Download An Unusual Presentation of Ménétrier`s Disease

CASE REPORT
An Unusual Presentation of Ménétrier's Disease
Farina Mohammed Hanif1, Nasir Hassan Luck1, Zaigham Abbas1, Syed Mujahid Hassan1,
Sabhita Shabir1 and Muhammad Mubarak2
ABSTRACT
Ménétrier's Disease (MD) is a rare acquired hypertrophic gastropathy characterized by giant hypertrophic rugal folds,
hypochlorhydria, and hypoproteinemia. The definitive etiology of MD is controversial, although infection with Helicobacter
pylori (H. pylori) has been implicated in adults. It presents as a constellation of symptoms including epigastric pain, fatigue,
vomiting, weight loss, anorexia, and edema. None of these signs and symptoms is specific for the disease. The
gastrointestinal symptoms and the degree of hypoalbuminemia can be profound, the latter resulting from the leakage of
protein from the gastric lining. The disease is more common in males. Herein, we report a case of a young woman
presenting with the chief complaint of peripheral edema with minimal gastrointestinal symptoms, which was diagnosed as
MD on endoscopic evaluation and histopathological examination of gastric biopsy. A high index of suspicion is needed to
correctly diagnose this condition for its optimal management.
Key Words: Endoscopy. Hypochlorhydria. Hypoproteinemia. Hypertrophic gastropathy. Ménétrier’s disease.
INTRODUCTION
Ménétrier's Disease (MD) was first described in 1888 by
Pierre Ménétrier.1 It is an uncommon acquired disorder
of unknown etiology characterized by giant hypertrophy
of the rugal folds. Patients present with a unique
constellation of signs and symptoms that include
abdominal pain, nausea and vomiting, hypochlorhydria
(due to markedly reduced, if not absent, number of
parietal cells), and edema of peripheral tissues (due to
leakage of protein across the gastric mucosa). They may
also develop anemia.2 It is more common in men (male
to female ratio=3:1), between fourth and sixth decades
of life.
Herein, we report a case, for the first time in our country,
of a 30-year-old woman presenting with the main
complaint of peripheral edema and diagnosed as MD on
endoscopic biopsy.
CASE REPORT
A 30-year-old woman with no known co-morbid condition
presented to the out patient department (OPD) with the
main complaint of gradual swelling of both legs
extending to the knees. On further questioning, she
gave history of dyspepsia and vague abdominal pain.
She described no abdominal distention, heartburn,
dysphagia, melena, hematemesis, diarrhea, fever, night
sweats, or other cardiopulmonary or urinary symptoms.
Department of Hepatogastroenterology1 / Histopathology2,
Sindh Institute of Urology and Transplantation (SIUT),
Karachi.
Correspondence: Dr. Farina Mohammed Hanif, Flat 101,
Khanani Centre, Bahadurabad, Karachi.
E-mail: [email protected]
Received: March 26, 2013; Accepted: October 24, 2013.
Her past medical history was unremarkable. She was
not using any medications and denied drug addictions.
She smoked Huqqah and had non-significant family
history. Family history was negative for gastrointestinal
disease. Physical examination was unremarkable
except for bilateral pitting edema upto the knees. It was
neither warm nor red and was non-tender.
Her laboratory investigations showed complete blood
count with hemoglobin (Hb) of 10.7 g/dl, Mean
Corpuscle Volume (MCV) of 84.6 fl and platelets at
464 x 103 per microliter. Markedly decreased serum
albumin of 1.4 g/dl and increased serum globulin of
6.8 g/dl was found. The liver function tests and serum
chemistry were within normal limits. Urine analysis
showed no proteinuria. Ultrasound abdomen was
reported normal.
Esophagoduodenoscopy (EGD) demonstrated mosaic
pattern of gastric mucosa with prominent rugal folds.
Biopsy of gastric body was obtained which showed
marked foveolar hyperplasia with elongated, dilated and
tortuous gastric pits. No evidence of Helicobacter (H.)
pylori or malignancy was observed. Histopathological
findings were consistent with MD.
Patient was started on Proton Pump Inhibitors (PPIs)
and advised for follow-up. However, the patient was lost
to follow-up.
DISCUSSION
MD was first described by Ménétrier in 1888.1 It
represents the diffuse giant mucosal growth of stomach
lining in the shape of wide, long, twisted cerebral-like
folds. This morphological change is attended by the loss
of proteins from the stomach and consequential
hypoproteinemia (protein losing gastroenteropathy). In
adults, the disease has a progressive course with
Journal of the College of Physicians and Surgeons Pakistan 2014, Vol. 24 (Special Supplement 3): S183-S185
S183
Farina Mohammed Hanif, Nasir Hassan Luck, Zaigham Abbas, Syed Mujahid Hassan, Sabhita Shabir and Muhammad Mubarak
is also not completely clear. There is an evidence that
Epidermal Growth Factor Receptor (EGFR) signaling is
involved in the pathogenesis of the disease.1
EGD shows massively thickened gastric rugal folds,
resembling cerebral convolutions, along the greater
curvature in body and fundus, usually sparing the
antrum with copious amounts of thick mucus.3 Markedly
hypertrophic and enlarged folds are subject to erosions.
Most often gastric pH is alkaline.
Figure 1: (A) Hematoxylin and eosin (H&E) staining showing marked
foveolar hyperplasia and mild atrophy of the fundic glands. H. pylori were not
seen. (H&E, x100). (B) High-power view showing dilated and tortuous gastric
pits lined by mucinous epithelium. (H&E, x400). (C) High-power view
showing almost complete absence of oxyntic cells in the gastric body glands.
(H&E, x400). (D) Periodic Acid-Schiff (PAS) staining showing marked
foveolar hyperplasia lined by PAS positive mucin secreting epithelial cells
(PAS, x100).
significant morbidity and mortality due to ongoing protein
loss and life-threatening gastrointestinal hemorrhage but
it is usually self-limited and may completely resolve in
patients younger than 10 years of age and in the
postpartum period.2-4
The disease commonly affects males between 30 to 50
years of age.5-7 Patients present clinically with signs and
symptoms of abdominal pain, anorexia, nausea and
vomiting and generalized edema. It has been reported
that peripheral edema occurs in about 90% of cases in
children in contrast to less than 25% of adults.5
Laboratory studies usually show low serum albumin,
high gastric pH and normal to slightly elevated serum
gastrin values and peripheral eosinophilia in MD
patients. Iron deficiency anemia can also develop due to
gastric loss.4
This case has certain unique features. In contrast to its
common occurrence in males, our patient was a young
female. There were vague and subtle gastrointestinal
symptoms and she presented to us with the main
complaint of peripheral edema. She had normal Hb with
normal MCV and severe hypoalbuminemia and no
peripheral eosinophilia. Gastric pH and serum gastrin
levels could not be measured because of unavailability
of these tests.
Etiology of MD is disputable, although possible causes
include toxins, immunologic, endocrinologic or
autoimmune disorders and dietary factors. H. pylori
infection has been reported in a few studies as strong
associated factor in both adults and children and
Cytomegalovirus (CMV) infection in children.1,8,9 In this
patient, gastric biopsy did not reveal concomitant
H. pylori or CMV infection. Pathogenesis of the disorder
S184
Histologically, MD shows striking foveolar hyperplasia
with massive expansion of surface mucous cells
associated frequently with reduced number of parietal
cells and chief cells. Gastric pits are often tortuous and
undergo cystic dilatation. Modest inflammation may be
noted in the lamina propria. The muscularis mucosa is
usually thickened, with strands of smooth muscle
extending into the lamina propria. Deep snare biopsies
or large capacity biopsies are essential for histological
evaluation of suspected MD.5
Gastric body biopsy in this patient revealed foveolar
hyperplasia with elongated, dilated and tortuous
gastric pits and atrophy of the oxyntic glands. The
morphological findings were consistent with MD.
No H. pylori or other infective organism was found.
Gastric mucosal thickening with prolonged PPIs use can
clinically imitate MD. But it can be excluded on the basis
of abundance of parietal cells in the biopsy. This patient
denied any use of PPIs and excess of parietal cells was
not documented on her gastric biopsy.
MD is also considered a premalignant disorder.
However, the magnitude of risk of malignancy in MD is
uncertain.
There are no evidence based guidelines available for
treatment strategy of MD. It usually has abrupt onset
and spontaneous resolution in children while an
insidious onset and progressive course characterizes
the disease in adults.5 Spontaneous remissions are rare
except in CMV-associated disease in children. 1
Empirical treatment with anticholinergic therapy,
octreotide, H2-receptor blockers, glucocorticoids,
antifibrinolytic agents, or monoclonal antibody against
EGFR, as well as eradication of H. pylori, has not
provided constant benefit. Surgical intervention has
been reserved for patients with biopsy proven
malignancy or dysplasia, high amount of protein loss
and uncontrolled and/or recurrent bleeding. We were not
able to document the response of this patient to PPI use,
as she was lost to follow-up. This is one of the major
drawbacks of our health care system and the society.
In summary, this case highlights the variation in the
presentation of the disease. A high index of suspicion
along with scrupulous and diligent endoscopic and
histological evaluation will help in an accurate diagnosis
of the condition.
Journal of the College of Physicians and Surgeons Pakistan 2014, Vol. 24 (Special Supplement 3): S183-S185
Ménétrier's disease presenting with edema
REFERENCES
1. Burdick JS, Chung E, Tanner G, Sun M, Paciga JE, Cheng JQ,
et al. Treatment of Ménétrier's disease with a monoclonal
antibody against the epidermal growth factor receptor. N Engl
J Med 2000; 343:1697-701.
2. Coffey RJ, Washington MK, Corless CL, Heinrich MC.
Ménétrier disease and gastrointestinal stromal tumors:
hyperproliferative disorders of the stomach. J Clin Investig
2007; 117:70-80.
3. Chung M, Pittenger J, Flomenhoft D, Bennett J, Lee EY,
Shashidhar H. Atypical clinical and diagnostic features in
Ménétrier's disease in a child. Case Rep Gastrointest Med
2011; 2011:480610.
4. Rothenberg M, Pai R, Stuart K. Successful use of octreotide to
treat Ménétrier's disease: a rare cause of abdominal pain,
weight loss, edema, and hypoalbuminemia. Dig Dis Sci 2009;
54:1403-7.
5. Graham-Maar RC, Russo P, Johnson AM, Baldassano R,
Mamula P. A 2-year-old boy with emesis and facial edema.
Med Gen Med 2006; 8:75.
6. Rich A, Toro TZ, Tanksley J, Fiske WH, Lind CD, Ayers GD,
et al. Distinguishing Ménétrier's disease from its mimics. Gut
2010; 59:1617-24.
7. Famularo G, Sajeva MR, Gasbarrone L. Beyond gastritis and
before cancer: the strange case of Ménétrier's disease. Intern
Emerg Med 2011; 6:369-71.
8. Fretzayas A, Moustaki M, Alexopoulou E, Nicolaidou P.
Ménétrier's disease associated with Helicobacter pylori: three
cases with sonographic findings and a literature review.
Ann Trop Paediatr 2011; 31:141-7.
9. Kawasaki M, Hizawa K, Aoyagi K, Nakamura S, Fujishima M.
Ménétrier's disease associated with Helicobacter pylori
infection: resolution of enlarged gastric folds and hypoproteinemia after antibacterial treatment. Am J Gastroenterol
1997; 92:1909-12.
Journal of the College of Physicians and Surgeons Pakistan 2014, Vol. 24 (Special Supplement 3): S183-S185
S185