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Protein-Losing Enteropathy

Simon S Rabinowitz, MD, PhD, Professor of Clinical Pediatrics, New York Medical College; Chairman, Chief and Medical Administrator, Department of Pediatrics, Chief, Pediatric Gastroenterology and Nutrition, Richmond University Medical Center

Updated: Aug 17, 2009

Introduction

Background

Protein-losing enteropathy (PLE) is not a single disease but a consequence of a range of pathophysiologic processes that result in the loss of serum proteins into the GI tract. Although enteropathy is defined as an intestinal disease, protein-losing enteropathy includes loss of protein from the esophagus and stomach as well. Some authors have used the term protein-losing gastroenteropathy.

Protein-losing enteropathy can be either a primary manifestation or a subclinical component of various diseases. 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 protein-losing enteropathy. 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 protein-losing enteropathy. This approach has identified various conditions that have subclinical protein-losing enteropathy as a component of the disease process.

Pathophysiology

No single explanation accounts for the loss of protein into the GI tract seen in various clinical conditions. Recent experimental work has focused on the loss of heparan sulfate proteoglycans from the basolateral surface of the intestinal epithelial cell. Although 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 protein-losing enteropathy.

In vitro analyses have demonstrated that loss of this proteoglycan not only directly causes protein-losing enteropathy but also potentiates the effects of other reputed factors such as inflammatory cytokines and increased pressure.1 In addition, infants and children with various forms of congenital glycosylation defects, another potential mechanism for loss of heparin sulfate proteoglycans, also have protein-losing enteropathy secondary to increased intestinal permeability.2

Protein-losing enteropathy must always be distinguished from the loss of protein through other organs, most commonly the kidney and skin. One potential clue is that renal losses of protein are usually limited to smaller proteins such as albumin where as the GI tract and skin losses are less discriminating. In addition, hypoalbuminemia may be secondary to synthetic dysfunction or excessive catabolism rather than the result of increased losses.

For practical purposes, the disease processes that cause protein-losing enteropathy can be grouped into the following 3 major categories: (1) protein-losing enteropathy secondary to lymphatic obstruction, (2) protein-losing enteropathy secondary to mucosal erosion or ulceration, and (3) protein-losing enteropathy secondary to epithelial cell dysfunction in the absence of macroscopic compromise.

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 protein-losing enteropathy due to primary intestinal lymphangiectasia, Whipple disease, or constrictive pericarditis. In cases of protein-losing enteropathy 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 protein-losing enteropathy, 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.

Frequency

United States

No published data have reported an accurate incidence or prevalence of protein-losing enteropathy in any parts of the United States.

International

No published have reported an accurate incidence or prevalence. The incidence is highest in areas with significant infectious enterocolitis. A recent multicenter European review of over 3000 patients with Fontan procedure describes a prevalence of 3.9%.3  These authors used stringent criteria; three fourths of the patients had effusions and edema. Other studies have reported an even higher prevalence after this surgery.

Mortality/Morbidity

Morbidity and mortality is dependent on these diseases that are the cause of the protein-losing enteropathy and the availability of prompt recognition and treatment. In the European cohort of Fontan patients described above, medical treatment was ineffective in 75%, with a mortality of 46%, and surgical treatment was ineffective in 81%, with a mortality of 62%.

Clinical

History

Consider protein-losing enteropathy (PLE) in any patient presenting with edema. When considering protein-losing enteropathy, 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 protein-losing enteropathy.
  • 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 protein-losing enteropathy.
  • The finding of high blood pressure may suggest renal or cardiac disease.
  • GI findings compatible with protein-losing enteropathy include the following:
    • Diarrhea
    • Abdominal tenderness
    • Macroscopic or microscopic blood and mucus in the stool
  • Localized edema is suggestive of primary intestinal lymphangiectasia.

Causes

As indicated above, many disease processes can lead to protein-losing enteropathy. The following is an approach to categorizing the underlying etiology.

Lymphatic losses

  • Enteric lymphatic obstruction
    • Primary enteric lymphatic obstruction
      • Malrotation
      • Tuberculosis
      • Lymphoma
      • Sarcoidosis
      • Radiation enteritis
      • Retroperitoneal fibrosis or tumor
      • Arsenic poisoning
      • Secondary to unusual causes of bowel infiltration -Gaucher disease4 and Langerhans cell histiocytosis5
    • Cardiac causes of increased systemic venous pressure
      • Constrictive pericarditis
      • Congestive heart failure
      • Cardiomyopathy
      • Post–Fontan procedure 
  • Primary intestinal lymphangiectasia
  • Secondary intestinal lymphangiectasia
  • Whipple disease

Genetic causes

  • Congenital disorders of glycosylation (may involve enterocyte disruption without any ulceration)

Inflammation of the GI tract

  • Infectious causes
      • Bacterial overgrowth (may involve enterocyte disruption without any ulceration)
      • Clostridium difficile
      • Clostridium perfringens
      • Colonic malakoplakia
      • Cytomegalovirus
      • Giardia lamblia
      • Helicobacter pylori
      • Malaria (may involve enterocyte disruption without any ulceration)
      • Measles (may involve enterocyte disruption without any ulceration)
      • Rotavirus (may involve enterocyte disruption without any ulceration)
      • Salmonella
      • Schistosomiasis (may involve enterocyte disruption without any ulceration)
      • Strongyloides stercoralis
  • Noninfectious causes with ulceration
    • Anastomotic ulceration/ischemia
    • Cow's milk/soy protein allergy (may involve enterocyte disruption without any ulceration)
    • Eosinophilic gastroenteritis (may involve enterocyte disruption without any ulceration)
    • Erosive gastritis
    • Graft versus host disease
    • Henoch-Schönlein purpura (may involve enterocyte disruption without any ulceration)
    • Hirschsprung disease
    • Inflammatory bowel disease
    • Multiple polyposis
    • Necrotizing enterocolitis
    • Peptic esophagitis
    • Ulcerative jejunitis
  • Noninfectious causes with breakdown of enterocyte barrier
    • Gluten sensitive enteropathy
    • Hypertrophic gastropathy (Menetrier disease)
    • Juvenile rheumatoid arthritis
    • Malnutrition
    • Systemic lupus erythematosus
    • Systemic phenobarbital hypersensitivity
    • Tropical sprue

Differential Diagnoses

Atopic Dermatitis
Kwashiorkor
Burns, Chemical
Liver diseases that compromise synthetic function
Burns, Electrical
Nephrotic Syndrome
Burns, Thermal
Noonan Syndrome
Burns: Surgical Perspective

Other Problems to Be Considered

See Causes.

Workup

Laboratory 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, protein-losing enteropathy was often considered a diagnosis of exclusion; however, several approaches for determining abnormal protein loss in the GI tract are currently noted. The ideal test for protein-losing enteropathy is able to detect a serum protein in the stool that is not secreted, digested, or reabsorbed in the GI tract. However, no ideal test is available.

Three established types of tests have been used to evaluate for protein-losing enteropathy. 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. A recent publication described the use of MRI as an alternative method to diagnose and localize this condition.6

  • History of radiolabeled proteins
    • Use of radiolabeled proteins to measure albumin turnover dates back to 1950 with Kinsell.7
    • 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 protein-losing enteropathy, Citrin reported that the131 I-albumin lost in the stomach was degraded and the free131 I was then absorbed and excreted in the urine, making the measurement of131 I in the stools unreliable.
    • Gordon reported the use of polyvinylpyrrolidone iodine I 125 (131 I-PVP) as a marker for protein metabolism.8 PVP is a macromolecule that is not digested by intestinal enzymes and is poorly absorbed when taken by mouth. In patients with protein-losing enteropathy, intravenously administered131 I-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, the131 I 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. The51 Cr 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 protein-losing enteropathy as determined by51 Cr-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 efficacy of using fecal A1-AT levels and A1-AT clearance for diagnosis and follow-up care in patients with protein-losing enteropathy.
  • Nuclear scintigraphy (described below)

Imaging Studies

  • Nuclear scintigraphy
    • Several radiopharmaceuticals tagged to proteins have been used to examine protein-losing enteropathy, including indium-111 (111In)–transferrin, technetium-99m (99mTc)–human serum albumin, and 99mTc-dextran. The latter compound is reported to be superior for numerous technical reasons.
    • This technique has been reported to be useful in the diagnosis of protein-losing enteropathy, 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 protein-losing enteropathy (ie, stomach vs small intestine or even regional differences in the small bowel).
  • MRI: MRI was able to reveal abnormalities in both the intestine and mesentery and documented dilated thoracic duct and mesenteric lymphatic as well as prominent subcutaneous lymphatics in the extremity.6

Procedures

  • In addition to the investigations listed above to document and localize the protein-losing enteropathy, a thorough orderly evaluation is required in the patient with protein-losing enteropathy to determine the underlying etiology of the protein loss. This usually begins with cultures for the infectious causes listed above, serologic evaluation for the immune conditions listed above, and radiographic studies (contrast studies, CT scans, MRI) to localize the area of involvement and identify characteristic patterns.
  • Often, endoscopy is also performed to assess for specific features such as the hypertrophic gastric folds of Menetrier disease, the pseudomembranes of C difficile colitis, the scalloping of the duodenum in sprue, and the stigmata of inflammatory bowel disease. At the time of endoscopy, biopsies are obtained to confirm the histological findings listed below.

Histologic Findings

  • Intestinal and more rarely gastric biopsies are at times required to definitively diagnose the underlying diseases that are the cause of the protein-losing enteropathy. Examples include Crohn disease, ulcerative colitis, celiac disease, graft versus host disease, Whipple disease, lymphoma, Hirschsprung disease, pseudomembranous colitis, eosinophilic gastroenteritis, allergic enteropathy, and some infectious diseases.
  • Lymphangiectasia is also a histologic diagnosis, revealing dilated lacteals in the mucosa.

Treatment

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 protein-losing enteropathy is noted. 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 protein-losing enteropathy 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 protein-losing enteropathy, 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.
  • Protein-losing enteropathy 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).9
    • As many as 13.4% of patients undergoing a Fontan procedure develop protein-losing enteropathy 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.
    • The use of steroids has produced temporary clinical and pathological resolution of protein-losing enteropathy.
    • Heparin has also been reported to improve protein-losing enteropathy 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.
    • Although heparin has been successfully used to treat some patients with protein-losing enteropathy that develops after the Fontan procedure, it is by no means the treatment of choice for all the etiologies of protein-losing enteropathy.
  • Corticosteroids have been used in patients with protein-losing enteropathy 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 protein-losing enteropathy. Immunosuppressive drugs should not be used in cases of protein-losing enteropathy 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 protein-losing enteropathy, 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 protein-losing enteropathy 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.10

Diet

  • In patients whose protein-losing enteropathy is related to lymphatic pathology, decreasing the lymphatic circulation provides some benefit. This requires dietary limitation of long-chain triglycerides because their absorption from the gut stimulates lymphatic flow. In order to provide adequate energy, medium-chain triglycerides must be added as an alternative source of lipid calories. 
  • As described below, fat soluble vitamins must also be supplemented because their absorption is compromised in these patients.

Medication

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 protein-losing enteropathy because the small amounts available in a regular diet are insufficient in the face of the malabsorption that occurs.


ADEK vitamins (AquADEKs Pediatric Liquid, ADEKs Chewable)

PO multinutrient specially formulated for use under medical supervision to provide nutritional supplementation in individuals with malabsorptive conditions. Each 1 mL dose contains water-miscible forms of fat-soluble vitamins A (5,751 U), D (400 U), E (65 U), and K (400 mcg) plus other nutrients, including vitamin C (15 mcg), B-complex vitamins, biotin, selenium (10 mcg), and zinc gluconate (5 mg). Available as chewable tab or pediatric drops.

Dosing

Adult

Pediatric

<12 months: 1 mL PO qd
1-3 years: 2 mL PO qd
4-10 years: 1 tab PO qd
>10 years: 2 tabs PO qd

Interactions

Best administered with supplementary pancreatic enzymes for individuals who require enzyme therapy for control of steatorrhea or improved fat absorption; vitamin K interferes with actions of anticoagulant drugs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Do not exceed recommended doses; contraindicated in pregnancy if vitamin A exceeds RDA; exclude pernicious anemia before using because folic acid in doses >0.1 mg/d may mask symptoms; for chewable tab, chew or crush tab thoroughly before swallowing


Vitamin A (Aquasol A)

Needed for night vision and growth of skin, bones, male reproductive organs, and female reproductive organs.

Dosing

Adult

Pediatric

Doses given PO qd
<1 year: 375 mcg
1-3 years: 400 mcg
4-6 years: 500 mcg
7-10 years: 700 mcg
>10 years: 800-1000 mcg
Adolescent males: 1000 mcg
Adolescent females: 800 mcg
Retinol equivalents (RE): 0.3 mcg RE = 1 U vitamin A

Interactions

Cholestyramine and colestipol decrease effects; mineral oil and neomycin may decrease absorption of vitamin A

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Safe in pregnancy

Precautions

Pregnancy category X if dose exceeds RDA


Ergocalciferol (Calciferol, Drisdol)

Form of vitamin D used in vitamin supplements, necessary for strong bones and teeth.

Dosing

Adult

Pediatric

Premature infants: 10-20 mcg/d PO (400-800 U), not to exceed 750 mcg/d (300,000 U)
Infants and healthy children: 10 mcg/d PO (400 U)
1 mcg = 40 USP U

Interactions

Colestipol, mineral oil, and cholestyramine may decrease absorption from small intestine; thiazide diuretics may increase effects of vitamin D

Contraindications

Documented hypersensitivity; hypercalcemia, malabsorption syndrome

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Pregnancy category C per manufacturer; expert analysis category A, category D if dosage exceeds RDA; adequate dietary calcium needed for clinical response; maintain adequate fluid intake; caution in impaired renal function, renal stones, heart disease, or arteriosclerosis


Vitamin E (Vita-Plus E Softgels, Vitec)

Protects polyunsaturated fatty acids in membranes from attack by free radicals and protects red blood cells against hemolysis.

Dosing

Adult

Pediatric

1 U/kg/d PO of water-miscible vitamin E

Interactions

Mineral oil decreases absorption; delays absorption of iron and increases effects of anticoagulants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Pregnancy factor is C with large doses of vitamin E; may induce vitamin K deficiency; necrotizing enterocolitis may occur when large doses of vitamin E given


Vitamin K (AquaMEPHYTON)

Fat-soluble vitamin absorbed by the gut and stored in the liver; necessary for the function of clotting factors in the coagulation cascade; used to replace essential vitamins not obtained in sufficient quantities in the diet or to further supplement levels.

Dosing

Adult

Pediatric

2.5-5 mg/d PO
1-2 mg/dose as a single dose IV/IM

Interactions

Effects of warfarin, sodium, and dicumarol are antagonized by phytonadione

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Ineffective in hereditary hypoprothrombinemia; rapid infusion may result in flushing and a feeling of constriction in chest; relatively nontoxic, even in massive doses

Follow-up

Further Outpatient Care

  • Patients who develop protein-losing enteropathy (PLE) after Fontan procedures represent a particularly vulnerable cohort with a high rate of significant morbidity and mortality.
  • Close follow-up coupled with an aggressive approach to reverse this problem is warranted.

Miscellaneous

Medicolegal 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 protein-losing enteropathy with fat-soluble vitamins (ie, A, D, E, K)
  • Failure to recognize the poor prognosis of patients with protein-losing enteropathy after Fontan.

References

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Keywords

protein-losing enteropathy, PLE, chronic diarrhea, hypoproteinemia, hypoalbuminemia, protein-losing gastroenteropathy, idiopathic hypoproteinemia, edema disease, nephrosis without nephrosis, nephrotic syndrome, liver disease, jaundice, splenomegaly, ascites, malrotation, tuberculosis, lymphoma, sarcoidosis, arsenic poisoning, Gaucher disease, Langerhans cell histiocytosis, constrictive pericarditis, congestive heart failure, cardiomyopathy, Clostridium difficile, Clostridium perfringens, Giardia lamblia, Helicobacter pylori, colonic malakoplakia, cytomegalovirus, malaria, measles, rotavirus, salmonella, schistosomiasis, graft versus host disease, Henoch-Schönlein purpura, Hirschsprung disease, inflammatory bowel disease, necrotizing enterocolitis, juvenile rheumatoid arthritis, malnutrition, systemic lupus erythematosus, tropical sprue, treatment, diagnosis

Contributor Information and Disclosures

Author

Simon S Rabinowitz, MD, PhD, Professor of Clinical Pediatrics, New York Medical College; Chairman, Chief and Medical Administrator, Department of Pediatrics, Chief, Pediatric Gastroenterology and Nutrition, Richmond University Medical Center
Simon S Rabinowitz, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Gastroenterology, American Gastroenterological Association, American Medical Association, New York Academy of Sciences, North American Society for Pediatric Gastroenterology and Nutrition, Phi Beta Kappa, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology and Nutrition, Associate Professor, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania
Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

David A Piccoli, MD, Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine
David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, Children's Hospital at Downstate, SUNY-Downstate Medical Center
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Barry K Wershil, MD, to the original writing and development of this article.

Further Reading

  • Proujanksy R. Protein-Losing Enteropathy. In Walker, Durie, Hamilton, et al eds: Pediatric Gastrointestinal Disease. BC Decker Inc. 2002.
  • Levin MS. Miscellaneous diseases of the small intestine: Protein-losing gastroenteropathy. In Tadataka Y, ed: Textbook of Gastroenterology. KB Lippincott. 1996.

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