PEDIATRICS Vol. 107 No. 2 February 2001, pp. 416-417

EXPERIENCE AND REASON:
A Case of Protein-Losing Enteropathy Caused by Intestinal Lymphangiectasia in a Preterm Infant

	ABSTRACT

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Intestinal lymphangiectasia is characterized by obstruction of lymph drainage from the small intestine and lacteal dilation that distorts the villus architecture. Lymphatic vessel obstruction and elevated intestinal lymphatic pressure in turn cause lymphatic leakage into the intestinal lumen, thus resulting in malabsorption and protein-losing enteropathy. Intestinal lymphangiectasia can be congenital or secondary to a disease that blocks intestinal lymph drainage. We describe the first case of intestinal lymphangiectasia in a premature infant. The infant presented with peripheral edema and low serum albumin; high fecal concentration of ₁-antitrypsin documented intestinal protein loss. Endoscopy showed white opaque spots on the duodenal mucosa, which indicates dilated lacteal vessels. Histology confirmed dilated lacteals and also showed villus blunting. A formula containing a high concentration of medium chain triglycerides resulted in a rapid clinical improvement and normalization of biochemical variables. These features should alert neonatologists to the possibility of intestinal lymphangiectasia in newborns with hypoalbuminemia and peripheral edema. The intestinal tract should be examined for enteric protein losses if other causes (ie, malnutrition and protein loss from other sites) are excluded. The diagnosis rests on jejunal biopsy demonstrating dilated lymphatic lacteal vessels.

Protein-losing gastroenteropathy (PLGE) includes a large group of diseases characterized by enteric loss of plasma proteins in abnormal amounts.¹ In most instances, PLGE is caused by enhanced mucosal permeability to proteins consequent to cell damage, mucosal erosions or ulcerations, and lymphatic obstruction. Protein-losing gastroenteropathy includes nonulcerative diseases (eosinophil gastroenteritis and Menetrier's disease); ulcerative diseases (erosive gastritis and inflamed bowel disease); and disorders resulting from lymphatic obstruction (congenital intestinal lymphangiectasia and Whipple's disease).

Intestinal lymphangiectasia is characterized by obstruction of lymph drainage from the small intestine and dilated lacteal vessels that distort the villus architecture. It is often observed in adults and older children; it has been described prenatally and in 2 full-term siblings.^2,3 There are no previous reports of this entity in premature infants.

	CASE REPORT

This infant boy, born at 30 weeks gestation and weighing 1210 g, had hyaline membrane disease and grade II intraventricular cerebral hemorrhage during the first days of life. He was admitted to the neonatal intensive care unit and given expressed breast milk and a formula for preterm infants (Similac Special Care Formula, Ross Laboratories, Columbus, OH). He developed edema on the legs and head during the first week of life. Concentrations of serum albumin (2.0 g/dL), immunoglobulin G (IgG) (324 mg/dL), and transferrin were low. Serum immunoglobulin A (IgA) (6.2 mg/dL) and immunoglobulin M (IgM) concentrations were normal. Blood cell count excluded lymphocytopenia. Proteinuria, inadequate protein intake, and liver and heart diseases were excluded. High ₁-antitrypsin stool levels (>3 mg/g dry-weight sample) and fecal ₁-antitrypsin clearance (65 mL/die) indicated enteric loss of plasma proteins. Upper intestinal endoscopy, performed with a neonatal fiberscope (5.5 mm diameter; Olympus, Turin, Italy), without sedation showed white opaque spots on the duodenum mucosa, and 2 biopsies were taken from the areas most affected. Duodenal histology showed a distorted villus profile attributable to dilated lymphatic channels and areas of villus blunting intermingled with seemingly normal areas (Fig 1). The esophageal and gastric mucosa appeared histologically normal. Ultrasound examination of the heart and abdomen excluded secondary causes of lymphangiectasia (ie, chronic congestive heart failure, constrictive pericarditis, pericardial effusion, abdominal masses, and intestinal malrotation). The final diagnosis was congenital intestinal lymphangiectasia.

View larger version (136K): [in this window] [in a new window]   Fig. 1.   Histologic image of the duodenal mucosa showing the villus architecture distorted by dilatation of the lymphatic vessels. Note the normal villus on the left.

Breast milk and adapted formula were replaced by a formula with a high concentration of medium chain triglycerides (Portagen, Mead Johnson Nutritionals, Rome, Italy), which caused a rapid clinical improvement. At follow-up, the serum albumin level had increased remarkably (3.1-3.8 g/dL) and ₁-antitrypsin stool levels were normal; edema had regressed and the infant had gained weight. When the infant was 6 months old, beikost and medium chain triglycerides were introduced as the sole sources of fat in his diet. At present, the infant is 1 year old and is growing well.

	DISCUSSION

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Intestinal lymphangiectasia is characterized by obstruction of the intestinal lymphatic vessels and increased lymphatic pressure that cause PLGE and malabsorption of chylomicrons and fat-soluble vitamins. Intestinal lymphangiectasia is a primary disorder in cases of malformation of lymphatic vessels at intestinal level or in other areas of the body. It can also occur secondary to diseases that cause intestinal lymphatic obstruction, eg, abdominal or retroperitoneal tumors, retroperitoneal fibrosis, chronic pancreatitis, mesenteric tuberculosis, Crohn's disease, intestinal malrotation, Whipple's disease, celiac disease constrictive pericarditis, and chronic congestive heart failure.^1,4,5

We describe the first case of intestinal lymphangiectasia in a preterm infant. This entity is rarely suspected in the differential diagnosis of a tiny newborn with peripheral edema and hypoalbuminemia. These features should alert pediatricians to the possibility of enteric loss of proteins if other causes, such as malnutrition and hepatic and renal diseases, are excluded. In our case, an excessive concentration of ₁-antitrypsin measured in random dry stool and the high plasma clearance of ₁-antitrypsin demonstrated an abnormal enteric loss of proteins. In earlier studies, both tests have detected abnormal enteric loss of proteins.^6,7 Differently, radioactive methods, including intravenous administration of ⁵¹Cr albumin or ⁵¹Cr chloride, are cumbersome and expensive, and are rarely used because radioactive macromolecules are not widely available.

Although lymphocytopenia is supposedly a marker of intestinal lymphatic channel obstruction, it was not found in our patient. This coincides with reports that lymphopenia was not present during the early phases of intestinal lymphangiectasia in young children.^2,3 Furthermore, drainage of lymphocytes through the lamina propria can be unremarkable in the absence of inflammatory activation in the intestinal mucosa.³

Endoscopy of the upper intestinal tract was crucial in establishing the diagnosis of intestinal lymphangiectasia. In fact, white opaque spots detected on the duodenal mucosa and biopsies sampled during endoscopy showed dilated lymphatic channels. Because the mucosal lesions in intestinal lymphangiectasia are often patchy and localized, endoscopy is an aid to selecting regions for biopsy. Differently, multiple mucosal biopsies may be necessary if peroral jejunal sampling is used.⁸ In our case, ultrasound excluded other causes of lymphatic obstruction and excessive protein efflux into the intestinal tract, eg, constrictive pericarditis, pericardial effusion, superior vena cava obstruction, heart failure, intestinal malrotation, and intestinal tumors.

	CONCLUSION

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In summary, although intestinal lymphangiectasia primarily affects children and young adults, it should be included in the diagnostic work-up in preterm infants presenting with peripheral edema and hypoproteinemia when there is excessive enteric protein loss. An early diagnosis of intestinal lymphangiectasia in newborns and small infants may prevent such severe complications as lymphocytopenia and malnutrition. Endoscopy can be successfully performed even in preterm neonates to explore the upper gastrointestinal mucosa.

	ACKNOWLEDGMENT

We thank Jean Ann Gilder for editing the text.

Gennaro Salvia, MD
Concetta F. Cascioli, MD
Filippo Ciccimarra, MD, PhD^*
Gianluca Terrin, MD
Salvatore Cucchiara, MD, PhD
Gastrointestinal Endoscopy and Motility Unit
^* Neonatal Intensive Care Unit
Department of Pediatrics
University of Naples, "Federico II'
Via Sergio Pansini 5, I-80131, Naples, Italy

	FOOTNOTES

Received for publication Feb 25, 2000; accepted May 9, 2000.

Address correspondence to Salvatore Cucchiara, MD, Department of Pediatrics, Gastrointestinal Motility and Endoscopy Unit, University of Naples "Federico II,' Via Sergio Pansini 5, I-80131 Naples, Italy. E-mail: cucchiar{at}unina.it

	ABBREVIATIONS

PLGE, protein-losing gastroenteropathy, Ig, immunoglobulin.

	REFERENCES

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