestinal microvilli into the lumen of the GI tract. If the loss of albumin exceeds the rate of synthesis, hypoalbuminemia and, eventually, edema develop. In addition to the loss of albumin, other important components of lymph are also lost into the bowel, including lymphocytes and immunoglobulins.

Lymphopenia is a common finding associated with PLE due to primary intestinal lymphangiectasia, Whipple disease, or constrictive pericarditis. In cases of PLE associated with lymphatic obstruction, alleviating the obstruction corrects the lymphopenia. A decrease in the circulating levels of immunoglobulins is also a feature of lymphatic obstruction, but because the synthetic machinery remains intact, response to antigenic challenge is usually good.

In patients with lymphatic obstruction, fat malabsorption may also develop secondary to damage produced to the lymphatics. In these patients, deficiencies in the fat-soluble vitamins (ie, A, D, E, K) can occur. A wide variety of infectious diseases and noninfectious diseases can produce inflammation and ulceration of the GI mucosa resulting in PLE, and each of these processes has its own unique pathophysiology. However, because lymphatic obstruction does not play a role in these conditions, lymphopenia and loss of immunoglobulins are not seen.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

History

Consider protein-losing enteropathy (PLE) in any patient presenting with edema. When considering PLE, certain aspects of the history and physical examination should be emphasized.

• A complete dietary history should be obtained to evaluate for possible protein malnutrition, which is a cause of diminished albumin synthesis.
• Query about possible renal diseases (increased protein loss) or hepatic diseases (decreased protein synthesis) that could cause hypoalbuminemia. Usually nephrotic syndrome or liver disease would be the only cause for the hypoalbuminemia, but both can increase the pressure in the intra-abdominal lymphatic system, producing PLE.
• Obtain a complete GI history, looking for gut sources of excessive protein loss. For example, patients should be questioned about the following:
• • Dietary intake (nutritional history)
  • Urinary tract issues (urinary frequency, urine color, pain with urination)
  • History of high blood pressure to evaluate for possible renal disease
  • Alcohol intake
  • History of hepatitis, fatigue, jaundice to evaluate for liver disease
  • History of diarrhea, hematochezia, and abdominal pain to evaluate for GI disease
• Primary lymphangiectasia may be long-standing; therefore, questions about symptoms may date back to the neonatal period.
• Query the patient or parents about other lymphatic abnormalities that might have been present.
• Obtain a cardiac history, including congenital heart disease, prior episodes of pericarditis, serious streptococcal infection, and prior heart surgery.

Physical

• Begin the physical examination by taking appropriate anthropometric measurements, including the following:
• • Head circumference
  • Height
  • Weight
  • Triceps skinfold thickness as an assessment of the nutritional status (if available)
• Emphasize that weight alone may be misleading because fluid retention can occur in the setting of hypoalbuminemia.
• Examine the patient for evidence of the following:
• • Acute liver disease (eg, enlarged liver, tenderness in the right upper quadrant)
  • Signs of chronic liver disease (eg, jaundice, splenomegaly, abdominal wall venous prominence due to collateral circulation)
• Perform a careful cardiac examination to evaluate for hepatomegaly, ascites, and jugular vein distention suggestive of increased right-sided pressures in the heart as the cause for PLE.
• The finding of high blood pressure may suggest renal or cardiac disease.
• GI findings compatible with PLE include the following:
• • Diarrhea
  • Abdominal tenderness
  • Macroscopic or microscopic blood and mucus in the stool
• Localized edema is suggestive of primary intestinal lymphangiectasia.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Other Problems to be Considered

Lymphatic obstruction
Primary intestinal lymphangiectasia
Secondary intestinal lymphangiectasia
Arsenic poisoning
Familial illnesses
Heart disease

Genetic causes
Congenital disorders of glycosylation

Inflammatory causes
Nephrotic syndrome
Noonan syndrome
Mucosal erosions or ulcerations

Infectious causes
Clostridium difficile
Clostridium perfringens
Colonic malakoplakia
Cytomegalovirus
Giardia lamblia
Helicobacter pylori
Hypertrophic gastropathy (Menetrier disease)
Measles
Rotavirus
Salmonellosis
Strongyloides stercoralis

Noninfectious causes
Anastomotic ulceration/ischemia
Atopic dermatitis
Burns
Cow's-milk–protein allergy
Eosinophilic gastroenteritis
Gluten sensitive enteropathy
Graft versus host disease
Henoch-Schönlein purpura
Inflammatory bowel disease
Juvenile rheumatoid arthritis
Malnutrition
Multiple polyposis
Necrotizing enterocolitis
Peptic esophagitis
Systemic lupus erythematosus
Systemic phenobarbital hypersensitivity

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Lab Studies

• Patients with edema and documented hypoalbuminemia but without clinical or biochemical evidence of liver or renal disease should have a thorough evaluation for protein-losing enteropathy (PLE). In the past, PLE was often considered a diagnosis of exclusion, but several approaches for determining abnormal protein loss in the GI tract currently exist. The ideal test for PLE would be able to detect a serum protein in the stool that is not secreted, digested, or reabsorbed in the GI tract. However, no ideal test currently exists.
• Three types of tests have been used to evaluate for PLE. The first involves the intravenous administration of a radiolabeled substrate followed by the determination of radioactivity in the feces. The second type of test directly measures endogenous proteins in the feces. A third approach is the use of nuclear scintigraphy, not only for diagnosis, but also to identify potential regional or localized areas of protein loss.
• History of radiolabeled proteins
• • Use of radiolabeled proteins to measure albumin turnover dates back to 1950 with Kinsell.
  • In the late 1950s, Swartz, and later Citrin, administered iodine 131–albumin to patients in an attempt to measure albumin turnover. In a patient with hypertrophic gastritis and PLE, Citrin reported that the ¹³¹I-albumin lost in the stomach was degraded and the free ¹³¹I was then absorbed and excreted in the urine, making the measurement of ¹³¹I in the stools unreliable.
  • Gordon reported the use of polyvinylpyrrolidone iodine I 125 (¹³¹I-PVP) as a marker for protein metabolism. PVP is a macromolecule that is not digested by intestinal enzymes and is poorly absorbed when taken by mouth. In patients with PLE, intravenously administered ¹³¹I-PVP results in detectable levels of radioactivity in the stool. The problem with this substance is that it is not a normal metabolite, has a wide range of molecular weights, and can be partially absorbed and secreted. More importantly, the ¹³¹I is easily released from the carrier, which then can be absorbed and excreted in the urine. This is problematic if urine contamination of the stool occurs as in pediatric patients.
  • In 1961, the next radioactive substrate used was chromium 51–albumin. This method had several advantages. The ⁵¹Cr bound tightly to albumin and was poorly absorbed from the GI tract. Thus, little or no radioactivity was detectable in the urine.
  • In practice, approaches using radiolabeled compounds are now rarely used because 48-72 hours of stool collection is required in the hospital, care must be taken to avoid contamination of stool collection with urine, and the tests involve radiation exposure.
• Measurement of endogenous proteins
• • In 1977, Crossley and Elliot demonstrated that the stools of patients with PLE as determined by ⁵¹Cr-albumin excretion also had high levels of A1-AT.
  • A1-AT is an endogenous protein not present in the diet; the molecular weight is similar to albumin. It is not actively secreted, absorbed, or digested.
  • A1-AT is stable in feces at 37°C, allowing collection over several days.
  • Because A1-AT is not excreted in urine, urine contamination of the stool sample does not alter the spot determination of fecal A1-AT.
  • Stool samples are simply lyophilized, and A1-AT is extracted by solubilization.
  • Fecal A1-AT can then be detected by immunoassay. Measurement of fecal A1-AT can be used as a spot determination or to calculate the clearance of A1-AT using the following formula:
    A1-AT clearance = [(fecal A1-AT concentration) (stool volume/24 h]/(A1-AT serum concentration)
  • Many studies have demonstrated the utility of using fecal A1-AT levels and A1-AT clearance for diagnosis and follow-up care in patients with PLE.
• Nuclear scintigraphy
• • Several radiopharmaceuticals tagged to proteins have been used to examine PLE, including indium-111 (111In)–transferrin, technetium-99m (99mTc)–human serum albumin, and 99mTc-dextran. The latter compound is reported to be superior for a number of technical reasons.
  • This technique has been reported to be useful in the diagnosis of PLE, but no studies have compared the sensitivity of scintigraphy with fecal A1-AT determination. However, it may be extremely useful in identifying sites of involvement in PLE (ie, stomach vs small intestine or even regional differences in the small bowel).

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Medical Care

Therapeutic approaches for protein-losing enteropathy (PLE) depend on the underlying etiology.

• In patients with primary intestinal lymphangiectasia, no direct method to address the PLE exists. Replacing fat in the diet with medium-chain triglycerides (MCTs) can improve fat malabsorption and the nutritional status of the patient. Supplementing fat-soluble vitamins (ie, A, D, E, K) is also important.
• In PLE associated with lymphatic obstruction, relieving the pressure in the lymphatic system decreases intestinal protein loss. Obstruction of lymphatics has been reported with structural heart disease, constrictive pericarditis, cardiomyopathy, and surgical repair of congenital heart disease. When obstruction of the intra-abdominal lymphatic system is the cause of PLE, malabsorption of the fat-soluble vitamins can occur secondary to the dilatation and rupture of the lacteals. The use of MCT oil in these cases does not relieve any inflammation, but because MCT oil is not absorbed via the lymphatic system, it reduces the pressure of the lacteals.
• PLE that results after heart surgery (with increased pressure in the right side) is sometimes reversible after the use of corticosteroids or heparin or after surgical intervention (baffle fenestration of heart transplant). As many as 13.4% of patients undergoing a Fontan procedure develop PLE within 10 years of surgery, and the mortality rate associated with this complication has been reported to be as high as 56% in 5 years. Use of steroids has produced temporary clinical and pathological resolution of PLE. Heparin has also been reported to improve PLE in children after the Fontan procedure. Heparin is thought to possibly have a stabilizing effect on the capillary endothelium, reducing protein leakage into the extravascular space and gut lumen, although the precise mechanism of action is unknown. Even though heparin has been successfully used to treat some patients with PLE that develops after the Fontan procedure, it is by no means the treatment of choice for all the etiologies of PLE.
• Corticosteroids have been used in patients with PLE associated with collagen vascular diseases, inflammatory bowel disease, heart surgery, and others. Sporadic case reports have documented the successful use of other agents such as cyclosporine for PLE. Immunosuppressive drugs should not be used in cases of PLE secondary to infections.

Surgical Care

• In patients who have undergone a Fontan procedure, fenestration of the baffle that separates the systemic venous pathway from the pulmonary venous atrium has been performed to treat PLE, and in some cases the symptoms have resolved, presumably because of the decrease in systemic venous pressure.
• Cardiac transplantation has also been performed for the management of intractable PLE related to previous heart surgery, with complete resolution of symptoms.
• Conner et al reported a case in which localized resection of the involved bowel successfully treated the condition.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Drug Category: Vitamins

In protein-losing enteropathy (PLE), providing supplementation with fat-soluble vitamins (eg, A, D, E, K) is important. These agents are necessary for growth and health. For healthy individuals, they are needed in small amounts only and are available in the foods of a daily diet. However, soluble vitamin supplementation is essential in patients with PLE because the small amounts available in a regular diet are insufficient in the face of the malabsorption that occurs.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider protein-losing enteropathy (PLE) in any patient who presents with edema
• Failure to review all measurements during physical examination because weight alone may be misleading because of fluid retention
• Failure to supplement diets of patients with PLE with fat-soluble vitamins (ie, A, D, E, K)

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Miscellaneous
• References

• Bac DJ, Van Hagen PM, Postema PT, et al. Octreotide for protein-losing enteropathy with intestinal lymphangiectasia. Lancet. Jun 24 1995;345(8965):1639. [Medline].
• Bai JC, Sambuelli A, Niveloni S, et al. Alpha 1-antitrypsin clearance as an aid in the management of patients with celiac disease. Am J Gastroenterol. Aug 1991;86(8):986-91. [Medline].
• Belamarich PF, Ortiz A, Mones RL. Severe hypoproteinemia and edema in association with varicella infection. Clin Pediatr (Phila). Jan 1991;30(1):56-8. [Medline].
• Boccon-Gibod LA, Krichen HA, Carlier-Mercier LM, et al. Digestive tract involvement with exudative enteropathy in Langerhans cell histiocytosis. Pediatr Pathol. Jul-Aug 1992;12(4):515-24. [Medline].
• Bode L, Murch S, Freeze HH. Heparan sulfate plays a central role in a dynamic in vitro model of protein-losing enteropathy. J Biol Chem. Mar 24 2006;281(12):7809-15. [Medline].
• Bouhnik Y, Chaussade S, Robin P, et al. Protein-losing enteropathy syndrome caused by a localization of Kaposi''s sarcoma in AIDS [in French]. Gastroenterol Clin Biol. Oct 1989;13(10):838-40. [Medline].
• Bryan RL, Newman J, Alexander-Williams J. Giant inflammatory polyposis in ulcerative colitis presenting with protein losing enteropathy. J Clin Pathol. Apr 1990;43(4):346-7. [Medline]. [Full Text].
• Chiu NT, Lee BF, Hwang SL, et al. Protein-losing enteropathy: diagnosis with 99mTc-labeled human serum albumin scintigraphy. Radiol. Apr 2001;219(1):86-90.
• Cho CS, Min JK, Park SH, et al. Protein losing enteropathy associated with Henoch-Schonlein purpura in a patient with rheumatoid arthritis. Scand J Rheumatol. 1996;25(5):334-6. [Medline].
• Cohen HA, Shapiro RP, Frydman M, Varsano I. Childhood protein-losing enteropathy associated with Helicobacter pylori infection. J Pediatr Gastroenterol Nutr. Aug 1991;13(2):201-3. [Medline].
• Connor FL, Angelides S, Gibson M, et al. Successful resection of localized intestinal lymphangiectasia post-Fontan: role of (99m)technetium-dextran scintigraphy. Pediatrics. Sep 2003;112(3 Pt 1):e242-7. [Medline]. [Full Text].
• Couper RT, Durie PR, Stafford SE, et al. Late gastrointestinal bleeding and protein loss after distal small- bowel resection in infancy. J Pediatr Gastroenterol Nutr. Nov 1989;9(4):454-60. [Medline].
• 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. Jun 1996;22(6):932-7. [Medline].
• Desmazures C, Giraudeaux V, Florent C, et al. Intestinal clearance of alpha 1 anti-trypsin: a simple technique for diagnosis of protein losing enteropathy (author''s transl) [in French]. Nouv Presse Med. May 31 1980;9(24):1691-4. [Medline].
• 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. Mar 1997;130(3):474-8. [Medline].
• Ehringhaus C, Dominick HC, Schuller M. Protein-losing enteropathy associated with Clostridium perfringens infection [letter]. Lancet. Jul 29 1989;2(8657):268-9. [Medline].
• 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. Oct 1981;81(4):777-80. [Medline].
• Ghilain JM, Martiat P, Fiasse R, et al. Exudative enteropathy caused by an acute graft-vs-host reaction. Apropos of a case report [in French]. Acta Gastroenterol Belg. Sep-Dec 1990;53(5-6):488-98. [Medline].
• Gordon RS. J Polym Sci. 1957;31:191.
• Grill BB, Hillemeier AC, Gryboski JD. Fecal alpha 1-antitrypsin clearance in patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1984;3(1):56-61. [Medline].
• Groisman GM, George J, Berman D, Harpaz N. Resolution of protein-losing hypertrophic lymphocytic gastritis with therapeutic eradication of Helicobacter pylori. Am J Gastroenterol. Sep 1994;89(9):1548-51. [Medline].
• Hardikar W, Smith AL, Chow CW. Neonatal protein-losing enteropathy caused by intestinal lymphatic hypoplasia in siblings. J Pediatr Gastroenterol Nutr. Aug 1997;25(2):217-21. [Medline].
• Henley JD, Kratzer SS, Seo IS, Davis T. Endometriosis of the small intestine presenting as a protein-losing enteropathy. Am J Gastroenterol. Jan 1993;88(1):130-3. [Medline].
• Inoue Y, Ohtake T, Koga H, et al. Tc-99m albumin scintigraphy in protein-losing gastroenteropathy caused by gastric polyposis. Clin Nucl Med. May 1998;23(5):322-3. [Medline].
• Jacobs ML, Rychik J, Byrum CJ, Norwood WI Jr. Protein-losing enteropathy after Fontan operation: resolution after baffle fenestration. Ann Thorac Surg. Jan 1996;61(1):206-8. [Medline].
• Jain A, Reif S, O''Neil K, et al. Small intestinal bacterial overgrowth and protein-losing enteropathy in an infant with AIDS. J Pediatr Gastroenterol Nutr. Nov 1992;15(4):452-4. [Medline].
• Jarnum S, Westergaard H, Yssing M, Jensen H. Quantitation of gastrointestinal protein loss by means of FE59-labeled iron dextran. Gastroenterology. Aug 1968;55(2):229-41. [Medline].
• Karbach U, Ewe K, Dehos H. Antiinflammatory treatment and intestinal alpha 1-antitrypsin clearance in active Crohn''s disease. Dig Dis Sci. Mar 1985;30(3):229-35. [Medline].
• Karbach U, Ewe K, Bodenstein H. Alpha 1-antitrypsin, a reliable endogenous marker for intestinal protein loss and its application in patients with Crohn''s disease. Gut. Aug 1983;24(8):718-23. [Medline].
• Keaney NP, Kelleher J. Faecal excretion of alpha 1-antitrypsin in protein-losing enteropathy. Lancet. Mar 29 1980;1(8170):711. [Medline].
• 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. Aug 1998;73(8):777-9. [Medline].
• Kinsell L, Margen S, Tarver H. J Clin Invest. 1950;29:238.
• Koga H, Iida M, Aoyagi K, et al. Generalized giant inflammatory polyposis in a patient with ulcerative colitis presenting with protein-losing enteropathy. Am J Gastroenterol. May 1995;90(5):829-31. [Medline].
• Konar A, Brown CB, Hancock BW, Moss S. Protein losing enteropathy as a sole manifestation of non-Hodgkin''s lymphoma. Postgrad Med J. May 1986;62(727):399-400. [Medline].
• Korman SH, Bar-Oz B, Mandelberg A, Matoth I. Giardiasis with protein-losing enteropathy: diagnosis by fecal alpha 1- antitrypsin determination. J Pediatr Gastroenterol Nutr. Feb 1990;10(2):249-52. [Medline].
• Laine L, Politoske EJ, Gill P. Protein-losing enteropathy in acquired immunodeficiency syndrome due to intestinal Kaposi''s sarcoma. Arch Intern Med. Jun 1987;147(6):1174-5. [Medline].
• Laster L, Waldmann TA, Fenster LF, Singleton JW. Albumin metabolism in patients with Whipple''s disease. - Fenster LF. May 1966;45(5):637-44. [Medline].
• Madina EH, Soliman AT, Morsi MR. Protein losing enteropathy in the different forms of protein-energy malnutrition. J Trop Pediatr. Oct 1987;33(5):254-6. [Medline].
• Matoth I, Granot E, Gorenstein A, et al. Gastrointestinal protein loss in children recovering from burns. J Pediatr Surg. Oct 1991;26(10):1175-8. [Medline].
• Mertens L, Hagler DJ, Sauer U, et al. Protein-losing enteropathy after the Fontan operation: an international multicenter study. PLE study group. J Thorac Cardiovasc Surg. May 1998;115(5):1063-73. [Medline].
• Meuwissen SG, Ridwan BU, Hasper HJ, Innemee G. Hypertrophic protein-losing gastropathy. A retrospective analysis of 40 cases in The Netherlands. The Dutch Menetrier Study Group. Scand J Gastroenterol Suppl. 1992;194:1-7. [Medline].
• Molina JF, Brown RF, Gedalia A, Espinoza LR. Protein losing enteropathy as the initial manifestation of childhood systemic lupus erythematosus. J Rheumatol. Jul 1996;23(7):1269-71. [Medline].
• Nakano S, Kuramochi S, Hosoda Y, Miura S. Protein-losing enteropathy due to intestinal lymphangiectasia accompanied by mesenteric lymph node fibrosis. Pathol Int. Nov 1996;46(11):883-6. [Medline].
• Nakase H, Itani T, Mimura J, et al. Transient protein-losing enteropathy associated with cytomegalovirus infection in a noncompromised host: a case report. Am J Gastroenterol. Jun 1998;93(6):1005-6. [Medline].
• Petersen VP, Hastrup J. Protein losing enteropathy in constrictive pericarditis. Acta Med Scand. 1963;173:401.
• Rybolt AH, Bennett RG, Laughon BE, et al. Protein-losing enteropathy associated with Clostridium difficile infection. Lancet. Jun 17 1989;1(8651):1353-5. [Medline].
• Rychik J, Piccoli DA, Barber G. Usefulness of corticosteroid therapy for protein-losing enteropathy after the Fontan procedure. Am J Cardiol. Sep 15 1991;68(8):819-21. [Medline].
• Sierra C, Calleja F, Picazo B, Martinez-Valverde A. Protein-losing enteropathy secondary to Fontan procedure resolved after cardiac transplantation. J Pediatr Gastroenterol Nutr. Feb 1997;24(2):229-30. [Medline].
• Strober W, Wochner RD, Carbone PP, Waldmann TA. Intestinal lymphangiectasia: a protein-losing enteropathy with hypogammaglobulinemia, lymphocytopenia and impaired homograft rejection. The Journal of Clinical Investigation. Oct 1967;46(10):1643-56. [Medline].
• Su J, Smith MB, Rerknimitr R, Morrow D. Small intestine bacterial overgrowth presenting as protein-losing enteropathy. Dig Dis Sci. Mar 1998;43(3):679-81. [Medline].
• Sunagawa T, Kinjo F, Gakiya I, et al. Successful long-term treatment with cyclosporin A in protein losing gastroenteropathy. Intern Med. May 2004;43(5):397-9. [Medline].
• Sunheimer RL, Finck C, Mortazavi S, et al. Primary lupus-associated protein-losing enteropathy. Ann Clin Lab Sci. May-Jun 1994;24(3):239-42. [Medline].
• Sutton DL, Kamath KR. Giardiasis with protein-losing enteropathy. J Pediatr Gastroenterol Nutr. Feb 1985;4(1):56-9. [Medline].
• 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. Aug 1999;82(2):241-3. [Medline]. [Full Text].
• Tift WL, Lloyd JK. Intestinal lymphangiectasia. Long-term results with MCT diet. Arch Dis Child. Apr 1975;50(4):269-76. [Medline].
• Tsutsumi A, Sugiyama T, Matsumura R, et al. Protein losing enteropathy associated with collagen diseases. Ann Rheum Dis. Mar 1991;50(3):178-81. [Medline].
• Tusseau F, Beaugerie L, Cardon B, et al. Anasarca caused by exudative enteropathy due to digestive Kaposi''s sarcoma [in French]. Presse Med. Sep 16 1989;18(28):1393. [Medline].
• Waldmann TA. Gastrointestinal protein loss demonstrated by 51Cr-labelled albumin. Lancet. 1961;July:121-3.
• Wargny D, Dichy J, de Broucker F, et al. Protein-losing enteropathy caused by intestinal metastases of melanosarcoma [in French]. J Radiol. Oct 1989;70(10):577-9. [Medline].
• Westphal V, Murch S, Kim S, et al. Reduced heparan sulfate accumulation in enterocytes contributes to protein-losing enteropathy in a congenital disorder of glycosylation. Am J Pathol. Dec 2000;157(6):1917-25. [Medline]. [Full Text].
• Wing-Harkins DL, Dellinger GW, Lynch C, Mihas AA. Eosinophilic gastro-enteritis associated with protein-losing enteropathy and protein C deficiency. J Int Med Res. Jan-Feb 1996;24(1):155-63. [Medline].
• Yamada M, Sumazaki R, Adachi H, et al. Resolution of protein-losing hypertrophic gastropathy by eradication of Helicobacter pylori. Eur J Pediatr. Mar 1997;156(3):182-5. [Medline].
• Yoshikawa I, Murata I, Tamura M, et al. A case of protein-losing gastropathy caused by acute Helicobacter pylori infection. Gastrointest Endosc. Feb 1999;49(2):245-8. [Medline].
• Zellers TM, Brown K. Protein-losing enteropathy after the modified Fontan operation: oral prednisone treatment with biopsy and laboratory proved improvement. Pediatr Cardiol. Mar-Apr 1996;17(2):115-7. [Medline].

Article Last Updated: Aug 24, 2006