Case of pediatric Ménétrier disease with cytomegalovirus and <i>Helicobacter pylori</i> co‐infection

Abstract

Ménétrier disease is characterized by protein-losing enteropathy and the finding of giant mucosal gastric folds. Cytomegalovirus (CMV) is thought to have a causative role in childhood Ménétrier disease. In adult Ménétrier disease, there are reports where therapy given for Helicobacter pylori infection has resulted in resolution of adult Ménétrier disease. We report a case of childhood Ménétrier disease in which co-infection with CMV and H. pylori was found and we discuss the correlations between Ménétrier disease and these pathogens. An 18-month-old boy was referred to our hospital because of abdominal distention and eyelid edema. Additional symptoms included fever, diarrhea and cough, which began 6 days prior to admission, and lower extremity edema, which appeared 3 days prior to admission. His history was significant for bronchial asthma, which was well controlled. On admission his general condition was good and vital signs were normal. Examination was significant for edema of the eyelids and lower limbs. Blood tests revealed hypoproteinemia (3.4 g/dL), hypoalbuminemia (1.4 g/dL) and hypoglobulinemia (immunoglobulin [Ig] G 208 mg/dL). White blood cell count was 9200 (29.7% neutrophils, 56.8% lymphocytes, 7.4% monocytes, 5.6% eosinophils). Hemoglobin was 13.6 g/dL. Electrolytes, blood urea nitrogen, creatinine, transaminases and cholesterol were within normal limits. Urinalysis revealed absence of proteinuria and stool alpha1-antitrypsin was elevated (23.8 mg/dL). Cell immunity was normal. The 99mTc-labeled albumin scintigraphy showed protein leakage from the intestine. An ultrasound exam revealed gastric wall hypertrophy, mesenteric edema and lymphadenopathy. Gastrointestinal endoscopy (GIE) was performed on day 9 of admission. Visual findings were enlarged erythematous gastric folds and thick mucus at the body (Fig. 1a) and nodular erosions at the pyloric antrum (Fig. 1b). We diagnosed the patient as having Ménétrier disease. Histological studies of the biopsy specimens showed swelling of the glandular epithelium with intranuclear inclusions (Fig. 2a), which were positive for CMV early antigen immunostain (Fig. 2b). There was infiltration with eosinophils, plasma cells, lymphocytes, neutrophils, and rod-shaped bacteria in the Giemsa-stained specimen (Fig. 2c). H. pylori antigen in the stool was positive at 11 days after admission. Findings of the first gastrointestinal endoscopy. (a) Enlarged erythematous gastric folds and thick mucus in the body. (b) Nodular erosions in the pyloric antrum. Pathological findings. (a) Swollen glandular epithelium. (b) Swollen glandular epithelium, which was positive with cytomegalovirus early antigen immunostain. (c) Helicobacter pylori-like bacteria with Giemsa stain (arrows). The patient received infusions of albumin and gamma globulin to achieve appropriate urine output, to improve edema, and to keep levels of albumin and IgG above 2 g/dL and 200 mg/dL, respectively. GIE was repeated on day 32 of admission. The gastric folds in the body were less enlarged than on day 9 and nodular erosions at the pyloric antrum had decreased. The glandular epithelium remained swollen and positive for CMV early antigen immunostain, but no rod-shaped bacteria were seen on the Giemsa-stain specimen. A culture for H. pylori was not obtained during the first GIE. A culture for H. pylori from the pyloric antrum at the second GIE was negative. Therefore eradication therapy for H. pylori was not provided. H. pylori antigen in the stool turned out to be negative at 2 months after admission. In the early course of his illness, CMV DNA was detected in all specimens (plasma, saliva, gastric juice and urine). CMV polymerase chain reaction (PCR) in plasma and saliva became negative after 3 months. CMV PCR remained detectable in the urine and gastric juice one year after the onset of symptoms, and disappeared 14 months after the onset of symptoms (Fig. 3). Upper graphic chart shows the cytomegalovirus (CMV) DNA titer in each specimen. Lower graphic chart shows values of immunoglobulin (Ig) G and albumin. G-globulin, gamma globulin; GIE, gastrointestinal endoscopy; PCR, polymerase chain reaction. GIE was performed again at the 14-month follow up. The gastric and duodenal mucosae were almost normal in appearance. Histologically, the glandular epithelium was not swollen and CMV early antigen immunostain was negative. H. pylori culture was negative. Fifteen months after the onset of illness, the patient was symptom-free and had normal laboratory test results. An association between gastric infection and Ménétrier disease has been reported. CMV, in particular, is often found in pediatric Ménétrier disease.1,2H. pylori is thought to have a role in Ménétrier disease in adults but its role in pediatric Ménétrier disease has not yet been established. Tokuhara et al. reported a case of pediatric Ménétrier disease that had co-infection with CMV and H. pylori.3 After eradication therapy for H. pylori, the thickened gastric folds regressed significantly. They concluded that this case of pediatric Ménétrier disease was secondary to H. pylori infection rather than CMV infection. Similarly to Tokuhara's case, H. pylori might have contributed to the disease activities in our patient. Serum albumin remained above 2 g/dL without infusion of albumin after the second GIE by which time H. pylori had been naturally eradicated. On the other hand, the glandular epithelium still revealed positive staining for CMV early antigen immunostain. CMV DNA was also present in the gastric juice. These findings confirmed the presence of acute active CMV infection in the gastric mucosa. Because of these findings, we propose that H. pylori rather than CMV had a causative role in Ménétrier disease in our patient. We detected CMV DNA in urine and gastric juice one year after our patient's onset of symptoms. Murph and coworkers reported the natural history of acquired CMV infection among children in group day care.4 The duration of CMV excretion varied between 3.0–12.0 months in saliva and 5.0–28.0 months in urine, with a mean duration of 7.0 ± 2.7 months and 13.0 ± 9.1 months, respectively. Kumar and coworkers reported that viruria lasted at least one year in infants who had a CMV infection in early life.5 Patients congenitally infected with CMV are known to excrete CMV for a longer period of time than patients with acquired infection. Pass and coworkers observed that 26 (84%) of 31 patients with congenital CMV infections continued to excrete CMV in the fifth year of life; some patients excreted CMV for more than seven years.6 According to these reports, the excretion period of CMV in our patient was not abnormally long. The indication for anti-CMV therapy in acquired CMV infection in immunocompetent patients is life-threatening visceral organ dysfunction.7 Although the protein-losing gastropathy of this case required the administration of hematological products for three months, our patient had no indication for anti-CMV therapy. H. pylori, in addition to CMV, has a causative role in pediatric Ménétrier disease. It is important to look for evidence of both CMV and H. pylori infections when encountering a case of pediatric Ménétrier disease.