AUTHOR INFORMATION

Section 1 of 10

Authored by 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

Coauthored by Alfredo Garcia, MD, Consulting Staff, Department of Pediatrics, Darin M Camarena Health Centers

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

Edited by Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Associate Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; David Piccoli, MD, Chief, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia; Professor, Department of Pediatrics, University of Pennsylvania School of Medicine; Steven M Schwarz, MD, FAAP, FACN, Chair, Department of Pediatrics, Long Island College Hospital; Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; and Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, The Johns Hopkins University School of Medicine

Author's Email:	Barry K Wershil, MD
Editor's Email:	Robert Baldassano, MD

eMedicine Journal, August 24 2006, VOLUME 7, Number 8

INTRODUCTION

Section 2 of 10

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 10

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 10

Atopic Dermatitis
Burns, Chemical
Burns, Electrical
Burns, Thermal
Burns: Surgical Perspective
Cytomegalovirus Infection
Esophagitis
Giardiasis
Graft Versus Host Disease
Helicobacter Pylori Infection
Henoch-Schoenlein Purpura
Malnutrition
Measles
Necrotizing Enterocolitis
Nephrotic Syndrome
Noonan Syndrome
Salmonella Infection
Strongyloidiasis
Systemic Lupus Erythematosus

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 10

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 10

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 10

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.

Drug Name	ADEK vitamins (ADEKs) -- PO multinutrient specially formulated for use under medical supervision to provide nutritional supplementation in individuals with malabsorptive conditions. Each dose contains water-miscible forms of fat-soluble vitamins A, D, E, and K plus other nutrients, including vitamin C, B-complex vitamins, biotin, folic acid, and zinc. Available as chewable tab or pediatric drops.
Pediatric Dose	<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
Contraindications	Documented hypersensitivity
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
Pregnancy	A - Safe in pregnancy
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

Drug Name	Vitamin A (Aquasol A) -- Needed for night vision and growth of skin, bones, male reproductive organs, and female reproductive organs.
Pediatric Dose	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
Contraindications	Documented hypersensitivity
Interactions	Cholestyramine and colestipol decrease effects; mineral oil and neomycin may decrease absorption of vitamin A
Pregnancy	A - Safe in pregnancy
Precautions	Pregnancy category X if dose exceeds RDA

Drug Name	Ergocalciferol (Calciferol, Drisdol) -- Form of vitamin D used in vitamin supplements, necessary for strong bones and teeth.
Pediatric Dose	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
Contraindications	Documented hypersensitivity; hypercalcemia, malabsorption syndrome
Interactions	Colestipol, mineral oil, and cholestyramine may decrease absorption from small intestine; thiazide diuretics may increase effects of vitamin D
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

Drug Name	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.
Pediatric Dose	1 U/kg/d PO of water-miscible vitamin E
Contraindications	Documented hypersensitivity
Interactions	Mineral oil decreases absorption; delays absorption of iron and increases effects of anticoagulants
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

Drug Name	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.
Pediatric Dose	2.5-5 mg/d PO 1-2 mg/dose as a single dose IV/IM
Contraindications	Documented hypersensitivity
Interactions	Effects of warfarin, sodium, and dicumarol are antagonized by phytonadione
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

MISCELLANEOUS

Section 8 of 10

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)

TEST QUESTIONS

Section 9 of 10

CME Question 1: Which one of the following is true about the diagnosis of protein-losing enteropathy (PLE)?

A: It is a diagnosis of exclusion.
B: Diagnosis can only be confirmed by the use of radioactive substances.
C: Determination of fecal alpha1-antitrypsin (A1-AT) is the preferred diagnostic method.
D: Stool contamination with urine is a problem for the determination of fecal A1-AT.
E: Once PLE has been diagnosed, no further workup is required.

The correct answer is C: Since methods to identify serum proteins in stools exist, PLE is no longer a diagnosis of exclusion. Even though tests using radioactive substances can be used to confirm the diagnosis of PLE, the preferred method currently involves the determination of A1-AT. Because A1-AT is not excreted in urine, urine contamination of the stool sample does not alter the spot determination of fecal A1-AT.

CME Question 2: Which of the following regarding the diagnosis of protein-losing enteropathy (PLE) is most correct?

A: Heparin is the treatment of choice for all cases of PLE.
B: Corticosteroids are useful in all cases of PLE secondary to inflammation and ulceration.
C: Supplementation of vitamins A, D, E, and K is important in the management of PLE secondary to lymphatic obstruction.
D: Medium-chain triglyceride (MCT) oil is required to reduce inflammation in cases of PLE secondary to inflammation and ulceration.
E: Once PLE is established in patients who have undergone a Fontan procedure, it is irreversible.

The correct answer is C: Even though heparin has been successfully used to treat some patients in whom PLE has developed after the Fontan procedure, it is by no means the treatment of choice for all the different etiologies of PLE. Corticosteroids have been used in patients with PLE associated with collagen vascular diseases, inflammatory bowel disease, heart surgery, and others. They are not used in cases of PLE secondary to infections. 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. 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. The 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).

Pearl Question 1 (T/F): Protein-losing enteropathy (PLE) is a process that results in the loss of serum proteins into the GI tract and has been identified as a subclinical component of a variety of other disease processes.

The correct answer is True: PLE is a pathophysiologic process that results in the loss of serum proteins into the gastrointestinal tract. The protein loss from PLE must be differentiated from the loss of ingested proteins due to other disease processes, such as protein malabsorption. The basic problem in these patients is an increase in protein turnover. The most important advance in this area was the establishment of a simple and reliable test for PLE that involves measuring alpha1-antitrypsin (A1-AT) levels in the stool. This approach has been used to identify a variety of conditions that have subclinical PLE as a component of the disease process.

Pearl Question 2 (T/F): Patients with protein-losing enteropathy (PLE) secondary to lymphatic obstruction have lymphocytopenia and loss of immunoglobulins.

The correct answer is True: Obstruction of lymphatics from any cause can produce increased pressure throughout the lymphatic system of the gastrointestinal 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 gastrointestinal 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, a good response to antigenic challenge usually occurs. 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 exist that can produce inflammation and ulceration of the gastrointestinal 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.

Pearl Question 3 (T/F): A patient presents to the pediatrician's office complaining of edema. The pediatrician should consider protein-losing enteropathy (PLE) as one of the differential diagnoses and take an appropriate history.

The correct answer is True: PLE should be considered 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. The history should explore possible renal diseases (increased protein loss) or hepatic diseases (decreased protein synthesis) that could cause hypoalbuminemia. A complete GI history should also be obtained to evaluate for gut sources of excessive protein loss. For example, patients should be questioned about dietary intake (nutritional history); urinary frequency, urine color, and pain with urination; history of high blood pressure to evaluate for possible renal disease; alcohol intake; history of hepatitis, fatigue, and jaundice to evaluate for liver disease; and 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. Questioning the patient or parents about other lymphatic abnormalities that might have been present is also important. Finally, a cardiac history should be obtained, including congenital heart disease, prior episodes of pericarditis, serious streptococcal infection, and prior heart surgery.

Pearl Question 4 (T/F): The presence of liver disease or nephrotic syndrome excludes the need to evaluate for protein-losing enteropathy (PLE) as the cause of hypoalbuminemia.

The correct answer is False: In most cases, liver disease or nephrotic syndrome would be the only cause for the hypoalbuminemia, but both can increase the pressure in the intra-abdominal lymphatic system, producing PLE.

BIBLIOGRAPHY

Section 10 of 10

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