A CASE PRESENTATION
A 23 year old male patient (P. C.) from Cyprus was referred to outpatients, in order to confirm or rule out Familial Mediterranean Fever (FMF), as his symptoms were thought to be those of FMF.
After examining the patient and taking his Medical History, FMF was ruled out as he was not fulfilling the FMF criteria and the MEFV test was negative for the related mutations.
The recent medical history was based on episodes of intense nausea and prolonged and multiple severe vomiting over 3-10 days, cycling for 3 months, then a remission for some months. The vomiting was always associated with epigastric pain, palpitations, sweating and fatigue. No migraine–type headaches are mentioned. The last attack lasted for a week with more than 4 vomits per hour, with episodes of about 8 hours and the patient was hospitalized for IV fluids replacement for 5 days.
Going back to the past medical history at 3 years old he suffered his first attack, then over the years he had fewer attacks of intense nausea and vomiting with epigastric pain, then a period of well being with rare episodes but at the age of 16 he had another flare up. Since the age of 18 and to this date he developed a pattern of Cyclic Vomiting with several episodes of intense nausea and vomiting lasting for several hours to several days. The patient describes cyclice episodes occurring every 6 months, every 3 months and every 2 months lasting up to 10 days. Visiting the Emergency Department was a routine for the patient usually requiring IV fluids, antiemetics and hospital admission for several days. The stereotypical pattern of vomiting was followed by a return to baseline health.
From the family history the most significant is that his grandmother and aunt (maternal) had Migraines and that his parents are third cousins.
Symptoms could not be attributed to any other disease, no drug abuse is mentioned and over the years various examinations were performed, by different specialists, in order to set up a diagnosis, but these tests revealed nothing specific… (Blood tests-specific & orientated, urinanalysis, CXR, Gastroscopy, Colonoscopy, U/S of abdomen, CT Abdomen, Laparoscopies, Biopsies, MRI Brain, EEG, and many other tests for eg. Coeliac disease, and in the end the patient was referred to Mental Health care.
Having in mind the symptoms of the patient for almost 20 years and according to the criteria of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the revised Rome III criteria, the patient is suffering from Cyclic Vomiting Syndrome.
Description & Clinical presentation of Cyclic Vomiting Syndrome (CVS)
CVS is an orphan disease which affects a small percentage of the population. It was first described in children by Dr. Samuel Gee (The father of Coeliac Disease-His contribution led to the eponym Gee’s disease. Gee is credited with the first English language description of Cyclic Vomiting Syndrome) in 1882, as a chronic functional disorder of unknown etiology that is characterized by paroxysmal, recurrent episodes of intense vomiting.
The pathophysiology is unknown, but data suggest a strong genetic component in children with CVS, with evidence of mitochondrial heteroplasmies, mtDNA,that predispose to CVS and other related disorders such as migraine. Other theories include autonomic dysfunction and, possibly, corticotrophin-releasing factor (CRF) because stress is known to be a trigger for these episodes.
CVS is characterized by recurrent, discrete, stereotypical episodes of rapid-fire vomiting between varying periods of completely normal health. This on-and-off stereotypical pattern of vomiting is nearly pathognomonic. Recent studies suggest that the condition could be as common in adults as in children.
The illness has four phases: The inter-episode phase, during which the patient is relatively symptom free; the prodrome, which begins when the patient begins to sense the approach of an episode, has nausea of varying intensity, but is still able to retain oral medications; the emetic phase, characterized by intense, persistent nausea , severe vomiting and other symptoms; and the recovery phase, which begins with the subsidence of nausea and ends when hunger, tolerance of oral intake and vigor return to normal.
Because no biochemical markers for CVS have been identified, physicians must initially look for alarming symptoms and then tailor the subsequent workup accordingly. Depending on the presenting symptoms and signs other than vomiting, different diagnostic approaches are recommended. In the absence of known pathophysiology, treatment of CVS remains empiric.
The Rome III diagnostic criteria for CVS in children include the following, both of which must be met:
- At least 2 periods of intense nausea and unremitting vomiting or retching, lasting hours to days
- A return to the usual state of health that lasts weeks to months
Because this 2-episode cutoff resulted in a significant number of misdiagnoses, the guidelines were modified by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) as follows (all criteria must be met)
- At least 5 episodes, or a minimum of 3 over a 6-month period
- Episodic attacks of intense nausea and vomiting lasting 1 hour to 10 days, occurring at least 1 week apart
- Stereotypical pattern and symptoms in the individual patient
- Vomiting during episodes occurs at least 4 times an hour for at least 1 hour
- A return to baseline health during episodes
- Symptoms cannot be attributed to another disorder
The Rome III revised criteria for CVS in adults include the following:
- Stereotypical episodes of vomiting regarding onset (acute) and duration (< 1 week)
- A minimum of 3 discrete episodes in the preceding year
- Absence of nausea and vomiting between episodes
- No metabolic, gastrointestinal (GI), or central nervous system (CNS) structural or biochemical disorders
Supportive criteria include a history of migraine headaches and/or a family history of migraine headaches.
The vomiting in CVS is typically much more severe and intermittent than that of gastroesophageal reflux. When children with CVS were compared with children with chronic vomiting, they had a much higher peak rate of emeses per hour (12.6 vs. 1.9) but far fewer episodes per month (1.5 vs. 36). A cutoff criterion of at least 4 emeses per hour at peak and fewer than 2 episodes per week was 92% sensitive and 100% specific for the final diagnosis of CVS.
With a larger cohort, the median peak rate of emeses was still 6 times per hour. Only Bacillus cereus food poisoning matches this high intensity of emesis. This singularly severe vomiting (so-called cyclic vomiting pattern) typifies patients with CVS and helps point toward a disorder that is localized outside the GI tract.
The stereotypical “on-off” pattern often begins with a prodrome of nausea and pallor. Vomiting peaks in the first hour and then begins to decline over the ensuing 4-8 hours, lasting a mean of 24 hours (median, 43 hours). Episodes commonly occur in the early morning (2:00-4:00 AM) or upon awakening (6:00-8:00 AM). The recovery period from the end of vomiting to the point of being able to eat and play lasts a mere 5 hours. Despite the implication of the term “cyclic,” only one half of patients have a stable periodicity; the rest have sporadic episodes.
Besides vomiting, patients may also experience other GI symptoms. Abdominal pain is present in 80% of patients and may initially be severe enough to mimic acute abdomen and result in a laparotomy. Patients may also have epigastric pain secondary to peptic injury of the esophagus.
Most patients experience retching (79%) and nausea (82%). They typically describe the nausea as the most distressing symptom: It is unrelenting, is completely unrelieved by vomiting, and disappears only when the patient is asleep or the episode is over. Many of the behavioral symptoms commonly observed in patients with CVS (e.g., fetal positioning, social withdrawal, and turning off lights and televisions) are attempts to lessen this severe nausea.
Fever, diarrhea, or both are noted in approximately one third of CVS patients, complicating the differentiation of this condition from gastroenteritis. These findings are likely due to associated autonomic symptoms, which are also common, particularly lethargy (93%) and pallor (91%).Lethargy may be profound, and patients may be unable to walk or talk or may appear comatose. Excessive lacrimation and salivation can also be dramatic.
Many patients with CVS have neurologic symptoms, which support the relation between migraines and CVS. Symptoms include headache (42%), photophobia (38%), phonophobia (30%), and vertigo (26%). As less than half of the patients with CVS have classic migraine symptoms, these symptoms cannot be used as diagnostic criteria for a migraine variant.
Approximately 68% of families are able to identify events that appear to precipitate a patient’s episode.The most common precipitating event is infection like sinusitis (40%). Psychological stresses (34%) and food products, including chocolate, cheese, and monosodium glutamate (MSG), rank close behind chronic sinusitis. Positive excitement, such as birthdays, holidays, vacations, and school outings, appear to trigger more episodes than do negative stresses.
Others recognize physical exhaustion or lack of sleep (18%), atopic events (13%), motion sickness (9%), and menses (13%) as triggers.Many patients experience remission in the summer, when the number of infections and school stressors decline.
The terms “cyclic vomiting syndrome” and “abdominal migraine” have often been used interchangeably because of the considerable overlap in clinical criteria. Indeed, except for vomiting, the key criteria for abdominal migraines are identical to those for CVS and include the following:
- Recurrent, stereotypical, and severe episodes of abdominal pain
- Punctuating well periods
- Autonomic symptoms (e.g. pallor, lethargy)
- Family history of migraine headaches
Because 80% of patients with CVS have abdominal pain, and 50% of those with abdominal pain vomit, many can be diagnosed with either CVS or abdominal migraine. When both symptoms are present, the majority of the clinicians use the predominant or more consistent symptom as the primary label.
The following 3 additional criteria help strengthen the diagnosis of CVS.
- Negative screening test results to exclude common GI, hepatobiliary, renal, metabolic, neurological and endocrine disorders
- Subsequent development of migraine headaches
- A positive response to anti-migraine medications.
Because no biochemical markers for cyclic vomiting syndrome (CVS) have been identified, the guidelines formulated by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) suggest that physicians must initially look for alarming symptoms and then tailor the workup accordingly.
In the absence of known pathophysiology, treatment of cyclic vomiting syndrome (CVS) remains empiric.The following management strategies are used for CVS.
- Avoidance of triggers
- Prophylactic and abortive therapy(Hot showers and sleep during the prodrome phase)
- Supportive care during acute episodes
- Family support
Medications used to prevent, ameliorate, or abort vomiting episodes include cyproheptadine, amitriptyline, propranolol, ondansetron, promethazine, prochlorperazine, sulpiride, sumatriptan, coenzyme Q10 and L-carnitine.
Dr. Vick Atamyan. MB, MD,
General Internal Medicine.
Cyclic Vomiting Syndrome - UNC School of Medicine
Cyclic Vomiting Syndrome - Medscape Reference
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Cyclic Vomiting Syndrome
*Published by the kind permission of a patient and the society of Cyclic Vomiting Syndrome.*
I am CVS...
Most likely you don't know me, unless you are one of hundreds and maybe thousands that suffer everyday because of me.
I affect thousands, not only the ones I attack but the ones that are the Caregivers.
I disrupt life; I destroy social lives; I don't kill; I do something much worse.
I make people vomit uncontrollably for hours and even days, leaving people gasping for air between vomiting....I hide in the darkness, attacking in the early morning hours.
You can't find me; no test can find me, and only my past tells you who I am.
I don't care who I attack; I attack infants, children, and adults.
I tear apart families; I control people’s lives, many times to the point where they have to be taken to the hospital.
I disrupt children’s schooling.
I can last for hours or days and sometimes weeks at a time.
I put people through cycles maybe once a year, maybe 4 times a year, sometimes once a month even to the point of 2 or 3 times a week.
Doctors don't know me, but I have been around since the late 1800's
I am called rare, but people find out about me daily.
I am normally not found for 4 or 5 years and it’s not uncommon for a person I attack not to find out who I am for 10 or 15 years.
I am EVIL for I don't kill, but torture people for years on end.
I may leave for a while, but I normally find my way back to you.
You most likely don't know me, but chances are you know someone I attack
I cost thousands of dollars in medical care and testing every year.
The people I control fear me; they know that in the darkness I will come again.
I am an invisible disorder that is a disability just as much as the visible disabilities.
Maybe you do know me.
I am Cyclic Vomiting Syndrome or CVS.
I don’t kill; I do worse. I may stay with you the rest of your life.