What other non-missable diagnoses should be considered in a patient with hyperacidity and flatulence, potentially with a history of nonsteroidal anti-inflammatory drug (NSAID) use or Helicobacter pylori (H. pylori) infection, beyond gastroesophageal reflux disease (GERD)?

Critical Non-Missable Diagnoses Beyond GERD

In patients presenting with hyperacidity and flatulence, particularly with NSAID use or H. pylori infection history, you must actively exclude peptic ulcer disease, celiac disease, ovarian cancer (in women ≥50 years), gastroparesis/functional dyspepsia, and small intestinal bacterial overgrowth (SIBO).

Peptic Ulcer Disease and Upper GI Pathology

Upper endoscopy is mandatory for patients over 40 years with dyspeptic symptoms and bloating, especially in regions with high H. pylori prevalence 1. This directly visualizes esophageal and gastric mucosa to identify:

• Peptic ulcers - Both H. pylori and NSAIDs independently cause gastroduodenal ulcers and complications 2. The combination creates additive risk, though H. pylori eradication provides modest benefit in NSAID users with prior ulcer complications 2.
• Erosive esophagitis - Los Angeles B or greater esophagitis requires long-term PPI therapy 1
• Barrett's esophagus or peptic stricture - These mandate indefinite acid suppression 1

The key pitfall: Do not rely solely on PPI response to confirm GERD diagnosis, as symptom improvement may result from mechanisms other than acid suppression 3.

Celiac Disease

Screen with tissue transglutaminase IgA and total IgA levels in all patients with bloating, distention, and altered bowel habits 1. This is critical because:

• Celiac disease presents with bloating and distention with or without bowel habit changes 1
• Alarm symptoms (weight loss, iron-deficiency anemia, direct symptom association with gluten ingestion) mandate small bowel biopsy 1
• IgA deficiency affects test interpretation, requiring total IgA measurement 1
• Small bowel biopsy remains the diagnostic gold standard when serology is positive 1

Some patients have nonceliac gluten sensitivity where fructans (not gluten) cause symptoms, requiring targeted elimination 1.

Ovarian Cancer in Women ≥50 Years

Bloating and abdominal fullness are often presenting symptoms of ovarian cancer, with highest risk in women 50 years or older 1. This represents a life-threatening diagnosis that cannot be missed. Maintain high clinical suspicion and pursue appropriate imaging (transvaginal ultrasound, CA-125) in this demographic presenting with new-onset bloating.

Gastroparesis and Functional Dyspepsia

These conditions exist on a spectrum of gastric neurodysfunction 1:

• Approximately 40% of gastroparesis patients report bloating correlating with nausea, fullness, and pain 1
• Gastric scintigraphy or wireless motility capsule should be considered in patients with severe nausea/vomiting or postprandial functional dyspepsia subtype 1
• Severe constipation occurs in >30% of patients with gastroparesis symptoms and associates with delayed small bowel/colonic transit 1

The critical distinction: Bloating symptoms do not correlate with degree of gastric emptying delay on scintigraphy 1, so testing is reserved for those with severe upper GI symptoms, especially with weight loss.

Small Intestinal Bacterial Overgrowth (SIBO)

Consider SIBO in patients with 1:

• Chronic watery diarrhea
• Signs of malnutrition and weight loss
• Systemic or structural diseases causing small bowel dysmotility (cystic fibrosis, Parkinson disease)

These high-risk patients may need diagnostic testing or empiric antibiotic treatment 1.

Chronic Pancreatitis

Bloating accompanied by pain despite adequate pancreatic enzyme replacement warrants fecal elastase testing 1. This diagnosis is particularly relevant in patients with risk factors for pancreatic disease (alcohol use, prior pancreatitis).

Anorectal Disorders

Patients with functional defecation disorders (dyssynergic defecation) frequently experience constipation and bloating related to visceral hypersensitivity and retained stool with colon distention 1. Complete history regarding defecation patterns is essential.

H. Pylori-Specific Considerations

The relationship between H. pylori and GERD remains complex 4, 5:

• H. pylori presence does not directly correlate with GERD 4
• Successful eradication does not impact GERD emergence or exacerbation 4, 6
• However, H. pylori eradication is recommended in patients requiring long-term PPI therapy to prevent development of atrophy and intestinal metaplasia 4
• CagA-positive H. pylori infections associate with lower rates of Barrett's esophagus and esophageal adenocarcinoma 4

Bottom line: Screen and treat H. pylori independent of GERD diagnosis, except mandate eradication before long-term PPI therapy 4.

Practical Diagnostic Algorithm

For patients >40 years with hyperacidity/flatulence:

1. Perform upper endoscopy to exclude peptic ulcer, erosive esophagitis, Barrett's, malignancy 1, 3
2. Screen for celiac disease with tTG-IgA and total IgA 1
3. In women ≥50 years, maintain high suspicion for ovarian cancer 1
4. If severe nausea/vomiting or postprandial symptoms, consider gastric emptying studies 1
5. If alarm features (weight loss, anemia, severe pain), pursue comprehensive evaluation including fecal elastase, imaging 1