Ménétrier’s disease in a patient with refractory ulcerative colitis: a clinical challenge and review of the literature
- 1 IBD-unit, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
- 2 Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Sicilia (omit), Italy
- Correspondence to Professor Walter Fries; fwalter@unime.it
Abstract
Ménétrier’s disease (MD) is a rare disease of the stomach, characterised by hypertrophic gastric folds leading to protein loss. The association with ulcerative colitis (UC) is rare but has been reported in the literature. We report a case of a 29-year-old male affected by UC with an additional diagnosis of MD 3 years after UC diagnosis. UC was refractory to several treatment lines (thiopurines, infliximab, vedolizumab and ustekinumab), and the patient underwent colectomy. Octreotide was administered for MD normalising blood biochemistry, but it was not effective in inducing endoscopic remission of the stomach. Treatment options in patients with MD and UC are discussed.
BACKGROUND
Ménétrier’s disease (MD) is a rare disorder characterised by hypertrophic gastric folds leading to protein loss. Clinical symptoms related to the stomach are non-specific with epigastric pain, nausea and vomiting. It affects males more frequently than females in an age range between 30 and 60 years. It is considered a premalignant lesion, and patients with MD have an increased mortality rate.1 Macroscopic differential diagnoses include gastric lymphoma, polyposis syndromes, gastric adenocarcinoma, hypertrophic lymphocytic gastritis and Zollinger-Ellison syndrome. Diagnosis is based on histological evaluation showing foveolar hyperplasia and on cystic dilation of gastric glands together with atrophy of the oxyntic mucosa, including a reduction in parietal and chief cells. Its association with inflammatory bowel disease (IBD) has been sporadically reported over the past 30 years.
Case presentation
A 29-year-old male was admitted to our hospital for persistent vomiting and progressive weight loss. His medical history included type 2 diabetes mellitus, induced by corticosteroids, prescribed for subtotal ulcerative colitis diagnosed at age 26 years. At 29 years, he was hospitalised for a severe flare-up with weight loss (9 kg in 1 year). During hospitalisation, a thoracic CT scan was performed showing pulmonary embolism with thromboembolic filling defects of the main left pulmonary artery, extended to some segmental branches. At this point, a coagulation screening was performed with negative results with the exception of plasma factor VIII activity, of 283%. For this reason, he was started on low-molecular-weight heparin (LMWH). An esophagogastroduodenoscopy (EGD) at that time point showed thickened gastric folds with cerebriform appearance involving almost the entire surface of the stomach. Biopsies were taken and a diagnosis of eosinophilic gastritis was made. After discharge, the patient remained in remission over the following 2 years while on mesalazine and LMWH.
Two years later, the patient experienced a sudden deterioration with vomiting, bloody diarrhoea, severe weakness and dramatic weight loss (15 kg lost in 3 months). At admission in our clinic, the patient presented with anaemia (82 g/L, mean corpuscular volume 69 fl), 44 g/L of total protein, with hypoalbuminaemia (22.7 g/L), but without oedemas. Colonoscopy revealed a moderately active pancolitis (endoscopic Mayo 2 grade) (figure 1), whereas on gastroscopy the mucosa of the fundic and corpus region and, to a lesser extent, of the antrum had a diffused, significant pseudopolypoid aspect with folds that, in some portions, assumed a cerebriform appearance and were distensible, with difficulty, by insufflation (figure 2A). Histology revealed diffused foveolar hyperplasia associated with erosions and ulcers and focal glandular atrophy (figure 2B) compatible with MD. Duodenal mucosa was normal. The patient was stabilised with albumin replacement, intravenous iron and steroids, and was discharged with omeprazole 40 mg/day, mesalazine 800 mg three times a day and apixaban 10 mg/day, due to former thromboembolism.
(A) Endoscopic appearance of the colon at the time of the first admission of the patient, showing mucosal lesions and the absence of vascular pattern; (B) histology of a biopsy specimen (H&E staining, original magnification 10×) with marked inflammatory infiltrate, crypt abscesses and superficial erosions.
(A) Endoscopic view of the stomach showing hypertrophic gastric folds, and (B) H&E staining showing cystic enlarged glands and mild inflammation (original magnification 20×).
Six months later, worsening of his clinical condition occurred and several attempts with infliximab (primary failure), vedolizumab (secondary failure), and finally, ustekinumab together with azathioprine 100 mg (secondary failure after the fourth administration) failed and the patient finally agreed to surgery: a proctocolectomy with a temporary ileostomy was performed.
For the diagnosis of MD, proton pump inhibitor (PPI) treatment was tried but failed, and octreotide LAR off-label was started with 20 mg/month subcutaneously.
Outcome and follow-up
After 1 year, albumin levels were stable with 37 g/L while on ocreotide LAR 20 mg monthly without further need for intravenous supplementation. He gained 13 kg with a normal output from the ostomy. Blood biochemistry normalised, but an EGD performed after 1 year of treatment did not reveal any change from baseline. However, the patient remained well without clinical symptoms.
Discussion
The simultaneous occurrence of MD and IBD is rare, and the current report represents the 14th patient over the past 30 years. Former reports on this association are not limited to specific geographic areas since they come from Ireland,2 Japan,3 Spain,4 Serbia,5 Algeria,6 Australia,7 Turkey,8 USA,9 10 Iran11 and Canada.12 In a database of over 7.4 million patients of the Mayo Clinic, two cases were identified by Anderson et al between 1994 and 2014.10 With the exception of two cases, the patients were male and MD was diagnosed after or concomitantly with the diagnosis of UC or Crohn’s disease (CD). The median age at diagnosis of MD was 33.5 years (range 21–68 years) (table 1).
Reported cases in the literature with patient demographics and disease characteristics; therapy of inflammatory bowel disease (IBD) when available; Helicobacter pylori (HP) and cytomegalovirus (CMV) status when available; treatment for Ménétrier’s disease (MD) and outcome
| Source | Gender, age at MD diagnosis | IBD type and time to MD diagnosis | IBD treatment before MD | Hp and CMV status | Treatment | Outcome of MD |
| Arthurs and Fielding2 | Female, 52 years | CD—16 years | N/A | N/A | Cimetidine 1000 mg/day Azathioprine 50 mg/day |
Stabilisation |
| Sasaki et al 3 | Male, 68 years | UC—20 years | Salazopyrin | N/A | Cimetidine 800 mg | ? |
| Ojeda et al*4 | Male, 61 years | UC—7 years | N/A | N/A | Octreotide (dosing?) | Remission |
| Mirković et al 5 | Male, 21 years | UC—10 years | N/A | N/A | Gastrectomy | Gastrectomy |
| Belhocine and Chaoui6 | Male 31 years Male 21 years |
UC—2 years UC—concomitant |
Mesalazine N/A |
N/A N/A |
Steroids, omeprazole 40 mg/day, than gastrectomy | Steroid dependency, gastrectomy, death regression |
| Hemmings7 | Male, 42 years | UC—10 years (colectomy) | N/A | N/A | Steroids Gastrectomy | Gastrectomy |
| Hatemi et al 8 | Male, 21 years | UC—concomitant PSC |
Steroids | Hp –ve CMV –ve |
Lansoprazolo 30 mg/day, steroids for UC | Regression with UC remission |
| Nguyen et al 9 | Male, 33 years | UC—7 years | Mesalazine +steroids | Hp +ve CMV –ve |
Cetuximab Gastrectomy | Gastrectomy |
| Anderson and Sweetser10 | Female, 28 years | UC— concomitant | N/A | Hp +ve, CMV –ve |
Pantoprazole, Hp eradication | ? |
| Rahimi et al 11 | Male, 34 years Male, 53 years |
UC—8 years UC—35 years |
Mesalazine 6-mercaptopurine Adalimumab |
N/A N/A |
Cetuximab Cetuximab |
Symptom resolution Symptom resolution |
| Hussameddin et al 12 | Male, 43 years | UC—4 years | Azayhioprine Infliximab |
N/A | Vedolizumab | Regression |
| Present case | Male, 29 years | UC—2 years | Mesalazine +steroids | Hp –ve CMV –ve |
Octreotide Colectomy for UC |
Remission |
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*Information obtained from Hatemi et al 8
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CD, Crohn’s disease; N/A, data not available; PSC, primary sclerosing cholangitis; UC, ulcerative colitis; –ve, negative; +ve, positive.
Concerning aetiopathogenic hypotheses, infection with Helicobacter pylori 13 or with cytomegalovirus, the latter especially in paediatric patients,14 and low vitamin D levels11 were discussed. More recently, transforming growth factor-α (TGF-α), found to be overexpressed in both MD and UC, shows a TGF-α excess, respectively, in gastric and colonic mucosa.10 In particular, in MD, TGF-α stimulates gastric mucosal hyperplasia through enhanced epidermal growth factor receptor (EGFR) activation. In UC, upregulation of TGF-α occurs during epithelial regeneration.9 This latter hypothesis may be supported by a symptomatic improvement after initiation of cetuximab, an EGFR inhibitor, in two out of three patients with both MD and UC, but no data were available on regression of gastric lesions in these patients.10
Four patients were operated on performing total gastrectomy; other reports described a symptomatic remission of MD with different therapies (cimetidine, azathioprine, octreotide or steroids). In one patient, regression of gastric lesions was reported with lansoprazole and corticosteroids.8
In some patients with isolated MD, that is, without IBD, treatment with cetuximab led to a regression of gastric lesions15 and normalisation of the cell proliferation marker K-67,16 after 12–15 months of treatment. Finally, full treatment success with endoscopic and histological normalisation of the gastric mucosa was reported with vedolizumab in a patient under maintenance therapy for UC.12 Unfortunately, in the present case, vedolizumab failed to induce remission of UC; thus, we opted for octreotide obtaining clinical but not endoscopic remission of MD after proctocolectomy for UC. The efficacy of octreotide in controlling protein loss but without improving gastric lesions was first described in 199317 and in several cases thereafter in isolated MD. Due to the rarity of MD, clinical trials are unlikely to be carried out.
In conclusion, on a cost-efficacy base, octreotide seems to be the best candidate for symptom control induced by gastric lesions. Unlike octreotide, cetuximab may have some beneficial effects on improving gastric lesions. While octreotide failed in a clinical trial in UC,18 no data are available for cetuximab in UC. Only one very recent case report showed normalisation of gastric lesions under vedolizumab12 and may thus represent a starting point for future therapeutic approaches in both isolated and IBD-associated MD. Vedolizumab may represent a potential treatment option because its benefits are well documented in UC, and at least in one case, it was successful in inducing normalisation of the gastric lesions.
Learning points
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Ménétrier’s disease (MD) is a rare disease of the stomach with a potential for neoplastic degeneration.
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Association with ulcerative colitis, a chronic and disabling disease, has been described in case reports. This association is rare and represents a clinical challenge because a standardised medical approach is lacking.
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Octreotide is a possible treatment option for MD although its benefit, as in our case, is often limited to clinical but not endoscopic/histological remission, whereas cetuximab, an epidermal growth factor receptor inhibitor, may lead to regression of gastric lesions
Ethics statements
Patient consent for publication
Acknowledgments
The authors are grateful to Professors Socrate Pallio and Antonio Ieni for their dedication and readiness in carrying out endoscopy and histopathological evaluation.
Footnotes
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Contributors AV was involved in planning and conducting of the study. SR was involved in manuscript drafting. OK was involved in revision of the manuscript. WF was involved in planning and conducting of the study, and revision of the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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