Differentiating Zollinger-Ellison Syndrome (ZES) from other causes of refractory peptic ulcer disease involves clinical suspicion and specific investigations.
ZES should be suspected in patients with refractory or recurrent peptic ulcers despite optimal management, especially when Helicobacter pylori infection has been excluded or eradicated, and NSAID use is ruled out.
Key clinical features suggestive of ZES include multiple or atypical ulcers, ulcers located beyond the duodenal bulb, severe gastro-oesophageal reflux disease, diarrhoea, and ulcers refractory to standard proton pump inhibitor (PPI) therapy.
Biochemical testing for elevated fasting serum gastrin levels is essential to differentiate ZES from other causes.
Referral to a gastroenterologist for specialist investigations, including secretin stimulation test and imaging to localize gastrin-secreting tumours (gastrinomas), is recommended if ZES is suspected.
Other causes of refractory ulcers such as malignancy, non-adherence to therapy, persistent H. pylori infection, inadvertent NSAID or ulcerogenic medication use should be excluded first.
In summary, the differentiation relies on clinical suspicion in refractory cases, exclusion of common causes, biochemical gastrin testing, and specialist referral for further diagnostic workup NICE CKS,NICE CKS,NICE CG184.