Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Otolaryngologic Manifestations of Gastroesophageal Reflux Gastroesophageal reflux is the retrograde flow of gastric contents back into the esophagus. It is one of the most common problems encountered by physicians in all specialties, affecting nearly 30% of Americans. In the pathologic state esophageal, pulmonary or laryngeal complications may arise. All branches of our specialty encounter manifestations of gastroesophageal reflux disease (GERD). Patients traditionally present with a multitude of vague complaints for which no clear etiology can be identified. Inappropriate or incomplete treatment may be instituted or the patient's complaints might be dismissed as supratentorial. In this presentation, the otolaryngologic signs and manifestations of GERD will be reviewed. The pathophysiology and diagnosis of GERD will then be discussed followed by an outline of the currently accepted treatment protocol. A review of the otolaryngologic literature reflects the relatively recent and diverse association between GERD and various laryngopharyngeal conditions. The following conditions have been reported, some of which will be discussed later in more detail: laryngeal carcinoma, subglottic stenosis, chronic laryngitis, contact ulcer, laryngeal granuloma, cricoarytenoid fixation, intubation granuloma, laryngomalacia, pachydermia, laryngospasm, chronic cough, chronic pharyngitis, dysphagia, globus pharyngeus and Zenker's diverticulum. Causality is difficult to establish in medicine, however several clinical and laboratory studies have been performed which link GERD to laryngeal injury. Pepsin is the primary injurious component of the refluxate. Pepsin injury is characterized by mucosal ulceration, erosion and extensive submucosal hemorrhage. Exposure to acid, bile, and trypsin results in minimal submucosal edema. Though most active in an acidic environment, pepsin maintains 70% of its maximal activity at Ph 4.5. Kaufman recently demonstrated intermittent application of pepsin causes mucosal damage. Pachydermia laryngitis was first described clinically by Rudolf Virchow in 1858. Most investigators consider laryngeal contact ulcers and vocal cord granulomas (granulation tissue) to be a continuum of the same pathologic process. Delahunty and Cherry experimentally produced vocal process granulomas in two dogs by applying gastric juices to the laryngeal mucosa. Ward demonstrated GERD in 72% of patients with contact granulomas. Hill concluded that vocal process granulomas arise from GERD, vocal abuse and intubation. Though frequently attributed solely to intubation, GERD has been postulated to have an etiologic role independent from intubation. Little actually created subglottic stenosis in dogs by painting the subglottic region with gastric juices every other day. Gaynor demonstrated that the extent of tissue damage correlated with the duration of refluxate exposure. In 1983, Bain reported a case of idiopathic subglottic stenosis which completely resolved after the patient underwent a Nissen fundoplication. There are numerous reports of spontaneous resolution of subglottic granulation tissue after GERD was successfully treated. After reviewing his experience with laryngotracheal reconstruction, Gray, recently recommended that every patient undergoing LTR be evaluated for GERD, and if discovered, the reflux should be addressed prior to proceeding with surgery. Koufman found the incidence of GERD by Ph manometry in patients with subglottic stenosis to be 78%. Globus hystericus was first described by Hippocrates nearly 2000 years ago. Globus sensation accounts for 4.1% of all otolaryngologic office complaints and is rarely due to psychogenic causes. Symptoms represent referred discomfort from esophagitis, esophageal dysmotility, cricopharyngeal hypertension or direct irritation of laryngeal structures. Several investigators have demonstrated a strong association between reflux and globus. Reported incidence of reflux ranging from 73-92% in patients with globus pharyngeus. The relationship between asthma and GERD has been established in both adults and children. In 1990, Irwin et al demonstrated GERD to be the third most common cause of chronic cough in nonimmunosuppressed patients, accounting for 21% of all cases, behind post nasal drip and asthma. Of particular interest is that chronic cough was the sole presenting manifestation of GERD in 43% of the patients studied. Synergism has already been established for alcohol and tobacco in the development of carcinoma. The relationship between GERD and the development of carcinoma of the upper digestive tract has already been established with adenocarcinoma and Barrett's esophagitis. Koufman recently demonstrated GERD by pH manometry in 71% of his laryngeal cancer patients. Tobacco and alcohol predispose to reflux by directly decreasing LES pressure, impairing mucosal resistance, promoting esophageal dysmotility, delaying gastric emptying and stimulating gastric hypersecretion. Thus smoking and alcohol adversely modify all of the physiologic defenses against GERD. Gabriel and Jones were first to report a series of patients in which they believed chronic laryngitis had progressed to the development of carcinoma in 1958. In 1983 Olson reported of vocal process carcinoma thatresembled contact ulcer with granuloma formation on physical examination. More recently Morrison reported six cases of laryngeal carcinoma developing in lifetime nonsmokers with GERD and in 1988 Ward and Hanson reported 19 cases of carcinoma of the larynx developing in lifetime nonsmokers. Interestingly, three of the patients had documented benign disease though secondary to their reflux which evolved into carcinoma over 5-8 year period.Symptoms arise as a direct effect of inflammation, reflex stimulation, referred pain or acquired structural changes. Symptoms which should arouse clinical suspicion of pathological reflux include pyrosis, dysphonia, otalgia, odynophagia, hemorrhage, water brash, hoarseness, globus, regurgitation, aspiration, chronic cough, dry or sore throat, hyperphlegmia, lateral cervical pain, laryngospasm, halitosis and aphonia. Koufman found the most common symptoms to be hoarseness (71%), followed by cough (51%), globus (47%) and hyperphlegmia (42%). It is important to note that GERD which causes otolaryngologic symptoms usually is not associated with typical symptoms of dyspepsia and heartburn. This finding is consistent throughout the literature. Kouffman found 57% of his patients to be free of typical GERD complaints and illustrated the occult nature of this disease. The diagnosis is challenging to establish and starts with strong clinical suspicion. The association between hiatal hernia and GER is no longer considered clinically important, since 40-60% of totally asymptomatic patients have easily demonstrable hiatal hernias. Barium esophagography is sensitive for reflux only 20-33% of the time. Treatment with H2 blockers fails in nearly 40% of patients, making the therapeutic trial a questionable diagnostic test. Most of the diagnostic methods either test for esophagitis or test for reflux itself. Prolonged pH manometry has become the gold standard. The sensitivity and specificity approach 100%. It is the only test which records the reflux event itself. When properly placed the distal probe is located 5 cm above the LES and the proximal probe is situated 2 cm above the UES. Normal subjects should not experience an esophageal pH below 4, 6.3% of the time in the upright position, 1.2% of the time in the supine position or 4.2% of the total time. False negative results can occur secondary to technical probe failure or inappropriate sampling. Several factors contribute to the occurrence of reflux. The presence of refluxate in the esophagus perpetuates the reflux cycle by poorly understood neurophysiologic mechanisms. Decreased LES pressure results in the greatest risk for reflux. A list of foods, drugs and hormones which affect the LES is summarized in table form. Abnormal esophageal motility, as seen in neuromuscular disease or post laryngectomy patients also predisposes to reflux. Abnormal mucosal resistance can result from radiation therapy and predispose to mucosalinjury. Delayed gastric emptying can be seen in gastric outlet obstruction or high fat intake. Increased intra-abdominal pressure results from tight clothing, obesity or pregnancy, overeating, exercising, or consuming carbonated beverages. Gastric hypersecretion is associated with major life stress. Therapy is based on dietary and lifestyle modification with antacids, usually under the guidance of a gastroenterologist. Three phases of treatment are usually employed. Phase 1: Therapy consists of dietary and lifestyle modification, with the use of antacids. Fat decreases LES pressure and delays gastric emptying. Protein intake, on the other hand, increases LES pressure and should be encouraged. It is advisable to avoid chocolate, mints, carbonated beverages, caffeine and ethanol. Overeating should be avoided as should lying down within 3 hours of eating. Lifestyle modifications include quitting cigarette smoking, not wearing tight clothing, weight loss if obese and elevation of the head of the bed at least 6 inches. Patient education regarding reflexogenic medications is helpful. Liquid antacids given one hour after meals have been shown to decrease acid production for three hours by suppressing pepsin release. Phase 1 treatment alone is insufficient for patients with severe disease or complications. Patient compliance relates directly with the amount of time and effectiveness of the physician/patient counseling sessions. Phase 2 therapy adds medications which decrease gastric acid production and enhance LES tone while promoting gastric emptying. H2 blockers effectively and safely depress acid secretion. These agents selectively inhibit the stimulation of the parietal cell by histamine. H2 blockers available to the clinician are cimetidine, ranitidine, and famotidine. Cholinergic agents have several beneficial effects. They have been shown to increase LES pressure, increase the amplitude of esophageal peristalsis, and to promote gastric emptying. Available agents are bethanechol, metoclopramide and Cisapride. Use of prokinetic agents had been limited in the past by undesirable side effects; however Cisapride, a new cholinergic agent, is effective without dry mouth, urinary retention, mental confusion or blurred vision. Phase 3: Anti-reflux treatment has traditionally consisted of surgical repair of the hiatal hernia with the reestablishment of the LES. The most common procedure being employed in the surgical treatment of GERD is the Nissen fundoplication. Surgical treatment is highly effective with success rates nearing 90%( mortality 0.4%, complication 5-20%, re-operation rate of 8-18%). Generally accepted indications for surgery are reflux related symptoms intolerably severe and/or persistent despite compliance with maximal anti-reflux medical therapy; or if complications develop that demand effective and prompt remedial therapy. The most promising new option is the H+K+ATPase inhibitors which stop the last stage of hydrogen production in the acid secretion pathway. Omeprazole (Prilosec) is the only currently available form and is administered orally 20mg q day. This drug totally inhibits both stimulated and basal hydrogen ion production, usually within 24 hours of administration. Omeprazole has repeatedly demonstrated therapeutic results superior to any other previous medical treatment. No studies are available to address the question of effectiveness or duration of treatment in the otolaryngologic patient. Irwin found that of all the subgroups of patients with chronic cough, the cough took the longest to resolve in the GERD group, averaging 179 days. The delayed recovery is thought due to the fact that mucosal healing is delayed in the face of continued reflux insult. SUMMARY: 1. The otolaryngologist, both the generalist and the specialist, will see patients in their practice with GERD related problems. 2. GERD is associated with a host of laryngopharyngeal conditions which range from mildly symptomatic to life-threatening.3. GERD is commonly an occult disease in otolaryngology patients and demands a high degree of clinical suspicion.4. Prolonged pH manometry is the diagnostic gold standard.5. Patient compliance is paramount if the prescribed dietary, lifestyle and medical therapy is to work.6. Patients may need to be treated for over six months before improvement is seen. A 40-year-old white male was referred to the Otolaryngology service for evaluation of right sided ear pain, hoarseness, and chronic cough. He had no history of cigarette or alcohol use and had recently undergone a negative pulmonary workup. Head and neck examination was remarkable for mild erythema of the external auditory canal and moderate inflammation of the arytenoid mucosa with cobblestoning of the interarytenoid region. The otalgia and hoarseness worsened and he developed significant lateral cervical pain despite treatment with oral antibiotics and Cortisporin Otic suspension. Audiometric evaluation revealed normal sensitivities and reflexes bilaterally with type A tympanograms. Thyroid studies were normal. Flexible fiberoptic nasopharyngoscopy revealed an abnormality of the right TVC. Upon referral, a laryngeal granuloma was discovered. Gastroesophageal reflux was suspected despite an absence of typical gastrointestinal complaints such as heartburn or regurgitation. Barium esophagography failed to demonstrate gastroesophageal reflux, esophagitis, hiatal hernia or gastric outlet obstruction. The patient subsequently underwent direct laryngoscopy with biopsy of the granuloma. A prolonged pH manometric study was recommended but the patient refused. In coordination with the gastrointestinal service, a treatment regimen consisting of dietary and lifestyle modification, antacids and an H2 blocker was instituted. The patient continues to suffer from intermittent laryngitis and chronic cough, however the otalgia and cervical pain have completely resolved. 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