What is the differential diagnosis (Ddx) for an adult patient without significant past medical history presenting with two episodes of vomiting, normal laboratory results, and a non-remarkable physical exam?

Differential Diagnosis for Two Episodes of Vomiting with Normal Labs and Physical Exam

For an adult with only two episodes of vomiting and completely normal labs and physical exam, the most likely diagnosis is self-limited viral gastroenteritis or foodborne illness, which typically resolves without specific treatment. 1, 2

Immediate Considerations

Rule Out Red Flags First

• Bilious vomiting is a surgical emergency requiring urgent upper GI series to exclude malrotation with volvulus or other obstruction, even with normal initial exam 3, 4
• Severe headache, altered mental status, or focal neurologic signs mandate head imaging to exclude intracranial pathology 5, 6
• Pregnancy must be excluded in all women of childbearing age 1, 5

Most Common Causes in Adults with Brief Vomiting

• Viral gastroenteritis is the leading cause of acute vomiting, characterized by sudden onset, mild fever, diarrhea, and short duration (typically resolves within days) 3, 1, 2
• Foodborne illness presents similarly but often has identifiable food exposure within 6-72 hours 1, 2
• Medication adverse effects should always be suspected, particularly with recent medication changes 1, 2, 5
• Acute migraine can present with isolated vomiting, often with associated headache or photophobia 1

When to Consider More Serious Diagnoses

Cyclic Vomiting Syndrome (CVS)

CVS should be considered only if the patient has had at least 3 discrete episodes in the past year, with 2 occurring in the prior 6 months, each lasting less than 7 days, separated by at least 1 week of complete wellness. 3, 4, 7

• Two episodes alone do not meet diagnostic criteria for CVS 3, 4
• CVS episodes are stereotypical (same pattern each time) with prodromal symptoms including impending doom, panic, anxiety, or diaphoresis 3, 7, 8
• Personal or family history of migraines supports CVS diagnosis 3, 7
• Screen for cannabis use: use >4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome (CHS) rather than CVS 3, 7, 8

Cannabinoid Hyperemesis Syndrome (CHS)

• Requires chronic cannabis use (typically >1 year, >4 times weekly) before symptom onset 3
• Characterized by cyclic vomiting with compulsive hot water bathing behavior (though this also occurs in 48% of CVS patients without cannabis use) 3, 7
• Symptoms resolve after 6 months of cannabis cessation 3

Food Protein-Induced Enterocolitis Syndrome (FPIES)

• Primarily affects infants and young children, not typical in adults 3, 4
• Requires vomiting 1-4 hours after specific food ingestion, with repetitive episodes after the same food 3
• Diagnosis requires major criterion (vomiting 1-4 hours post-ingestion without IgE symptoms) plus ≥3 minor criteria 3

Practical Management Approach

For Two Isolated Episodes with Normal Exam

• No extensive workup is needed if the patient appears well, is tolerating oral intake, and has no alarm features 1, 2, 5
• Provide supportive care: small frequent meals, oral rehydration, avoid trigger foods 1
• Antiemetics (ondansetron 4-8 mg) can be used if symptoms persist and prevent oral intake 1, 9
• Reassess if vomiting continues beyond 7 days or if new symptoms develop 1, 5

When to Investigate Further

• Vomiting persisting >1 month requires comprehensive evaluation including esophagogastroduodenoscopy if alarm features present 5
• Recurrent stereotypical episodes warrant consideration of CVS with detailed history of episode pattern, triggers, and cannabis use 3, 4, 7
• Dehydration, electrolyte abnormalities, or inability to maintain oral intake requires IV fluid replacement 1, 9, 5

Common Pitfalls to Avoid

• Do not diagnose CVS based on only two episodes - this is insufficient to meet diagnostic criteria and viral gastroenteritis is far more common 3, 4
• Do not overlook medication review - many drugs cause nausea and vomiting as adverse effects 1, 2, 5
• Do not miss pregnancy - always obtain urine pregnancy test in women of reproductive age 1, 5
• Do not assume hot water bathing equals CHS - this behavior occurs in nearly half of CVS patients without cannabis use 3, 7