Gastroesophageal Reflux Disease

Pathophysiology

Factors determining the esophageal manifestations of reflux include the duration of esophageal exposure (a product of the frequency and duration of reflux episodes), the causticity of the refluxate, and the susceptibility of the esophagus to damage. The LES, defined as a high-pressure zone by manometry, is supported by the crura of the diaphragm at the gastroesophageal junction, together with valve-like functions of the esophagogastric junction anatomy, form the antireflux barrier. In the context of even the normal intraabdominal pressure augmentations that occur during daily life, the frequency of reflux episodes is increased by insufficient LES tone, by abnormal frequency of LES relaxations, and by hiatal herniation that prevents the LES pressure from being proportionately augmented by the crura during abdominal straining. Normal intraabdominal pressure augmentations may be further exacerbated by straining or respiratory efforts. The duration of reflux episodes is increased by lack of swallowing (e.g., during sleep) and by defective esophageal peristalsis. Vicious cycles ensue because chronic esophagitis produces esophageal peristaltic dysfunction (low-amplitude waves, propagation disturbances), decreased LES tone, and inflammatory esophageal shortening that induces hiatal herniation, all worsening reflux.

Transient LES relaxation (TLESR) is the primary mechanism allowing reflux to occur, and is defined as simultaneous relaxation of both LES and the surrounding crura. TLESRs occur independent of swallowing, reduce LES pressure to 0-2 mm Hg (above gastric), and last 10-60 sec; they appear by 26 wk of gestation. A vagovagal reflex, composed of afferent mechanoreceptors in the proximal stomach, a brainstem pattern generator, and efferents in the LES, regulates TLESRs. Gastric distention (postprandially, or from abnormal gastric emptying or air swallowing) is the main stimulus for TLESRs. Whether GERD is caused by a higher frequency of TLESRs or by a greater incidence of reflux during TLESRs is debated; each is likely in different persons. Straining during a TLESR makes reflux more likely, as do positions that place the gastroesophageal junction below the air–fluid interface in the stomach. Other factors influencing gastric pressure–volume dynamics, such as increased movement, straining, obesity, large-volume or hyperosmolar meals, gastroparesis, a large sliding hiatal hernia, and increased respiratory effort (coughing, wheezing) can have the same effect.

Epidemiology and Natural History

Infant reflux becomes evident in the first few mo of life, peaks at 4 mo, and resolves in up to 88% by 12 mo and in nearly all by 24 mo. Happy spitters are infants who have recurrent regurgitation without exhibiting discomfort or refusal to eat and failure to gain weight. Symptoms of GERD in older children tend to be chronic, waxing and waning, but completely resolving in no more than half, which resembles adult patterns ( Table 349.1 ). The histologic findings of esophagitis persist in infants who have naturally resolving symptoms of reflux. GERD likely has genetic predispositions: family clustering of GERD symptoms, endoscopic esophagitis, hiatal hernia, Barrett esophagus, and adenocarcinoma have been identified. As a continuously variable and common disorder, complex inheritance involving multiple genes and environmental factors is likely. Genetic linkage is indicated by the strong evidence of GERD in studies with monozygotic twins. A pediatric autosomal dominant form with otolaryngologic and respiratory manifestations has been located to chromosome 13q14, and the locus is termed GERD1.

Clinical Manifestations

Most of the common clinical manifestations of esophageal disease can signify the presence of GERD and are generally thought to be mediated by the pathogenesis involving acid GER ( Table 349.2 ). Although less noxious for the esophageal mucosa, nonacid reflux events are recognized to play an important role in extraesophageal disease manifestations. Infantile reflux manifests more often with regurgitation (especially postprandially), signs of esophagitis (irritability, arching, choking, gagging, feeding aversion), and resulting failure to thrive; symptoms resolve spontaneously in the majority of infants by 12-24 mo. Older children can have regurgitation during the preschool years; this complaint diminishes somewhat as children age, and complaints of abdominal and chest pain supervene in later childhood and adolescence. Occasional children present with food refusal or neck contortions (arching, turning of head) designated Sandifer syndrome. The respiratory presentations are also age dependent: GERD in infants may manifest as obstructive apnea or as stridor or lower airway disease in which reflux complicates primary airway disease such as laryngomalacia or bronchopulmonary dysplasia. Otitis media, sinusitis, lymphoid hyperplasia, hoarseness, vocal cord nodules, and laryngeal edema have all been associated with GERD. Airway manifestations in older children are more commonly related to asthma or to otolaryngologic disease such as laryngitis or sinusitis. Despite the high prevalence of GERD symptoms in asthmatic children, data showing direction of causality are conflicting.

Neurologically challenged children are one group that is recognized to be at an increased risk for GERD. It is not well established if the greater risk is conferred due to inadequate defensive mechanisms and/or inability to express symptoms. A low clinical threshold is important in the early identification and prompt treatment of GERD symptoms in these individuals.

Diagnosis

For most of the typical GERD presentations, particularly in older children, a thorough history and physical examination suffice initially to reach the diagnosis. This initial evaluation aims to identify the pertinent positives in support of GERD and its complications and the negatives that make other diagnoses unlikely. The history may be facilitated and standardized by questionnaires (e.g., the Infant Gastroesophageal Reflux Questionnaire, the I-GERQ, and its derivative, the I-GERQ-R), which also permit quantitative scores to be evaluated for their diagnostic discrimination and for evaluative assessment of improvement or worsening of symptoms. The clinician should be alerted to the possibility of other important diagnoses in the presence of any alarm or warning signs : bilious emesis, frequent projectile emesis, gastrointestinal bleeding, lethargy, organomegaly, abdominal distention, micro- or macrocephaly, hepatosplenomegaly, failure to thrive, diarrhea, fever, bulging fontanelle, and seizures. The important differential diagnoses to consider in the evaluation of an infant or a child with chronic vomiting are milk and other food allergies, eosinophilic esophagitis, pyloric stenosis, intestinal obstruction (especially malrotation with intermittent volvulus), nonesophageal inflammatory diseases, infections, inborn errors of metabolism, hydronephrosis, increased intracranial pressure, rumination, and bulimia. Focused diagnostic testing, depending on the presentation and the differential diagnosis, can then supplement the initial examination.

Most of the esophageal tests are of some use in particular patients with suspected GERD. Contrast ( usually barium) radiographic study of the esophagus and upper gastrointestinal tract is performed in children with vomiting and dysphagia to evaluate for achalasia, esophageal strictures and stenosis, hiatal hernia, and gastric outlet or intestinal obstruction ( Fig. 349.1 ). It has poor sensitivity and specificity in the diagnosis of GERD as a result of its limited duration and the inability to differentiate physiologic GER from GERD. Furthermore, contrast radiography neither accurately assesses mucosal inflammation nor correlates with severity of GERD.

Extended esophageal pH monitoring of the distal esophagus, no longer considered the sine qua non of a GERD diagnosis, provides a quantitative and sensitive documentation of acidic reflux episodes, the most important type of reflux episodes for pathologic reflux. The distal esophageal pH probe is placed at a level corresponding to 87% of the nares-LES distance, based on regression equations using the patient's height, on fluoroscopic visualization, or on manometric identification of the LES. Normal values of distal esophageal acid exposure (pH <4) are generally established as <5 to 8% of the total monitored time, but these quantitative normals are insufficient to establish or disprove a diagnosis of pathologic GERD. The most important indications for esophageal pH monitoring are for assessing efficacy of acid suppression during treatment, evaluating apneic episodes in conjunction with a pneumogram and perhaps impedance, and evaluating atypical GERD presentations such as chronic cough, stridor, and asthma. Dual pH probes, adding a proximal esophageal probe to the standard distal one, are used in the diagnosis of extraesophageal GERD, identifying upper esophageal acid exposure times of 1% of the total time as threshold values for abnormality.

Endoscopy allows diagnosis of erosive esophagitis ( Fig. 349.2 ) and complications such as strictures or Barrett esophagus; esophageal biopsies can diagnose histologic reflux esophagitis in the absence of erosions while simultaneously eliminating allergic and infectious causes. Endoscopy is also used therapeutically to dilate reflux-induced strictures. Radionucleotide scintigraphy using technetium can demonstrate aspiration and delayed gastric emptying when these are suspected.

The multichannel intraluminal impedance is a cumbersome test, but with potential applications both for diagnosing GERD and for understanding esophageal function in terms of bolus flow, volume clearance, and (in conjunction with manometry) motor patterns associated with GERD. Owing to the multiple sensors and a distal pH sensor, it is possible to document acidic reflux (pH <4), weakly acidic reflux (pH 4-7), and weakly alkaline reflux (pH >7) with multichannel intraluminal impedance. It is an important tool in those with respiratory symptoms, particularly for the determination of nonacid reflux, but must be cautiously applied in routine clinical evaluation because of limited evidence-based parameters for GERD diagnosis and symptom association.

Esophageal manometry is not useful in demonstrating gastroesophageal reflux but might be of use to evaluate transient LES relaxations and pressures.

Laryngotracheobronchoscopy evaluates for visible airway signs that are associated with extraesophageal GERD, such as posterior laryngeal inflammation and vocal cord nodules; it can permit diagnosis of silent aspiration (during swallowing or during reflux) by bronchoalveolar lavage with subsequent quantification of lipid-laden macrophages in airway secretions. Detection of pepsin in tracheal fluid is a marker of reflux-associated aspiration of gastric contents. Esophageal manometry permits evaluation for dysmotility, particularly in preparation for antireflux surgery.

Empirical antireflux therapy, using a time-limited trial of high-dose proton pump inhibitor (PPI), is a cost-effective strategy for diagnosis in adults; although not formally evaluated in older children, it has also been applied to this age group. Failure to respond to such empirical treatment, or a requirement for the treatment for prolonged periods, mandates formal diagnostic evaluation.