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BMJ Case Rep. 2010; 2010: bcr09.2009.2294.
Published online 2010 April 29. doi:  10.1136/bcr.09.2009.2294
PMCID: PMC3047282
Findings that shed new light on the possible pathogenesis of a disease or an adverse effect

Gastric antral vascular ectasia (GAVE) in a non-cirrhotic patients with diabetes: case report and possible pathophysiological mechanism

Abstract

Gastric antral vascular ectasia (GAVE) syndrome is an uncommon but well-described cause of recurrent upper gastrointestinal bleeding or iron deficiency anaemia. Atiology is unknown but several associated diseases have been reported like connective tissue or autoimmune disorders or cirrhosis. Cases have been reported in systemic sclerosis, achlorhydia, atrophic gastritis and chronic renal failure. The most common cause is portal hypertension and portal hypertensive gastropathy. This is especially so after eradication of oesophageal varices by sclerotherapy or banding. Diabetic complications are characterised by microvascular diseases especially in the retina, glomerulus and vasa nervorum. It involves apoptosis and remodelling of endothelial cells. Hyperglycaemia is an essential cause of reactive oxygen species (ROS)-mediated oxidative stress in this complication. Angiopathy of gastric mucosa in diabetes mellitus has not been reported so far in the literature. We are presenting an interesting case of diabetes mellitus with gastric vascular ectasia without evidence of any other systemic illness.

Background

This is the first unique case of GAVE in a patient with diabetes without any other systemic illness or portal hypertension. We put forward the possible pathophysiological mechanism of GAVE and highlight the importance of a thorough workup of anaemia in any patient.

Case presentation

A 39-year-old woman with type 2 diabetes mellitus on insulin presented with progressively increasing pallor, loss of appetite and fatigue of 6 months’ duration. The patient had no other illness, but had undergone laser photocoagulation for diabetic retinopathy 4 years ago. Examination revealed moderate pallor, normal blood pressure and normal systemic examination. Fundoscopic examination confirmed scarring of photocoagulation. Haemoglobin level was 8.1 gm/dl (normal value 13–15 gm/dl for female). Peripheral blood smear was consistent with iron deficiency anaemia. Serum iron was low and total iron binding capacity high. Liver enzymes were normal as was serum albumin, urea and creatinine. Lipid profile was acceptable as the patient was on statins. A 24-h urine sample showed microalbuminuria of 413 mg. Fecal occult blood testing was positive and the patient was prepared for oesophago-gastoduodenoscopy (OGD). An unusual finding of antral vascular ectasia—‘watermelon stomach’—was found (figure 1). Workup for cirrhosis of liver was started and ultrasonography of the abdomen revealed normal liver, portal vein, spleen and other organs. There was no feature of portal hypertension. Large bowel screening by colonoscopy was normal. The patient was started on omperazole and iron and referred for argon–plasma photocoagulation.

Figure 1
Endoscopic picture showing gastric antral vascular ectasia.

Investigations

Complete blood counts and peripheral blood smear, oesophago-gastroduodenoscopy, colonoscopy, immune markers and ultrasonography of the abdomen.

Differential diagnosis

Cirrhosis of the liver and portal hypertensive gastropathy.

Treatment

Argon plasma photocoagulation and iron replacement.

Outcome and follow-up

The patient is improving.

Discussion

GAVE is a rare disorder causing up to 4% of non-variceal upper gastrointestinal bleeding. GAVE is often associated with systemic illnesses, such as cirrhosis of the liver, autoimmune connective tissue disorders, bone marrow transplantation and chronic renal failure.1 The syndrome was first described in 1953 by Ryder et al in the gastrectomy specimen of an elderly woman. It was not until 1984 when Jabbari et al described the unique endoscopic appearance as ‘prominent erythematous stripes radiating in a spoke like fashion from the pylorus to the antrum’. This led Jabbari et al to coin the term ‘watermelon stomach’ for this condition.2 The pathophysiological changes leading to GAVE have not been fully explained and remain controversial. Patient presentation varies from chronic iron deficiency anaemia to heavy acute gastrointestinal bleeding. Histopathological features are vascular ectasia, thrombi, spindle cell proliferation and fibrohialinosis, similar to findings of volvulus, intussuscepcion and mucosal trauma, suggesting that GAVE lesions may be acquired lesions in which mucosal stress may play a pivotal role.3

Diabetic complications are characterised by microvascular diseases, especially in the retina, glomerulus and vasa nervorum. It involves apoptosis and remodelling of endothelial cells. Hyperglycaemia is an essential cause of ROS-mediated oxidative stress in this complication.4 Proliferative diabetic retinopathy is a wound healing-like response in which neovascularisation is accompanied by an influx of inflammatory cells and development of myofibroblasts. Several growth factors have been shown to play a role in proliferative diabetic retinopathy—for example, vascular endothelial growth factor-A (VEGF-A), transforming growth factor-ß, hepatocyte growth factor, platelet-derived growth factor and the pro-fibrotic connective tissue growth factor (CTGF). VEGF is considered to be the primary angiogenesis factor in this sequence of events.57

Angiogenesis is a pivotal process in all types of wound healing, including the healing of gastric ulcers. It is regulated by pro-angiogenic factors, including VEGF, fibroblast growth factor and endothelial growth factor (EGF), and by antiangiogenic factors such as endostatin. Platelet aggregation is a cardinal feature of vascular repair. A variety of potent angiogenic stimulators, including VEGF, platelet-derived endothelial cell growth factor, EGF and platelet-derived growth factor, are stored in platelets and released during clotting at the wound. Activation of platelets by α-thrombin stimulates angiogenesis in the chick chorioallantoic membrane.8 Furthermore, platelets have been shown to stimulate endothelial cell proliferation and capillary tubular structure formation in vitro.9

Thus, in proliferative diabetic retinopathy and GAVE it is stress and hypoxia that is common and the consequences are neovascularisation. Hypoxia has been well-documented in gastric mucosa in portal hypertensive gastropathy—the most common cause of GAVE.10

Thus, the hypothesis that GAVE in diabetes mellitus could be induced by microvascular disease of the stomach due to chronic ischaemia and the same pathogenesis holds true for other causes of GAVE. As hyperglycaemia is an essential cause of ROS-mediated oxidative stress,4 GAVE can occur in diabetes mellitus in the absence of any other known cause.

GAVE has been reported in chronic iron deficiency anaemia with a mean duration of 48 years. Our patient had anaemia of short duration and was the result rather than the cause of GAVE. Cases have been reported in chronic renal failure, systemic sclerosis, acholrhydia, bone marrow transplantation, autoimmune and collagen vascular disorders, and Alzehiemer’s disease.11 A review of the literature did not reveal any case of GAVE in patients suffering from diabetes mellitus alone.

In conclusion, this case report, the first of its kind, has put forward the possible pathophysiological mechanism of GAVE, which has been controversial so far.

Learning points

  • GAVE must be considered as a cause of iron deficiency anaemia.
  • The presence of GAVE must be looked for in a patient with diabetes with microvascular disease but with preserved renal function.
  • Reactive oxygen species released as a result of hypoxia or hyperglycaemia contribute to the genesis of GAVE mediated by various growth factors.

Acknowledgments

We acknowledge the support provided by our secretary, Miss Mecciya Hadi, and Miss Fadwa Bawazir, Director Patient Safety and Quality Advocacy.

Footnotes

Competing interests: None.

Patient consent: Patient/guardian consent was obtained for publication.

REFERENCES

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