Cyclical Vomiting Syndrome Vomiting in Children with emphasis on Cyclical Vomiting Syndrome

The patient 10 year old girl Admitted with acute onset vomiting for 1 day. Started as food, then became yellow/green Abdominal pain Weakness, lethargy Precipitated by “ asthma attack” – used asthma inhaler Previous similar episodes No diarrhoea or constipation

Past medical history Recurrent episodes of vomiting – since infancy Diagnosed with gastro-oesophageal reflux disease as infant Episodes of vomiting more frequent, severe in past 2 years (occur every 1-3 months) Almost always preceded/ precipitated by “asthma attack”. Sometimes even by laughing a lot Frequently resulting in hospital admission – not for bronchospasm but for dehydration and intractable vomiting

Been extensively investigated (Cape Town) – barium meal, Xrays, gastroscopy, ?others => all negative Apparently given medication in hospital each time admitted, but not on chronic medication other than steroid inhaler and bronchodilator Parents have not been given a diagnosis as yet – very distressed Past surgical history Nil

Birth history Social Family History Term, nil of significance Recently moved from Cape Town (in past month) Grade 4 at school, doing well, apparently happy 8 year old brother, well Stable, caring family environment Family History Father has asthma (mild) No known history of migraine in family

Clinical Findings Well–grown child Miserable, lethargic, and uncomfortable due to abdominal pain, but awake and cooperative Haemodynamically stable but looked 5% dehydrated with sunken eyes BP – 104/65mmHg Low-grade fever – 37.5deg Chest – clear CVS – normal

Abdomen – scaphoid, soft but generally tender Abdomen – scaphoid, soft but generally tender. No masses felt, bowel sounds heard. PR not done CNS – Awake, but withdrawn. No meningism, no focal signs. No papilloedema. FBC, urea and electrolytes normal except potassium borderline low (3.1 mmol/l) Urine Dipstix – nil of note. No glycosuria Ultrasound abdomen – normal CT scan brain - normal

Management Admitted to ward Rehydrated with IV fluids Allowed to take orally as desired Panado, Cyclizine for vomiting

Progress Still vomiting in ward for about 2 days Temperature settled in ward Did not require nebuliser for bronchospasm Very quiet, withdrawn and miserable for 2 days By third day, was walking around looking better and vomiting had settled

Vomiting in Children Vomiting is a symptom, presenting complaint in multitude of disorders Range from gastrointestinal pathology to disease in distant organ (otitis media or intracranial lesion) In children, especially infants, must distinguish from regurgitation – effortless expulsion of gastric contents Integrated response to noxious stimuli, coordinated by central nervous system

Centres responsible for vomiting Vomiting centre Nucleus solitarius and series of nuclei in brainstem medulla Stimulation results in integrated motor responses involved in vomiting associated vasomotor activity (pallor, flushing), salivation, bulbar responses Afferent input arises from posterior pharynx, GIT, brain

Chemoreceptor trigger zone Stimulated by humoral stimuli such as opiates, cytotoxins, ketones, ammonia Lies in area postrema – floor of 4th ventricle, outside blood-brain barrier Processes most of afferent input for the vomiting centre Receptors and neurotransmitters involved Dopamine (D2), histamine (H1), serotonin (5-HT3), vasopressin, substance P

Diagnostic evaluation Before finding cause of vomiting, in any child should first Assess hydration status, attend to life-threatening complications Ascertain whether Bilious – suggests gastrointestinal obstruction Blood is present – diagnosis and management different If non-bilious and non-bloody, 2 important variables => temporal pattern and age of patient

Duration either Acute – short-term episode, abrupt onset Recurrent – at least 3 episodes over 3-month period => chronic - relatively mild episodes that occur frequently => cyclic – recurrent, intense episodes separated by asymptomatic periods

Acute Vomiting Neonate/ Infant Child/ adolescents With fever Sepsis, meningitis, UTI Tonsillitis, otitis media, gastroenteritis If no signs sepsis Pyloric stenosis/ outlet obstruction Metabolic Neurologic Endocrine Child/ adolescents With fever (but otherwise well) Gastroenteritis, esp if also have diarrhoea With lethargy/ altered mental status Neurologic Metabolic Endocrine Drugs, toxins, alcohol

Investigations for acute vomiting Thorough examination “Septic workup” – blood cultures, urine, FBC, CRP, LP Upper GI radiology – Barium swallow/ meal, AXR, ultrasound abdomen, endoscopy Metabolic investigations – blood gas, ammonia, blood and urine organic acids

Management Depends on specific cause While investigating/ treating underlying pathology – replace lost fluids, maintain hydration If mild and child able to drink, can try oral rehydration. Intravenous may also be required Pharmacologic agents not usually recommended May mask signs of serious disease Undesirable side-effects in children

Ongoing underlying pathology, therefore may be more worrying Recurrent vomiting Ongoing underlying pathology, therefore may be more worrying Numerous causes GIT Infections – H. pylori, Giardia, oesophageal candidiasis Hepatitis, pancreatitis, partial intestinal obstruction Metabolic, neurologic, renal

Recurrent Vomiting Infants Older child/ Adolescent GIT – feed intolerance Renal Metabolic – lethargy, poor feeding, failure to thrive, seizures, abnormal tone Neurologic – raised pressure – meningitis, tumour, hydrocephalus Older child/ Adolescent GIT Chronic sinusitis Drug intoxication Migraine Bulimia Pregnancy

Investigations Guided by history Timing - early morning (or nocturnal) – reflux, peptic ulcer (empty stomach), intracranial mass lesion, pregnancy Relation to eating - worse with food- suggests upper GIT abnormalities. Description – projectile suggests outlet obstruction (stomach, duodenum, more distal intestine) faeculent – colonic obstruction, intestinal stasis, bowel ischaemia

Special investigations Examination Jaundice – liver/ gallbladder pathology Neurologic examination important Special investigations Sinus Xrays MRI/CT brain Stool occult blood/ parasites FBC, LFT, U&E, Amylase, ESR Urinalysis and culture Toxicology screen

If no diagnosis still, consider Upper GI contrast study, ultrasound abdomen Gastroscopy PLUS biopsy – high diagnostic yield, ease of performance, safe

Cyclic Vomiting Syndrome (CVS) Paroxysmal, especially severe, recurrent vomiting disorder Mysterious disorder, unknown aetiology, and pathophysiology Substantial increase in interest and understanding of disease in past decade Previously considered rare, may be 2nd only to GORD as cause of recurrent vomiting in children

Under-recognised Prevalence No specific laboratory, radiographic or endoscopic markers for CVS Typically misdiagnosed for years – viral GE, food poisoning, GORD, psychogenic vomiting => leads to inappropriate therapy Surgery Psychiatric hospitalisation Very distressing to patients and families Prevalence Being diagnosed with increasing frequency, but actual prevalence remains unknown 0.04-2% among school-aged children Overdiagnosed sometimes, and often underdiagnosed

Age and Sex distribution Females>males Similar to distribution in migraine sufferers All races, nut more in Caucasians Usually affects children of 4-7 yrs but some as young as 6 mths Bimodal peaks: 4.8 and 35 yrs!

Course Often delays in diagnosis Median age of resolution 10 years Average 2.7 years = ±20 episodes in children Median age of resolution 10 years In those whose vomiting resolves, about 1/3 develop migraine headaches around same time Children ill <10% of time, but causes substantial medical and academic morbidity Recurrent school absences Recurrent admissions for IV fluids Recurrent outpatient visits, hospital stays, missed work for parents

Features Hallmark – cyclic vomiting pattern => severe, recurring, discrete, stereotypical high intensity, low frequency More often require IV rehydration Higher incidence of family members with migraine Migraine symptoms – headaches, photophobia, phonophobia Investigate causes outside GIT Chronic low intensity, high frequency, daily pattern Investigate causes inside GIT

Cyclic Chronic Idiopathic If other cause – extraintestinal Neurologic Renal Metabolic Endocrine Chronic GIT disorders Peptic oesophagitis

Clinical Features Short prodromal phase Episode itself Recovery phase 1.5 hours Nonspecific premonitory signs such as pallor, lethargy, anorexia, nausea Episode itself Defined by median of 15 emeses, duration of 24 hours Recovery phase From last emesis to point of tolerating liquids and food, resume play – remarkably short 6 hours, often marked by sleep. “Turning off a switch”

Other Symptoms Other than vomiting 3 categories Systemic Lethargy &/or pallor, withdrawal, flushing, fever, drooling Extreme pallor could even mimic shock Profound lethargy , inability to walk, talk, or interact can simulate semi-coma, confuse with meningitis, toxin ingestion

GI symptoms Neurologic symptoms Anorexia, nausea, retching, abdominal pain (common), diarrhoea fever and diarrhoea could confuse with viral GE – except for stereotypical recurrences. Also CVS patients look sicker, are often more dehydrated Abdominal pain can mimic acute abdomen Neurologic symptoms Headache, photophobia, phonophobia, vertigo <50% have classic migraine symptoms, but high occurrence of these symptoms supports link to migraines Adolescents may assume foetal position to cope with hypersensitivity to light, sound, touch, upright positioning

Features (cont) Periodicity Over 24 period – most common onset between 2am-4am and 6am-8am ?relationship to Corticotropin Releasing Factor Over 1-3 month period – commonly every 4 weeks, but only half can predict next episode within 1 week on either side. Rest are sporadic Seasonal – many worse in winter

Triggers Numerous events can trigger episode Parents can often identify trigger Most common Psychologic – usually positive excitement rather than negative Infectious – URTI’s, sinusitis, streptococcal pharyngitis Also physical exhaustion, lack of sleep, dietary (chocolate, cheese, MSG), menstruation, motion sickness, asthma, allergies

Differential Diagnosis Recurrent vomiting may be caused by neurologic, metabolic, endocrine, renal, gastrointestinal pathology Cyclic vomiting - 12% have surgically-correctable lesion or metabolic disorder => therefore not Idiopathic CVS NB: exclude malrotation, intermittent volvulus => if unrecognised could result in bowel resection Genitourinary – acute hydronephrosis due to uretero-pelvic junction obstruction mimics CVS. Also nephrolithiasis CNS – subtentorial neoplasms

Non-surgical GIT problems – GORD, food allergy to milk, wheat proteins Chronic sinusitis Metabolic – mitochondrial enzymopathies – infants, toddlers. Acute intermittent porphyria – adolescents – fasting and alcohol Endocrine – Addison’s disease Psychological – Munchausen-by-proxy, anxiety

Approach guided by need to exclude treatable underlying disorders Diagnosis Approach guided by need to exclude treatable underlying disorders Imaging First-line => Small bowel radiography, abdominal ultrasound/CT – exclude structural defects Usually when child well – so can retain oral contrast Second-line => sinus CT, CT or MRI head. Also gastroscopy if peptic disorders suspected

Laboratory Investigations U&E, Glucose, lactate, ammonia, amino acids, urine organic acids Assess complications (dehydration) and assist with diagnosis (metabolic disorders) Screening for metabolic, endocrine disorders best done during episode as may be intermittently symptomatic How much testing should be done? High cost of complete testing vs potential morbidity of missed diagnosis Single most useful test is small bowel series

Move on to 2nd line tests OR repeat 1st line tests for Frequent, severe, prolonged episodes requiring repeated hospitalisations Atypical features – severe headache Refractory to medical management

Relationship to migraine CVS thought to be migraine variant Often family history of migraine High rate of improvement on anti-migraine therapy Can progress to migraine headaches once CVS episodes have ceased

Only empiric therapy at present 5 aspects Treatment Only empiric therapy at present 5 aspects Avoidance of precipitating factors Food and stressful events possible Mostly unavoidable Prophylactic agents Anti-migraine – propranolol, amitryptiline Anti-epileptic – phenobarbital, valproate Prokinetic agents – erythromycin Abortive agents

Supportive care Parenteral Anti-migraine agents – Sumatriptan (5HT1B/1D agonist) Anti-emetic agents – Ondansetron (5HT3 antagonist), even more effective with benzodiazepine (Lorazepam) Supportive care IV fluids – 10% dextrose-containing electrolyte solution – rehydration, terminate ketosis Quiet, dark, non-stimulating environment Sedatives –help to sleep, sleep may initiate recovery phase Phenothiazine anti-emetics INEFFECTIVE in CVS Opiates for pain may help but can worsen nausea

Family support Crucial – unpredictable, disruptive, unexplained illness, often misdiagnosed, few definitive answers