In a 22‑year‑old woman with previously treated gastritis (proton pump inhibitor therapy) who now presents with recurrent epigastric pain, bloating, post‑prandial belching, nightly drenching sweats, and low‑grade nausea, what are the key differential diagnoses and appropriate investigations?

Differential Diagnosis and Investigations for Recurrent Epigastric Pain with Night Sweats

In this 22-year-old woman with recurrent epigastric symptoms and concerning night sweats, the differential diagnosis must prioritize life-threatening conditions first, then address common functional disorders, with investigations tailored to exclude malignancy and serious pathology before attributing symptoms to benign causes.

Immediate Life-Threatening Exclusions

Cardiac Evaluation

• Obtain an ECG immediately to exclude myocardial ischemia, as acute coronary syndrome can present atypically with epigastric pain and carries 10-20% mortality if missed, even in young women 1, 2

Hematologic and Inflammatory Markers

• Order complete blood count to assess for anemia (suggesting occult bleeding or malignancy), comprehensive metabolic panel, C-reactive protein, and serum lactate to evaluate for inflammatory or ischemic processes 1, 2
• Check vital signs for tachycardia ≥110 bpm, fever ≥38°C, or hypotension, which predict serious complications like perforation or sepsis 1, 2

Key Differential Diagnoses

Malignancy (Priority Given Night Sweats)

• Lymphoma or gastric malignancy: Nightly drenching sweats combined with epigastric symptoms and nausea warrant urgent consideration of hematologic malignancy or gastric cancer 3
• The combination of persistent upper GI symptoms with constitutional symptoms (night sweats) is atypical for functional dyspepsia and demands investigation for systemic disease 3
• Note: While age <40 typically suggests lower gastric cancer risk, the presence of alarm features (night sweats as a constitutional symptom) overrides age-based reassurance 1, 2

Peptic Ulcer Disease and H. pylori Infection

• Test for Helicobacter pylori infection using breath or stool testing (higher specificity than serology), as eradication eliminates peptic ulcer mortality risk 1, 2
• Despite previous PPI treatment, recurrent symptoms may indicate inadequately treated H. pylori or NSAID use 3, 1

Functional Dyspepsia Subtypes

• Postprandial distress syndrome (PDS): Characterized by postprandial fullness, bloating, and belching—all present in this patient 4, 5, 6
• Epigastric pain syndrome (EPS): Defined by epigastric pain or burning 4, 5
• Fullness, bloating, and belching originate primarily from the stomach and decrease as food moves to the small intestine, suggesting gastric pathophysiology 6

Gastroparesis

• Consider gastroparesis given the combination of nausea, bloating, and postprandial symptoms 3, 7
• Rule out gastroparesis in the subset of patients with nausea and vomiting through gastric emptying studies if symptoms persist 3

GERD with Functional Overlay

• Gastric belching related to GERD may explain post-meal belching 3
• However, early satiation and vomiting are risk factors for poor response to PPIs in GERD patients, suggesting functional dyspepsia overlap 8

Food Intolerance

• Carbohydrate intolerance (lactose, fructose, sucrose) is common in functional GI disorders, with fructose intolerance seen in 60% and lactose intolerance in 51% of patients 3
• The simplest diagnostic approach is a 2-week dietary restriction trial, with symptom resolution as a positive predictor 3

Algorithmic Investigation Strategy

First-Line Laboratory Tests

• Complete blood count (to exclude anemia from occult bleeding or malignancy) 1, 2
• Comprehensive metabolic panel 1, 2
• C-reactive protein and serum lactate (if inflammatory or ischemic process suspected) 1, 2
• H. pylori breath or stool test 1, 2
• Consider serum amylase or lipase if pancreatic pathology suspected 1

Imaging Considerations

• Abdominal ultrasound or CT abdomen/pelvis with IV contrast if constitutional symptoms persist or if physical examination reveals concerning findings 3
• CT identifies extraluminal gas in 97% of perforations, fluid/fat stranding in 89%, and ascites in 89% 9

Endoscopy Indications (Urgent Given Night Sweats)

• Refer for urgent upper endoscopy given the presence of constitutional symptoms (night sweats) that may represent an alarm feature 3, 1, 2
• Endoscopy should evaluate for erosive esophagitis (Los Angeles classification), Barrett's esophagus (Prague classification with biopsy), hiatus hernia, and gastric/duodenal pathology 3
• Persistent vomiting and nausea beyond typical functional dyspepsia warrant endoscopy, as vomiting is atypical for functional dyspepsia and suggests organic pathology 3, 9

Specialized Testing if Initial Workup Negative

• Gastric emptying breath test if gastroparesis suspected (nausea, vomiting, early satiation) 3, 7, 6
• Hydrogen breath testing for carbohydrate intolerance (lactose, fructose, sucrose) if symptoms persist after dietary trial 3
• Ambulatory impedance monitoring with high-resolution manometry to differentiate gastric belching (involuntary, related to GERD) from supragastric belching (voluntary) 3

Empiric Treatment Pending Investigations

Acid Suppression

• Initiate full-dose PPI therapy (omeprazole 20-40 mg once daily, 30-60 minutes before meals) for 4-8 weeks while awaiting H. pylori results 3, 1, 2
• If H. pylori positive, treat with triple therapy: omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg, all twice daily for 10 days 2

Symptom-Specific Therapy

• For predominant postprandial fullness and bloating (PDS phenotype), consider prokinetic agents after excluding gastroparesis, though cisapride is contraindicated due to cardiac toxicity 3, 7
• For predominant epigastric pain (EPS phenotype), full-dose PPI therapy is first-line 3, 1, 2

Critical Pitfalls to Avoid

• Do not attribute persistent symptoms with constitutional features (night sweats) to functional dyspepsia without excluding malignancy 3
• Do not delay endoscopy in patients with alarm features, as missing serious pathology leads to poor outcomes 1, 9
• Do not assume all epigastric symptoms are acid-related; early satiation and vomiting predict poor PPI response and suggest functional overlay or alternative diagnoses 8
• Recognize that bloating and abdominal fullness are presenting symptoms in ovarian cancer, with highest risk in women ≥50 years, though younger women are not immune 3

Follow-Up Strategy

• Reassess at 4 weeks; if symptoms persist despite adequate PPI trial and negative H. pylori, proceed to endoscopy regardless of age given the presence of night sweats 2
• If endoscopy is negative and symptoms continue, consider gastric emptying studies, breath testing for carbohydrate intolerance, and impedance monitoring for belching characterization 3, 6
• Taper PPI to the lowest effective dose once adequate symptom control is achieved 3, 1