Rudolph's Pediatrics, 22nd Ed.

CHAPTER 390. Protein-Losing Enteropathy

Richard J. Noel

PATHOPHYSIOLOGY

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.

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

^* Right atrial to pulmonary arterial anastomosis.

CLINICAL FEATURES AND DIFFERENTIAL DIAGNOSIS

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-forage, 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 steator-rhea. 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.

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.

DIAGNOSTIC EVALUATION

Fecal α₁-antitrypsin excretion in the stool has largely replaced radioisotopic techniques¹ for the evaluation for protein-losing enteropathy.² It is a serum protein that is not present in the diet, and fecal levels reflect protein originating in the serum and leaking into the bowel. Its molecular weight of 50,000 is similar to that of albumin. As a protease inhibitor it resists intraluminal proteolysis and is excreted without degradation in the stool. Urine contamination of the stool specimen will not invalidate the result, a feature that is particularly helpful in pediatric patients. Stool α₁-antrypsin levels show little variation with repeated sampling, allowing the use of randomly obtained samples rather than a timed stool collection. In addition, the fecal α₁-antitrypsin is stable at room temperature and is not degraded, allowing convenient transport and storage of specimens for assay. α₁-Antitrypsin is digested in gastric juice, so the reliability of fecal α₁-antitrypsin in detecting esophageal or gastric protein loss is questionable. Testing is not meaningful until after 1 week of age because meconium contains rather large amounts of α₁-antitrypsin.

Computed tomography may demonstrate bowel wall thickening suggestive of lymphangiectasia or occult inflammatory disorders, or small bowel capsule endoscopy may aid in identifying lesions such as lymphangiectasia. Primary gastrointestinal disorders are identified by endoscopy with biopsy, stool culture, and ova and parasite examination. Lymphangiography is often challenging in children but may identify a specific lymphatic obstruction.

TREATMENT

Although treatment of protein-losing enter-opathy requires treatment of the underlying disease, some patients with protein-losing enteropathy following Fontan procedures have been reported to respond to steroids and low-molecular-weight heparin,³ correction of hypocalcemia, or sildenafil.⁴ Octreotide injections have been anecdotally reported to be effective.⁵ Oral mannose therapy is effective in treating the carbohydrate-deficient glycoprotein syndrome 1b.⁶ When specific therapy is not available, high protein intakes should be encouraged to compensate for the protein loss. Occasionally, intermittent albumin infusion is required to improve the patient’s quality of life.