Protein-losing gastropathy associated with cytomegalovirus in two sisters - Case reports and review of the literature.

Ménétrier's disease is a protein-losing gastropathy that is uncommon in childhood. Its symptoms are unspecific, with abdominal pain, vomiting, and edema. Blood tests show hypoproteinemia and hypoalbuminemia, and upper digestive endoscopy reveals giant gastric folds. In children, cytomegalovirus has been identified as a possible cause. Here we describe two sisters presenting with Ménétrier's disease, 2 years apart. This diagnosis should be considered in the presence of hypoalbuminemia in children when a nephrotic syndrome is excluded.

Cytomegalovirus-associated protein-losing gastropathy in childhood.

Menetrier's disease is an uncommon disease in childhood, characterized by gastric hypertrophy and hypoalbuminemia secondary to protein loss through the gastric mucosa. This paper describes a series report of protein-losing gastropathy associated with cytomegalovirus (CMV) infection in children and reviews the literature. We reviewed the medical records of eight children with diagnosis of Menetrier's disease or protein-losing gastropathy with evidence of acute CMV infection. During a five-year period there were eight children that were diagnosed with CMV-associated protein-losing gastropathy, all in one medium-sized pediatric ward in a general hospital. The mean age was 32 months and there was no gender predominance. The most common presenting symptoms were vomiting and edema. Average symptoms' duration prior to admission was 3.2 weeks and mean albumin at presentation was 1.8 g/dl (range, 1.5-2.5 g/dl; normal values, 3.5-5 g/dl). All eight children fully recovered. In conclusion, CMV infection should be suspected in every child who presents with protein-losing gastropathy. The availability of newer, rapid diagnostic techniques such as polymerase chain reaction (PCR) may facilitate diagnosis, as serology studies may be misleading. Usually, only supportive care is required, but treatment with ganciclovir may be considered for severe or prolonged cases.

[Ménétrier's disease of childhood and acute cytomegalus virus infection]. / Enfermedad de Ménétrier infantil e infección aguda por citomegalovirus.

Menetrier's disease of childhood, or protein-losing hypertrophic gastropathy, is a rare entity of unknown etiology, characterized by hypertrophy of the gastric mucosa as well as secondary protein loss. Most published cases are associated with infection, mainly viral. These infections could alter the factors regulating growth and the function of gastric cells. In children, the disease is mild and resolved within a few weeks. We present the case of a 15-month-old child with a 72-hour history of intractable vomiting, hypoproteinemia and generalized progressive edema. We describe the characteristics of this case, as well as the clinical, ultrasonographic and endoscopic findings required for a diagnosis of this disease.

[Cytomegalovirus-induced protein-losing gastropathy: a case report]. / Un raro caso di gastroenteropatia ipertrofica protido-disperdente da CMV.

Protein-losing gastropathy is an uncommon disease of uncertain etiology, known also as Menetrier's disease. In medical literature only 50 pediatric cases have been described. These childhood forms, in contrast to classic adult Menetrier's disease, have a typical benign and transient course, and require only supportive therapy. The role of Cytomegalovirus (CMV) in the pathogenesis has been demonstrated by gastric biopsy in one third of the cases. Also other infectious, allergic and immunological factors have been hypothesized. We describe a case of hypertrophic gastropathy with important protein-loss, admitted to our Pediatric Department for evaluation because of vomit, weight loss, abdominal pain and hypoalbuminemia. Gastric mucosal biopsy revealed a morphological evidence of CMV infection.

[Ménétriers disease associated with cytomegalovirus infection]. / Enfermedad de Ménétrier asociada a infección por citomegalovirus.

Menetrier's disease is a rare entity in children, characterized by a protein-losing gastroenteropathy with thickening of the gastric mucosa and generalized edema. The most common etiology is viral, and cytomegalovirus is the agent most frequently implicated. Unlike in the adult, it is a self-limited disorder with a good prognosis in children. Four patients (three boys and one girl) diagnosed with Ménétrier disease in the past five years were reviewed. The mean age at presentation was 28.7 months (range: 10-48 months). The most common clinical symptoms were fever, vomiting, and edema. Endoscopy showed thickened gastric folds and erosions in several stages. All patients had an associated gastric cytomegalovirus infection, and a favorable outcome, with resolution of the disorder,was observed within a few weeks.

Menetrier's disease associated with cytomegalovirus infection in a child.

Menetrier's disease is a rare disease with unknown etiology characterized by protein-losing hypertrophic gastropathy and hypoproteinemia. We report on a 4-year-old boy who presented with a 2-week history of vomiting and periorbital edema. Upper gastrointestinal endoscopy revealed prominent gastric rugae, while pathological examination showed hyperplastic mucosa with proliferation, elongation, and basal cystic dilatation of the gastric glands replaced by mucous-secreting epithelium, confirming the diagnosis of Menetrier's disease. Virus isolation from urine revealed cytomegalovirus (CMV); and CMV immunoglobulin G and immunoglobulin M antibodies were detected in the serum. His condition gradually improved under omeprazole, with complete histological recovery after 3 months.

Cytomegalovirus-associated Ménétrier's disease in adults. Demonstration by polymerase chain reaction (PCR).

Ménétrier's disease (MD) is a rare form of hypertrophic or hyperplastic gastropathy characterized by conspicuous thickening of the gastric mucosal folds and foveolar (crypt) hyperplasia. We examined the presence of cytomegalovirus (CMV) in 2 cases of MD in adults, one associated with gastric carcinoma, using the polymerase chain reaction (PCR). None of the cases showed intranuclear inclusions consistent with CMV infection. Both revealed, besides the features of MD, a peculiar pattern of "chronic active plasmacellular gastritis". Although the samples had been stored in formalin for more than 10 years CMV-DNA was recovered with good yield from both samples. The demonstration of CMV in MD in adults may helps to explain present knowledge of the complex relationships between this virus and gastric mucosa, and strongly suggests a pathogenetic role of the virus with variable phenotypic expression along the years.

[Chronic active plasmacytic gastritis associated with cytomegalovirus]. / Gastritis plasmocelular crónica activa asociada a citomegalovirus.

Chronic active plasmacytic gastritis (CAPG) is characterized by the presence of chronic inflammatory cell infiltrates, mainly formed by plasma cells, involving the neck of gastric glands. This lesion, as well as Ménétrier disease, has been linked to cytomegalovirus (CMV). To test this association we evaluated the foveolar/glandular (F/G) index and the presence of CMV DNA (desoxirribonucleic acid) by means of polymerase chain reaction (PCR) in 12 cases of CAPG and 13 controls. Cases exhibiting CAPG included 2 with Ménétrier disease, 6 with foveolar hyperplasia, and 3 with normal foveolar/glandular (F/G) index. None showed either lymphocytic gastritis or CMV inclusions. Three CAPG cases were associated with gastric carcinoma. The F/G index was less than 1 in all controls. Eleven out of the 12 cases with CAPG showed amplification for CMV DNA while all controls were negative. Findings suggest a very close association, probably in progressive stages, between CMV infection, CAPG, foveolar hyperplasia (with or without Ménétrier disease) and gastric carcinoma. CAPG might be a histologic marker for CMV infection in the germinative zone of the neck of gastric glands. These findings resemble those of hepatitis B virus (HBV) infection, chronic hepatitis, cirrhosis, and hepatocellular carcinoma saga.

[Protein losing gastroenteropathy and possible relationship to cytomegalovirus infection: Ménétrier disease in a child]. / Gastroenteropatía perdedora de proteínas y posible relación con una infección por citomegalovirus: Presentación de un caso de enfermedad de Ménétrier infantil.

Ménétrier's disease is a childhood protein-losing gastroenteropathy characterized by hypertrophy of the gastric mucosa, of unknown etiology, although most of reported cases have been associated with viral infections. Clinical manifestation is edema and biochemically there are hypoproteinemia and hypoalbuminemia. This disease is very rare in children and they have a benign and self-limiting course in contrast to adults where tend to be chronic and occasionally to become malignant. We present a child with Ménétrier disease with edema and ascites possibly associated with a cytomegalovirus infection.

Gastroenteropatía perdedora de proteínas y posible relación con una infección por citomegalovirus: Presentación de un caso de enfermedad de Ménétrier infantil / Protein losing gastroenteropathy and possible relationship to cytomegalovirus infection: Ménétrier disease in a child

La enfermedad de Ménétrier infantil es una gastroenteropatía perdedora de proteínas caracterizada por hipertrofa de la mucosa gástrica, de causa desconocida, aunque la mayoría de los casos informados se han asociado a infecciones virales. Se manifesta clínicamente por edema y bioquímicamente por hipoproteinemia e hipoalbuminemia. Es poco común en los niños, en quienes tiene un carácter benigno y autolimitado, a diferencia de los adultos, en los que tiende a cronifcarse y, en ocasiones, a malignizarse. Se presenta un caso de enfermedad de Ménétrier infantil con síndrome ascítico edematoso posiblemente asociado a una infección por citomegalovirus.

Ménétrier's disease is a childhood protein-losing gastroenteropathy characterized by hypertrophy of the gastric mucosa, of unknown etiology, although most of reported cases have been associated with viral infections. Clinical manifestation is edema and biochemically there are hypoproteinemia and hypoalbuminemia. This disease is very rare in children and they have a benign and self-limiting course in contrast to adults where tend to be chronic and occasionally to become malignant. We present a child with Ménétrier disease with edema and ascites possibly associated with a cytomegalovirus infection.

Cytomegalovirus-associated protein losing gastropathy in an immunocompetent adult: a case report.

Cytomegalovirus infection of the gastro-intestinal tract is frequent and may be serious in the immunocompromised patient. We report a case of cytomegalovirus infection in an immunocompetent young man who presented total food intolerance, pleural effusion and oedema as the result of severe protein losing hypertrophic gastropathy. Hypertrophic gastropathy with severe mucosal protein loss has been described in Menetrier's disease, a condition of unknown cause which involves foveolar hyperplasia of the gastric mucosa. Related hypoalbuminemia is responsible for a clinical picture of diffuse edema. In adults, the natural course of the disease is marked by a chronic course and carries a bad prognosis. In our case, the disease ran a protracted disabling course, likely shortened by ganciclovir therapy, followed by slow clinical, endoscopic and biochemical resolution after several' months course.

Diagnosis of cytomegalovirus infection in pediatric Menetrier's disease by in situ hybridization.

A previously healthy 7-year-old boy presented with a protein-losing enteropathy secondary to a hypertrophic gastropathy. The diagnosis of cytomegalovirus (CMV) infection was established by detection of CMV inclusion bodies in gastric biopsy samples and by hybridization with a CMV probe. This report further strengthens the association between CMV and pediatric Menetrier's disease.

Cytomegalovirus-induced transient protein-losing hypertrophic gastropathy in an immunocompetent adult.

Transient protein-losing hypertrophic gastropathy with similarity to Ménétrier's disease is described. Acute infection with cytomegalovirus (CMV) could be shown to play a causative role. Immunodeficiency was ruled out. The 34-year-old patient had complete resolution of the disease without antiviral treatment. To our knowledge the present report is the first case of CMV-associated protein-losing hypertrophic gastropathy in an immunocompetent adult. To date, a similar disorder has only been described in children. CMV infection should be considered in patients with acute and symptomatic protein loss of gastrointestinal origin.

Acute cytomegalovirus infection in a child with Ménétrier's disease.

The cause of Ménétrier's disease is unknown, although allergic, autoimmune, and infectious, particularly viral, causes have been postulated. This case report describes a 3-year-old child with Ménétrier's disease in whom evidence of acute cytomegalovirus (CMV) infection was found. To our knowledge, this is the first case with evidence of acute infection, indicated by the presence of CMV-specific immunoglobulin M antibody in the acute serum as well as a seroconversion to CMV. CMV was also found in a gastric mucosal biopsy specimen using monoclonal antibodies to the early antigen of CMV.

Marked gastric foveolar hyperplasia associated with active cytomegalovirus infection.

Transient protein-losing gastropathy with marked gastric rugal hypertrophy, a Menetrier's disease-like process, is an uncommon condition of unknown etiology. Most of these cases have been reported in pediatric patients; the clinical course is usually favorable. Cytomegalovirus infection has been implicated as a possible etiology in many of the reported cases. This type of Ménétrier's-like disease has not been well documented in adult patients. We describe here an elderly man who presented with severe protein-losing gastropathy and large polypoid nodules in the stomach. Gastric mucosal biopsies revealed marked gastric foveolar hyperplasia with morphological evidence of cytomegalovirus (CMV) infection. Immunohistochemical analysis demonstrated an aberrant topographic distribution of staining for transforming growth factor-alpha and transforming growth factor-beta receptor II, as described in other cases of Ménétrier's disease in the literature. This transient Ménétrier's-like disease associated with CMV infection should be considered in the differential of both pediatric and adult patients with GI protein loss.

Cytomegalovirus-associated discrete gastrointestinal masses in macaques infected with the simian immunodeficiency virus.

Cytomegalovirus (CMV)-associated gastrointestinal masses have been reported in human acquired immune deficiency syndrome patients. This is the first report on CMV-associated gastrointestinal masses in simian immunodeficiency virus (SIV)-infected macaques. Two SIV-infected macaques presented at necropsy with multiple nodular or umbilicated masses within the gastrointestinal tract. In one animal, the masses were located throughout the gastrointestinal tract, whereas in the other, the masses were restricted to the proximal small intestine. Grossly, the masses were indistinguishable from those caused by neoplastic conditions such as lymphoma and, histologically, were composed of hyperplastic glandular tissue, dense neutrophilic infiltrates within the lamina propria, and multifocal proprial hemorrhage. Frequent cytomegalic cells with basophilic intranuclear inclusions were found in affected regions. Immunohistochemistry for CMV demonstrated frequent immunopositive cells within affected areas. Furthermore, immunohistochemistry for the proliferation marker Ki-67 demonstrated increased proliferation in hyperplastic glands and crypts. CMV should be considered a cause of discrete mass lesions in the gastrointestinal tract of SIV-infected macaques.

Ménétrier disease of childhood: role of cytomegalovirus and transforming growth factor alpha.

OBJECTIVE: Because the role of cytomegalovirus in Ménétrier disease in children remains unclear and recent studies have implicated transforming growth factor alpha in the pathogenesis of this disease in adults, we investigated the possibilities that (1) cytomegalovirus is etiologic in Ménétrier disease in children and (2) transforming growth factor alpha mediates its development. METHODS: The presence of a cytomegaloviral infection and the pattern of transforming growth factor alpha immunolocalization were determined in the gastric mucosa of four pediatric patients with Ménétrier disease, in control subjects (children with normal gastric mucosa, gastritis, or prostaglandin E1-induced antral hyperplasia), and in adults with Ménétrier disease. RESULTS: Evidence of a cytomegaloviral infection was present only in the four children with Ménétrier disease. The pattern of transforming growth factor alpha immunostaining was identical in the specimens from pediatric and adult patients with Ménétrier disease. This pattern was distinct from that found in the pediatric control specimens. CONCLUSIONS: These data strengthen the possibilities that cytomegalovirus is etiologic in children and that transforming growth factor alpha is involved in the pathogenesis of Ménétrier disease in both children and adults.