Protein-losing Enteropathy

Protein-losing enteropathy (PLE) occurs in a number of gastro-intestinal conditions that cause excessive loss of serum proteins into the gastrointestinal (GI) tract.¹
Three main mechanisms are involved:

Mucosal disease with ulceration with protein loss across disrupted mucosal surface

• Chronic gastric ulcer
• Gastric carcinoma
• Lymphoma
• Inflammatory bowel disease
• Idiopathic ulcerative jejunoileitis

Lymphatic obstruction causing loss of protein rich chyle

• Primary intestinal lymphangectasia
• Secondary obstruction due to heart disease,² infection, neoplasm, retroperitoneal fibrosis or sarcoidosis

Idiopathic alterations in mucous capillary permeability

• Menetrier's Disease
• Zollinger-Ellison syndrome
• Acute viral or eosinophilic gastroenteritis
• Coeliac sprue
• Allergic protein losing enteropathy
• Giardiasis and hookworm infections
• Amyloidosis
• Common variable immunodeficiency
• SLE.

Because the condition is so multi-factorial, the prevalence rate is not known.

Consider PLE in any patient presenting with oedema, especially if this is against a background of GI disease.

History

• A dietary history should be taken to exclude malnutrition as a cause of reduced albumin synthesis.
• Check the patient's medical history for information about renal disease (increased protein loss) or hepatic disease (reduced albumin synthesis).
• Ask about GI symptoms, in particular any symptoms suggestive of enteritis (e.g. diarrhoea, abdominal pain).
• Ask about alcohol intake.
• Check for a history of congenital heart disease, episodes of pericarditis, serious streptococcal infection, or prior heart surgery (increased interstitial pressure can be a cause).

Examination

• Check the general nutritional status of the patient - e.g. height, weight, head circumference in children.
• Look for signs of acute liver disease (e.g. enlarged liver, tenderness in the right upper quadrant).
• Look for signs of chronic liver disease (e.g. jaundice, splenomegaly, prominent veins on the abdomen).
• Check for signs of right heart failure - e.g. ascites and jugular vein distension.
• The finding of high blood pressure may suggest renal or cardiac disease.
• Look for signs of GI pathology - e.g. abdominal tenderness, macroscopic or microscopic blood and mucus in the stool.

• Atopic dermatitis
• Burns - chemical, electrical or thermal
• Congestive heart failure
• Cytomegalovirus Infection
• Oesophagitis
• Giardiasis
• Graft versus host disease
• Helicobacter pylori infection
• Henoch-Schonlein purpura
• Liver disease
• Malnutrition
• Measles
• Necrotising enterocolitis
• Nephrotic syndrome
• Noonan syndrome
• Salmonella infection
• Strongyloidiasis
• Systemic lupus erythematosus³
• Waldenstrom macroglobulinemia⁴

• Serum proteins - by definition hypoalbuminaemia will be present.
• Liver and renal disease should be excluded by the appropriate function tests.
• Evidence of protein loss via the GI tract should be investigated in patients with oedema, hypoalbuminaemia and normal renal and liver function tests.
• Raised alpha1-antitrypsin levels in stools is a marker for protein loss⁵ but is not very specific as this is also seen in liver disease.
• Scintigraphy is a more accurate test. It involves the use of radio-labelled substances which are administered intravenously and then detected by the use of serial abdominal X-rays. The two common agents used are technetium labelled (Tc-99m) dextran⁶ or human serum albumin.⁷ These substances have been chosen because they are readily available (and therefore cheap), easy to administer and inert.

Non-drug

In lymphatic obstruction patients should in theory be helped by low fat diet with medium chain triglyceride supplement.⁸ However, in practice this results in increased blood flow with no reduction in faecal protein loss.

Drugs

• The underlying cause should be treated (e.g. diuretics for congestive cardiac failure).
• Octreotide has been shown to be useful in some patients.⁹ It is a potent inhibitor of many hormones affecting the gut and has a marked effect on reducing blood flow to the intestines.
• Supplementation with fat-soluble vitamins may be helpful.
• PLE is a common complication of the Fontan operation. This is a procedure carried out in children with severe congenital heart disease in which venous blood is diverted from the right atrium to the pulmonary arteries without passing through the right ventricle. Heparin produces benefits independent of its anticoagulant effect.¹⁰ Steroids can also be helpful, but the beneficial effect tends to be transient.¹¹

Surgery

• In patients who have undergone the Fontan procedure, making a window in the baffle that separates the systemic venous pathway from the pulmonary venous atrium has helped to resolve PLE, presumably due to a reduction in systemic venous pressure.
• In patients whose PLE is secondary to a cardiac cause (e.g. restrictive cardiomyopathy, constrictive pericarditis, tricuspid valvar stenosis and insufficiency), restoration of the unobstructed flow of blood in the superior or inferior caval vein may be curative. Post-Fontan patients may benefit, but are unlikely to be cured.¹²
• Cardiac transplant is occasionally used to treat intractable PLE in patients who have had previous heart surgery.
• PLE after a Fontan operation associated with lymphangiectasia (blockage of the intestinal lymphatics) has been successfully treated by resection of the affected area of bowel.¹³

This depends on the underlying disease, but improved management techniques are reducing mortality and morbidity of many causes. More than half the patients presenting with PLE now reach partial or complete remission, but require regular monitoring of their nutritional status.¹⁴