Protein-losing enteropathy

What is protein-losing enteropathy?

Protein-losing enteropathy (PLE) is a rare condition characterised by a loss of serum protein into the gastrointestinal (GI) tract, resulting in hypoproteinaemia which can be complicated by oedema, ascites, pleural and pericardial effusions and malnutrition.¹

Protein-losing enteropathy occurs in a number of GI conditions that cause excessive loss of serum proteins into the GI tract. Three main mechanisms are involved, as below.

Mucosal disease with ulceration with protein loss across disrupted mucosal surface

• Chronic gastric ulcer.

• Gastric carcinoma.

• Lymphoma.

• Inflammatory bowel disease.²

• Idiopathic ulcerative jejunoileitis.

Lymphatic obstruction causing loss of protein-rich chyle

• Primary intestinal lymphangectasia.³

• Secondary obstruction due to:

  • Heart disease.⁴

  • Infection.

  • Neoplasm.

  • Retroperitoneal fibrosis.

  • Sarcoidosis.

Idiopathic alterations in mucous capillary permeability

• Ménétrier's disease.⁵

• Zollinger-Ellison syndrome.

• Acute viral or eosinophilic gastroenteritis.

• Coeliac disease.

• Allergic protein-losing enteropathy.

• Giardiasis and hookworm infections.

• Amyloidosis.

• Common variable immunodeficiency.

• Systemic lupus erythematosus (SLE).⁶

Protein-losing enteropathy is also common after the Fontan or Fontan Kreutzer procedure which is the culmination of staged, surgical palliation of functional single ventricle congenital heart disease. As patients with Fontan circulation are now living longer, a variety of complications involving almost every organ system may occur. Protein-losing enteropathy is a major cause of morbidity and mortality after the Fontan operation, occurring more often in patients with adverse haemodynamics and presenting weeks to years after Fontan surgery. ⁷⁸

Protein-losing enteropathy can also occur secondary to graft versus host disease.⁹

Because the condition is multifactorial, the prevalence rate is not known.

Protein-losing enteropathy is a common complication of Fontan's operation.¹ 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.

The clinical presentation is very variable, depending on the underlying cause but mainly consists of oedema due to hypoproteinaemia.¹ Consider protein-losing enteropathy 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 (eg, 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 - eg, height, weight, head circumference in children.

• Look for signs of acute liver disease (eg, enlarged liver, tenderness in the right upper quadrant).

• Look for signs of chronic liver disease (eg, jaundice, splenomegaly, prominent veins on the abdomen).

• Check for signs of right heart failure - eg, ascites and jugular vein distension.

• The finding of high blood pressure may suggest renal or cardiac disease.

• Look for signs of GI pathology - eg, abdominal tenderness, macroscopic or microscopic blood and mucus in the stool.

• Collagenous and lymphocytic colitis.

• Hypoalbuminaemia.

• Hypogammaglobulinaemia.

• Inflammatory bowel disease.

• Malabsorption.

• Mycoplasma infections.

• Pericarditis.

• Restrictive cardiomyopathy.

• Salmonellosis.

• Yersinia enterocolitica.

The initial step in the evaluation of any patient with hypoproteinaemia and/or low albumin levels is to exclude other, more common causes, such as malnutrition, liver, and renal diseases.

• Serum proteins - by definition low albumin levels 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.

• Alpha-1-antitrypsin (A1AT):

  • A1AT is a protein synthesised in the liver that is neither actively secreted nor absorbed.

  • Gastrointestinal protein loss is assessed by quantitating fecal alpha₁ -antitrypsin in a random stool sample, or more accurately, by measuring alpha₁ -antitrypsin clearance in a 24-hour stool collection with simultaneous serum measurement.¹¹

• Viral serologies may be useful.

• Scintigraphy is an 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 Tc ^99m labelled dextran or human serum albumin.¹² This test is expensive and time-consuming and is usually reserved for patients who have a negative A1AT test.¹⁰

• Endoscopy and biopsy can reveal anatomical malformations, obstruction, mucosal inflammation, ulceration, dilated lacteals and lymphangiectasia, and neoplasms.¹¹ To evaluate the intestines distal to the ligament of Treitz, video capsule endoscopy or double-balloon enteroscopy is used.

There is no specific treatment for protein-losing enteropathy and so management is directed at the underlying cause and treatment for malnutrition and micronutrient deficiencies.¹

Non-drug treatment

Dietary therapy is the mainstay of treatment for primary intestinal lymphangiectasia and consists of high protein (2 g/kg/day) and low-fat content (<25 g/day). ¹³

Drug treatment

• The main principle is to treat the underlying cause. One study reported the resolution of protein-losing enteropathy by the simple measure of treating the patient's chronic diarrhoea with loperamide. The use of diuretics for congestive heart failure is another example.¹⁴

• Octreotide has been shown to be useful in some patients.¹⁵ 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.

• Total parenteral nutrition with a protein rich oral nutrition has also been used to support recovery.¹⁶

Surgery for protein-losing enteropathy patients

• In patients who have undergone Fontan's 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 (eg, 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.¹⁷

• Cardiac transplant is occasionally used to treat intractable PLE in patients who have had previous heart surgery.