Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 3-8

Two-Year-Old Girl

KAMILLAH N. WOOD

HISTORY OF PRESENT ILLNESS

The patient is a 2-year-old African-American female who presents with vomiting for 1 week. The emesis is nonbloody and nonbilious occurring daily. After vomiting, the patient refuses to eat for the rest of the day. She has normal activity level and normal urine and stool output. The patient’s mother feels that the child’s face is swollen but denies any history of fever, diarrhea, and abdominal pain or weight loss.

MEDICAL HISTORY

She is a 36-week infant born via cesarean section secondary to fetal distress. She remained in the neonatal intensive care unit for 8 days, but has no residual problems. She has not required any surgery.

PHYSICAL EXAMINATION

T 36.5°C; RR 22/min; HR 111/min; BP 94/67 mmHg

Weight (14.8 kg) 75th percentile; Length (91 cm) 50th percentile

General examination reveals an alert child in no acute distress. Her cardiac and pulmonary examinations are normal. She has no hepatomegaly and no splenomegaly or costovertebral angle tenderness. Her examination was notable only for peri-orbital swelling and pitting edema of both lower extremities.

DIAGNOSTIC STUDIES

Laboratory evaluation revealed 14 600 white blood cells/mm3 with 6% band forms, 34% segmented neutrophils, 55% lymphocytes, 6% eosinophils, and 5% monocytes. The hemoglobin was 14.7 g/dL and the platelet count was 383 000 cells/mm3. Serum chemistries were as follows: sodium, 130 mmol/L; potassium, 3.5 mmol/L; chloride, 103 mmol/L; bicarbonate, 24 mEq/L; blood urea nitrogen, 9 mg/dL; creatinine, 0.4 mg/dL; glucose, 103 mg/dL; bilirubin, 0.1 mg/dL; ALT, 36 U/L; AST, 49 U/L; albumin, 1.4 g/dL; cholesterol, 122 mg/dL; ESR, 0 mm/h; and urinalysis negative (no protein). Chest and abdominal radiographs were normal.

COURSE OF ILLNESS

The patient was evaluated for a protein losing enteropathy because of hypoalbuminemia without proteinuria. An upper gastrointestinal contrast procedure and endoscopy were performed which confirmed the diagnosis (Figure 3-11).

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FIGURE 3-11. Upper gastrointestinal barium study.

DISCUSSION CASE 3-8

DIFFERENTIAL DIAGNOSIS

The patient was noted to have generalized edema associated with vomiting. Generalized edema may be caused by four mechanisms: (1) increased capillary permeability, (2) decreased oncotic pressures, (3) increased hydrostatic pressures, or (4) impaired lymphatic drainage. Once cardiovascular disease has been ruled out as the cause of generalized edema it is usually secondary to hypoproteinemia of renal origin. This patient’s generalized edema was attributed to decreased oncotic pressure from hypoproteinemia. Hypoproteinemia is due to either decreased production of proteins by the liver or increased renal or gastrointestinal losses. The causes of hypoalbunemia are summarized in Table 3-9. A negative urinalysis for protein and no evidence of hepatic disease makes a protein-losing enteropathy much more likely. Differential diagnosis of a protein-losing enteropathy includes celiac disease, Crohn disease, cystic fibrosis, intestinal lymphangiesctasia, gastritis, and eosinophillic gastritis, and Ménétrier disease.

TABLE 3-9. Causes of hypoalbunemia.

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DIAGNOSIS

After determining that the patient most likely had a protein-losing enteropathy, she underwent an upper gastrointestinal barium study that showed evidence of hypertrophic gastric folds (thumb printing and enlarged folds within the gastric antrum) (Figure 3-11). The upper endoscopy performed the next day showed normal anatomy with histologic proof of Ménétrier disease including foveolar (pits) hyperplasia and marked oxyntic glandular loss with accompanying cystic changes. Cytomegalovirus (CMV) serum IgM was positive and CMV was isolated from the urine by rapid shell vial testing.

INCIDENCE AND EPIDEMIOLOGY OF MÉNÉTRIER’S DISEASE

Ménétrier disease is an extremely rare condition with about 60 reported cases in the pediatric population. Initially described in 1888, it is characterized by a protein-losing gastropathy, gastric rugae hyperplasia, and hypoproteinemia. The gastric hyperplasia is a result of an increase of mucous cells with parietal cell atrophy, creating an altered gastric mucosa that secretes massive amounts of mucous. This results in low plasma protein levels with subsequent edema. Over a third of all pediatric cases show acute evidence of CMV infection, and some cases have been linked to Helicobacter pylori infection. The condition usually occurs in children under 10 years of age with a mean age of 5.6 years and a three to one male predominance. The etiology is felt to be due to an elevated transforming growth factor alpha (TGF-a) that triggers abnormal regulation of gastric epithelial growth factors.

TYPICAL PRESENTATION

The onset of clinical symptoms is abrupt, usually occurring 1 to 2 weeks after a viral prodrome. Gastrointestinal symptoms predominate with almost 80% having emesis, 50% with abdominal pain or anorexia, and 10% with frank upper gastrointestinal bleeding. Almost all patients present with generalized edema and a third with pleural effusions. Characteristic laboratory abnormalities include a low serum albumin and low total serum protein levels.

DIAGNOSTIC RATIONALE

Diagnosing Ménétrier disease when the clinical presentation is supportive depends on a combination of laboratory evaluation, radiographic findings, and endoscopic results.

Complete blood count. Laboratory findings are nonspecific and include a mild normochromic, normocytic anemia in 20% and eosinophilia in 60%.

Hepatic function panel. A low serum albumin, usually less than 2 g/dL, is supportive. Examination of the hepatic enzymes helps to discern whether a dysfunction of synthetic function is causing the hypoalbuminemia, but should be relatively normal in Ménétrier disease.

Upper gastrointestinal barium study. Contrast radiographs show swollen gastric rugae of the fundus and body with antral sparing which are pathonomonic for this disease. Diagnosis by ultra-sonography has also been described.

Endoscopy. Endoscopy shows swollen convoluted rugae. Histologicfeatures include tortuous pits with cystic dilatations that may extend into the muscularis mucosae and submucosa, and an edematous lamina propria with increased numbers of eosinophils, lymphocytes, and round cells. Mucosal thickening, glandular atrophy, and hypochlorhydria occur. In addition, infectious studies can be obtained from the biopsy, including testing for H. pylori.

TREATMENT

Treatment for Ménétrier disease is mostly supportive including a high-protein diet, acid blockers to treat gastric inflammation, and diuretics to reduce edema. Appropriate therapy should be instituted in cases associated with H. pylori. The condition is self-limited usually resolving within weeks to months without recurrence or sequelae. Cases in adults tend to be more chronic, commonly requiring surgery and are also associated with an increased risk of gastric cancer.

SUGGESTED READINGS

1. Menetrier’s Disease Feldman: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. 6th ed. W. B. Philadelphia: Saunders Company; 1998:724-726.

2. Hassall E. Peptic diseases. In: Rudolph CD, Rudolph AM, eds. Rudolph’s Pediatrics. 21st ed. New York: McGraw-Hill; 2003:1429-1435.

3. Meuwissen SG, Ridwan BU, Hasper HJ. Hypertrophic protein-losing gastropathy: a retrospective analysis of 40 cases in the Netherlands (The Dutch Menetrier Study Group). Scan J Gastroenterol. 1992;194:s1-s7.

4. Zenkl B, Zieger MM. Menetrier disease in a child of 18 months: diagnosis by ultrasonograph. Eur J Pediatr. 1988;147:330-331.

5. Fretzayas A, Moustaki M, Alexopoulou E, Nicolaidou P. Menetrier’s disease associated with Helicobacter pylori: three cases with sonographic findings and a literature review. Ann Trop Paediatr. 2011;31(2):141-147.

6. Iwama I, Kagimoto S, Takano T, Sekijima T, Kishimoto H, Oba A. Case of pediatric Menetrier disease with cytomegalovirus and Helicobacter pylori co-infection. PediatrInt. 2010;52(4):200-203.