What is the most likely diagnosis for a patient with recurrent episodes of nausea, vomiting and watery diarrhea every 3–4 weeks, no preceding abdominal pain, mild abdominal soreness after the episode, and no identifiable dietary triggers?

Cyclic Vomiting Syndrome

The most likely diagnosis is Cyclic Vomiting Syndrome (CVS), a functional disorder of gut-brain interaction characterized by stereotypical recurrent episodes of intense nausea, vomiting, and watery diarrhea occurring every 3-4 weeks, separated by symptom-free intervals. 1

Why This Diagnosis Fits

Your patient's presentation is classic for CVS based on several key features:

• Stereotypical episodic pattern: Episodes occurring every 3-4 weeks with complete resolution between attacks is pathognomonic for CVS 1, 2
• Acute-onset vomiting with diarrhea: The simultaneous nausea, vomiting, and watery diarrhea lasting less than 7 days fits the Rome IV criteria 1, 2
• Absence of abdominal pain before episodes: While abdominal pain occurs in most CVS patients, its absence does not exclude the diagnosis; the post-episode soreness is consistent with muscle strain from retching 1
• No dietary triggers: CVS episodes are typically not food-related, distinguishing it from food allergies or intolerances 1

Critical First Step: Cannabis Screening

Before confirming CVS, you must screen for cannabis use >4 times weekly for >1 year, as this pattern suggests Cannabinoid Hyperemesis Syndrome (CHS) rather than CVS. 3, 1, 2 This is non-negotiable because:

• CHS presents identically to CVS with cyclic vomiting episodes 3
• Hot-water bathing behavior occurs in 71% of CHS patients but also in 48% of CVS patients without cannabis use, so it is not pathognomonic 3, 4
• CHS requires 6 months of cannabis cessation (or duration equal to 3 typical cycles) to differentiate from CVS 1, 2

Diagnostic Workup

Perform a one-time basic evaluation to exclude structural and metabolic causes 2:

• Laboratory tests: Complete blood count, serum electrolytes, glucose, liver function tests, lipase, urinalysis 2
• One-time esophagogastroduodenoscopy or upper GI imaging to exclude obstructive lesions, peptic ulcer disease, or malignancy 2
• Do not repeat endoscopy unless new symptoms develop 2
• Avoid gastric emptying scans during episodes as results are uninterpretable; few CVS patients have delayed emptying 2

Confirm CVS Diagnosis

The patient meets Rome IV criteria if they have 1, 2:

• Stereotypical episodes of acute-onset vomiting lasting <7 days
• At least 3 discrete episodes in the past year (with 2 in the prior 6 months)
• Episodes separated by at least 1 week of baseline health

Assess Disease Severity to Guide Treatment

Classify as moderate-severe CVS if ≥4 episodes per year, each lasting >2 days, requiring ED visits or hospitalization; classify as mild CVS if <4 episodes per year, each <2 days, without ED visits. 1

Your patient with episodes every 3-4 weeks (approximately 13-17 episodes per year) clearly has moderate-severe CVS requiring both prophylactic and abortive therapy 1.

Treatment Plan for Moderate-Severe CVS

Prophylactic Therapy (First-Line)

Start amitriptyline 25 mg at bedtime, titrating by 10-25 mg every 2 weeks to a target of 75-150 mg nightly (1-1.5 mg/kg). 1, 2 This approach has a 67-75% response rate 1, 2.

• Obtain baseline ECG before starting to screen for QTc prolongation risk 1, 2
• Slow titration improves tolerability compared to rapid escalation 1
• Administer at night to minimize daytime sedation and anticholinergic effects (dry mouth, blurred vision, constipation, weight gain) 1

Abortive Therapy Education

Educate the patient to recognize prodromal symptoms and take abortive medications immediately, as the probability of aborting an episode is highest when medications are taken at symptom onset. 1, 2

Prodromal symptoms to watch for (present in ~65% of CVS patients) 1, 2:

• Impending sense of doom or panic
• Fatigue or mental fog
• Restlessness or anxiety
• Diaphoresis or flushing
• Headache or bowel urgency

Standard abortive regimen 1:

• Sumatriptan 20 mg intranasal spray (can repeat once after 2 hours, maximum 2 doses per 24 hours)
• Ondansetron 8 mg sublingual every 4-6 hours during the episode

Administer sumatriptan in a head-forward position to optimize medication contact with anterior nasal receptors 1.

Essential Lifestyle Modifications

All CVS patients require 1, 2:

• Regular sleep schedule (avoid sleep deprivation)
• Avoid prolonged fasting
• Stress management techniques
• Identify and avoid individual triggers (present in 70-80% of patients) 1

Screen for Psychiatric Comorbidities

Screen for anxiety, depression, and panic disorder, as these are present in 50-60% of CVS patients, and treating underlying anxiety can decrease episode frequency. 1, 2 Consider referral to psychiatry or psychology if positive 1.

Common Pitfalls to Avoid

• Missing the prodromal window: Abortive therapy effectiveness drops dramatically if not taken immediately at symptom onset 1
• Overlooking retching and nausea: These symptoms are equally disabling as vomiting itself and require aggressive treatment 1
• Repeated imaging: Do not perform repeated endoscopy or imaging unless new symptoms develop 2
• Using opioids: Avoid opioids as they worsen nausea and carry high addiction risk 3, 2

Alternative Diagnoses to Consider

If cannabis use is confirmed >4 times weekly for >1 year, the diagnosis shifts to Cannabinoid Hyperemesis Syndrome, which requires cannabis cessation as the definitive treatment 3, 1. Other differentials include gastroparesis (requires gastric emptying scintigraphy), mechanical obstruction (excluded by imaging), and rumination syndrome (different behavioral pattern) 2, 4.