A 17-year-old girl presented to her pediatrician with facial swelling, swelling of her legs, and abdominal distension. She was in her usual state of health until 2 weeks prior to her visit, when she noticed that her face appeared “puffy.” The next day, her legs were swollen and her lower abdomen appeared bloated. She had gained two pounds over the past 2 weeks. She also complained of diffuse abdominal pain and fatigue.
There was no history of fever, vomiting, chest pain, difficulty breathing, diarrhea, or constipation. There was no dysuria or hematuria. There were no sick contacts and no significant recent travel.
Her past medical history, past surgical history and family history were unremarkable.
On physical examination, she was well developed and afebrile with stable vital signs. Her examination was notable for generalized edema with facial swelling. Her breath sounds were normal. Cardiac examination revealed normal first and second heart sounds without murmurs, rubs, or gallops. Peripheral pulses were 2+, and capillary refill time was less than 2 seconds. The abdomen was distended and tympanic with shifting dullness. No hepatosplenomegaly or masses were palpable. Pretibial pitting edema was noted bilaterally.
The initial laboratory evaluation included a complete blood count, electrolytes, liver function tests, C-reactive protein (CRP), and urinalysis. Significant presenting lab values included hypoalbuminemia (albumin 2.5 g/dL). Urinalysis was normal with no proteinuria. Fecal alpha 1-antitrypsin (fecal A1-AT) was elevated (246 mg/dL), consistent with protein-losing enteropathy (normal fecal A1-AT < 2 mg/dL).
Our initial assessment was that this was a 17-year-old girl with generalized edema, hypoalbuminemia, and protein-losing enteropathy.
Upper gastrointestinal series revealed grossly thickened gastric folds in the fundus and body of the stomach. Esophagogastroduodenoscopy showed edematous and thickened gastric folds (Figure). Gastric biopsies showed foveolar hyperplasia and glandular dilatation.
Figure. Esophagogastroduodenoscopy showed thickened gastric folds.All images courtesy of Prita H. Mohanty, MD. Reprinted with permission..
Cytomegalovirus (CMV) was isolated from the gastric mucosa. The patient was placed on a high-protein diet. After 1 month, the pedal edema and ascites had almost completely resolved. The albumin normalized at 3.7 g/dL with no further symptomatic recurrences.
Ménétrier’s disease is an uncommon disease in childhood that is characterized by gastric hypertrophy involving predominantly the fundus and body and hypoalbuminemia secondary to protein loss through the gastric mucosa.
Although allergic and immunologic causes have been described, CMV is postulated to be an important cause of pediatric Ménétrier’s disease. One-third of the children with Ménétrier’s disease reportedly have CMV-associated Ménétrier’s disease, which usually resolves spontaneously in 2 to 4 weeks. CMV was isolated from the gastric mucosa, and the condition was self-limiting in the patient described. CMV infections are relatively uncommon in adults with Ménétrier’s disease, with the exception of immunocompromised hosts. In contrast, Helicobacter pylori infection is more prevalent in Ménétrier’s disease in adults than in children.1
The pathogenesis of Ménétrier’s disease is not well understood. It is thought that it involves increased signaling of the epidermal growth factor receptor (EGFR), which results in proliferation of epithelial cells of the mucous cell compartment. The enhanced activity of EGFR in Ménétrier’s disease is related to overproduction of transforming growth factor-alpha, (TGF-alpha), a ligand that can bind and activate EGFR.2
This patient presented with ascites, generalized edema, and hypoalbuminemia. Patients with Ménétrier’s disease can present with a variety of clinical features, including epigastric pain, nausea, vomiting, gastrointestinal bleeding, diarrhea, and protein-losing gastroenteropathy.3 Additional clinical features include peripheral edema, ascites, and pleural and pericardial effusions. Generalized edema is less common, being present in fewer than 25% of patients.4
Laboratory abnormalities, such as reduced serum concentrations of albumin, gamma globulin (IgA, IgG, IgM), fat-soluble vitamins, fibrinogen, transferrin, alpha-1 antitrypsin, and ceruloplasmin, are similar to those seen in other forms of protein-losing gastroenteropathy.
The child described here exhibited significant protein-losing enteropathy with hypoproteinemia. Other causes of protein-losing enteropathy include eosinophilic gastroenteritis, celiac disease, hypertrophic gastropathy in association with Helicobacter pylori infection, and inflammatory bowel disease.
The diagnosis of Ménétrier’s disease is established on biopsy by the demonstration of foveolar hyperplasia with glandular dilatation in a patient with striking enlargement of gastric folds seen on endoscopy or barium radiography. Tests for CMV and Helicobacter pylori should be performed because these infectious agents should be treated if found. In contrast to adults, children usually have self-limited disease, shorter duration, and mostly require only supportive care.
Antiviral therapy is rarely required. Antacids, anticholinergics, prednisone, H2-receptor blockers, proton pump inhibitors, and prostaglandins have been used in Ménétrier’s disease, but none have proven to be consistently beneficial. Studies have shown clinical and biochemical improvement after treatment with a monoclonal antibody directed against the EGFR. No prospective, randomized controlled trials that examine the effectiveness of ganciclovir treatment in childhood Ménétrier’s disease have been conducted. Ganciclovir should be considered in CMV gastrointestinal infection in immunocompromised hosts, neonates, and healthy infants that do not improve with supportive treatment after 2 weeks.5
Pediatricians should consider protein-losing enteropathies in an edematous patient with hypoalbuminemia and absence of proteinuria. Although Ménétrier’s disease of childhood is uncommon, it is important to keep this self-limited, spontaneously resolving condition in the differential diagnosis of protein-losing enteropathy in children (see Table).
Table. Causes of protein-losing enteropathy in children
Protein-losing enteropathy should be considered in an otherwise healthy patient with a low albumin and normal urinalysis. CMV should be suspected in a child who presents with protein-losing gastropathy. Treatment is largely supportive, but ganciclovir may be considered for severe or prolonged cases. Childhood Ménétrier’s disease remits spontaneously and has very good prognosis.
- Bayerdorffer E, Ritter M, Hatz R, Brooks W, Ruckdeschel G, Stolte M. Healing of protein losing hypertrophic gastropathy by eradication of Helicobacter pylori – is Helicobacter pylori a pathogenic factor in Menetrier’s disease?Gut. 1995;35(5):701–704. doi:10.1136/gut.35.5.701 [CrossRef]
- Dempsey PJ, Goldenring JR, Soroka CJ, et al. Possible role of transforming growth factor alpha in the pathogenesis of Ménétrier’s disease: supportive evidence form humans and transgenic mice. Gastroenterology. 1992;103(6):1950.
- Meuwissan SG, Ridwan BU, Hasper HJ, Innemee G. Hypertrophic protein losing gastropathy. A retrospective analysis of 40 cases in The Netherlands. Scand J Gastroenterol Suppl.1992;194:1–7.
- Canan O, Ozcay F, Bilezikci B. Ménétrier’s disease and severe gastric ulcers associated with cytomegalovirus infection in an immunocompetent child: a case report. Turk J Pediatr. 2008;50(3):291–295.
- Megged O, Schlesinger Y. Cytomegavirus-associated protein-losing enteropathy. Eur J Pediatr2008; 167(11):1217–1220. doi:10.1007/s00431-008-0791-1 [CrossRef]
Causes of protein-losing enteropathy in children
||CMV, Helicobacter pylori, Clostridium difficile, Giardia lamblia, measles, bacterial overgrowth
||Inflammatory bowel disease, celiac disease, Ménétrier’s disease, allergic gastroenteropathy, eosinophilic gastroenteritis, Henoch-Schonlein purpura, system lupus erythematosus
||Congenital enterocyte heparin sulphate deficiency, congenital disorders of glycosylation
||Thoracic duct damage, intestinal lymphangiectasia
||Heart failure, pericarditis, post-Fontan procedure
||Post-chemotherapy, graft-versus-host disease