This work was supported in part by grants DK77678-2 and DK082792-01 (SN) and DK073713 (RR).
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35. Shay S, Richter J. Direct comparison of impedance, man- ometry, and pH probe in detecting refl ux before and after a meal. Dig Dis Sci. 2005;50:1584–1590.
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S E C T I O N 3
Disorders of the Stomach and Intestine
12. Gastroesophageal Refl ux Disease
13. Gastritis and Peptic Ulcer Disease
14. Abdominal Wall Defects
15. Atresias, Webs, and Duplications
16. Infl ammatory Bowel Disease
17. Food Allergy and Intolerance
18. Celiac Disease
19. Disorders of Gastrointestinal Motility
20. Short Bowel Syndrome
21. Surgical Emergencies
22. Polyps and Tumors of the Intestines
CHAPTER 12
Gastroesophageal Refl ux Disease
Benjamin D. Gold
DEFINITIONS AND EPIDEMIOLOGY
Gastroesophageal reflux (GER) refers to the passage of gastric contents into the esophagus or oropharynx, with or without vomiting.1,2 GER can be a daily, normal phys- iological occurrence in infants, children, and adolescents.
Most episodes of GER in healthy individuals last 3 minutes, occur in the postprandial period, and cause few or no troublesome symptoms. Regurgitation or “spit- ting up” is the most obviously visible symptom. It is characterized by effortless emesis and is seen particularly in a very young child, occurring daily in about 50% of infants3 months of age. Regurgitation resolves sponta- neously in most healthy infants by 12–14 months of
age.3,4 Refl ux episodes sometimes trigger vomiting: the forceful expulsion of gastric contents from the mouth.
Vomiting associated with GER is thought to be the result of stimulation of pharyngeal sensory afferents by refl uxed gastric contents. Rumination refers to the effortless regur- gitation of recently ingested food into the mouth with subsequent mastication and re-swallowing. Rumination syndrome is a distinct clinical entity with regurgitation of ingested food within minutes following meals due to the voluntary contraction of the abdominal muscles.
Gastroesophageal reflux disease (GERD) refers to the symptoms and complications that may develop sec- ondary to persistent GER.1,2 Differentiating GER from GERD is critical for the clinician in order to avoid unnecessary diagnostic testing and exposure to medica- tions. Recently, there have been three critically impor- tant publications1,2,5 that offer the clinician a complete characterization of the evidence-based defi nitions of GER and GERD, particularly GERD-related complica- tions as well as the diagnostic and therapeutic approach to the child with GERD. Complications of GERD in children include esophagitis, growth disturbance, and feeding aversion as well as extraesophageal disease such as respiratory disorders. The fi rst of the two “defi nition”
publications was the Montreal defi nition of GERD in adults published by Vakil et al. in 2006,5 and the second, using similar methodology for the establishment of the defi nitions, was the Global evidence-based consensus on the defi nition of GERD in children (Figures 12–1 and 12–2)1 Shortly thereafter, a joint committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the Euro- pean Society for Gastroenterology, Hepatology and Nutrition (ESPGHAN) published recommendations for the management of children with refl ux.2
KEY CONCEPTS
• Gastroesophageal refl ux (GER) frequently resolves most commonly by 1 year of age. However, gastroesophageal refl ux disease (GERD) can become a chronic condition in some children.
• Regurgitation is the predominant symptom in infantile GERD. In older children, abdominal pain predominates.
Both groups can present with extraesophageal symptoms (e.g., respiratory manifestations).
• GERD is optimally diagnosed by clinical suspicion and a response to therapy (i.e., most frequently acid suppression), but diagnostic testing such as upper endoscopy may be indicated to assess for GERD-related complications and/or its mimics (e.g., eosinophilic esophagitis).
• Conservative and lifestyle measures may be adequate to treat uncomplicated, mild GERD in infants, and should be employed in older children and adolescents with GERD, even in the face of pharmacological and/or surgical therapy.
FIGURE 12–1 ■ Global Consensus defi nition of pediatric GERD. The diagram depicts the overall defi nition of GERD in children as determined by the Global Consensus Committee. In addition, the diagram provides the designated groups of esophageal and extraesophageal diseases that the Global Consensus Committee determined to be most likely associated with GERD. In specifi c, the Global Consensus defi nitions subdivide the esophageal GERD manifestations into symptoms purported to be due to GERD, symptomatic GERD syndromes, and syndromes associated with esophageal injury, as well as those extraesophageal manifestations that are defi nitively associated with GERD and those with possible association. Adapted by permission from Ref.1 (Macmillan Publishers Ltd).
• Sandifer’s syndrome
• Dental erosion
Syndromes with esophageal injury
Definite associations
Possible associations
• Reflux esophagitis
• Reflux stricture
• Barrett’s esophagus
• Adenocarcinoma
∗Where other causes have been ruled out (e.g. food allergy, especially in infants)
Symptoms purported to be due to GERD∗ Infant or younger child (0–8 years), or older without
cognitive ability to reliably report symptoms
Symptomatic syndromes Older child or adolescent
with cognitive ability to reliably report symptoms
Esophageal
• Excessive regurgitation
• Feeding refusal/anorexia
• Unexplained crying
• Choking/gagging/
coughing
• Sleep disturbance
• Abdominal pain
• Asthma
• Pulmonary fibrosis
• Bronchopulmonary dysplasia
• Pathological apnea
• Bradycardia
• Apparent life- threatening events
GERD in pediatric patients is present when reflux of gastric contents is the cause of troublesome symptoms and/or complications1
• Typical reflux syndrome
Extraesophageal
Rhinological and otological
• Sinusitis
• Serous otitis media
Infants Bronchopulmonary
Laryngotracheal and pharyngeal
• Chronic cough
• Chronic laryngitis
• Hoarseness
• Pharyngitis
FIGURE 12–2 ■ Montreal defi nition and classifi cation of GERD (adults). The diagram depicts the overall Montreal defi nition and classi- fi cation of GERD in adults as determined by the Global Consensus Committee of experts in adult refl ux-related disease. In addition, the diagram provides the designated groups of esophageal and extraesophageal diseases that the Montreal Classifi cation committee deter- mined to be most likely associated with GERD. In specifi c, the Montreal classifi cation subdivides GERD into symptomatic syndromes and syndromes associated with esophageal injury. Moreover, the Montreal classifi cation subdivides the extraesophageal manifestations into those with established associations and proposed associations.
• Reflux cough syndrome
• Reflux laryngitis syndrome
• Reflux asthma syndrome
• Reflux dental syndrome
• Reflux esophagitis
• Reflux stricture
• Barrett’s esophagus
• Adenocarcinoma
Established associations
Proposed associations
• Pharyngitis
• Sinusitis
• Idiopathic pulmonary fibrosis
• Recurrent otitis media
Syndromes with esophageal injury
• Reflux chest
• Pain syndrome
Symptomatic syndromes
Esophageal
GERD is a condition which develops when the reflux of gastric contents causes troublesome symptoms and/or complications
Extraesophageal
• Typical reflux syndrome
allowing refl ux to occur more readily, and (3) the increased amount of time infants spend in the supine rather than upright position. Mechanisms for GERD in age groups have been carefully studied and characterized, and are similar across age groups, whether comparing infants, older children or adolescents, and adults (even those that are premature) with GERD to those subjects of similar age that have no GERD. Aerodigestive refl exes (oral, pharyn- geal, and esophageal coordinated functions) are fully developed in most children before delivery, by an esti- mated 38 weeks of gestational age. If there is dysfunction of motility, troublesome GER-related symptoms can ensue. These mechanisms include:
■ transient relaxation of the lower esophageal sphincter (LES);
■ inhibition of esophageal body peristalsis;
■ persistent decrease or absence of LES resting tone.14–18 Refl ux episodes occur most often during transient LES relaxations unaccompanied by swallowing, which permit gastric contents to fl ow upward into the esopha- gus. A minor proportion of refl ux episodes occur when the LES fails to increase pressure during a sudden increase in intra-abdominal pressure, or when LES rest- ing pressure is chronically reduced.
Alterations in protective mechanisms allow physi- ological GER to become GERD. These include:
■ insuffi cient clearance and buffering of refl uxate;
■ delayed gastric emptying;
■ abnormalities in esophageal epithelial repair;
■ decreased protective refl exes;
■ hiatal hernia.
In hiatal hernia, the anti-refl ux barriers at the LES (including the crural support, intra-abdominal segment, and angle of His) are compromised and transient LES relaxations also occur with greater frequency. Erosive esophagitis by itself may promote esophageal shortening and cause hiatal herniation. Hiatal hernia is prevalent in adults and children with severe refl ux complications, and hernia size is a major determinant of GERD severity.