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Protein-losing enteropathy is due to leakage of serum proteins through the mucosal lining into the lumen of the intestine. This may result from disruption of the mucosal surface by inflammation or erosion, rupture of lacteals from high pressure in the thoracic duct, or damage to the mucosal surface with disruption of the mucosal barrier.

Protein-losing enteropathy is a process with an extensive differential diagnosis. Symptoms of the underlying illness, including diarrhea, abdominal pain, and allergic phenomena, may be elicited in the history. Weight-for-age, height-for-age, and weight-for-height can rule out malnutrition as a cause of hypoalbuminemia. Edema is a frequent finding, and asymmetric lymphedema may suggest an underlying malformation of lymphatic channels such as primary intestinal lymphangiectasia.

Conditions associated with protein-losing enteropathy are listed in Table 390-1 and are discussed in other sections of this chapter. Fifty percent to 60% of children with Crohn disease have mild to pronounced hypoalbuminemia. Protein-losing enteropathy and finger clubbing have been reported as complications of gastroesophageal reflux. Protein-losing enteropathy with hypoalbuminemia occurs in 25% of patients after bone marrow transplantation as a result of graft-versus-host disease of the intestine. Intestinal lymphangiectasia causes protein loss, including immunoglobulins, lymphocytes, hypogammaglobulinemia, and steatorrhea. The intestine may be the only site of lymphatic obstruction, or it may coexist with multifocal lymphatic dysplasia (eg, Noonan syndrome). Cardiac disorders or surgical procedures in which elevated right atrial pressure is transmitted to the superior vena cava and thoracic duct, including the Fontan procedure and clinically silent constrictive pericarditis, can cause intestinal lymphangiectasia and protein-losing enteropathy. Ménétrier disease is characterized by hypoalbuminemia due to protein losses from hypertrophic gastric folds (see Chapter 409). Newly described entities in which protein-losing enteropathy is prominent include the carbohydrate-deficient glycoprotein syndrome 1b and congenital heparan sulfate deficiency. Intestinal lymphangiectasia has been found in intestinal biopsy specimens of some children with idiopathic nephritic syndrome and protein-losing enteropathy.

Table 390-1. Protein-Losing Enteropathy in Pediatric Population

Other causes of hypoalbuminemia, such as renal disease, liver disease, and malnutrition, should be excluded by urinalysis and liver function studies. A reliable estimate of hepatic synthetic function is provided by the prothrombin time. Vitamin K deficiency resulting from intestinal malabsorption can lead to an abnormal result, but this should correct promptly after a parenteral dose of vitamin K.

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