Gastroesophageal Reflux Disease

GENERAL PRINCIPLES

Gastroesophageal reflux disease (GERD) is defined as symptoms and/or complications resulting from reflux of gastric contents into the esophagus and more proximal structures.

DIAGNOSIS

Clinical Presentation

• Typical esophageal symptoms of GERD include heartburn and regurgitation. GERD can also present as chest pain, so it is important to exclude a cardiac source before initiating GI evaluation.⁵³

• Extraesophageal manifestations of GERD can include cough, laryngitis, asthma, and dental erosions.

• Symptom response to a therapeutic trial of PPIs can be diagnostic, but a negative response does not exclude GERD.⁵⁴

Differential Diagnosis

Other disorders that can result in esophagitis include the following:

• Eosinophilic esophagitis (EoE), characterized by eosinophilic infiltration of esophageal mucosa, is increasingly recognized as an etiology for foregut symptoms.

î Atopy (i.e., allergic rhinitis, eczema, asthma) is common, and food allergens may trigger the process. î Dysphagia is prominent, but symptoms can also mimic GERD.

î Common EGD findings include furrows, luminal narrowing, corrugations, and whitish plaques in the esophageal mucosa. The following establish a diagnosis of EoE: (1) symptoms related to esophageal dysfunction (such as dysphagia or food impaction), (2) #8805;15 eosinophils per HPF on esophageal biopsies, and (3) exclusion of secondary causes of esophageal eosinophilia (such as GERD).⁵⁵ î First-line therapy for EoE consists of either PPIs, which also treats concomitant GERD, or topical steroids (swallowed fluticasone, 880-1760 #956;g#8725;d in two to four divided doses; or swallowed budesonide, 2 mg/d in two to four divided doses).⁵⁶ Yield of food allergen testing is typically low. Elimination of trigger foods can include a 6-food elimination diet (eggs, milk, soy, gluten, tree nuts, seafood), although 2-food elimination (milk, gluten) may provide adequate benefit.

• Infectious esophagitis typically presents with dysphagia or odynophagia and is seen most often in immunocompromised states (e.g., AIDS, organ transplant recipients), esophageal stasis (abnormal motility [e.g., achalasia, scleroderma], mechanical obstruction [e.g., strictures]), malignancy, diabetes mellitus, and antibiotic use; however, it can rarely occur in the normal healthy host. The presence of typical oral lesions (thrush, herpetic vesicles) may suggest an etiologic agent.

î Candida esophagitis is the most common esophageal infection, typically seen in esophageal stasis, impaired cell-mediated immunity from immunosuppressive therapy (e.g., with steroids or cytotoxic agents), malignancies, or AIDS. Endoscopic visualization of typical whitish plaques has near 100% sensitivity for diagnosis. Empiric antifungal agents are appropriate when concurrent oropharyngeal thrush is present, reserving endoscopy for nonresponse to therapy. Fluconazole 100-200 mg/d or itraconazole 200 mg/d for 14-21 days is recommended as initial therapy for Candida esophagitis; nystatin (100,000 units/mL, 5 mL tid for 3 weeks) and clotrimazole troches (10 mg four to five times a day for 2 weeks) are alternatives for oropharyngeal candidiasis. For infections refractory to azoles, a short course of parenteral amphotericin B (0.3-0.5 mg/kg/d) can be considered.⁵⁷

î HSV esophagitis is characterized by small vesicles and well-circumscribed ulcers on endoscopy and typical giant cells on histopathology. Viral antigen or DNA can be identified by immunofluorescent antibodies. Treatment consists of acyclovir (400-800 mg PO five times a day for 14-21 days or 5 mg/kg IV q8h for 7-14 days).

î CMV esophagitis, which occurs almost exclusively in immunocompromised hosts, can cause erosions or frank ulcerations. Ganciclovir (5 mg/kg IV q12h) or foscarnet (90 mg/kg IV q12h for 3­6 weeks) can be used as initial therapy. Oral valganciclovir may also be effective.

o Symptomatic relief can be achieved with 2% viscous lidocaine swish and swallow (15 mL PO q3- 4h PRN) or sucralfate slurry (1 g PO qid).

• Chemical esophagitis

î Ingestion of caustic agents (e.g., alkalis, acids) or medications such as oral potassium, doxycycline, quinidine, iron, NSAIDs, aspirin, and bisphosphonates can result in mucosal irritation and damage. The offending medication should be discontinued if possible. Mucosal coating agents (e.g., sucralfate) and acid-suppressive agents may help.

î With caustic ingestions, cautious early EGD can evaluate the extent and degree of mucosal damage, and CT can rule out transmural esophageal necrosis or perforation in the setting of mucosal necrosis.⁵⁸ A second caustic agent to neutralize the first is contraindicated.

Diagnostic Testing

• Endoscopy with biopsies is primarily indicated for avoiding misdiagnosis of alternate causes of esophageal symptoms (e.g., EoE), identification of complications, and evaluation of treatment failures. Alarm symptoms of dysphagia, odynophagia, early satiety, weight loss, or bleeding should prompt

endoscopy.³⁰

• Ambulatory pH or pH impedance monitoring can be used to quantify esophageal acid exposure and reflux events and/or to assess reflux-symptom correlation in patients with ongoing symptoms despite acid suppression (especially if endoscopy is negative) or those with atypical symptoms. pH impedance testing detects all reflux events regardless of pH and is best performed off PPI therapy to increase yield; abnormal studies can predict symptomatic response to medical or surgical antireflux therapy.

• Esophageal manometry, particularly HRM, may identify motor processes contributing to refractory symptoms.

TREATMENT

Medications

• Intermittent or prophylactic over-the-counter antacids, H₂ receptor antagonists (H₂RAs), and PPIs are effective with mild or intermittent symptoms.

• PPIs are more effective than standard-dose H₂RAs and placebo in symptom relief and endoscopic healing of GERD. Modest gain is achieved by doubling the PPI dose in severe esophagitis or persistent symptoms. Continuous long-term PPI therapy is effective in maintaining remission of GERD symptoms, but the dose should be decreased after 8-12 weeks to the lowest dose that achieves symptom relief.⁵⁴ Abdominal pain, headache, and diarrhea are common side effects. Bone demineralization, enteric infections, community-acquired pneumonia, and reduced circulating levels of vitamin B₁₂ are reported in observational studies, but conclusive cause-and-effect data are lacking, and benefits of PPI therapy continue to outweigh risks in patients with proven GERD.⁶⁰

• Standard doses of H₂RAs can result in symptomatic benefit and endoscopic healing in up to half of patients. Dosage adjustments are required in renal insufficiency.

• Reflux inhibitors consist of #947;-aminobutyric acid (GABA) type B receptor agonists that block transient LES relaxations. Baclofen, the prototype agent, reduces reflux events, but central side effects can be limiting.⁶¹

Surgical Management

• Indications for surgical fundoplication include the need for continuous PPIs, nonadherence, or intolerance to medical therapy in patients who are good surgical candidates, ongoing nonacid reflux despite adequate medical therapy, and patient preference for surgery.⁵⁴ When symptoms are controlled on PPI therapy, medical therapy and fundoplication are equally effective.

• Typical GERD symptoms, PPI response, elevated esophageal acid exposure, and correlation of symptoms to reflux events on ambulatory reflux monitoring predict a hi gher likelihood of a successful surgical outcome.

• Patients with medical treatment failures need careful evaluation to determine whether symptoms are indeed related to acid reflux before surgical options are considered; these patients often have other diagnoses including EoE, esophageal motor disorders, visceral hypersensitivity, and functional heartburn.^54,61

• Potential complications of surgery include dysphagia, inability to belch, gas-bloat syndrome, and

bowel symptoms including flatulence, diarrhea, and abdominal pain.

• In patients with obesity, GERD symptoms improve from a roux-en-Y gastric bypass; however, a sleeve gastrectomy can worsen GERD symptoms and should not be offered to obese individuals with GERD.

Lifestyle/Risk Modification

• Patients with nocturnal GERD symptoms may benefit from elevating the head of the bed and avoiding meals within 2-3 hours before bedtime.

• Weight loss may benefit certain overweight patients with GERD.

• Lifestyle modifications alone are unlikely to resolve symptoms in the majority of GERD patients and should be recommended in conjunction with medications.

Complications

• Esophageal erosion and ulceration (esophagitis) can rarely lead to overt bleeding and iron deficiency anemia.

• Strictures can form when esophagitis heals, leading to dysphagia. Endoscopic dilation and maintenance PPI therapy typically resolve dysphagia from strictures.

• Barrett esophagus (BE) is a reflux-induced change from normal squamous esophageal epithelium to specialized intestinal metaplasia and carries a 0.5% per year risk of progression to esophageal adenocarcinoma. Endoscopic screening for BE should be considered for patients with GERD who are at high risk (long duration of GERD symptoms, #8805;50 years of age, male gender, Caucasian); patients with BE should undergo periodic surveillance every 3-5 years in the absence of dysplasia. If dysplasia is found in the setting of BE, endoscopic therapy (usually radiofrequency ablation) is preferred to surveillance or surgery.⁶³