Clinical Pearls & Morning Reports
Published August 23, 2023
Protein-losing enteropathy is an uncompensated loss of plasma proteins through the intestine. It is a syndrome, not a disease; therefore, it is important to identify the underlying cause. Read the NEJM Review Article here.
Q: What are the two principle pathophysiological mechanisms known to lead to protein-losing enteropathy?
A: The two principal pathophysiological mechanisms that compromise epithelial retention of interstitial contents are direct mucosal damage (either erosive or nonerosive) and failed lymph drainage, causing backflow through the epithelium into the lumen. Some diseases involve other pathophysiological mechanisms in addition to or instead of these two mechanisms.
Q: How does protein-losing enteropathy manifest clinically?
A: Protein-losing enteropathy is characterized by nonselective depletion of all plasma proteins. The presenting features of protein-losing enteropathy are hypoproteinemia, edema, nutritional deficiencies, infections, and gastrointestinal symptoms, including diarrhea, steatorrhea, abdominal pain, and vomiting. Hypoproteinemia is nonselective, with reduced albumin and immunoglobulin levels. Edema (of the face and arms and legs) and effusions (peritoneal, pleural, and pericardial) are caused by reduced oncotic pressure in blood. Infections can result from hypogammaglobulinemia and lymphopenia. In children, malabsorption and malnutrition may be severe, resulting in retarded growth and development.
A: Mucosal diseases cause loss of plasma proteins into the gut lumen. This is commonly seen in Crohn’s disease, ulcerative colitis, erosive gastritis, the Zollinger-Ellison syndrome, and pseudomembranous colitides. Other inflammatory conditions with erosive protein-losing enteropathy include sarcoidosis, graft-versus-host disease, and gastrointestinal amyloidosis. Infections can also precipitate inflammatory mucosal damage. Nonerosive mucosal epithelial permeability occurs with inflammation, infection, allergic reactions, or a genetic abnormality affecting the mucosa. Protein-losing enteropathy can occur in systemic lupus erythematosus, Sjögren’s syndrome, Henoch-Schönlein purpura, and pemphigus vulgaris. Celiac disease is frequently associated with protein-losing enteropathy. In intestinal lymphangiectasia (primary or secondary), lymph proteins are massively lost into the lumen, causing severe protein-losing enteropathy. Widespread or metastatic abdominal cancers can block lymph drainage, causing protein-losing enteropathy. Protein-losing enteropathy can be both a cause and a consequence of thrombotic disease.
A: Protein-losing enteropathy is diagnosed by ruling out other causes of hypoproteinemia and diarrhea or malabsorption; documenting enteric protein loss; performing imaging studies of the cardiovascular, thoracic, and abdominopelvic structures; assessing systemic manifestations of protein-losing enteropathy; and carrying out histopathological and, possibly, genetic testing. 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. The approach to care involves diagnosing and correcting the underlying disease while managing the manifestations of protein-losing enteropathy, principally with treatments that mitigate gastrointestinal protein loss and its sequelae, as well as providing emotional and family support. Correcting the underlying cause offers the best hope for long-term disease control.