The diagnosis of uncomplicated esophageal reflux is usually established on the basis of a good history, and a thorough examination, with attention to the child's growth, nutritional, respiratory, neurological, and atop-ic status. A validated questionnaire has been developed for symptom assessment in infants and translated into multiple languages; others designed specifically for older children are now in use in epidemiological studies but must be further tested for reliability and validity , . Complicated, unresponsive, and atypical presentations of GERD are indications for specialized investigations such as those discussed in the following section.
An upper endoscopy, particularly when supplemented by histology, is the most accurate method of demonstrating esophageal damage by reflux, and for differentiating GERD from other diagnostic possibilities (Fig. 2a—c). It is performed as an outpatient procedure, and is less cumbersome than a 24-hour pH metry. Histologic abnormalities may be present in biopsies sampled from grossly normal esophageal mucosa. A review of endoscopic evaluation of reflux in 402 neurologically normal children, between 18 months and 25 years of age and without congenital esophageal disease, revealed erosive esophagitis in more than one-third, strictures in 1 to 2%, and suspected Barrett's esophagus (but without histologic confirmation) in nearly 3%.
A diagnostic upper endoscopy in children is almost always supplemented by distal esophageal biopsies. Biopsies at two levels are important to demonstrate differential eosinophilia in eosinophilic esophagitis. Histologic findings of reflux esophagitis are epithelial hyperplasia (the upper limit of normal basal layer thickness and papillary height in infants is 25% and 53%, respectively ), intraepithelial inflammation, vascular dilatation in papillae, balloon cells, and ulceration (Fig. 3a-c) . Due to the often superficial, fragmented, and randomly oriented nature of biopsies in children, cellular inflammatory infiltrate may be the only recognizable finding . Neutrophils are seen in about 20% or less of pediatric cases of reflux esophagitis, appearing in the most severe cases, and are hence not a sensitive marker. Eosinophils are not normally present in the epithelium of young children and can be indicators of GERD, but in concentrations greater than 20/high-power field (hpf) are likely to represent eosi-nophilic esophagitis, making them nonspecific for GERD. A few intraepithelial lymphocytes ("squiggle cells") are normally found, but > 6 squiggle cells/hpf indicate reflux esophagitis .
Esophageal pH-probe monitoring Esophageal pH monitoring (EpHM) is widely accepted as a safe and reliable method for detecting acid reflux. Perhaps its greatest utilities are in clarifying the relationship between reflux and discrete respiratory events such as apnea (with pneumogram), in quantifying acid reflux in extraesophageal GERD, and in assessing the efficacy of antisecretory therapy. In a retrospective analysis of children evaluated for GERD, EpHM detected reflux episodes at a higher rate com pared with barium examinations (83% versus 43%), and showed a lower false negative rate (7% versus 48%) . Its utility in infants and children may be limited in the presence of structural upper airway or GI anomalies, and due to the buffering effect of non-acidic infant formula; probe placement, patient positioning, and dietary factors may contribute to day-to-day variability in pH-metry results . Parents of chil dren undergoing pH studies also perceive changes in their child's feeding pattern and activities during EpHM investigations, but the large majority regarded it as a well-tolerated test . The utility of three different formulas to calculate pH probe placement based on patient height has been the subject of recent analyses , . Fluoroscopy and, rarely in pediatrics, manometry are also used to verify probe positioning.
Fig. 2a-c. Endoscopic images from children with (a) a normal esophagus, (b) an esophagus with erosive reflux esophagitis,and (c) an esophagus affected by eosinophilic esophagitis. Eosino-philic esophagitis, distinct from GERD, often appears as in this image, with furrowing of the esophageal mucosa, and white specks on the surface resembling candidiasis
Conventional pH metry normative data includes reflux index (the percentage of time during a 24-hour day that the esophageal pH is <4), number of episodes and number of episodes longer than five minutes. Scores have been developed to associate reflux with respiratory disease, but are not widely used currently , . Symptom association with reflux episodes comprises a frequently used function of EpHM , . Dual pH monitoring, with the upper probe in upper esophagus, pharynx, or even the airways, is suggested as a potentially useful technique in patients with reflux and airway symptoms, but the limited pe-diatric data are conflicting and warrant further validation , . The value of combining pH metry with impedance to improve the diagnostic yield and to clarify the pathogenetic role of non-acid reflux is now being explored in infants and children. , . An exciting development is the application of the
Bravo pH capsule system in children with GERD, sparing the patient the discomfort of an indwelling transnasal probe; this technique has the potential for higher quality data acquisition than conventional pH metry .
Fluoroscopic evaluation of swallowing and of the upper gastrointestinal tract is often important in the evaluation of the child presenting with obstructive gastrointestinal symptoms or chronic respiratory symptoms. It may also disclose other diagnoses: py-loric stenosis, malrotation, achalasia, and strictures. It has a low sensitivity and specificity for diagnosing reflux and is only a brief snapshot of overall reflux . Barium esophagography or specialized swallowing studies may be useful in identifying abnormalities of pharyngeal, laryngeal, or upper esophageal
Fig. 3a-c. Biopsies of the esophagus from children with (a) normal histology, (b) morphometric changes of reflux manifest in papillary lengthening and basal layer thickening, and (c) eosinophilic esophagitis. Extensive esophageal epithelial eo-sinophilia, as shown in this image (>20eos/hpf), along with papillary elongation and basal layer hyperplasia, constitute the histological features of eosinophilic esophagitis.
function that may prompt aspiration during swallowing and during reflux.
Scintigraphy, also referred to as "a milk scan", is generally performed in infants and children suspected of reflux to gather information regarding reflux-associated aspiration, and to quantify gastric emptying times. The study employs liquid (generally in infants) or solid meals labeled with technetium 99m - for its short (6 hour) half-life and limited radiation burden. It offers the advantage of detecting non-acid reflux in the post-prandial period, but is technically demanding and restrictive for a child. Scintigraphy has a sensitivity of 79% and specificity of 93%, when pH metry is used to define reflux -.
The multiple intraluminal impedance technique is a valuable tool for diagnosing reflux, and its relationship to respiratory events, particularly in infants, in whom post-prandial reflux is non-acidic (Fig. 1) ; it also evaluates esophageal clearance and swallowing. In an early report of its use in infants, the sensitivity of impedance was 98.7%, compared with 18.9% for pH metry in identifying all reflux . Despite time-consuming and visually complex analysis, impedance studies are gradually being applied to the evaluation of pediatric GERD, and its therapies , , .
The identification of lipid-laden macrophages in tracheal aspirates is generally considered a useful marker for aspiration but lacks the sensitivity or specificity for it to be considered a highly reliable test , . Scores are computed, based on the number of lipid-laden macrophages in a given sample, and used to grade the probability of aspiration. Moderate to large number of macrophages may imply aspiration but does not differentiate between reflux- and swallow-related aspiration. Pepsin in tracheal aspirates, sputum, and saliva has been proposed as a more reliable and specific test of reflux aspiration. A strong association has been reported between positive tracheal pepsin assays in children with reflux or respiratory symptoms, particularly in those with coexisting symptoms , .
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