Pediatric Extraesophageal Reflux Disease: A Diagnostic Dilemma

The true incidence of EERD is unknown, but it certainly appears to be a condition that is overdiagnosed. I believe that the overdiagnosis is inadvertent, and can be attributed to several factors. Most at fault is the lack of a sensitive and specific diagnostic test for reflux disease. For many years, pH probe testing, considered superior to radiographic studies, was touted as the gold standard for diagnosing GERD. Its shortfall in diagnosing EERD was readily apparent to those of us who frequently observed children who responded well to antireflux medication despite having normal single, or even double, pH probe studies.2 Interestingly, despite the pH probe’s widespread use, the criteria for pathologic reflux at the upper probe were never established by controlled outcome studies.

The low sensitivity, the lack of reproducibility, and the burden of obtaining a pH probe study prompted the emergence of the next phase of diagnosis-using the response to empiric antireflux therapy as a primary diagnostic test. The relative inefficacy and the early development of tolerance to H2 receptor antagonists justified the rationale for initiating treatment with proton pump inhibitors (PPIs). Insurance companies often failed to approve PPI therapy in the absence of a prior trial of H2 receptor antagonists, or a letter of medical necessity, validating the use of this superior class of antireflux medications. Although a trial of empiric therapy is cheaper than a diagnostic study for reflux disease, it is nevertheless a costly approach. At a local large chain pharmacy in the Washington, DC, area, a 12-week supply of Zantac suspension (rantidine hydrochloride, 15 mg/mL, 45 mg) for a 20-kg child costs $490, while a similar supply of Prevacid (lansoprazole) is $495 (30 mg Solutab) or $558 (30 mg capsule). (The price difference for a three-month supply is not as striking as one would suspect, given the reluctance of insurance companies to approve first-line PPI therapy.)

The difficulty obtaining insurance approval for PPIs is not their only shortcoming. They must be administered in a careful fashion to ensure their efficacy. Although it is common knowledge that PPIs block hydrogen ion production by the gastric parietal cells, it is less well known that their effect is systemic and not local at the gastric level. Consequently, PPIs must be administered 30 minutes before a meal to allow for absorption from the duodenum into the systemic system. Prior to the advent of pleasant-tasting suspensions and soluble tablets, the content of PPI capsules was sometimes sprinkled into a concealing, palatable food before administration. However, placement of the enteric coated beads of PPIs in something other than a weakly acidic solution, such as applesauce or yogurt, rendered the medication inactive. Inappropriate administration lessened the value of using PPI therapy as a diagnostic study.

Other Diagnostic Methods

Newer on our horizon, and yet to be refuted as a valuable study, is the multichannel intraluminal impedance (MII) test. While it is similar to pH probe testing, this relatively new study allows the detection of both acidic and nonacidic reflux events by measuring changes in impedance along a series of ring electrodes on an esophageal catheter. Nonacidic reflux events may account for up to four-fifths of reflux events in pediatric patients, particularly infants, and may explain the insensitivity of pH probe testing, as well as the relative inefficacy of acid-reducing antireflux medications.3 Institutions are understandably a bit cautious about purchasing this relatively new, expensive equipment and software to replace their functioning pH probe equipment at a cost of nearly $25,000. Reviewing the MII study after it has been scored by the software program is relatively labor-intensive but will likely become less so as technology improves.