Cyclic Vomiting Syndrome (CVS)

Cyclic vomiting syndrome (CVS), an idiopathic disorder primarily seen in children, is characterized by recurrent, stereotypical episodes of vomiting with varying asymptomatic periods.

Epidemiology & Demographics

Incidence & Prevalence

•Cross-sectional study of school-age children in Aberdeen, Scotland, estimated that 1.6% fulfilled diagnostic criteria.
•Average age of time of diagnosis: 9.6 yr.
•Average age of onset of symptoms: 5.3 yr.
•This study showed gender ratio was equivalent, although isolated reports say it may be more common in girls.
•In adults, no population studies exist to extrapolate prevalence. In one study with 17 patients followed over a 10-yr interval, it was found that average age of onset was 35 yr, but diagnosis was 41 yr. Gender distribution was again found to be equal.

Genetics

Mutations in mitochondrial DNA (mtDNA) have been associated with cyclical vomiting syndrome and neuromuscular disease in pediatric patients.

These mutations were also more commonly associated with migraines, irritable bowel syndrome, and hypothyroidism.

Evidence shows that the mtDNA mutations seen in pediatric patients have a maternal inheritance pattern.

Physical Findings & Clinical Presentation of Cyclic Vomiting Syndrome

•There is a stereotypical pattern to the vomiting episodes. They normally begin in the early morning hours and may involve a prodrome that includes pallor, nausea, abdominal pain, or lethargy.
•High rates of emeses per hour with the peak in the first hour with a decline in the next 4 to 8 hr. These episodes normally last up to 24 hr.
•Many patients may have neurologic symptoms, including headache, photophobia, or vertigo, which supports the genetic relation between Cyclic Vomiting Syndrome and migraines.

What causes Cyclic Vomiting Syndrome?

•mtDNA mutations that were also associated with migraines in pediatric patients with two mtDNA polymorphisms in particular, 16519T and 3010A, that are expressed in high frequency in subjects with Cyclic Vomiting Syndrome. In adults, CVS is not associated with these polymorphisms.
•Sympathetic hyperresponsiveness and autonomic dysregulation may contribute to the pathogenesis of Cyclic Vomiting Syndrome. Elevated corticotropin, cortisol, vasopressin, and catecholamines have been described in patients with vomiting, lethargy, and hypertension. Studies in animals suggest that corticotropin-releasing factor induces gastric stasis, leading to emesis. Stress responses, which are mediated by the hypothalamic-pituitary-adrenal axis, can therefore potentially induce episodes of vomiting. Triggers of stress responses can be infectious, psychological, or physical.

Differential Diagnosis

•Acute porphyria
•Abdominal migraines
•Diabetic ketoacidosis
•Helicobacter pylori infection
•Cannabis hyperemesis syndrome
•Jamaican vomiting sickness
•Munchausen syndrome by proxy
•Mechanical obstruction
•Gastrointestinal malignancies
•Intestinal malrotation

How is Cyclic Vomiting Syndrome diagnosed?

•CVS is a clinical diagnosis because there are no biochemical markers or imaging that exist to make the diagnosis.
The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) has set forth criteria (all criteria must be met). In adults, Rome IV criteria should be met to make diagnosis.
Supportive criteria in addition to either set of guidelines include a personal or family history of migraine headaches. Rome IV also divides patients with prolonged excessive cannabis use from CVS into cannabinoid hyperemesis syndrome (CHS).
It also differentiates chronic nausea vomiting syndrome from CVS by distinct temporal characteristics of weekly acute episodes.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Criteria for Cyclic Vomiting Syndrome

•At least five episodes over any interval or a minimum of three attacks over a 6-mo period
•Episodic attacks of intense nausea and vomiting lasting from 1 hr to 10 days and occurring at least 1 wk apart
•Stereotypical in the individual patient
•Vomiting during attacks occurs at least four times per hour for at least 1 hr
•A return to baseline health between episodes

Rome IV Diagnostic Criteria for Cyclic Vomiting Syndrome

Must include all of the following:

•Stereotypical episodes of vomiting regarding onset (acute) and duration (<1 wk)
•At least two acute-onset episodes in the past 6 mo, each occurring at least 1 wk apart and persisting less than 1 wk
•Absence of nausea and vomiting between episodes but other, milder symptoms can occur between cycles

•All patients with suspected CVS should be questioned about cannabis use to rule out cannabis hyperemesis syndrome.

Supportive Criterion

History or family history of migraine headaches

Laboratory Tests

In the evaluation for possible GI disease as an etiology of vomiting, screening blood work should be performed. CBC, basic metabolic panel (BMP), liver function tests, pancreatic amylase and lipase, and erythrocyte sedimentation rate (ESR) should be done. Screening for endocrine and metabolic disorders is also warranted and can include lactic acid, ammonia, amino acids, adrenocorticotropic hormone (ACTH), and antidiuretic hormone (ADH) as well as urinary ketones, organic acids, porphobilinogen, and aminolevulinic acid. Drug screening should also be considered if CHS is a possibility.

Imaging Studies

An upper GI series with small bowel follow-through, CT/MRI of the head, and endoscopy should be performed in between episodes. In adults, a CT of the abdomen and pelvis should be done in addition to the mentioned testing to exclude malignancy. Additional testing may include antroduodenal manometry to assess for neuropathy or myopathy, esophageal pH testing to rule out vomiting as an atypical presentation of GERD, and CT of head to rule out space-occupying lesions.

Treatment

•Treatment of Cyclic Vomiting Syndrome includes avoidance of certain triggers that precipitate attacks as well as pharmacologic therapy divided into prophylactic, abortive, and supportive treatment.
•Patients with regular use of cannabis should be asked to abstain for a short period and if symptoms resolve or improve then cannabis hyperemesis syndrome is likely.

Nonpharmacologic Therapy

•Avoidance of dietary triggers such as chocolate, cheese, or monosodium glutamate (MSG) may prevent episodes.
•Stress management techniques for psychosocial stressors may decrease the frequency of episodes exacerbated by stress.

Acute General Treatment

Treatment can be considered as prophylactic, abortive, or supportive.

•Prophylactic therapy is reserved for patients who have more than one attack per month or with attacks that are severe enough to cause hospitalization. A trial of prophylactic antimigraine medications is recommended even in the absence of personal or family history of migraine headaches. Prophylactic therapy includes cyproheptadine, amitriptyline, propranolol, erythromycin, and topiramate. Some specialists recommend starting amitriptyline at 0.5 mg/kg per day in children older than 5 yr. It often is increased to 1 mg/kg per day, with effects typically taking a few months to become evident.
•There is emerging evidence that carnitine and coenzyme Q10 along with strict dietary protocol can reduce episodes.
•Abortive therapy is used during episodes. Agents that are used in migraine attacks such as triptans have also been found to be effective in aborting episodes in CVS. If abortive therapy fails, antiemetic therapy with ondansetron can be used as supportive therapy. If attack is severe, ondansetron may be used in conjunction with a benzodiazepine or diphenhydramine.

Disposition

If episode is severe, the patient may need hospital admission. Treatment includes IV fluids, antiemetics, and analgesics. Otherwise, this can be managed on an outpatient basis.

Referral

Referral should be made to a gastroenterologist for thorough investigation of vomiting until definitive diagnosis of Cyclic Vomiting Syndrome can be established. If certain neurologic findings or laboratory study results suggest a metabolic disorder, early referral to a metabolic specialist or neurologist should be considered.

Pearls

CVS is a clinical diagnosis that is seen in pediatric and adult populations. Laboratory testing and appropriate imaging should be done to rule out other differential diagnoses. A thorough history including family history, onset and duration of episodes, alarming symptoms, and so on as well as a complete physical examination will allow clinician to narrow differential diagnoses.

Prevention

There is emerging evidence of carnitine and coenzyme Q10 in a certain subtype of patients to prevent frequent attacks. Prophylactic therapy includes pharmacologic agents stated earlier. Avoidance of stress and dietary triggers are also warranted if this can be identified as causative etiology.

Patient & Family Education

Families are encouraged to visit https://cvsaonline.org for more information and education about the disease.

Cyclic Vomiting Syndrome (CVS)