Background
Protein-losing enteropathy is characterized by the severe loss of serum proteins into the intestine. [1] Normal protein loss in the gastrointestinal tract mainly consists of sloughed enterocytes and pancreatic and biliary secretions. Albumin loss through the gastrointestinal tract normally accounts for 2-15% of the total body degradation of albumin, but, in patients with severe protein-losing gastrointestinal disorders, the enteric protein loss may reach up to 60% of the total albumin pool.
The serum protein level reflects the balance between protein synthesis, metabolism, and protein loss. Protein-losing enteropathy is characterized by more loss of proteins via the gastrointestinal tract than synthesis leading to hypoalbuminemia. It is not a single disease, but an atypical manifestation of other diseases. [2]
Pathophysiology
The pathophysiology of this disorder is directly related to the excessive leakage of plasma proteins into the lumen of the gastrointestinal tract. Mechanisms for gastrointestinal protein loss include lymphatic obstruction, mucosal disease with erosions, ulcerations, or increased mucosal permeability to proteins as a result of cell damage or death. Proteins entering the gastrointestinal tract are metabolized into constituent amino acids by gastric, pancreatic, and small intestinal enzymes and are reabsorbed. When the rate of gastrointestinal protein loss exceeds the body's capacity to synthesize new proteins, hypoproteinemia develops. [3]
Etiology
Primary gastrointestinal mucosal diseases (typically ulcerative/erosive) include the following:
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Erosions or ulcerations of the esophagus, stomach, or duodenum
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Regional enteritis
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Graft versus host disease
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Pseudomembranous colitis (Clostridium difficile) [4]
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Mucosal-based neoplasia
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Carcinoid syndrome
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Idiopathic ulcerative jejunoileitis
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Amyloidosis [5]
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Protein dyscrasia
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Neurofibromatosis
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Cytomegalovirus infection [6]
Increased interstitial pressure or lymphatic obstruction leading to protein loss can be caused by the following:
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Retroperitoneal fibrosis
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Lymphoma
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Intestinal endometriosis
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Lymphoenteric fistula
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Cardiac disease (constrictive pericarditis or congestive heart failure)
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Intestinal lymphangiectasia [7]
Nonerosive upper gastrointestinal diseases include the following:
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Cutaneous burns [8]
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Whipple disease
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Connective tissue disorders
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Acquired immunodeficiency syndrome (AIDS) [2]
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Enteropathy, such as angioedema (idiopathic or hereditary) and Henoch-Schönlein purpura
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Tropical sprue
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Allergic gastroenteritis
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Eosinophilic gastroenteritis
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Bacterial overgrowth
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Intestinal parasites
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Microscopic colitis
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Dientamoeba fragilis [12]
Cases in which protein-losing enteropathy was the initial manifestation of systemic lupus erythematosus have been reported. [13, 14, 15, 16]
Protein-losing enteropathy can also occur as a complication of the Fontan procedure, an operation for several congenital heart abnormalities; the surgery allows systemic venous blood to reach the lungs without circulating through a ventricle. [17, 18, 19, 20] In children, protein-losing enteropathy may occur before or after the procedure, especially in the setting of hemodynamic disturbances. [21] Children potententially more affected with protein-losing enteropathy and plastic bronchitis may be those who are older when undergoing Fontan procedure and have a dominant right single ventricle. [22]
Epidemiology
United States statistics
The prevalence rate is not known.
International statistics
The prevalence rate is not known.
Race-, sex-, and age-related demographics
No racial, sexual, or age predilection exists.
Prognosis
A retrospective study by John et al indicated that the survival rate has increased for patients who develop protein-losing enteropathy as a complication of the Fontan procedure, an operation for the treatment of several types of congenital heart abnormalities. Although the 5-year mortality rate has been reported to be 50% for patients who develop protein-losing enteropathy following the surgery, the investigators found that in 42 such patients identified from Mayo Clinic clinical databases, the survival rate at 5 years after the diagnosis of enteropathy was 88%. [18]
The survival rate tended to be lower, however, in patients with a high Fontan pressure, reduced ventricular function (ejection fraction < 55%), and a New York Heart Association functional classification of greater than 2. Treatments associated with a higher survival rate included spironolactone, octreotide, and sildenafil, as well as the creation of fenestrae and Fontan obstruction relief. [18]
Mortality/Morbidity
Morbidity and mortality of this condition directly relate to its cause, either primary gastrointestinal disease or a multisystem disorder.
