• Users Online: 54
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 2  |  Page : 64-73

Cyclic vomiting syndrome in children: a single-center experience


Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission01-Jan-2020
Date of Acceptance10-Mar-2020
Date of Web Publication5-Oct-2020

Correspondence Address:
MD, PhD Ahmed F Khalil
Lecturer of Pediatrics and Pediatric Gastroenterology, Department of Pediatrics, Alexandria University, Alexandria 2164655
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJOP.AJOP_20_20

Rights and Permissions
  Abstract 


Background Cyclic vomiting syndrome (CVS) is a functional disorder characterized by recurrent episodes of intractable vomiting separated by symptom-free periods. The onset starts at any age from infancy to adulthood. Little is known about its etiology. The diagnosis is based on the fulfillment of Rome IV criteria. CVS is usually a misrecognized disorder, and delayed diagnosis is very common.
Aim The purpose was to evaluate the prevalence, clinical characteristics, prereferral management, and response to treatment among children with proved CVS in our institution.
Patients and methods This was a retrospective study that included all children with CVS attending the Gastroenterology Clinic at Alexandria University Children’s Hospital between January 2016 and the end of June 2019. All patients were followed up for at least 6 months. The diagnosis is based on the fulfillment of Rome IV criteria. The following data were retrieved from the medical records including demographic information, evaluation steps performed for diagnosis, analysis of CVS characteristics, prereferral management, and finally, the treatment algorithm and response to treatment during follow-up.
Results The study included 79 patients, and two-thirds of them were females. They constituted 2–5% of the cases referred yearly to our clinic. Evaluation for possible organic cause was indicated in 22.7%. No abnormalities were found in the barium studies. Other investigations including gastroscopies were not diagnostic for other organic causes. The mean age at onset of symptoms was 6±3.3 years. Overall, 25.3% of patients reported specific triggers, and 62.5% reported recognizable prodromes. The episodes were stereotypic among all patients. Overall, 52% experienced the start of the episodes at night. The interval between episodes was 2.5±1.8 months. The mean duration of each episode was 2.4±2 days. Listlessness and pallor were the commonest during the vomiting phase. The vomiting was bilious in 65.8%and contained blood in 50.8%. Personal history of migraine was positive in 9%. Family history of migraine and motion sickness was positive in two-thirds. The mean duration before referral of the patients was 12.5+8 months. Overall, 78% of the episodes were interpreted as episodes of gastroenteritis, food poisoning, or acid peptic disorders. Moreover, 54.4% were admitted at least once. The overall response to the first-line prophylactic therapy is 89.3%, with no significant adverse effects.
Conclusion The prevalence and clinical characteristics were similar to other similar reports. Barium studies are not necessary in most of the patients. CVS is prevalent yet an underdiagnosed health problem. Propranolol is effective and safe and may be considered as a first-line prophylaxis in patients older than 5 years of age.

Keywords: cyclic vomiting syndrome, diagnosis, Rome IV


How to cite this article:
Khalil AF. Cyclic vomiting syndrome in children: a single-center experience. Alex J Pediatr 2020;33:64-73

How to cite this URL:
Khalil AF. Cyclic vomiting syndrome in children: a single-center experience. Alex J Pediatr [serial online] 2020 [cited 2020 Oct 20];33:64-73. Available from: http://www.ajp.eg.net/text.asp?2020/33/2/64/297241




  Introduction Top


Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder characterized by recurrent episodes of severe intractable nausea and vomiting separated by symptom-free periods [1]. The onset of this disorder can start at any age from infancy to adulthood, but it usually begins in childhood, mainly in preschool-age children. Data suggest a community prevalence of 0.2–1.9% for CVS [2],[3].

Although some authors consider CVS to be a migraine equivalent, little is known about its etiology or pathogenesis. Recent investigations support roles of mitochondrial DNA mutations and dysfunction, hypothalamic–pituitary–adrenal axis activation, and autonomic nervous system dysfunction [4],[5],[6].

Multiple studies have reported a developmental progression from CVS to abdominal migraine and migraine headaches (median ages 5, 9, and 11 years) [7]. This natural history that begins with CVS and ends with migraines was labeled as ‘the periodic syndrome’ [8],[9].

No specific diagnostic test is available for definite diagnosis of CVS [10]. The diagnosis of CVS is based on the presence of typical clinical presentation, and by exclusion of other possible organic causes of recurrent or episodic vomiting [1]. The fulfillment of Rome IV criteria for diagnosis of CVS in the absence of red flags in history and physical examination is the mainstay for diagnosis [11]. Rome IV criteria require the occurrence of two or more attacks of intense, unremitting nausea, and paroxysmal vomiting, lasting hours to days within a 6-month period. The attacks are stereotypical for the individual patient and separated by weeks to months with return to baseline health between episodes and the symptoms cannot be attributed to another condition after appropriate medical evaluation.

The diagnosis of CVS is usually supported by the self-limited nature of the attacks, presence of prodrome phase before the start of intense vomiting, and family history of migraine headaches and/or motion sickness. The most common symptoms in the prodromal phase are listlessness, pallor, and nausea. During the vomiting phase, the commonest accompanying symptoms are nausea, abdominal pain, headache, motion sickness, photophobia, and lethargy and may be also associated with mild fever, dehydration, and diarrhea [10].

The most challenging aspect of CVS is the choice of effective treatment and the duration of medical therapy. No specific therapy is curative for CVS in controlled trials [12]. The goals of treatment are to reduce the frequency and severity of episodes, enhance functionality, and improve quality of life. The NASPGHAN consensus statement recommendations on treatment are based upon therapeutic responses from case series and expert opinion of the task force. The main recommendations include the use of cyproheptadine (a first-generation antihistamine) or amitriptyline (a tricyclic antidepressant). Propranolol (a beta-blocker) is used as the second line of prophylactic treatment. In patients with infrequent attacks, triptans should be considered as an abortive agent for those more than 12 years. For rescue therapy, during acute episodes, IV rehydration with high-dose ondansetron (0.3–0.4 mg/kg/dose) is also recommended [1],[10].

CVS is usually a misrecognized episodic vomiting disorder. Children and adolescents with CVS experience a recurring, unpredictable, and disruptive disorder with frequent visits to emergency departments and repeated hospital admissions because of delayed diagnosis [13]. CVS is not studied well in our community, and delayed diagnosis is unfortunately very common owing to lack of laboratory or imaging investigations in addition to insufficient medical awareness among general practitioners and pediatricians.


  Aim Top


The purpose of this study was to evaluate the prevalence, clinical characteristics, prereferral management, and response to treatment among children with proved CVS in our institution.


  Patients and methods Top


The study included all children diagnosed with CVS attending the Gastroenterology Clinic at Alexandria University Children’s Hospital, between the period from January 2016 and the end of June 2019. Children with other causes of episodic vomiting such as intermittent obstruction owing to malrotation with intermittent volvulus or inborn errors of metabolism were excluded. Children with any developmental or neurological disorders were also excluded. All patients were followed up for at least 6 months. The following data were retrieved from the medical records including demographic information, evaluations steps (diagnostic algorithm) performed for diagnosis of CVS, analysis of CVS characteristics, prereferral management, and finally, the treatment algorithm and response to treatment during follow-up in our clinic. A written consent was taken from the parents or caregivers of all included children. The study was approved by the Ethics Committee, Faculty of Medicine, Alexandria University.

Demographic data included age, sex, social status, and residence.

Evaluation steps for suspected cases of cyclic vomiting syndrome

In children with episodic vomiting pattern and suspected CVS, the diagnosis was based on the fulfillment of Rome IV criteria in the absence of red flags in history and/or physical examination, which may point to other serious organic disorders [11]. A trial of empiric prophylactic therapy was started for all cases with suspected CVS to prevent the recurrence of the vomiting episodes. If the patient responded to therapy with at least a 50% reduction in episode frequency and/or severity of vomiting during attacks, then further evaluation was not done, and a final diagnosis of CVS was made. If any red flags were detected during the initial evaluation or if the patient does not improve with initial therapy during a 2-month period, further evaluation was performed to exclude other organic causes of episodic vomiting before a final diagnosis of CVS is done. This evaluation was performed routinely in all children younger than 2 years, to exclude any possible underlying neurologic, metabolic, or surgical disorders. If these disorders were suspected, the case was referred to the specialized clinic in our institution for further evaluation and management. The results of laboratory tests and imaging or endoscopic investigations done to confirm CVS in these situations were reported. The algorithm used in our clinic for evaluation of patients with suspected CVS was adopted from the NASPGHAN guidelines [1] ([Figure 1]).
Figure 1 Flow chart for diagnosis of cases with suspected cyclic vomiting syndrome.

Click here to view


Analysis of cyclic vomiting syndrome characteristics

Clinical characteristics of the CVS episodes were reported in detail, including age at onset; the precipitating factor(s) if any; frequency, timing, and duration of episodes; symptoms during the prodrome phase; vomiting phase characteristics; and any associated gastrointestinal symptoms. Personal history and family history of migraine or motion sickness were retrieved together with any associated chronic gastrointestinal disorders.

Prereferral management of the cyclic vomiting syndrome episodes

The diagnosis of the recurrent vomiting episodes, the workup done, the duration of disease, and number of local hospital admissions before referral to our institution were reported.

Treatment algorithm and response to treatment

All cases diagnosed with CVS were treated and were followed in the clinic for at least 6 months. The parents of children with CVS were advised to avoid any known triggers that may precipitate the vomiting episodes. Unfortunately, abortive medications are not readily available in Egypt. Thus, it was not used in most of the indicated cases. Daily prophylactic therapy was the mainstay of treatment available for our patients to prevent the next episodes or to at least reduce the frequency, duration, or intensity of episodes. The first-line treatment was cyproheptadine (0.25–0.5 mg/kg, single nighttime dose) for children younger than 5 years and propranolol (0.5–2.0 mg/kg postoperative b.i.d.) for the older children (≥5 years). The second-line treatment was used if the improvement in the frequency or the severity of the vomiting episodes was less than 50% when compared with the pretreatment period. In this situation, propranolol was used in children younger than 5 years and amitriptyline in older children (0.2–0.3 mg/kg and advance to 1–1.5 mg/kg per day at night). The response to treatment and any associated adverse effects were recorded. All patients were given a written medical emergency plan for any breakthrough episodes. This plan includes recommendations for the local health care professionals who may be not familiar with the specific management needed during the vomiting episodes and indications for referral to our institution in case of a severe attack.

Statistical analysis

Statistical analysis was carried out using SPSS statistics software, version 23 (IBM SPSS Statistics for Windows, Version 23 Armonk, NY: IBM Corp). Data were expressed as percentage of the total for categorical variables, as mean with SD for normally distributed continuous variables, or as median with interquartile range for skewed distributed variables.


  Results Top


A total of 89 patients were diagnosed with CVS during the study period. They constituted 2–5% of the cases referred yearly to our clinic during the study period. A total of 10 patients were excluded because they were not compliant on treatment or because their records showed incomplete follow-up (<6 months). The study included 79 patients, and two-thirds of them were females (62%). Almost 70% of the cases were more than 5 years in age. Almost two-thirds were from rural areas (63.3%) ([Table 1]).
Table 1 Demographic and clinical characteristics of the study group

Click here to view


Evaluation steps for suspected cases of cyclic vomiting syndrome

All patients were interviewed with their families in the outpatient clinic in the inter-ictal periods. Physical examination of the recruited cases revealed nondiagnostic findings. A total of eight patients were underweight, and 12 patients had mild iron-deficiency anemia.

Evaluation for possible organic cause for the episodic vomiting was indicated in 18 (22.7%) patients because they were younger than 2 years of age (n=2) or had red flags during their evaluation or had incomplete response to the initial prophylactic therapy (n=5). No abnormalities were found in the barium studies (upper gastrointestinal series and small bowel follow through) performed for 12 cases to rule-out possible malrotation. Serum lipase was normal in two cases with suspected recurrent pancreatitis. Three patients with inter-ictal headache had brain MRI, which showed no intracranial abnormalities. Gastroscopy was performed in five patients. Three patients had chronic gastritis owing to Helicobacter pylori infection with no mucosal ulceration, and the other three had nonerosive reflux esophagitis.

Analysis of cyclic vomiting syndrome characteristics

The mean age at onset of symptoms was 6±3.3 years, whereas the mean age for diagnosis was 6.5±3.4 years. A total of 20 (25.3%) patients reported a specific trigger for their CVS episodes ([Table 1]). The reported precipitating events in order were psychological stress (n=7), upper respiratory infections (n=5), lack of sleep (n=3), and menses (n=3). Two patients developed the CVS episode only in the spring and summer seasons.

The CVS episodes were stereotypic among all the patients. For each patient, the vomiting episodes characteristically started at the same time of the day, extended for the same duration every time, and the attacks recurred at the same interval. Among the included patients, 52% of them always experienced the start of the vomiting at night, whereas 30% had symptoms in the early morning, and the rest (18%) were awakened during midnight because of attacks. Almost two-thirds of the patients (62%) reported recognizable prodromes. The mean duration of the prodrome was 3±0.5 h. The most common symptoms encountered during the prodrome phase were listlessness and pallor.

Among our cases, interval between episodes of CVS was 2.5±1.8 months. The mean duration of each episode was 2.4±2 days. During the vomiting episodes, the mean frequency of vomiting per day was 21.3±4.5 per day. Listlessness, pallor, and intense nausea were reported in most patients during the vomiting phase. The vomiting was bilious in two-thirds and contained blood in half of the cases. Periumbilical colicky or dull aching abdominal pain and nonmucoid loose or frequent stools were reported in 82.3 and 30%, respectively.

In our cohort, functional constipation and gastroesophageal reflux disease (GERD) were the most common associated chronic gastrointestinal disorders. Personal history of migraine was positive in 9% of the cases. Family history of migraine headache and motion sickness was positive in almost two-thirds of the cases ([Table 2]).
Table 2 Associated disorders and family history

Click here to view


Prereferral management

The mean duration of disease before referral of the patients to our tertiary center was 12.5±8 months (range, 6–36 months). During this period, none of the patients got definite diagnosis of CVS in local hospitals. Most (78%) of the vomiting episodes were interpreted by the local health care professionals (general practitioners and/or pediatricians) as episodes of gastroenteritis, food poisoning, or acid peptic disorders. The other diagnoses included intestinal obstruction, attacks of Familial  Mediterranean fever More Details (FMF), intracranial space-occupying lesions, food allergy, gall bladder disorders, or hyperammonemia. All the patients had multiple emergency departments visits (ED) in local hospitals, and 54.4% of them were admitted at least once, because of unexplained acute severe episodes of vomiting. A total of 33 (41.8%) patients had been admitted once or twice, and 10 (12.6%) patients had been admitted for more than twice. The duration of hospitalization ranged from 2 to 7 days. During more than 700 ED visits and 87 hospital admissions, laboratory investigations such as complete blood count, erythrocyte sedimentation rate, C-reactive protein, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, serum electrolytes, stool analysis, urine analysis, and abdominal ultrasound were done repeatedly for all patients. All of these investigations showed nondiagnostic results. Gastroscopy was performed for five patients with recurrent hematemesis during the vomiting episodes, and no explanation for the vomiting was provided. Abdominal and cranial computed tomography was normal in seven patients. The episodic pattern of vomiting was noticed by the local pediatricians in four (5%) patients, and these patients were referred for evaluation of etiology of episodic vomiting.

Response to treatment

Abortive therapy in the form of nasal zolmitriptan, 5 mg, was available only for five patients (older than 5 years) among the patients who had infrequent attacks. It was successful in aborting the attacks in four patients ([Figure 2]). Prophylactic therapy was used for the rest of the patients (95%). The overall response to the first-line prophylactic therapy is 89.3%. No significant adverse effects were reported by the patients using the first-line therapy, except for mild and transient sedation caused by cyproheptadine. Constipation and sedation were reported by all patients using amitriptyline.
Figure 2 Treatment response.

Click here to view



  Discussion Top


CVS is a functional disorder affecting both children and adults. The diagnosis is very challenging and depends as all functional disorders on the fulfillment of Rome criteria in the absence of red flags [11].

There is a paucity of published data on the prevalence, clinical characteristics, and disease burden of CVS in Egypt. This study aimed to study these parameters to highlight this underestimated and underdiagnosed disorder. This study included all the CVS cases diagnosed in a 3.5-year period at the Gastroenterology Clinic at Alexandria University Children’s Hospital. Our institution is a busy university-based tertiary center serving four large governorates in northwest of Egypt.

Data about the prevalence of CVS are limited. Few community-based studies reported that the prevalence of CVS was 1.9–3.1% through screening for children with episodic vomiting in school children [2],[3],[14]. These reports show that CVS as a relatively common disease in the pediatric age group. In Egypt, there are no available data about the prevalence in the pediatric or adult populations. Patients with confirmed CVS constituted 2–5% of the cases referred yearly to our clinic during the study period. Based on these data and the improper diagnosis in local hospitals, we think that CVS in our country is a prevalent yet underdiagnosed health problem.

The study included 79 patients. Of them, two-thirds were females (62%), and 70% were more than 5 years in age. This demographic pattern is consistent with many other studies in different populations [2],[4],[14],[15].

Although the onset of CVS usually occurs in the preschool-age and early school-age period [2],[4],[14], some data suggest that the onset in infancy and preadolescent children is also possible. Adult-onset cases have also been reported [16],[17],[18]. Therefore, the clinician cannot exclude the diagnosis of CVS on the basis of the age. Similarly, in our series, the mean age at onset of symptoms in our series was 6.3 years and ranged from 8 months to 13.5 years. One-third of our cases were toddlers and preschool children and two (2.5%) patients were younger than 2 years.

Our patients experienced recurrent CVS episodes with recognizable prodromes and stereotypical attacks. The clinical characteristics of CVS episodes experienced by our cohort were similar to many other reports involving different populations [2],[14],[15],[17]. However, 52% of the vomiting episodes in our series started at night, which is opposite to other reports which described that the vomiting attacks usually started at early morning [4],[15],[17]. Almost two-thirds of our patients had a recognizable prodrome before the vomiting phase, which was more than that reported in of patients in other studies (25–38%) [3],[14]. This difference may be attributed to the occurrence of half of the episodes at night, which may have given the parents better chance to recognize longer durations of the prodromes in the afternoon and evening before the vomiting phase start at night.

Associated symptoms during the vomiting phase of CVS such as abdominal pain, headache, low-grade fever, and diarrhea had been reported by our patients in a similar pattern like other previous reports [2],[14],[15],[17]. In the presence of these symptoms, unexperienced general practitioners and pediatricians in the ED usually attribute the vomiting attacks to other more common disorders with similar symptoms like gastroenteritis, food poising, or intercurrent febrile illnesses, which may cause delayed diagnoses of CVS.

Bilious vomiting, coffee ground, or fresh hematemesis are common findings in children with CVS during the peak of vomiting episodes. These symptoms were reported in our series in 65.8, 33, and 17.8% of the cases, respectively. Bilious vomiting is usually very alarming to the attending physician, as it is commonly associated with intestinal obstruction and possible catastrophic disorders like malrotation with volvulus. Hematemesis refers to acid peptic disorders such as erosive GERD, severe gastritis, or peptic ulcer disease. Again, when a patient with CVS presents with these associated symptoms during the vomiting episodes, physicians in the ED will unlikely suspect an episode of CVS unless they had a high index of suspicion.

Migraine and CVS are two strongly related disorders. CVS is thought to be as a migraine variant by many researchers because of the similar findings in electroencephalographic and adrenergic autonomic abnormalities [6],[19]. The pathogenesis of CVS is still not very clear, but a lot of evidence suggests a role for mitochondrial DNA variants, which is maternally inherited and adversely affects energy metabolism and may precipitate episodes of CVS [20]. Similarly, in our series, 9% of the patients experienced episodes of migraine headache and two-thirds of the patients had strong family history of migraine (70.9%) and 8% of CVS, both are more from the maternal side of the family.

Some events or conditions (e.g. exciting mood, school phobia, foods, and poor sleeping) play a role in triggering episodes of CVS in 20–45% of patients [16],[17],[21]. Identification of these triggers and their avoidance may help these patients to decrease the frequency of the attacks. One-quarter of our patients have one or more identified events that trigger the episodes including psychological stress, infections and/or lack of sleep. Motion sickness is one of the triggers that may precipitate the vomiting episodes in some of the patients with CVS and also as a common association [21],[22],[23]. Interestingly, 31% of the patients and 55% of the patients’ families had motion sickness in early childhood as an associated disorder rather than a precipitating factor for the CVS episodes. Fleisher and Matar [16] and Haghighat et al. [17] reported the same association between CVS and motion sickness in their series. The relation between CVS and motion sickness may be explained by possible autonomic nervous system dysfunction which is one of the possible etiologies of CVS [6].

CVS is not a diagnosis of exclusion. It is recommended that the clinical diagnosis should be based on recommended clinical criteria through detailed history and physical examination to detect any possible red flags [7]. In this study, the diagnosis of CVS was based on Rome IV criteria [11]. Patients were diagnosed as having CVS if they had two or more episodes of intense paroxysmal vomiting within a 6-month period with symptom-free intervals. This diagnostic criterion is different from the recommendations of the Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome by NASPGHAN (2008), which requires the occurrence of at least five episodes of vomiting in a year before the diagnosis of CVS can be made [1]. The ‘minimum of two attacks’ criterion is more sensitive but may be less specific [24]. Studies using the Rome IV criterion showed similar prevalence rates to those adopting the NASPGHAN criterion, yet with the advantage of more rapid diagnosis [25],[26]. Based on these data and to minimize the significant morbidity related to delayed diagnosis, we preferred to use the Rome IV criteria in this work.

When the clinical characteristics match the diagnostic Rome IV criteria together with the absence of red flags, most of the cases can be correctly diagnosed without the need for invasive investigations such as gastroscopy or barium studies. Some authorities, however, recommended routine barium studies in every case [1],[27]. In this study, barium studies (upper gastrointestinal series and small bowel follow through) were performed only in atypical cases or those patients unresponsive to medical treatment. They were normal in 100% of our cases. Haghighat et al. [17] adopted the same approach, and 97% of their barium studies were normal.

CVS is not studied well in our community and delayed diagnosis is unfortunately very common owing to lack of laboratory or imaging investigations in addition to insufficient medical awareness among general practitioners and pediatricians. None of our patients were diagnosed as having CVS in local hospitals, although the majority of them had classic CVS episodes. The duration of illness before correct diagnosis extended over several months and sometimes years. The interval between onset of symptoms to proper diagnosis was 12±8 months. All the patients had frequent ED visits, and 54.5% had hospital admissions before they were referred to our center. Most of them received treatment for other conditions such as acute gastroenteritis, food poisoning, peptic disorders, or surgical conditions. The failure to suspect CVS as a cause of the recurrent acute vomiting episodes or at least recognition of the episodic vomiting pattern results in improper diagnosis and delayed referral. It also leads to delay in the initiation of preventive or abortive therapy and may subject the patient to unnecessary interventions, both diagnostic (e.g. endoscopy) and therapeutic (e.g. cholecystectomy). Recurrent debilitating episodes of vomiting owing to delayed diagnosis leads to frequent school absenteeism, interrupted activities, and psychological and financial burden on the family. Similar delays were reported in pediatric and adult studies in both developed and developing countries [13],[15],[17]. This highlights that general practitioners and pediatricians have little experience regarding the diagnosis, clinical presentation, and management of CVS all over the world.

Few randomized controlled trials evaluating the prophylactic therapy of CVS are published. The recommendations on prophylactic therapy depend on retrospective studies which showed favorable clinical responses with cyproheptadine, amitriptyline, and propranolol. Amitriptyline is a tricyclic antidepressant with moderate response rate which is usually used as a first-line therapy in older children. It is associated with multiple adverse effects, like constipation, sedation, ventricular arrhythmia, and behavioral changes (especially in young children). It is recommended to monitor the QTc interval before and after reaching the targeted dose. Propranolol is recommended in many reviews as the second-line therapy in all age groups. In the current study, we used propranolol as the drug of choice in older children. The response rate to cyproheptadine and propranolol was 87.5 and 90.1%, respectively, which is comparable to other published studies. Interestingly, Haghighat et al. [17] in a large series reported that the response rate to propranolol was 92% without significant adverse effects, whereas the response to amitriptyline was only 56% but with considerable adverse effects. In a randomized clinical trial, Badihian et al. [28] compared the efficacy of amitriptyline and cyproheptadine in children aged 3–15 years and concluded that no superiority of one of the medications over the other. These present data indicate that propranolol and cyproheptadine are as effective as amitriptyline yet with less adverse effects.

Abortive therapy should be considered for those who have sporadic short episodes or those who have breakthrough episodes while on prophylaxis. The most specific abortive therapy is the nasal or subcutaneous antimigraine triptans. The triptans are usually either fully effective or not at all, and more effective if administered early in episode. Nasal zolmitriptan was available only for five patients and was successful in 80% of them. If the nasal or subcutaneous triptans were more readily available in Egypt, its use will help many children with CVS to avoid the episodes without the use of chronic medications, which may be associated with adverse effects or drug–drug interactions.

In this work, all patients recruited during the study period were evaluated, their data analyzed, and were treated and followed for at least 6 months.


  Conclusion Top


In conclusion, this report is believed to be the first published study on childhood CVS in Egypt. The prevalence, age of onset, and clinical characteristics of our patients were similar to those in other regions of the world. Barium studies and other invasive investigations are not necessary in most of the patients. CVS in our country is a prevalent yet underdiagnosed health problem. There was a significant delay in the diagnosis of CVS, although most of the patients had typical clinical presentation. Propranolol is effective and has few adverse effects and may be considered a first-line prophylactic therapy for CVS.

This work was a retrospective study from a single tertiary care center, which is one of its limitations. The natural history of CVS and its possible evolution to abdominal migraine and migraine in some patients and the long-term efficacy and safety of the prophylactic medications could not be assessed owing to the short period of follow-up. Prospective studies involving multiple centers are needed to study these parameters and to evaluate the relation between migraine and CVS in our patients and their families. Randomized control studies to compare the effect of propranolol and amitriptyline are also recommended.

Education and training of the health care professionals including primary care physicians and pediatricians about the method of diagnosis of CVS and appropriate rescue therapy during the vomiting episodes is very important to avoid the diagnostic delay, avoid unnecessary diagnostic or therapeutic interventions in local health care facilities, and improve the referral policy to tertiary care centers. The improved awareness will decrease the CVS-related morbidities, improve the quality of life of patients, and reduce the financial effect on their families.

Acknowledgements

The research was supported by Alexandria Faculty of Medicine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Li BUK, Lefevre F, Chelimsky GG, Boles RG, Nelson SP, Lewis DW 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 2008; 47:379–393.  Back to cited text no. 1
    
2.
Abu-Arafeh I, Russell G. Cyclical vomiting syndrome in children: a population-based study. J Pediatr Gastroenterol Nutr 1995; 21:454–458.  Back to cited text no. 2
    
3.
Fitzpatrick E, Bourke B, Drumm B, Rowland M. The incidence of cyclic vomiting syndrome in children: population-based study. Am J Gastroenterol 2008; 103:991–995.  Back to cited text no. 3
    
4.
Ye Z, Xue A, Huang Y, Wu Q. Children with cyclic vomiting syndrome: phenotypes, disease burden and mitochondrial DNA analysis. BMC Gastroenterol 2018; 18:104.  Back to cited text no. 4
    
5.
Wang Q, Ito M, Adams K, Li BUK, Klopstock T, Maslim A et al. Mitochondrial DNA control region sequence variation in Migraine headache and cyclic vomiting syndrome. Am J Med Genet 2004; 131A:50–58.  Back to cited text no. 5
    
6.
Chelimsky TC, Chelimsky GG. Autonomic abnormalities in cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2007; 44:326–330.  Back to cited text no. 6
    
7.
Li BUK. Managing cyclic vomiting syndrome in children: beyond the guidelines. Eur J Pediatr 2018; 177:1435–1442.  Back to cited text no. 7
    
8.
Barlow C. The periodic syndrome. In: Barlow CF, editor. Headaches and migraine in childhood. London: Clin Dev Med; 1984. p. 76–92.  Back to cited text no. 8
    
9.
Evans RW, Whyte C. Cyclic vomiting syndrome and abdominal migraine in adults and children. Headache 2013; 53:984–993.  Back to cited text no. 9
    
10.
Donnet A, Redon S. Cyclic vomiting syndrome in children. Curr Pain Headache Rep 2018; 22:3.  Back to cited text no. 10
    
11.
Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, Van Tilburg M. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2016; 150:1456–1468.e2.  Back to cited text no. 11
    
12.
Hasler WL, Levinthal DJ, Tarbell SE, Adams KA, Li BUK, Issenman RM et al. Cyclic vomiting syndrome: pathophysiology, comorbidities, and future research directions. Neurogastroenterol Motil 2019; 31:e13607.  Back to cited text no. 12
    
13.
Lucia-Casadonte CJ, Whaley KG, Chogle AS. Yield and costs of evaluating children with cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2018; 67:13–17.  Back to cited text no. 13
    
14.
Ertekin V, Selimoğlu MA, Altnkaynak S. Prevalence of cyclic vomiting syndrome in a sample of Turkish school children in an urban area. J Clin Gastroenterol 2006; 40:896–898.  Back to cited text no. 14
    
15.
Liao KY, Chang FY, Wu LT, Wu TC. Cyclic vomiting syndrome in Taiwanese children. J Formos Med Assoc 2011; 110:14–18.  Back to cited text no. 15
    
16.
Fleisher DR, Matar M. The cyclic vomiting syndrome: a report of 71 cases and literature review. J Pediatr Gastroenterol Nutr 1993; 17:361–369.  Back to cited text no. 16
    
17.
Haghighat M, Rafie SM, Dehghani SM, Fallahi GH, Nejabat M. Cyclic vomiting syndrome in children: experience with 181 cases from southern Iran. World J Gastroenterol 2007; 13:1833–1836.  Back to cited text no. 17
    
18.
Venkatesan T, Tarbell S, Adams K, McKanry J, Barribeau T, Beckmann K et al. A survey of emergency department use in patients with cyclic vomiting syndrome. BMC Emerg Med 2010; 10:4.  Back to cited text no. 18
    
19.
Jernigan SA, Ware LM. Reversible quantitative EEG changes in a case of cyclic vomiting: evidence for migraine equivalent. Dev Med Child Neurol 1991; 33:80–85.  Back to cited text no. 19
    
20.
Yorns WR, Hardison HH. Mitochondrial dysfunction in migraine. Semin Pediatr Neurol 2013; 20:188–193.  Back to cited text no. 20
    
21.
Hikita T, Kodama H, Ogita K, Kaneko S, Nakamoto N, Mimaki M. Cyclic vomiting syndrome in infants and children: a clinical follow-up study. Pediatr Neurol 2016; 57:29–33.  Back to cited text no. 21
    
22.
Li BU, Murray RD, Heitlinger LA, Robbins JL, Hayes JR. Is cyclic vomiting syndrome related to migraine?. J Pediatr 1999; 134:567–572.  Back to cited text no. 22
    
23.
Moses J, Keilman A, Worley S, Radhakrishnan K, Rothner AD, Parikh S. Approach to the diagnosis and treatment of cyclic vomiting syndrome: a large single-center experience with 106 patients. Pediatr Neurol 2014; 50:569–573.  Back to cited text no. 23
    
24.
Zeevenhooven J, Koppen IJN, Benninga MA. The new Rome IV criteria for functional gastrointestinal disorders in infants and toddlers. Pediatr Gastroenterol Hepatol Nutr 2017; 20:1–13.  Back to cited text no. 24
    
25.
Aziz I, Palsson OS, Törnblom H, Sperber AD, Whitehead WE, Simrén M. The prevalence and impact of overlapping Rome IV-diagnosed functional gastrointestinal disorders on somatization, quality of life, and healthcare utilization: a cross-sectional general population study in three countries. Am J Gastroenterol 2018; 113:86–96.  Back to cited text no. 25
    
26.
Lewis ML, Palsson OS, Whitehead WE, van Tilburg MAL. Prevalence of functional gastrointestinal disorders in children and adolescents. J Pediatr 2016; 177:39–43.e3.  Back to cited text no. 26
    
27.
Olson AD, Li BUK. The diagnostic evaluation of children with cyclic vomiting: a cost-effectiveness assessment. J Pediatr 2002; 141:724–728.  Back to cited text no. 27
    
28.
Badihian N, Saneian H, Badihian S, Yaghini O. Prophylactic therapy of cyclic vomiting syndrome in children: Comparison of amitriptyline and cyproheptadine: a randomized clinical trial. Am J Gastroenterol 2018; 113:135–140.  Back to cited text no. 28
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Aim
Patients and methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed136    
    Printed8    
    Emailed0    
    PDF Downloaded41    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]