Cyclic Vomiting Syndrome Association Nordic

Cyclic vomiting syndrome, or cyclical vomiting syndrome, (CVS) is a chronic functional condition of unknown cause characterized by recurring attacks of intense nausea, vomiting, and sometimes abdominal pain, headaches, or migraines and prostration with no apparent cause. CVS typically develops during childhood but it may persist into adult life. Vomiting occurs at frequent intervals for hours or days. The episodes tend to be similar to each other in symptoms and duration and are self-limited with return of normal health between episodes.

The four phases of CVS

The illness has four phases:
1. The inter-episode phase, during which the patient is relatively symptom free.
2. The prodrome phase, which begins when the patient senses an oncoming episode.
3. The emetic phase, characterized by intense, persistent nausea, severe vomiting, and other symptoms.
4. The recovery phase begins with the subsidence of nausea and ends when hunger, tolerance of oral intake, and vigor return to normal.

Historical perspective

Cyclic vomiting syndrome (CVS) was first described in French literature in 1806 by Dr. W. Heberden, and in English literature in 1882 by Dr. Samuel Gee. Dr. Gee reported a series of patients, all of whom were children ranging in age from infancy to nine years. Many of his observations continue to be used as diagnostic criteria for CVS. Existing pathophysiologic evidence points towards CVS as a brain-gut disorder involving neuroendocrine pathways in genetically predisposed individuals. In the 1990s, renewed interest in CVS led to international conferences in 1994 and 1998.

Who gets CVS?

The onset of CVS may occur at any time, but most commonly develops between the ages of 3-7 years. It may persist for periods of time ranging from months to decades. Although CVS is most commonly recognized in children, it is apparent that adult onset CVS is more common than was once thought. Females are affected slightly more than males.

CVS sufferers are more likely than average to have a family history of migraine and/or travel sickness, but not all CVS sufferers have family histories of these problems.

Symptoms

Episodes may begin at any time, but most commonly occur during the night or early morning. There is relentless nausea with repeated bouts of vomiting or retching. The vomiting has been described as the most intense kind of nausea a human can experience. The person is pale and listless. They may experience intense abdominal pain and less often headache, low-grade fever and diarrhea. Prolonged vomiting may cause mild bleeding due to irritation of the esophagus. The symptoms are frightening to the person and family and may be life-threatening if delayed treatment leads to dehydration. CVS is very different from the normal vomiting. The most obvious thing is that the vomiting doesn’t stop. Only bacillus cereus food poisoning matches this high intensity of emesis in CVS.

Attacks tend to be stereotypical, in that a patient’s attacks tend to be similar each time, although attacks vary from person to person. 50% of CVS suffers experience the same progression and character of attack with every episode. Laboratory tests often reveal a persistent presence of lactic acid in the blood.

 

During CVS, these symptoms occur:
Severe and constant, unremitting nausea
Occurs in 76% of patients and is usually the most distressing symptom. It is unrelenting and completely unrelieved by vomiting, disappearing only when the episode is over. The vomiting has been described as the most intense kind of nausea a human can experience.
Repeated vomiting and retching, often violently, peaking at up to 5-6 times per hour or more
Vomiting typically begins during the night or early morning. It peaks in the first hour and is particularly severe, occurring up to 13 times an hour, and is accompanied by retching. The emesis is often projectile (50%), containing bile (76%), mucous (72%), or blood (32%).
Pallor, often extreme paleness of the skin
Low-grade fever
Headache
Headaches and fevers have been reported in about 25% of cases.
Abdominal pain
Pain around the belly button or epigastric pain is present in 80% of patients and may be severe enough to mimic an acute abdomen. Dr. David R. Fleisher has identified three types of functional abdominal pain that may affect CVS patients: Irritable Bowel Syndrome, abdominal migraines and abdominal pain that are symptom of panic.
Diarrhea
About 30% of patients have loose stools near the onset of the cyclic vomiting episodes, and some have severe diarrhea during the vomiting phase.
Lethargy or unresponsiveness/conscious coma
Patients describe being in a state of confusion and exhaustion during the episode, with no control over their body’s reactions. Patients still hear and know what is going around them but struggle to be able to respond. This has been named a “conscious coma”.
“Perplexing” or unusual behaviors
Many of the behavioral disturbances that may be observed are designed to lessen the nausea (e.g. fetal positioning, social withdrawal, compulsive drinking, turning off lights). The intense distress experienced by patients during the emetic phase of CVS may prompt behaviors that are in some cases mistaken to be psychotic or bulimic. Many patients who are normally pleasant and cooperative may become irritable, demanding and unable to think clearly or give an accurate history.
Excessive salivation, and/or spitting
Nausea increases salivation, but patients may be unwilling to swallow their saliva as this causes retching. They may dribble, spit or hold their saliva in their mouths, making speech difficult.
Extreme thirst
Thirst is often intense even though taking fluids results almost immediately in vomiting.
Dehydration
Dehydration and electrolyte imbalance may be severe during the vomiting phase, with about 60% requiring intravenous rehydration.
Vomiting blood
Many patients develop hematemesis from either peptic esophagitis or a Mallory-Weiss tear.
Weakness
Eye problems
Fatigue
Pathologic bathing behavior (prolonged hot baths or showers).
Many patients experience symptom relief when they take hot baths or showers.Several case reports implicate marijuana as a cause of intractable vomiting with prolonged hot baths or showers considered pathognomonic of “cannabinoid hyperemesis syndrome (CHS),” and this symptom has been used to distinguish CHS from CVS. Venkatesan and colleagues of the Medical College of Wisconsin conducted an internet survey among 514 CVS patients from members of the Cyclic Vomiting Syndrome Association USA in 2014, and sought to examine the relationship between marijuana use and CVS.

The study showed that marijuana use is associated with hot showers, but even though the frequency of prolonged hot baths or showers is higher among patients using marijuana, this phenomenon of this behavior was also seen in CVS patients who denied any use of it, and they concluded that this kind of bathing should not be interpreted as being pathognomonic of marijuana use.

 

Seek Help for Signs or Symptoms of Severe Dehydration
People who have any signs or symptoms of severe dehydration should call or see a healthcare provider right away

  • excessive thirst
  • dark-colored urine
  • infrequent urination
  • lethargy, dizziness, or faintness
  • dry skin

Infants, children, older adults, and people with weak immune systems have the greatest chance of becoming dehydrated. People should watch for the following signs and symptoms of dehydration in infants, young children, and people who are unable to communicate their symptoms:

  • dry mouth and tongue
  • lack of tears when crying
  • infants with no wet diapers for 3 hours or more
  • infants with a sunken soft spot
  • unusually cranky or drowsy behavior
  • sunken eyes or cheeks
  • fever

If left untreated, severe dehydration can cause serious health problems, such as organ damage, shock, or coma—a sleeplike state in which a person is not conscious.

 

How frequently do the episodes occur?

As the name suggests, cyclic activity is often a feature of this condition. Episode frequency is relatively constant for any given individual, but varies between individuals. Vomiting occurs at frequent intervals for hours or days. A patient may suffer from 1 to 70 episodes per year with an average of 12 episodes a year. Patients with uncomplicated CVS are asymptomatic between episodes; attacks have an “on-off ” pattern. About half of all sufferers show a strong regular pattern of vomiting episodes.

How long does an episode last?

The length of an episode varies from person to person, but are often consistent within the same individual. Most often the attacks last from 8 to 24 hours, but some experience only 1-2 hour episodes while others have episodes that last for days.

Triggers

Although some patients don’t know what may trigger attacks, many identify specific circumstances that seem to bring on their episodes. Colds, flus and other infections (such as sinus problems), intense excitement (birthdays, holidays, vacations), and menstrual periods are the most frequently reported triggers. Excitement and positive emotional stress may play a role, as well as negative stress such as anxiety, family problems, and the fear of being ill. Common triggers in children include emotional stress and excitement. Anxiety and panic attacks are more commonly triggers in adults.

Going without food for too long and sleep deprivation may also act as physical triggers. Less common triggers are anesthetics, cold temperatures, hot weather, food sensitivities, allergies, eating too much, or eating just before going to bed.

Most CVS attacks (68–80%) have associated trigger mechanisms. These include infection (41%, often chronic sinusitis and other upper respiratory infections), psychological stress (34%, both positive [birthdays and holidays] and negative [parental or interpersonal conflict]), physical stress (18%, often heavy exercise), inadequate sleep, diet (26%, especially chocolate, cheese, monosodium glutamate), motion sickness (9%), and onset of menses (named catamenial CVS and found in up to 13% of post-menarchal girls). Attacks tend to occur less commonly during the summer months.

Prevalence

The prevalence of CVS is not known. Li and Misiewicz estimated it to be 0.04% in children of central Ohio. In contrast, a population-based study performed in Aberdeen, Scotland indicated a prevalence of 1.9%. The discrepancy in these two studies may be due to the fact that, in the Ohio study, not all patients with CVS may have been referred to specialty centers and community physicians may have managed patients with milder forms of the disease. In the Scottish study, most patients were diagnosed by survey questionnaire and follow-up history, without detailed diagnostic evaluations to rule out organic etiologies for vomiting. Therefore, the actual incidence in the Scottish study might have been lower and it is likely that the true prevalence of CVS is somewhere between these two values.

Diagnosis

The diagnosis of CVS has been difficult because vomiting may be caused by a large number of more common disorders. The diagnosis of CVS requires that other known and treatable disorders be excluded. At present there are no diagnostic methods (tests) that can be used to directly diagnose the disorder. A diagnosis, or more correctly, a classification of CVS may take several years. Many sufferers will undergo numerous tests and sometimes misdiagnoses before their condition is recognized.

When a patient presents with acute vomiting, severe disorders can usually be excluded by patient history, physical examination, and basic laboratory studies (such as a complete blood count and a complete metabolic panel including liver function tests, amylase, and lipase, a urinalysis, a pregnancy test, and an upper GI series/small bowel follow through). Abdominal ultrasound of the liver, gallbladder, pancreas, kidneys, and adrenals may help in evaluation of possible gallstones, pancreatitis, and ureteropelvic junction obstruction.

An EGD (esophagogastroduodenoscopy) must be performed in patients with acute vomiting, often for hematemesis or on clinical suspicion of peptic ulcer disease. If the above tests are negative, structural lesions must be excluded with imaging studies such as head and abdominal/pelvis CT. An EEG may be obtained depending upon the clinical suspicion of seizure disorder. Patients presenting with cyclic symptoms of vomiting should be screened for metabolic disorders, including pituitary-adrenal disorders, organic acid, and amino acid disorders.

A common problem is differentiating CVS from chronic vomiting. Most patients who suffer from chronic vomiting do not have symptoms that follow a cyclic pattern, are less likely to have autonomic symptoms, usually vomit less than four times an hour, and often have no family history of migraine headaches. When a patient – a child or adult – with known CVS is seen during an episode, the physician must still consider other potential causes for the current vomiting episode.

Different sets of criteria of diagnostics

Cyclic vomiting syndrome (CVS) remains a diagnosis based upon the history and exclusion of alternative diagnoses. Multiple sets of criteria have been proposed based upon a consensus of experts.

There is no single agreed upon set of symptoms, which serves to highlight the problems in obtaining a diagnosis. In some people, the intense nausea is the predominant symptom. In CVS, the pattern of vomiting is such that at the peak this may be 5-6 times per hour. This is different from vomiting induced by most other causes.

In 1994,  CVSA UK and USA (with support from Glaxo Wellcome) sponsored a symposium held in London, UK. The conference established the criteria for a formal CVS diagnosis. Essential criteria is required for diagnosis. Supportive criteria may strengthen the diagnosis, but not all of the criteria may present in any one individual. Associated signs are features that are more difficult to quantify, but may be associated with CVS.

In many ways, this was a huge step forward in the recognition of CVS and its wider acceptance as a serious health issue.

 

1994: Criteria from symposium held in London.
Essential criteria
  • Recurrent, severe, discrete episodes of vomiting.
  • Various intervals of normal health between episodes.
  • Duration of vomiting episodes from hours to days.
  • No apparent cause of vomiting.
Supportive criteria
  • Pattern: Stereotypical: each episode similar within individuals as to time of onset, intensity, duration, frequency, and associated symptoms and signs.
  • Associated Symptoms: Nausea, Abdominal pain, Headache, Motion sickness, Photophobia.
  • Associated Signs: Fever, Pallor, Diarrhea, Dehydration, Excess salivation, Social withdrawal.

In 2006, The Rome Foundation, which is an independent not-for-profit organization that provides support for activities, designed to create scientific data and educational information to assist in the diagnosis and treatment of functional gastrointestinal disorders (FGIDs), launched it’s diagnostic criteria for CVS, what is called the Rome III criteria. This is the criteria mostly used in clinical practice.

ROME III included a set of diagnostic criteria both under B. Functional Gastroduodenal Disorders, G. Childhood Functional GI Disorders: Infant/Toddler and H. Childhood Functional GI disorders: Child/Adolescent, where the diagnostic criteria under G and H were identical.

 

2006: Rome III
B. Functional Gastroduodenal Disorders
B3. NAUSEA AND VOMITING DISORDERS
B3c. Cyclic Vomiting Syndrome
Must include all of the following:
  1. Stereotypical episodes of vomiting regarding onset (acute) and duration (less than one week).
  2. Three or more discrete episodes in the prior year.
  3. Absence of nausea and vomiting between episodes.
Supportive criterion
History or family history of migraine headaches.

 

2006: Rome III
G. Childhood Functional GI Disorders: Infant/Toddler
H. Childhood Functional GI disorders: Child/Adolescent
G3/H1a Cyclic Vomiting Syndrome
Diagnostic criteria must include both of the following:
  1. Two or more periods of intense nausea and unremitting vomiting or retching lasting hours to days.
  2. Return to usual state of health lasting weeks to months.

In 2008, The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guidelines for the diagnosis of CVS in children were formulated, as they found that the Rome III criteria didn’t fit childhood CVS.

 

2008: NASPHAGN guidelines for the diagnosis of CVS in children
  • At least 5 attacks in any interval, or a minimum of 3 attacks during a six-month period.
  • Episodic attacks of intense nausea and vomiting lasting 1 h –10 days and occurring at least one week apart.
  • Stereotypical pattern and symptoms in the individual patient.
  • Vomiting during attacks occurs at least 4 times/h for at least 1 hr.
  • Return to baseline health between episodes.
  • Not attributed to another disorder.

In 2013, Headache Classification Committee of the International Headache Society (IHS) published The International Classification of Headache Disorders, 3rd edition. They outlined the following sets of criteria for diagnosis of CVS.

 

2013: International Headache Society diagnostic criteria for CVS
  1. At least five attacks of intense nausea and vomiting, fulfilling criteria B and C.
  2. Stereotypical in the individual patient and recurring with predictable periodicity.
  3. All of the following:
    1. Nausea and vomiting occur at least four times per hour.
    2. Attacks last ≥1 hour and up to 10 days.
    3. Attacks occur ≥ 1 week apart.
  4. Complete freedom from symptoms between attacks.
  5. Not attributed to another disorder.

In 2017, The Rome Foundation launched the Rome IV criteria.

 

2017: Rome IV
B. Functional Gastroduodenal Disorders
B3. NAUSEA AND VOMITING DISORDERS
B3b. Cyclic Vomiting Syndrome
Must include all of the following:
  1. Stereotypical episodes of vomiting regarding onset (acute) and duration (less than one week).
  2. At least three discrete episodes in the prior year and two episodes in the past 6 months, occurring at least 1 week apart.
  3. Absence of vomiting between episodes, but other milder symptoms can be present between cycles.
Supportive Remark
History or family history of migraine headaches.

Minor changes to the cyclic vomiting syndrome criteria were made to acknowledge the observation that some affected adult patients report inter-episodic symptoms other than vomiting, and being free of vomiting for at least a week between episodes was a distinguishing feature in adults.

 

2017: Rome IV
H. Childhood Functional GI disorders: Child/Adolescent
H1a Cyclic Vomiting Syndrome
Must include all of the following:
  1. Two or more periods of intense, unremitting nausea and paroxysmal vomiting lasting hours to days within a 6-month period.
  2. Episodes are stereotypical in each patient.
  3. Episodes are separated by weeks to months with a return to baseline health between episodes.
  4. After appropriate medical evaluation, the symptoms cannot be attributed to another condition.

The committee has changed the statement “return to usual state of health lasting weeks to months” to “episodes are separated by weeks to months, with return to baseline health between episodes”. This change was made because the concept of “usual state of health” could have been misinterpreted as being asymptomatic between episodes and did not allow the coexistence of mild gastrointestinal symptoms at baseline.

 

2017: Rome IV
G. Childhood Functional GI Disorders: Infant/Toddler
G3. Cyclic Vomiting Syndrome
Must include all of the following:
  1. Two or more periods of intense, unremitting nausea and paroxysmal vomiting lasting hours to days within a 6-month period.
  2. Episodes are stereotypical in each patient.
  3. Episodes are separated by weeks to months with a return to baseline health between episodes.

The word nausea has been left out in the criteria for infants/toddlers as the working group was of the opinion that this symptom is difficult to assess in infants due to the inability to communicate the presence of nausea.

The Rome III/IV criteria has been criticized for specifying that episodes should last less than a week, when in fact patients can sometimes have much longer episodes based on experience.

The Rome committee criticize the NASPGHAN and IHC guidelines for specifying a minimum of 5 attacks of intense nausea and vomiting in any interval for the diagnosis of CVS in children. They say that no studies have showed a higher prevalence of CVS in studies that have used the ROME III criteria, rather than NASPGHAN and IHC guidelines.

Due to the impact of a CVS attack for the quality of life of the child and the family, the Rome IV working group decided that early diagnosis is important and left the minimum number of 2 episodes to diagnose CVS unchanged.

The disagreement about of the criteria for diagnosing CVS underscores the need for further research into the mechanism of CVS and development of better diagnostic tools.

Prognosis

Several studies have attempted to address the natural history of patients with CVS. However, consistent long-term follow-up was largely incomplete. Shared observations suggest that the majority of patients cease to have emetic episodes and remain asymptomatic, whereas some patients appear to transform emesis to migraine headaches. In the series by Hoyt and Stickler, follow-up was available for 38 of 44 patients. During the follow-up interval, 30patients (68%) had ceased to vomit. Of the 8 patients who had recurrent vomiting, the follow-up interval was less than five years. 14 of the 38 patients (37%) developed recurrent headaches, with most being diagnosed as migraine. Fleisher and Matar had follow-up data available for 29 of 71 patients in their series and 16 of these 29 patients (55%) were asymptomatic for more than one year at follow-up.

Li and Hayes evaluated 88 children in a series of 277 patients with CVS who were disease free. This is unpublished data, but it is cited by Li and Misicwicz in Cyclic vomiting: A brain-gut disorder. CVS was defined as being resolved if the symptom-free period lasted more than twelve months. Two-thirds of these patients did not have any symptoms, while one-third developed migraine headaches during the follow-up period. 7% developed abdominal migraines, and 5% progressed through all three disorders, from CVS to abdominal migraines to migraine headaches. The young age at onset in pediatric patients with CVS is likely correlated with a longer duration of illness. Those who suffer from the onset of CVS before they are 3 years, from 3 – 8 years, and older than 8 years reported suffering from the illness for 5.8 years, 4.9 years, and 2.9 years, respectively, and about 75% of patients eventually cease to vomit and have migraines by 18 years of age.

Josephine Hammond evaluated twelve adults between the ages of 17 and 27 who had CVS during childhood. Results indicated that up to 10 years after CVS resolved, 6 patients had abdominal pain, 7 patients had vomiting, and 8 patients had headaches, supporting the conclusion of others that children with CVS often have symptoms well into adulthood and that many later develop headaches.

 

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11. September 2018