eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Protein-Losing Enteropathy

Author: Barry K Wershil, MD, Professor and Chief, Division of Gastroenterology and Nutrition, The Children's Hospital at Montefiore, Department of Pediatrics, Albert Einstein College of Medicine
Coauthor(s): Alfredo Garcia, MD, Consulting Staff, Department of Pediatrics, Darin M Camarena Health Centers
Contributor Information and Disclosures

Updated: Aug 24, 2006

Introduction

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

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.

More on Protein-Losing Enteropathy

Overview: Protein-Losing Enteropathy
Differential Diagnoses & Workup: Protein-Losing Enteropathy
Treatment & Medication: Protein-Losing Enteropathy
Follow-up: Protein-Losing Enteropathy
References
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Further Reading

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Keywords

protein-losing enteropathy, PLE, chronic diarrhea, hypoproteinemia, hypoalbuminemia

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Contributor Information and Disclosures

Author

Barry K Wershil, MD, Professor and Chief, Division of Gastroenterology and Nutrition, The Children's Hospital at Montefiore, Department of Pediatrics, Albert Einstein College of Medicine
Barry K Wershil, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, North American Society for Pediatric Gastroenterology and Nutrition, Society for Mucosal Immunology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Alfredo Garcia, MD, Consulting Staff, Department of Pediatrics, Darin M Camarena Health Centers
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.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

David Piccoli, MD, Chief, Division of Gastroenterology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine
David 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, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health
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

Chief Editor

Steven M Altschuler, MD, President and CEO, Children's Hospital Foundation, Children's Hospital of Philadelphia
Disclosure: Nothing to disclose.

 
 
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