Complications

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GERD is associated with severe complications such as esophagitis, Barrett's esophagus, strictures and esophageal adenocarcinoma. The severity of the complications is not clearly related to the duration or severity of symptoms, as severe histological changes are detectable at the first investigation. Differences in esophageal mucosal resistance and genetic factors may partially explain the diversity of lesions and symptoms.16 Esophageal ulcers may be diagnosed in adults with dysphagia, odynopha-gia or esophageal bleeding, but are rarely seen in children.20,74

The incidence of congenital esophageal stenosis is approximately 1 in 25000 to 1 in 50000 live births, with associated esophageal atresia in one-third of cases.79 More than 40 years ago, in the absence of reflux treatment, esophageal strictures were reported in about 5% of children with reflux symptoms.80 Nowadays, except in Barrett's esophagus, esophageal stenosis and ulceration in children have become rare.20 Esophageal stenosis may be related to the initial severity of the esophagitis and the persistence of symptoms, even during treatment.16 Occasionally, esophageal stenosis is reported to have developed after an intervention for achalasia.81

Reflux esophagitis is reported in 2-5% of the general population.82 Children with GER symptoms present esophagitis in 15-62%, Barrett's esophagus in 1.5-3% and refractory GERD requiring surgery in 6-13%.20-24 In adults undergoing endoscopy, esophagitis is diagnosed in 15-80%.1,17,25,26 The differences in incidence are determined by patient recruitment and availability of acid-blocking drugs over the counter (self-treatment). A 10-year follow-up of esophagitis showed that over 70% had persisting symptoms, and 2% had strictures.19 Thus, esophagitis is not a necessary prerequisite for diagnosing GERD or starting therapy, either in children or in adults.

Abundant infiltration of the esophageal mucosa with eosinophils, as occurs in eosinophilic gastroenteritis and eosinophilic esophagitis, is increasing in prevalence and necessitates proper treatment (hypoallergenic feeding, corticoids, etc.). Patients with allergic esophagitis seem to have a younger age and common atopic features (allergic symptoms or positive allergy tests), but no specific symptoms. In children, eosinophilic esophagitis accounts for almost 1.0% of esophagitis in some selected series.83 Atopic features are reported in more than 90% and peripheral eosinophilia in 50% of patients. At endoscopy, a pale, granular, furrowed and occasionally ringed esophageal mucosa may appear.84 In reflux esophagitis, the distal and lower eosinophilic infiltrate is limited to less than 5 per high-power field (HPF) with 85% positive response to GER treatment, compared to primary eosinophilic esophagitis with >20 eosinophils per HPF.83-85 In adults, allergic esophagitis and eosinophilic esophagitis are rarely found, suggesting an age-related regression or a possible underinvestigation. Patients with primary eosinophilic esophagitis may respond to dietary elimination, cromolyn sodium or steroids.84 Recently, montelukast and fluticasone have also been reported to be of benefit.86,87

Barrett's esophagus is a premalignant condition with metaplastic columnar epithelium with goblet cells in the esophagus,88 detectable in up to 5-10% of the endoscopies performed in adults,16 but rarely seen in children. Children with severe reflux, as in those with neurological impairment, chronic lung disease (especially cystic fibrosis) and esophageal atresia, are at a higher risk of developing Barrett's esophagus.24 In addition to severe reflux, a genetic component is also suggested.20,24,88-91 In a series including 402 children with GERD without neurological or congenital anomalies, no case of Barrett's esophagus was detected.20 In another series including 103 children with long-lasting GERD, and not previously treated with H2-receptor antagonists or a proton pump inhibitor, Barrett's esophagus was detected in 13%. An esophageal stricture was present in five of the 13 patients with Barrett's esophagus (38%).90 Reflux symptoms during childhood were not different in the adults without, than in the adults with, Barrett's esophagus.88

Peptic ulcer, esophageal and gastric neoplastic changes in children are extremely rare. In adults, over the past 30 years, a decreased prevalence of gastric cancer and peptic ulcer with an opposite increase of esophageal adenocarcinoma and GERD have been noted.92 This has been attributed to independent factors amongst which are changes in dietary habits such as a higher fat intake, an increased incidence of obesity and a decreased incidence of Helicobacter pylori infection.17,92 Nevertheless, the frequency, severity and duration of reflux symptoms are related to the risk of developing esophageal cancer. Among adults with longstanding and severe reflux the odds ratios are 43.5 for esophageal adenocarcinoma and 4.4 for adenocarcinoma at the cardia.93 It is unknown whether mild esophagitis or GER symptoms persisting from childhood are related to an increased risk for severe complications in adults.

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