In Focus

Cyclic vomiting syndrome: A GI primer



Cyclic vomiting syndrome (CVS) is a chronic disorder of gut-brain interaction (DGBI) and is characterized by recurrent episodes of severe nausea, vomiting, and often, abdominal pain. Patients are usually asymptomatic in between episodes.1 CVS was considered a pediatric disease but is now known to be as common in adults. The prevalence of CVS in adults was 2% in a recent population-based study.2 Patients are predominantly white. Both males and females are affected with some studies showing a female preponderance. The mean age of onset is 5 years in children and 35 years in adults.3

Dr. Harrison Mooers, Medical College of Wisconsin, Milwaukee

Dr. Harrison Mooers

The etiology of CVS is not known, but various hypotheses have been proposed. Zaki et al. showed that two mitochondrial DNA polymorphisms 16519T and 3010A were associated with a 17-fold increased odds of having CVS in children.4 These polymorphisms were not associated with CVS in adults.5 Alterations in the brain-gut axis also have been shown in CVS. Functional neuroimaging studies demonstrate that patients with CVS displayed increased connectivity between insula and salience networks with concomitant decrease in connectivity to somatosensory networks.6 Recent data also indicate that the endocannabinoid system (ECS) and the hypothalamic-pituitary-adrenal axis are implicated in CVS with an increase in serum endocannabinoid concentration during an episode.7 The same study also showed a significant increase in salivary cortisol in CVS patients who used cannabis. Further, single nucleotide polymorphisms (SNPs) in the gene that encodes for the cannabinoid receptor type 1 (CB1R) are implicated in CVS.8 The CB1R is part of the ECS and is densely expressed in brain areas involved in emesis, such as the dorsal vagal complex consisting of the area postrema (AP), nucleus of the solitary tract (NTS), and also the dorsal motor nucleus of the vagus.9 Wasilewski et al. showed an increased risk of CVS among individuals with AG and GG genotypes of CNR1 rs806380 (P less than .01), whereas the CC genotype of CNR1 rs806368 was associated with a decreased risk of CVS (P less than .05).8 CB1R agonists – endocannabinoids and tetrahydrocannabinol (THC) – have acute antiemetic and anxiolytic effects.9-11 The apparent paradoxical effects of cannabis in this patient population are yet to be explained and need further study.

Diagnosis and clinical features of CVS

Phases of CVS

Figure 1: Phases of Cyclic Vomiting Syndrome12
Adapted from Fleisher DR, Gornowicz B, Adams K, Burch R, Feldman EJ. Cyclic Vomiting Syndrome in 41 adults: The illness, the patients, and problems of management. BMC Med 2005;3:20. This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, modification, and reproduction in any medium.

CVS consists of four phases which include the a) prodromal phase, b) the episodic phase, c) recovery phase, and d) the interepisodic phase; and was first described by David Fleisher.12 The phases of CVS are important for clinicians and patients alike as they have therapeutic implications. The administration of abortive medications during a prodrome can terminate an episode. The phases of CVS are shown above.

Most patients (~ 93%) have a prodromal phase. Symptoms during this phase can include nausea, abdominal pain, diaphoresis, fatigue, weakness, hot flashes, chills, shivering, increased thirst, loss of appetite, burping, lightheadedness, and paresthesia.13 Some patients report a sense of impending doom and many have symptoms consistent with panic. If untreated, this progresses to the emetic phase and patients have unrelenting nausea, retching, vomiting, and other symptoms. During an episode, patients may vomit up to 20 times per hour and the episode may last several hours to days. During this phase, patients are sometimes described as being in a “conscious coma” and exhibit lethargy, listlessness, withdrawal, and sometimes disorientation.14,15 The emetic phase is followed by the recovery phase, during which symptoms subside and patients are able to resume oral intake. Patients are usually asymptomatic between episodes but ~ 30% can have interepisodic nausea and dyspepsia. In some patients, episodes become progressively longer and the interepisodic phase is considerably shortened and patients have a “coalescence of symptoms.”12 It is important to elicit a thorough history in all patients with vomiting in order to make an accurate diagnosis of CVS since coalescence of symptoms only occurs over a period of time. Episodes often are triggered by psychological stress, both positive and negative. Common triggers can include positive events such as birthdays, holidays, and negative ones like examinations, the death of a loved one, etc. Sleep deprivation and physical exhaustion also can trigger an episode.12

Dr. Thangam Venkatesan, Medical College of Wisconsin, Milwaukee

Dr. Thangam Venkatesan

CVS remains a clinical diagnosis since there are no biomarkers. While there is a lack of data on the optimal work-up in these patients, experts recommend an upper endoscopy or upper GI series in order to rule out alternative gastric and intestinal pathology (e.g., malrotation with volvulus).16 Of note, a gastric-emptying study is not recommended as part of the routine work-up as per recent guidelines because of the poor specificity of this test in establishing a diagnosis of CVS.16 Biochemical testing including a complete blood count, serum electrolytes, serum glucose, liver panel, and urinalysis is also warranted. Any additional testing is indicated when clinical features suggest an alternative diagnosis. For instance, neurologic symptoms might warrant a cranial MRI to exclude an intracerebral tumor or other lesions of the brain.

Vidyard Video

The severity and unpredictable nature of symptoms makes it difficult for some patients to attend school or work; one study found that 32% of patients with CVS were completely disabled.12 Despite increasing awareness of this disorder, patients often are misdiagnosed. The prevalence of CVS in an outpatient gastroenterology clinic in the United Kingdom was 11% and was markedly underdiagnosed in the community.17 Only 5% of patients who were subsequently diagnosed with CVS were initially diagnosed accurately by their referring physician despite meeting criteria for the disorder.17 A subset of patients with CVS even undergo futile surgeries.13 Fleisher et al. noted that 30% of a 41-patient cohort underwent cholecystectomy for CVS symptoms without any improvement in disease.12 Prompt diagnosis and appropriate therapy is essential to improve patient outcomes and improve quality of life.

CVS is associated with various comorbidities such as migraine, anxiety, depression and dysautonomia, which can further impair quality of life.18,19 Approximately 70% of CVS patients report a personal or family history of migraine. Anxiety and depression affects nearly half of patients with CVS.13 Cannabis use is significantly more prevalent among patients with CVS than patients without CVS.20

Next Article: