Differential Diagnosis for Recurrent Vomiting in a 20-Year-Old Female
In a 20-year-old woman with recurrent vomiting, normal ultrasound, and no substance abuse history, the most critical initial step is to exclude Cannabis Hyperemesis Syndrome (CHS) through detailed cannabis use history, followed by systematic evaluation for Cyclic Vomiting Syndrome (CVS), gastroparesis, metabolic disorders, and gastrointestinal pathology.
Immediate Priority: Pattern Recognition and Red Flags
Critical Distinction
- Bilious vomiting is a surgical emergency until proven otherwise, requiring urgent fluoroscopy upper GI series to exclude obstruction distal to the ampulla of Vater 1
- Non-bilious recurrent vomiting suggests functional or metabolic causes rather than mechanical obstruction 1
Primary Differential Diagnoses
1. Cannabis Hyperemesis Syndrome (CHS)
- Cannabis use history is absolutely critical in this age group, even with reported "no substance abuse" 2
- CHS should be suspected if heavy cannabis use (including vaping, edibles, or "occasional" use) preceded symptom onset 2
- Definitive diagnosis requires 6 months of cannabis cessation or at least 3 typical cycle lengths without vomiting 2
- Common pitfall: Patients may not consider cannabis as "substance abuse" or may underreport use; direct, non-judgmental questioning is essential 2
2. Cyclic Vomiting Syndrome (CVS)
- Affects approximately 2% of the US population, more common in females 1, 3
- Diagnostic criteria: Stereotypical episodes of acute-onset vomiting lasting <7 days, with at least 3 discrete episodes per year, separated by at least 1 week of baseline health 1
- Key features to identify:
- Diagnosis is primarily clinical based on Rome IV criteria with limited testing to exclude mimics 1
3. Gastroparesis
- Diagnosed by gastric emptying scintigraphy performed for at least 2-4 hours after radiolabeled solid meal, or by 13C breath testing 1
- Consider if vomiting occurs several hours after meals or contains undigested food 4
4. Metabolic and Endocrine Disorders
- Hypercalcemia (malignancy, hyperparathyroidism) 2
- Hypothyroidism 2
- Addison's disease (adrenal insufficiency) 2
- Pregnancy (must be excluded in any woman of reproductive age) 4
5. Gastrointestinal Pathology
- Peptic ulcer disease or gastritis 4
- Partial bowel obstruction (adhesions, Crohn's disease) 5
- Superior mesenteric artery syndrome 6
6. Neurologic Causes
- Increased intracranial pressure (tumor, pseudotumor cerebri) 5
- Migraine-associated vomiting 4
- Vestibular disorders 4
7. Psychiatric and Functional Disorders
- Rumination syndrome 6
- Eating disorders (bulimia nervosa) 6
- Anxiety and depression (commonly associated with CVS) 3
Initial Diagnostic Workup
Mandatory Laboratory Testing
The American Gastroenterological Association recommends the following initial panel 2:
- Complete blood count (anemia, infection) 2
- Serum electrolytes (hypokalemia, hypochloremia, metabolic alkalosis from prolonged vomiting) 2
- Glucose (diabetes, hypoglycemia) 2
- Liver function tests 2
- Lipase (pancreatitis) 2
- Urinalysis 2
- Pregnancy test (essential in all reproductive-age women) 4
Additional Testing if Clinically Indicated
- Serum calcium (hypercalcemia) 2
- Thyroid-stimulating hormone (hypothyroidism) 2
- Morning cortisol or ACTH stimulation test (Addison's disease) 2
- Urine drug screen (despite reported no substance abuse, to assess for cannabis and other substances) 2
Imaging Studies
- One-time esophagogastroduodenoscopy (EGD) or upper GI imaging to exclude obstructive lesions 2
- Avoid repeated endoscopy or imaging studies unless new symptoms develop 2
- Gastric emptying study if gastroparesis suspected 1
Stepwise Management Approach
Initial Pharmacologic Management
Initiate dopamine receptor antagonists titrated to maximum benefit and tolerance 2:
Add 5-HT3 antagonist if symptoms persist after 4 weeks 2:
Administer antiemetics on scheduled basis rather than PRN, as prevention is far easier than treating established vomiting 2
Treatment of Specific Underlying Causes
If Gastroparesis or Gastritis Suspected
- Proton pump inhibitor or H2 receptor antagonist 2
- Continue metoclopramide as it promotes gastric emptying 2
If CVS Diagnosed
- Early intervention during prodromal phase with sumatriptan combined with ondansetron 1
- Prophylactic therapy: Tricyclic antidepressants (amitriptyline), antiepileptics (topiramate), or aprepitant in refractory cases 3
If Metabolic Abnormalities Identified
- Correct hypercalcemia 2
- Treat dehydration and electrolyte imbalances (particularly hypokalemia and hypomagnesemia) 2
- Address underlying endocrine disorders 2
Supportive Care Measures
- Ensure adequate fluid intake of at least 1.5 L/day 2
- Dietary modifications: Small, frequent meals 2
- Thiamin supplementation to prevent Wernicke's encephalopathy in patients with persistent vomiting 2
Critical Pitfalls to Avoid
Never use antiemetics in suspected mechanical bowel obstruction, as this can mask progressive ileus and gastric distension 2
Do not stigmatize patients with cannabis use; offer abortive and prophylactic therapy even with ongoing use, as treatments can still be effective 2
Avoid repeated endoscopy or imaging unless new symptoms develop 2
Monitor for extrapyramidal symptoms with dopamine antagonists, particularly in young patients; treat with diphenhydramine 50 mg IV if they develop 2
Do not assume "no substance abuse" excludes cannabis use; patients may not consider cannabis as substance abuse or may underreport use 2
Consider that patients may confuse heartburn with nausea; add H2 blocker or proton pump inhibitor if dyspepsia is present 2
Refractory Cases
If initial management fails after 4 weeks 2:
- Combine ondansetron with dexamethasone 10-20 mg IV, as this combination is superior to either agent alone 2
- Consider dronabinol 2.5-7.5 mg PO every 4 hours (FDA-approved cannabinoid for refractory nausea) 2
- Use multiple concurrent agents from different drug classes in alternating schedules 2
- Consider alternating routes (IV, rectal, sublingual) if oral route not feasible 2