What is the likely diagnosis and appropriate work‑up and treatment for a patient with recurrent, stereotyped episodes of nausea, vomiting and watery diarrhea occurring every 3–4 weeks, each lasting less than a day, and a mild transient elevation in liver enzymes?

Cyclic Vomiting Syndrome (CVS)

The clinical presentation—recurrent stereotyped episodes of nausea, vomiting, and watery diarrhea occurring every 3–4 weeks, each lasting less than one day, with mild transient liver enzyme elevations—strongly suggests Cyclic Vomiting Syndrome, and you should immediately screen for cannabis use (≥4 times weekly for >1 year) to exclude cannabinoid hyperemesis syndrome before confirming the diagnosis. 1, 2

Diagnostic Confirmation

Apply the Rome IV criteria systematically:

• The patient must have 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. 1, 3
• Episodes must be stereotypical—identical timing, duration, and associated symptoms across attacks. 1, 3
• The pattern described (every 3–4 weeks, lasting <1 day) fits the diagnostic criteria perfectly. 1

Critical screening step:

• Screen for cannabis use immediately: consumption ≥4 times weekly for >1 year indicates cannabinoid hyperemesis syndrome (CHS) rather than CVS, requiring 6 months of cessation for definitive differentiation. 1, 2
• Hot water bathing behavior occurs in 48% of CVS patients without cannabis use, so this finding alone does not distinguish CHS from CVS. 2, 3

Essential Work-Up

Minimal recommended testing includes:

• Upper endoscopy to exclude structural causes. 4
• Abdominal imaging (CT or MRI) to rule out mechanical obstruction or other pathology. 4
• Basic laboratory evaluation: complete blood count, serum electrolytes, glucose, liver function tests (already noted as mildly elevated), and lipase. 2
• Urine analysis and pregnancy testing in women of childbearing age. 2
• Screen for psychiatric comorbidities: anxiety, depression, and panic disorder are present in 50–60% of CVS patients, and treating these conditions decreases episode frequency. 2, 3

The mild transient liver enzyme elevations are consistent with CVS and likely reflect metabolic stress during episodes; they do not require extensive hepatobiliary work-up if they normalize between episodes. 2

Disease Severity Classification

Classify as mild versus moderate-severe CVS to determine treatment intensity:

• Mild CVS: <4 episodes/year, each lasting <2 days, no emergency department visits or hospitalizations—requires abortive therapy only. 2, 3
• Moderate-severe CVS: ≥4 episodes/year, lasting >2 days, requiring emergency department visits or hospitalizations—requires both prophylactic and abortive therapy. 2, 3

Based on the described pattern (episodes every 3–4 weeks = approximately 13–17 episodes/year), this patient has moderate-severe CVS and requires both prophylactic and abortive treatment. 2, 3

Treatment Algorithm

Prophylactic Therapy (First-Line)

Start amitriptyline immediately:

• Begin with 25 mg at bedtime, titrating by 10–25 mg every 2 weeks to a target of 75–150 mg nightly (goal dose 1–1.5 mg/kg). 2
• Obtain a baseline electrocardiogram before initiating therapy to screen for QTc prolongation risk. 2
• Administer at night to minimize daytime sedation and anticholinergic effects (dry mouth, blurred vision, constipation, weight gain). 2
• Response rate is 67–75% in clinical studies. 2, 3

If amitriptyline fails or is not tolerated, second-line options include:

• Topiramate: start 25 mg daily, titrate to 100–150 mg daily in divided doses; monitor electrolytes and renal function twice yearly. 2
• Levetiracetam: start 500 mg twice daily, titrate to 1000–2000 mg daily in divided doses; monitor complete blood count. 2
• Zonisamide: start 100 mg daily, titrate to 200–400 mg daily; monitor electrolytes and renal function twice yearly. 2

Abortive Therapy (Patient Education Critical)

Educate the patient to recognize prodromal symptoms immediately:

• Prodromal symptoms include impending sense of doom, panic, anxiety, diaphoresis, mental fog, restlessness, headache, bowel urgency, or flushing. 2
• The probability of aborting an episode is highest when medications are taken immediately at prodromal symptom onset—missing this window dramatically reduces effectiveness. 2, 3

Standard abortive regimen:

• Sumatriptan 20 mg intranasal spray (can repeat once after 2 hours, maximum 2 doses per 24 hours) plus ondansetron 8 mg sublingual every 4–6 hours. 2
• Administer sumatriptan in a head-forward position to optimize medication contact with anterior nasal receptors. 2
• Nearly all patients require combination therapy rather than monotherapy. 3

Additional abortive agents to consider:

• Promethazine 12.5–25 mg oral/rectal every 4–6 hours or prochlorperazine 5–10 mg every 6–8 hours (or 25 mg suppository every 12 hours). 2
• Sedatives (alprazolam, lorazepam, diphenhydramine) can help truncate episodes, though use caution in patients with substance abuse risk. 2

Emergency Department Management (If Abortive Therapy Fails)

Immediate interventions:

• Aggressive IV fluid replacement with dextrose-containing fluids for rehydration and metabolic support. 2, 3
• Ondansetron 8 mg IV every 4–6 hours as first-line antiemetic. 2, 3
• IV ketorolac 15–30 mg every 6 hours (maximum 5 days, daily maximum 120 mg) as first-line non-narcotic analgesia—avoid opioids as they worsen nausea and carry addiction risk. 2, 5
• IV benzodiazepines for sedation in a quiet, dark room to minimize sensory stimulation. 2, 3
• Check and correct electrolyte abnormalities immediately. 3

For refractory cases:

• Use droperidol or haloperidol as dopamine antagonists. 2, 3

Lifestyle Modifications (Essential for All Patients)

• Maintain a regular sleep schedule and avoid sleep deprivation. 2
• Avoid prolonged fasting. 2
• Implement stress management techniques. 2
• Identify and avoid individual triggers (present in 70–80% of patients). 2

Management of Comorbid Conditions

Screen and treat psychiatric comorbidities aggressively:

• Anxiety, depression, and panic disorder are present in 50–60% of CVS patients. 2, 3
• Treating underlying anxiety decreases CVS episode frequency. 2, 3
• Consider cognitive-behavioral therapy. 3, 6

Assess for associated conditions:

• Migraine headaches occur in 20–30% of CVS patients and indicate shared pathophysiology. 2, 4
• Postural orthostatic tachycardia syndrome (POTS) is observed in a substantial subgroup, suggesting overlapping autonomic dysfunction. 2

Critical Pitfalls to Avoid

• Do not underestimate disease severity: approximately one-third of adults with CVS become disabled. 3
• Do not misinterpret self-soothing behaviors (excessive water drinking, self-induced vomiting) as malingering—these are characteristic coping responses. 2, 3
• Do not overlook retching and nausea—these symptoms are equally disabling as vomiting and require aggressive treatment. 2, 3
• Do not administer opioids—they exacerbate nausea and carry high addiction risk. 2
• Do not miss the prodromal window—abortive therapy effectiveness drops dramatically if delayed. 2, 3

Special Consideration: Coalescent CVS

• A distinct subgroup experiences progressively longer and more frequent episodes, eventually leading to daily nausea and vomiting with few asymptomatic days. 2
• These patients require prophylactic therapy comparable to moderate-severe CVS (amitriptyline), acknowledging the heightened therapeutic challenge. 2