What are the other possible causes of recurrent epigastric pain in an adult?

Other Causes of Recurrent Epigastric Pain

Recurrent epigastric pain has a broad differential that extends well beyond peptic ulcer disease and GERD, including cardiac ischemia, pancreatitis, biliary disease, functional dyspepsia, irritable bowel syndrome, eosinophilic esophagitis, inflammatory bowel disease, gastroparesis, mesenteric ischemia, and gastric malignancy—each requiring a distinct diagnostic and therapeutic approach. 1, 2

Life-Threatening Causes That Must Be Excluded First

Cardiac Ischemia

• Myocardial infarction can present with epigastric pain, particularly in women, diabetics, and elderly patients who may lack classic chest pain 1, 2
• Obtain an electrocardiogram immediately in any patient with epigastric pain and exertional symptoms, shortness of breath, or cardiovascular risk factors 1, 2

Acute Aortic Syndromes

• Aortic dissection or leaking abdominal aortic aneurysm causes sudden, severe epigastric pain and must be excluded in patients over 50 years with vascular risk factors 1, 2

Perforated Peptic Ulcer

• Perforation presents with sudden, severe epigastric pain that generalizes, accompanied by fever and abdominal rigidity, requiring immediate surgical intervention with mortality reaching 30% if delayed 1, 2
• CT abdomen with IV contrast shows extraluminal gas in 97% of perforations, fluid or fat stranding in 89%, ascites in 89%, and focal wall defect in 84% 2

Acute Pancreatitis

• Pain radiating to the back with nausea and vomiting suggests pancreatitis 1, 2
• Check serum amylase (≥4× normal) or lipase (≥2× normal) with sensitivity and specificity of 80–90% 2
• Overall mortality is <10% but reaches 30–40% in necrotizing pancreatitis 2

Mesenteric Ischemia

• Chronic mesenteric ischemia presents with post-prandial abdominal pain, fear of eating, and weight loss—especially in elderly patients with atherosclerotic disease 3
• Pain out of proportion to examination findings is characteristic 2
• CT angiography is required when endoscopy is negative to evaluate mesenteric vascular insufficiency 3

Common Gastrointestinal Causes

Functional Dyspepsia

• Functional dyspepsia accounts for the majority (>50%) of patients undergoing endoscopy for dyspepsia and is the most common functional gastrointestinal disorder 2
• Diagnosis requires chronic or recurrent upper abdominal pain or discomfort lasting at least 8 weeks with no structural disease on endoscopy 2
• Rome IV criteria define epigastric pain syndrome as bothersome epigastric pain and/or burning that does not necessarily occur after meals, may occur during fasting, and can improve with eating 4
• Up to 50% of functional dyspepsia patients have overlapping irritable bowel syndrome, but the pain is unrelated to defecation 2

Irritable Bowel Syndrome (IBS)

• IBS presents with recurrent abdominal pain, on average at least 1 day per week in the last 3 months, associated with two or more of the following: related to defecation, associated with change in stool frequency, or associated with change in stool form 1
• The key distinguishing feature is that pain is related to defecation, unlike epigastric pain syndrome 1
• Symptoms must be present for the last 3 months with onset at least 6 months prior to diagnosis 1

Eosinophilic Esophagitis

• Should be considered in young children with GERD-like symptoms including feeding problems, and in older children and adults with GERD-like symptoms, especially those with dysphagia or esophageal food impaction 1
• In adults, the most common presenting symptoms are intermittent dysphagia (29–100%) and food impaction (25–100%), with eosinophilic esophagitis responsible for 50% of esophageal food impaction cases 1
• Symptoms are unresponsive or only partially responsive to acid blockade, distinguishing it from GERD 1
• Diagnosis is often delayed an average of 4.6 years (range 0–17 years) because symptoms overlap with GERD 1

Inflammatory Bowel Disease (IBD)

• Pediatric-onset IBD accounts for 10–15% of all IBD cases presenting before age 18 2
• In children with ulcerative colitis, extensive colitis occurs in 42–90% of cases, and atypical findings such as patchy inflammation or rectal sparing are seen in up to 30% 2
• Endoscopic evaluation of the upper and lower gastrointestinal tracts with mucosal biopsies remains the gold standard for diagnosis 2
• Clinical guidance advises against assuming functional dyspepsia without first excluding IBD, given the relatively high prevalence of organic disease in adolescents 2

Gastroparesis

• Manifests with nausea, vomiting, and post-prandial fullness that worsen at night because delayed gastric emptying prolongs gastric distension 2
• Present in roughly 20–40% of individuals with long-standing type 1 diabetes 2
• Hyperglycemia itself induces antral hypomotility and gastric dysrhythmias, contributing to nocturnal dyspeptic symptoms 2
• Severe early satiety (tolerating only one meal per day) requires urgent upper endoscopy to exclude mechanical obstruction, followed by gastric emptying scintigraphy if endoscopy is normal 2

Duodenogastric Bile Reflux

• Presents with bitter-tasting vomitus and epigastric discomfort, particularly in adolescents 5
• Unlike typical GERD, bile reflux often presents with bitter-tasting vomitus rather than heartburn 5
• Upper GI contrast studies should be used to delineate anatomy and assess motility disorders 5
• Combined pH and multichannel intraluminal impedance monitoring correlates symptoms with both acid and non-acid reflux events 5

Median Arcuate Ligament Syndrome

• Presents with post-prandial abdominal pain, fear of eating, and weight loss due to celiac artery compression 3
• CT angiography shows celiac artery compression by the median arcuate ligament with patent SMA and IMA 3
• Mesenteric angiography with lateral projections during inspiration and expiration confirms the diagnosis 3
• Surgical release provides symptomatic relief in approximately 84.6% of appropriately selected patients 3

Pregnancy-Specific Causes

Preeclampsia

• Can present with epigastric or right upper quadrant pain, headaches, visual changes, or swelling 2

HELLP Syndrome

• Should be considered with epigastric pain, nausea, vomiting, and malaise in pregnant patients 2

Acute Fatty Liver of Pregnancy

• May present with malaise, headache, nausea, vomiting, jaundice, and epigastric pain 2

Metabolic and Endocrine Causes

Diabetes Mellitus

• Contributes to nocturnal dyspepsia through both gastroparesis and autonomic neuropathy, which impair esophageal clearance and gastric motility 2
• Measurement of glycated hemoglobin (HbA1c) is recommended in any individual presenting with night-time dyspeptic symptoms 2

Thyroid Dysfunction

• Both hyper- and hypothyroidism can alter gastrointestinal motility, warranting thyroid-function testing as part of baseline work-up 2

Medication-Induced Causes

NSAID-Induced Gastropathy

• NSAIDs cause gastropathy and increase the risk of peptic ulcer disease, which can present with night-time epigastric pain 2
• NSAID-induced gastropathy or ulceration is a recognized medication-related cause of dyspeptic symptoms 2
• Nonsteroidal anti-inflammatory drugs should be avoided because they worsen peptic ulcer disease and increase the risk of gastrointestinal bleeding 2

Calcium-Channel Blockers

• Lower lower-esophageal sphincter pressure, thereby exacerbating reflux and nocturnal indigestion 2

Sleep-Related Disorders

Obstructive Sleep Apnea

• Generates negative intrathoracic pressure during apneic episodes, which promotes gastro-esophageal reflux and may trigger nocturnal indigestion 2
• Screening questions such as "Do you gasp or stop breathing at night?" and "Do you wake up without feeling refreshed?" are useful for detecting OSA-related reflux 2

Primary Sleep Disorders

• Insomnia, restless-legs syndrome, and parasomnias can cause nocturnal awakenings that are mistakenly attributed to gastrointestinal causes 2

Renal Causes

Chronic Kidney Disease

• May lead to xerostomia, prompting increased fluid intake that worsens nocturnal reflux symptoms 2
• Assessment of electrolytes, renal function, and urine albumin-to-creatinine ratio is advised when evaluating nocturnal dyspepsia in patients with possible renal impairment 2

Cardiac Causes Beyond Acute MI

Congestive Heart Failure

• Nocturnal redistribution of fluid from peripheral edema to the thorax can precipitate reflux-type symptoms and dyspnea, especially when patients lie supine 2
• Physical examination for ankle swelling and orthopnea helps identify heart-failure-related nocturnal discomfort 2

Algorithmic Diagnostic Approach

Step 1: Exclude Emergencies

• Check vital signs for tachycardia ≥110 bpm, fever ≥38°C, or hypotension, which predict perforation or sepsis 2
• Obtain ECG to exclude myocardial ischemia 2
• Assess for peritoneal signs (rigidity, rebound tenderness, absent bowel sounds) indicating perforation 2, 5
• Order chest and abdominal X-rays to exclude perforated viscus and intestinal obstruction 2

Step 2: Assess for Alarm Features

• Age ≥55–60 years with new-onset symptoms 2, 3
• Unintentional weight loss (≥10% body weight) 2, 3
• Anemia on complete blood count 2, 3
• Dysphagia or food sticking 2, 3
• Persistent vomiting 2, 3
• Hematemesis or melena 2, 3
• Palpable epigastric mass 2
• Epigastric tenderness on examination 2, 3

Step 3: Laboratory Work-Up

• Complete blood count to detect anemia 2, 3
• Serum electrolytes and glucose 2
• Liver and renal function tests 2
• Serum amylase or lipase to exclude pancreatitis 2
• HbA1c to evaluate diabetic control 2
• Thyroid-function tests 2
• Coeliac serology when overlapping IBS-type symptoms are present 3

Step 4: H. pylori Testing

• Perform H. pylori testing using ^13C-urea breath test or stool antigen (serology is not recommended) for any patient with epigastric pain 2, 3
• Eradication eliminates the mortality risk associated with peptic ulcer disease 3

Step 5: Imaging Strategy

• If alarm features present: Urgent CT abdomen and pelvis with IV contrast to identify perforation, malignancy, pancreatitis, or vascular causes 1, 2, 3
• If endoscopy is non-diagnostic in patients with weight loss and post-prandial pain: CT angiography to evaluate for chronic mesenteric ischemia or median arcuate ligament syndrome 3
• Upper GI series (barium study) is not recommended for routine diagnosis of GERD or dyspepsia; only for anatomical delineation of stricture, hiatal hernia, or malrotation 2, 5

Step 6: Endoscopy Timing

• Urgent endoscopy (within 2 weeks): Age ≥55 years with new-onset symptoms, or any alarm feature present 2, 3
• Non-urgent endoscopy (within 4–8 weeks): Treatment-resistant dyspepsia despite omeprazole 20–40 mg daily for 4–8 weeks, persistent epigastric tenderness, or H. pylori-positive with ongoing symptoms after eradication 2, 3
• No endoscopy required: Age <55 years without alarm features and symptoms improve with PPI therapy 2, 3

Step 7: Empiric Therapy While Awaiting Diagnosis

• Start high-dose proton-pump inhibitor therapy immediately (omeprazole 20–40 mg once daily before meals) 2, 3
• Full-dose PPI achieves 80–90% healing of duodenal ulcers and 70–80% healing of gastric ulcers 2, 3

Common Pitfalls to Avoid

• Missing cardiac causes: Epigastric pain with exertional symptoms can be acute coronary syndrome with mortality of 10–20% 2
• Attributing persistent vomiting to functional dyspepsia: Persistent vomiting is a red-flag that excludes functional dyspepsia and mandates investigation for structural disease 2, 3
• Delaying endoscopy in patients ≥55–60 years: Age alone is an alarm feature requiring urgent endoscopy regardless of symptom response to PPI 2, 3
• Assuming all epigastric symptoms are acid-related: Bile reflux presents with bitter-tasting vomitus rather than heartburn 5
• Not recognizing eosinophilic esophagitis: Symptoms are unresponsive to acid blockade and diagnosis is often delayed 4.6 years 1
• Overlooking gastroparesis in diabetics: Present in 20–40% of long-standing type 1 diabetes and worsens at night 2
• Missing chronic mesenteric ischemia: Post-prandial pain with food fear and weight loss in elderly patients with vascular disease requires CT angiography 3
• Failing to test for H. pylori: Eradication eliminates peptic-ulcer-related mortality 2, 3
• Ordering upper GI series for routine GERD/dyspepsia diagnosis: This is unsupported and may produce false-positive results 2