Olmesartan-associated severe gastritis and enteropathy

Abstract

Olmesartan is an angiotensin II receptor antagonist, used in the treatment of hypertension. We report a case of olmesartan-associated severe gastritis with enteropathy in a 74-year-old woman who presented with mainly upper gastrointestinal symptoms. There was significant endoscopic improvement in the mucosal inflammation on stopping the drug. Subsequent gastroscopy showed mucosal healing and normal gastric and duodenal mucosa. To our knowledge, this is the first case report of olmesartan-associated gastritis and enteropathy predominantly involving and affecting the whole of stomach with limited small bowel involvement.

Background

Olmesartan is an angiotensin receptor blocker (ARB), commonly used in the treatment of hypertension. Olmesartan-associated enteropathy is rare. It closely resembles coeliac disease and autoimmune enteropathy clinically and histologically. It can affect any part of the gastrointestinal tract as evidenced from case reports. Therefore, olmesartan-associated enteropathy presents a diagnostic challenge for clinicians.

Case presentation

A 74-year-old woman presented to gastroenterology clinic with a 5-month history of epigastric pain and weight loss. She reported that her abdominal pain was gradually getting worse and hence was started on omeprazole. Her symptoms did not improve and had lost nearly 7 kg in weight. She had nausea but no history of vomiting, reflux symptoms or dysphagia. There was no history of diarrhoea or bloating. She denied any symptoms suggestive of local or systemic infection or changes in her diet in the last few years.

Her medical history includes partial thyroidectomy due to autoimmune thyroid disease. Her medications include levothyroxine, olmesartan, omeprazole and citalopram. Her olmesartan was restarted 6 months prior to the patient’s presentation. She had been on olmesartan on and off in the past for nearly 12 years. On clinical examination, she had mild tenderness in the epigastric region with no palpable mass or organomegaly. There was no palpable lymphadenopathy.

Investigations

All her initial blood tests including renal functions, liver functions and bone profile were normal. Her anti-IgA tissue transglutaminase antibodies (tTG) were normal. Thyroid stimulating hormone was 1.27 mU/L (0.3–4.40). Serum electrophoresis, b-2-microglobulin, ACE level and lactate dehydrogenase was normal. Helicobacter pylori serology was negative.

She proceeded to have a gastroscopy which showed severe erosive gastritis as shown in figure 1 involving the whole stomach with moderate duodenitis involving the first part of the duodenum. Biopsies showed features of acute on chronic inflammation of gastric mucosa as shown in figure 2 with gastric ulceration and ulcer slough. Intraepithelial lymphocytes were noted in the gastric and duodenal biopsies. Surface of the duodenal mucosa was flattened with intraepithelial neutrophils. A large number of eosinophils were also seen which would be in keeping with a drug aetiology. She had a CT scan of her chest abdomen and pelvis which showed thickened antrum of the stomach with adjacent perigastric lymph nodes all measuring less than 10 mm. There were no features of inflammation in the small or large bowel.

Figure 1.

Gastroscopy shows severe gastritis with multiple gastric erosions seen around the antrum of the stomach.

Figure 2.

Biopsy of the gastric mucosa shows a pattern of active acute on chronic inflammation with no helicobacter pylori organisms seen. A large number of eosinophils were also noted.

The case was discussed in the regional lymphoma panel and lymphoma was ruled out.

Differential diagnosis

1. Drug-induced enteropathy—in our case olmesartan was the main differential.

2. Crohn’s disease—however, her gastric findings were not typical for Crohn’s disease.

3. Coeliac disease—ruled out with negative anti-IgA tTG and duodenal biopsies.

Treatment

Olmesartan was stopped and within a week her symptoms started to improve. Gastroscopy was repeated in 3 months which showed remarkable endoscopic improvement in the gastritis as shown in figure 3. Her repeat biopsies showed eosinophil rich chronic inflammation within lamina propria of the stomach and duodenum as shown in figure 4.

Figure 3.

Repeat gastroscopy shows remarkable improvement in the endoscopic appearance 3 months after stopping the drug. The ulcers seen in the initial endoscopy have all healed.

Figure 4.

Biopsy of the duodenum shows lesser degree of mucosal inflammation taken 3 months after stopping the drug.

Outcome and follow-up

Her repeat gastroscopy in 6 months was normal with normal biopsies. Her appetite improved and started to eat well. She reported feeling symptomatically better following stopping the drug and even started to gain weight giving a Naranjo score of 5, thus suggesting a high probable adverse effect caused by olmesartan.

Discussion

Sprue-like enteropathy associated with the ARB olmesartan was first described in 2012.¹ Olmesartan-associated enteropathy closely resembles coeliac disease. But, it can be differentiated by negative tTG, endomysial antibodies and by absent HLA-DQ2 and HLA-DQ8 heterodimer. In addition, there is absence of response to a gluten-free diet in olmesartan-associated enteropathy.² Although the pathophysiology of olmesartan-associated enteropathy is unknown, it has been suggested there may be a cell-mediated immune response that damages the small intestinal brush border.^2–6 Accordingly, in some studies, it has been found that people with autoimmune diseases have a higher predisposition.^{7 8} Severe chronic non-bloody diarrhoea and weight loss are the commonly reported symptoms. Contrast to majority of the reported cases in literature, our patient had predominant upper gastrointestinal symptoms with no significant lower gastrointestinal symptoms. Similarly, the endoscopic and pathological findings were mostly involving the stomach with limited findings in the duodenum. This demonstrates the variable presentation of effects of olmesartan on the gut. Deliberate rechallenge test with olmesartan was not indicated in our case because of the patient’s age and severity of her symptoms on presentation. Complete resolution of her symptoms with endoscopic evidence, in the absence of clinicopathological evidence of other causes, suggests that the association is not likely to be due to chance. To our knowledge, this is the first case report of a patient with olmesartan-associated severe gastritis in the absence of documented significant enteropathy.

Patient’s perspective.

I started to feel unwell November 2016 with discomfort in stomach, nausea and no appetite. I had first of four endoscopies in February 2017 which showed severe gastritis. The worrying part of all this was not knowing what was causing it and the significant weight loss. Within 6 weeks of coming off the medication, the nausea stopped and I was able to eat small amounts. I am so much better now. I have gained weight and eating well but still some mild discomfort in the stomach area. I am very grateful to the gastroenterology consultant and her team who came up with the reason why I was so poorly. Thank you for your interest. Hope this helps.

Learning points.

• Olmesartan is a rare but important cause of immune-mediated enteropathy with or without villous atrophy.

• Olmesartan-associated enteropathy can mimic coeliac disease and crohn’s disease clinically. It is crucial for clinicians to be aware of this, to avoid unnecessary extensive investigations and delay in the diagnosis, which in turn can have a major impact on the quality of life of our patients.