Asim Maqbool, B U.K. Li, Chris A. Liacouras
Cyclic vomiting syndrome (CVS) is an idiopathic disorder manifested as episodic vomiting, usually of sudden onset and high intensity/frequency (4/hr:12-15 episodes/day) of vomiting, with eventual resolution and return to a normal baseline between attacks. Typical bouts last for 24-48 hr, and usually respond promptly to hydration. To meet the criteria for CVS, identifiable organic disorders are excluded following an appropriate workup (Table 369.1 ).
Table 369.1
Consensus Definition for Diagnostic Criteria and Red Flags for Cyclic Vomiting Syndrome
| DIAGNOSTIC CRITERIA |
| RED FLAGS |
Modified from the Rome IV Criteria: Li BU, Lefevre F, Chelimsky GG, 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(3):379–393, 2008.
The prevalence of CVS in children is estimated at ~2% in predominantly Caucasian populations, although it does occur in those of African or Asian descent, and Hispanic ethnicity. There is a slight female predominance. The median age of onset is 5 yr, but it can begin in infancy and adolescence. Typically, there is a delay of 2.5 yr in making the diagnosis despite multiple episodes and emergency room visits. The natural history of CVS is that most children outgrow it during preadolescence or adolescence, and of those, many will develop migraines. There are also later pediatric-onset (mean age 13) and adult-onset (mean age 32) subgroups indicating that in a minority it can begin or persist in adulthood.
One key clinical feature of CVS is its consistent and stereotypical pattern of presentation within individuals. Typically, symptoms start at the same time, often during early morning hours, lasting the same duration and demonstrating identical autonomic symptoms of pallor and listlessness, unrelenting nausea, abdominal pain, and in less than half, headaches and photophobia. CVS bouts occur at a minimum 5 times, or 3 times over a 6-mo period. About half of cases occur on a cycle as often as monthly; some cycle as infrequently as every 3-4 mo. The other patients have unpredictable sporadic bouts that may be associated with a specific trigger. Potential triggers include infectious illnesses, stress and especially excitement (holidays), sleep deprivation (sleepovers), dietary triggers (chocolate, monosodium glutamate), food allergy, onset of menses, and weather changes. Typically, vomiting bouts are particularly intense, with greater than 4 bouts of emesis per hour at the peak, and can include gastric contents or frequent dry heaves. While most attacks last 2 days, an episode can last anywhere from hours and rarely up to 10 days. CVS attacks are debilitating, often necessitating IV rehydration, and resulting in hospitalization. Seasonal variation apparently occurs in approximately a third of patients, with more attacks in winter, fewer during summer. In some adolescent patients, a coalescent form develops with daily nausea between episodes of emesis (which becomes less frequent).
Multiple comorbid disorders can further comprise quality of life between episodes; these include anxiety, constipation-predominant irritable bowel syndrome, chronic fatigue or limited stamina, sleep disorders, postural orthostatic tachycardia syndrome, daily nausea, and complex regional pain syndrome.
In all cases of CVS, an underlying causative etiology (anatomical, infectious, inflammatory, neoplastic, and metabolic or endocrine) cannot be identified. There is typically a positive family history of migraines in children with CVS; attacks of both conditions share many clinical features. Although the pathophysiology is not fully known, there is suggestive evidence that an overresponsive hypothalamic-pituitary-adrenal axis (including corticotropin-releasing factor), autonomic nervous system dysregulation (sympathetic predominance), mitochondrial dysfunction (16519T and 3010A), and nuclear mutations (RYR2) may play contributory roles. Although the role of cannabis is unknown in CVS, cannabis-induced hyperemesis syndrome shares many features with CVS, including the relief of symptoms by hot showers (Chapter 140.3 ).
Patients with chronic vomiting should always be evaluated for potential etiologies other than CVS. The differential diagnosis includes GI anomalies (malrotation, duplication cysts, choledochal cysts, recurrent intussusceptions), CNS disorders (neoplasm, epilepsy, vestibular pathology), nephrolithiasis, cholelithiasis, hydronephrosis, metabolic-endocrine disorders (urea cycle, mitochondrial disorders, fatty acid metabolism, Addison disease, porphyria, hereditary angioedema, familial Mediterranean fever), chronic appendicitis, and inflammatory bowel disease. Laboratory evaluation is based on a careful history and physical examination and may include, if indicated, endoscopy, contrast GI radiography, brain MRI, and metabolic studies (lactate, organic acids, ammonia). Bilious emesis usually suggests a small bowel obstruction and is considered a red flag; however, children with CVS may have bile stained emesis. A tender abdomen is also unusual for CVS and warrants further workup. Acute and chronic appendicitis can mimic CVS. Prior abdominal surgery may increase risk for adhesion-related partial bowel obstructions (see Table 369.1 ).
Non-gastrointestinal causes of frequent vomiting include renal, metabolic, endocrine, and neurological disorders. Renal abnormalities to consider include acute or chronic ureteropelvic junction (UPJ) obstruction presenting with hydronephrosis (Dietl crisis) and nephrolithiasis. The clinician must also consider metabolic disorders, especially in the infant or toddler less than 2 yr of age. Fasting or high protein meals that provoke emesis raise a red flag for metabolic disorders, such as disorders of fatty acid oxidation, organic acidemias, or partial ornithine transcarbamylase deficiency. Acute intermittent porphyria can present in the adolescent triggered by alcohol or medications. Endocrine disorders, including diabetic ketoacidosis, Addison disease, and pheochromocytoma, can mimic CVS episodes. Although an atypical presentation, CNS tumors can have episodic vomiting and papilledema; altered mental status and focal neurological findings are red flags requiring neuroimaging. Pregnancy can present with CVS-like symptoms.
Children who meet the diagnostic criteria for CVS and have no red flags should have simple screening tests for electrolyte abnormalities, acidosis, hypoglycemia, and renal dysfunction during episodes, and an UGI radiograph to exclude malrotation. Presenting with gastrointestinal (bilious emesis, abdominal tenderness), metabolic (fasting or meal-induced), and neurological (papilledema, altered mental status) red flags warrants further evaluation (see Table 369.1 ).
In the management of acute episodes, early and aggressive hydration (especially with dextrose) may shorten episodes in addition to correcting fluid losses. Reducing extraneous sensory stimulation, similar to the management approach for migraines, may also be beneficial (Table 369.2 ). Regardless of intervention, episodes will eventually spontaneously resolve with return to a normal baseline. Triptans can be used as an abortive medication in patients with a family history of migraines, at the onset of symptoms. Ondansetron may reduce nausea and emesis. Sedation may reduce severity or stop a CVS episode; drugs include antihistamines such as diphenhydramine and promethazine. Lorazepam or rectal diazepam can be also used. These measures are empiric; a lack of evidence base limits our understanding of efficacy. For rare but severe refractory cases, general anesthetics have been used. A dramatic change in presentation of attacks suggests a red flag such as acute hydronephrosis or small bowel obstruction from volvulus.
Table 369.2
Supportive Care and Abortive Treatment Approaches in Cyclic Vomiting Syndrome
| SUPPORTIVE CARE | ||
| Fluid and electrolyte management | Dextrose containing fluid (D10) and normal saline as a single infusion or as a Y infusion | |
| Nutrition | ||
| Medications | Antiemetics |
Ondansetron Alternative: Granisetron |
| Sedatives |
Diphenhydramine Lorazepam 0.05-0.1 mg/kg/dose IV every 6 hr Chlorpromazine 0.5-1 mg/kg/dose every 6-8 hr + diphenhydramine IV |
|
| Analgesics | Ketorolac 0.5 mg/kg/dose IV every 6 hr (maximum dose 30 mg) | |
| Treatment of specific signs and symptoms |
Epigastric pain Diarrhea Hypertension |
|
| Treatment of specific complications | ||
| ABORTIVE CARE | ||
| Antimigraine (triptans) |
Sumatriptan |
|
| RECOVERY AND REFEEDING | ||
Medications listed above are for off-label use.
Modified from Li BU, Lefevre F, Chelimsky GG, 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(3):379–393, 2008.
Prophylactic management begins with lifestyle measures (maintenance fluid intake, adequate calories, sleep hygiene, and exercise), including avoidance of known triggering foods (allergens, chocolate, aged cheese, monosodium glutamate; Table 369.3 ). Recommendations for prophylactic regimens include cyproheptadine in patients less than 5 yr of age and amitriptyline in patients ≥5 yr; propranolol serves as a secondary agent in both age groups. Supplements such as coenzyme Q10 and L-carnitine have occasionally been reported to be useful adjuncts. When standard care fails, the addition of anticonvulsants such as topiramate has been implemented. For those with catamenial CVS, low-dose estrogen oral contraceptives or Depo-Provera may prevent episodes. Treatment of comorbid disorders , especially anxiety (cognitive behavioral therapy, antianxiety agents) and postural orthostatic tachycardia syndrome (fluids, salt, fludrocortisone), may be needed for effective management of CVS.
Table 369.3
Prophylactic Lifestyle Changes and Pharmacological Options for Cyclic Vomiting Syndrome
Medications listed above are for off-label use. CVS , cyclic vomiting syndrome.
Modified from Li BU, Lefevre F, Chelimsky GG, 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(3):379–393, 2008.