Chronic Hypertrophic Gastropathy in a Child Resembling Adult Menetrier's Disease

Abstract

Hypertrophic gastropathy in children is rare and usually benign and self-limiting. About 50 cases have been reported to date (1-4), 30% of which were associated with cytomegalovirus (CMV) infection (1,2). The adult and pediatric forms of the disease have been reported to differ in terms of the clinical course and prognosis (1,5). We present a further pediatric case that was unusually persistent, pointing to a possible link between pediatric hypertrophic gastropathy and adult Ménétrier's disease. CASE REPORT A girl 7 years and 4 months of age was seen because of sudden-onset vomiting and diarrhea, with right abdominal pain and fever (38.5°C). Laparotomy revealed ascites and mesenteric adenopathies. Culture of ascitic fluid was negative. Antimicrobial therapy was started with ampicillin, gentamycin, and metronidazole. The ascites recurred 10 days later and edema became generalized. The serum total protein was 28 g/L and the serum albumin 18 g/L. Urinalysis and liver function were normal. An upper gastrointestinal (GI) series showed prominent gastric fold thickening. Gastroscopy revealed multiple hypertrophic edematous gastric folds in the gastric fundus and body. CMV was detected in urine. The patient was treated with albumin infusions, and sodium and fluid restriction; the edema resolved but emesis persisted and total parenteral nutrition was started 40 days after onset. When referred to our center, the physical examination was normal except for signs of malnutrition. The serum albumin was 15 g/L and the serum gammaglobulin 4 g/L. Clearance of fecal alpha-1-antitrypsin was high at 36 ml/24 h (N < 2). Anti-CMV IgG antibodies were detected and blood and urine cultures were positive for CMV. A new gastroscopy was performed under general anesthesia and confirmed the presence of giant gastric folds and with a congestive mucosa and superficial erosions throughout the fundus and body. Histopathologic examination of a full-thickness biopsy specimen showed hypertrophic gastritis with foveolar hyperplasia and glandular atrophy. Cysts lined by mucous cells were found throughout the mucosa. Edema and inflammation were minimal and no increase in intraepitelial lymphocyte numbers was observed (Fig. 1). Immunohistochemical studies of a paraffin-embedded tissue section with a specific anti-CMV monoclonal antibody (clone E13, Biosoft, Paris, France) and histopathologic examination showed the presence of CMV in the gastric mucosa (Fig. 2). Screening for Helicobacter pylori on tissue sections stained by Giemsa was negative. Parenteral nutrition was continued and ranitidine (12 mg/kg/d) was started. Seventy-one days after onset, despite the lack of experience in the literature with anti-viral therapy in pediatric hypertrophic gastropathy, a 21-day course of IV gancyclovir was started because of complete dependence on parenteral nutrition. Although CMV was no longer detected in the blood, urine, or gastric mucosa, the serum albumin remained low (20 g/L), while endoscopic and histopathologic lesions remained unchanged and giant folds extended to the antrum. The emesis and abdominal pain gradually disappeared, and oral feeding was started four months after onset. The feeding catheter was removed two months later and the serum albumin remained above 30 g/L. No emesis or pain recurred. However, upper GI endoscopy performed 7, 11, 18, and 26 months later showed the same giant gastric folds in the fundus and antrum; histopathologic lesions improved slowly but incompletely, with persistance of foveolar hyperplasia and no mucosal cysts or CMV inclusion. DISCUSSION Pediatric hypertrophic gastropathy is a rare protein-losing gastropathy, the main manifestations of which are emesis, abdominal pain, and edema due to hypoalbuminemia (1). Upper GI series can reveal gastric rugal hypertrophy, whereas gastroscopy confirms the diagnosis by showing giant gastric folds in the body and fundus. Histologic findings are characteristic, with hypertrophic gastric mucosa, foveolar hyperplasia, and mucosal cysts. Some pediatric cases have been associated with CMV, but both the role of this virus and the pathophysiology of the disease are unclear (2). We report a new case of pediatric hypertrophic gastropathy associated with CMV infection in which the clinical course was unusual because of the persistence of gastric lesions (>26 months) and clinical manifestations (>20 weeks). Indeed, in a recent review, Occena et al. found that the mean duration of the disease in pediatrics was 5.8 ± 3.9 weeks (range 2-18 weeks) (1), with the exception of one patient who underwent gastrectomy for severe bleeding (6). The only other report of persistent endoscopic and histopathologic lesions was an Iranian child (3) who had a 15-year history of hypertrophic gastritis. Knight et al. have also reported the case of a child with a 6-month course in whom upper GI series were still pathologic at the fifth month but normal 5 years later (4). In their review, Occena et al. reported that radiologic or endoscopic follow-up examinations, when performed, were always normal 4 weeks to 5 months after onset (1). Recent advances in our understanding of Ménétrier's disease in adults show that patients can be separated into two groups according to histopathologic features, with no overlap: “hypertrophic lymphocytic gastritis” (HLG) and “massive foveolar hyperplasia and minimal inflammation” (MFH) (7). According to Wolfsen et al., the term Ménétrier's disease should be used only for patients with MFH (7). Despite the classic association with CMV infection, the pediatric case we report here was histopathologically similar to adult MFH. The chronic course raises questions as to the benign nature of pediatric hypertrophic gastropathy, which differs from the adult form in terms of the prognosis: most adult patients require gastrectomy because of persistent symptoms or bleeding, and the incidence of carcinoma is about 10% (5). The similitude between the reported case and adult Ménétrier's disease (chronic course, massive foveolar hyperplasia on histopathologic examination) emphasizes that, in children with chronic hypertrophic gastritis, strict monitoring for complications and carcinoma is required. Despite the disappearance of CMV during gancyclovir therapy, clinical and histologic manifestations did not improve. This suggests that the direct cytopathogenic effect of CMV was not responsible for the chronic course, although an immunologic mechanism related to CMV infection might be involved initially and self-perpetuated independently of the CMV infection. Another possible mechanism caused by CMV infection is the production of abnormal local transforming growth factor (TGF)-alpha, a polypeptide that stimulates cell proliferation of gastric mucosa, inhibits gastric secretion, and enhances mucus secretion. A possible role of TGF-alpha was suggested in adult Ménétrier's disease (8), but was not investigated in acute hypertrophic gastropathy in children. If the gancyclovir treatment had been started earlier, the course of the disease would have been improbably modified because all other cases of pediatric hypertrophic gastropathies related to CMV and not treated never presented a similar course and improved in a mean period of 6 weeks (1). In conclusion, this pediatric case of chronic hypertrophic gastropathy strongly ressembles adult Ménétrier's disease, supporting the distinction made by Bloom and McQuaide (9) between acute hypertrophic gastropathy in childhood and Ménétrier's disease, the latter diagnosis being reserved for adults and only for children with a chronic course.FIG. 1A:: Histopathology of a full-thickness biopsy of the stomach. The gastric mucosa is entirely pathologic with foveolar hyperplasia, glandular atrophy, and cysts lined by mucous cells throughout the mucosa. (H & E original magnification ×25.) B: A high-power field of the same section demonstrating the foveolar hyperplasia and a dilated gland lining by mucous cells. (H & E original magnification ×250.)FIG. 2.: Gastric biopsy demonstrating cytopathogenic effect of CMV on the mucosa. (H & E original magnification ×1250.)