430.
e8 Cyclic Vomiting Syndrome
BASIC INFORMATION
DEFINITION
Cyclic vomiting syndrome (CVS), an idio-
pathic disorder primarily seen in children,
is characterized by recurrent, stereotypical
episodes of vomiting with varying asymp-
tomatic periods.
SYNONYM
CVS
ICD-10CM CODES
G43.A0 Cyclical vomiting, not intractable
G43.A1 Cyclical vomiting, intractable
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 equiva-
lent, 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
• There is a stereotypical pattern to the vomit-
ing 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 symp-
toms, including headache, photophobia, or
Box E1 North American Society for Pediatric Gastroenterology, Hepatology,
and Nutrition (NASPGHAN) Criteria for Cyclic Vomiting Syndrome
• A t 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 hour 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 hour
• A return to baseline health between episodes
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vertigo, which supports the genetic relation
between CVS and migraines.
ETIOLOGY
• 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 fre-
quency in subjects with CVS. In adults, CVS
is not associated with these polymorphisms.
• Sympathetic hyperresponsiveness and auto-
nomic dysregulation may contribute to the
pathogenesis of CVS. Elevated corticotropin,
cortisol, vasopressin, and catecholamines
have been described in patients with vomit-
ing, lethargy, and hypertension. Studies in
animals suggest that corticotropin-releasing
factor induces gastric stasis, leading to eme-
sis. 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.
DIAGNOSIS
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
WORKUP
• 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). Box
E1 summarizes criteria. In adults, Rome IV
criteria should be met to make diagnosis. Box
E2 summarizes Rome IV criteria. 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 tem-
poral characteristics of weekly acute episodes.
• 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 sedimen-
tation rate (ESR) should be done. Screening
for endocrine and metabolic disorders is also
warranted and can include lactic acid, ammo-
nia, amino acids, adrenocorticotropic hormone
(ACTH), and antidiuretic hormone (ADH) as well
as urinary ketones, organic acids, porphobilino-
gen, 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
• T reatment of CVS includes avoidance of cer-
tain triggers that precipitate attacks as well
as pharmacologic therapy divided into pro-
phylactic, 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 choc-
olate, cheese, or monosodium glutamate
(MSG) may prevent episodes.
• Stress management techniques for psycho-
social stressors may decrease the frequency
of episodes exacerbated by stress.
ACUTE GENERAL Rx
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, amitripty-
line, propranolol, erythromycin, and topira-
mate. 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/
 Cyclic Vomiting Syndrome 430.e9

Box E2 Rome IV Diagnostic
Criteria for Cyclic
Vomiting Syndrome
Must include all of the following:
• Stereotypical episodes of vomiting
regarding onset (acute) and dura-
tion (<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
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 conjunc-
tion 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 CVS can be established. If certain neu-
rologic findings or laboratory study results suggest
a metabolic disorder, early referral to a metabolic
specialist or neurologist should be considered.
PEARLS &
CONSIDERATIONS
COMMENTS
CVS is a clinical diagnosis that is seen in pedi-
atric 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 examina-
tion 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 thera-
py 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 view https://.
cvsaonline.org for more information and educa-
tion about the disease.
AUTHOR: Fred F. Ferri, MD

SUGGESTED READINGS
Cyclic Vomiting Syndrome Association: Available at http://cvsaonline.org.
Li BU et al: North American Society for Pediatric Gastroenterology, Hepatology,
and Nutrition consensus statement on the diagnosis and management of
cyclic vomiting syndrome, J Pediatr Gastroenterol Nutr 47:379-393, 2008.
Rome III Criteria: Available at http://theromefoundation.org.

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For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.

These proofs may contain color figures. Those figures may print black and white in the final printed book if a color print product has not been planned. The color figures will appear in color
in all electronic versions of this book.