INFECTIOUS AND INFLAMMATORY DISORDERS

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1 Chapter 52 INFECTIOUS AND INFLAMMATORY DISORDERS Allen M. Seiden Infection or inflammation of the esophagus typically produces dysphagia and odynophagia, so these patients may frequently present to the otolaryngologist. Physical findings are often lacking, and therefore diagnosis often depends on a thorough history and an understanding of the epidemiology of these disorders. PEARL... One recent study found that esophageal candidiasis was the most common cause of dysphagia and odynophagia in a series of patients with AIDS, while estimates suggest that 75% of AIDS patients will have symptoms attributable to esophageal infection at some time during the course of their disease. INFECTIOUS ESOPHAGITIS In an otherwise immunocompetent individual, primary esophageal infection is rare without some predisposing factor. Typically this involves a disruption of normal esophageal defenses. For example, impaired peristalsis may lead to stasis of esophageal contents, providing a milieu for pathogenic infection. Conditions that may alter peristalsis include diabetes, scleroderma, and achalasia. The use of antimicrobial agents may alter the normal esophageal flora and allow colonization by pathogenic organisms, most frequently Candida species. More often esophageal infection is seen in patients who are immunocompromised, such as those with cancer, AIDS, or posttransplant immunosuppression. The incidence of infectious esophagitis in patients with cancer ranges from 2.8 to 13%, those with myeloproliferative disorders being at greater risk. FUNGAL INFECTION The most common fungal infection of the esophagus is caused by Candida albicans, typically as a result of antibiotic therapy suppressing bacterial commensals, immunosuppression, or the development of hematologic malignancies. Symptoms may range from mild dysphagia to refusing all oral intake because of associated pain. The dysphagia tends to be more pronounced after ingesting solids rather than liquids. Although manifestations of oral thrush may aid in the diagnosis, many of these patients have fungal infection limited to the esophagus. PITFALL... The absence of oral lesions does not rule out the possibility of esophageal candidiasis. 352

2 52 INFECTIOUS AND INFLAMMATORY DISORDERS 353 The diagnosis should be suspected in any high-risk patient complaining of dysphagia or odynophagia and can be verified by either barium swallow or endoscopy. PITFALL... In esophageal candidiasis, a barium swallow classically demonstrates a so-called shaggy or cobblestone appearance due to diffuse mucosal inflammation and ulceration. However, focal lesions have also been described. A false-negative rate of 25% has been reported. Second to Candida species, the most common organism causing esophagitis is herpes simplex virus type I (HSV-1). Although it is more common in immunocompromised patients or those with predisposing factors, it may also occur in otherwise healthy individuals. HSV-1 esophagitis generally starts as a cluster of vesicles within the lower third of the esophagus. In immunocompromised patients these lesions may progress to a diffuse ulcerative esophagitis. Patients typically present with extremely severe pain with swallowing. Labial herpes may precede or coincide with the esophageal infection. In immunocompetent patients the infection usually resolves within 2 weeks, whereas in those patients who are immunocompromised the disease may progress to severe hemorrhage, perforation, or dissemination. A barium esophagram may demonstrate focal areas of ulceration in the distal esophagus, or, if the infection is more diffuse, it may look very much like Candida esophagitis as described above. Endoscopy enables the collection of brushings or biopsy material for culture and characteristically will reveal discrete, punchedout ulcers.therapy is with acyclovir, while at the same time maintaining adequate hydration. BACTERIAL INFECTION Endoscopy is the most sensitive diagnostic technique and generally reveals raised white plaques with or without ulceration. Brushings may be obtained from these lesions. Oral imidazole derivatives such as fluconazole or ketoconazole generally provide effective treatment and are preferred over nystatin suspension. Amphotericin B is rarely necessary and is reserved for those patients who otherwise don t respond to less toxic therapy. If possible, it is also desirable to correct any predisposing factors. Although less common, esophagitis may also occur secondary to aspergillosis, histoplasmosis, and blastomycosis. VIRAL INFECTION Bacterial infection of the esophagus accounts for approximately 10 to 15% of cases of infectious esophagitis. It seems to largely reflect colonization after esophageal injury, for example, from nasogastric tubes, radiation therapy, or gastroesophageal reflux, and once again tends to occur in immunocompromised patients. Organisms are generally consistent with oral flora; however, therapy should be culture directed. GASTROESOPHAGEAL REFLUX DISEASE The term gastroesophageal reflux disease (GERD) is used to describe any condition in which symptoms or histopathologic change results from refluxed gastric acid.this includes esophagitis as well as extraesophageal manifestations. Estimates suggest that GERD affects 7 to 10% of the population on a daily basis, and 40% on a monthly basis. A certain amount of acid reflux is considered physiologic and generally occurs after meals. Whether it becomes pathologic depends on the frequency, volume, and duration of exposure. For example, although reflux episodes occur more often during the day, damage is more significant at night. This is because swallowing occurs much less frequently during sleep, averaging seven times an hour as opposed to 72 times an hour when awake. Refluxed material is therefore not cleared as rapidly and tends to pool in the lower esophagus. Defense mechanisms to gastroesophageal

3 354 ESOPHAGUS reflux, or the so-called antireflux barrier, include (1) the lower esophageal sphincter (LES), (2) peristaltic clearance of esophageal acid, (3) esophageal epithelial resistance, and (4) the upper esophageal sphincter. Lower esophageal sphincter pressure tends to be adversely affected by fatty foods, caffeine, chocolate, alcohol, and tobacco. Drugs such as theophylline, -agonists, -antagonists, birth control pills, and calcium channel blockers can have the same effect. CONTROVERSY It is often suggested that a hiatal hernia predisposes to reflux. However, opinion varies as to whether a hiatal hernia sufficiently lowers LES pressure. Although the ph of the refluxate is important, it is the pepsin concentration that seems to be responsible for the mucosal injury. Pepsin requires an acidic environment for its activity and retains 75% of its activity at a ph of up to 4.5. The most common symptom of GERD is heartburn, a retrosternal and epigastric burning pain that may radiate to the back, arm, pharynx, and ear when severe. Occasionally it must be distinguished from cardiac pain; however, if it dissipates rapidly with nitroglycerin, it is unlikely to be esophageal in origin. The severity of pain often does not correlate histologically with the amount of esophageal inflammation. Pain that is aggravated by hot or cold liquids, coffee, citrus juices, or alcohol suggests ulcerative esophagitis. PEARL... A sour (acid) or bitter (bilious) taste in the mouth may suggest reflux. Excess salivation known as waterbrash may occur secondary to lower esophageal irritation. Nocturnal aspiration, choking, and coughing may be presenting symptoms. DIAGNOSIS The diagnosis of GERD can often be made by history, after which it is reasonable to institute empirical therapy and gauge the patient s response. If the patient fails to respond or has atypical symptoms, or complications are suspected, a number of tests are available for verification. The 24-hour ph probe is currently considered the definitive test for reflux. It quantitates the number and magnitude of reflux episodes over a 24-hour period, as well as the time for esophageal clearance. A barium swallow is readily available but has a sensitivity of only 25 to 35%. Radionuclide scintigraphy has a sensitivity of about 68%, although it has been reported to be only 11% sensitive in patients with head and neck manifestations of reflux. Endoscopy may be helpful but is not essential in most cases. If symptoms do not respond to therapy, or the patient complains of associated dysphagia, odynophagia, or bleeding, then endoscopy is indicated. However, the presence of normal-appearing mucosa does not rule out the possibility of reflux disease because as many as 55% of patients with symptomatic reflux have a normal endoscopic examination. Aside from esophagoscopy, bronchoscopy with cytology may also be helpful, particularly in children. The presence of lipid-laden macrophages would suggest reflux aspiration with a sensitivity of 85%, although other inflammatory conditions can produce similar findings. TREATMENT Generally, the treatment for gastroesophageal reflux should proceed in a stepwise fashion. Initially this should include conservative measures such as dietary management, bed elevation, avoiding bedtime snacking, weight loss if indicated, and reducing alcohol and tobacco consumption. Over-the-counter antacids are also helpful. For those patients who fail conservative treatment, the second step involves more aggressive medical therapy. The H 2 -receptor antagonists have been shown to effectively reduce

4 52 INFECTIOUS AND INFLAMMATORY DISORDERS 355 gastric acid output, with a therapeutic gain of 10 to 24% relative to placebo. SPECIAL CONSIDERATION The so-called prokinetic drugs such as metoclopramide and bethanechol theoretically increase LES tone, encourage gastric emptying, and improve peristalsis. They have been shown to improve healing of mild to moderate esophagitis when combined with the H 2 blockers but are limited by their side effects. Proton pump inhibitors are the newest class of agents for treating GERD, and they block the hydrogen potassium adenosine triphosphatase (ATPase) pump responsible for the final step in the release of gastric acid. These agents have demonstrated a therapeutic gain of 57 to 74% relative to placebo, and have been shown to be effective in more than 80% of severe esophagitis cases resistant to H 2 -receptor antagonists. When medical therapy fails, and particularly if complications develop, antireflux surgery should be considered. The development of laparoscopic approaches has greatly reduced the morbidity of surgical intervention, and in wellselected patients these approaches have demonstrated a 90% efficacy rate. The two most common procedures are the Nissan fundoplication and the Toupet partial fundoplication, both of which aim to restore competence of the LES. HIATAL HERNIA The esophagus passes through a hiatus in the diaphragm before reaching the stomach, at which point it is stabilized by the diaphragmatic crura and the attachment of the phrenoesophageal membrane. The latter is simply a coalescence of the thoracic and abdominal e that line the diaphragm. A sliding hiatal hernia occurs when the gastric cardia herniates through the hiatus (Fig. 52 1). The phrenoesophageal membrane remains attached, though lax, so the herniated segment is not a free peritoneal sac. In contrast, a paraesophageal hiatal hernia occurs when a portion of the gastric fun- A Squamocolumnar junction Stomach Esophageal muscle Phrenoesophageal membrane Squamocolumnar junction B Esophageal mucosa Esophageal muscle Phrenoesophageal membrane Endothoracic Diaphragm Endoabdominal Peritoneum Stomach Peritoneal sac Endothoracic Diaphragm Endoabdominal Peritoneum FIGURE 52 1 Type I, sliding (A) and type II, paraesophageal (B) hiatal hernias.

5 356 ESOPHAGUS dus herniates through the hiatus adjacent to the esophagus. It generally occurs through a weakened portion of the phrenoesophageal membrane, while the LES remains in its subdiaphragmatic position. Eventually the gastroesophageal junction may be pulled upward through the defect, producing a combined sliding and paraesophageal hiatal hernia. The sliding type of hiatal hernia is more common, although the specific cause remains unknown. Estimates suggest that 10% of adults will demonstrate varying degrees of a sliding hiatal hernia during a routine barium swallow, whereas only 5% of these patients will have symptomatic gastroesophageal reflux. A sliding hiatal hernia generally does not require any specific therapy. However, as a paraesophageal hernia continues to dilate, complications such as volvulus, infarction, and perforation may ensue. Therefore, surgical correction of paraesophageal hernias is recommended. COMPLICATIONS CONTROVERSY A sliding hiatal hernia has long been implicated as a causative factor in GERD. However, more recent investigations indicate that it is the competency of the lower esophageal sphincter, independent of its relationship to the diaphragm, that determines whether reflux will occur. The presence of a hiatal hernia does not necessarily predispose to the development of symptomatic reflux. The most common complications of gastroesophageal reflux are ulceration, hemorrhage, stricture, and Barrett s esophagus. Esophageal ulceration tends to occur in those patients with delayed esophageal and gastric emptying. Such patients typically complain of dysphagia and odynophagia but may experience a deep, boring pain that radiates to the back and is relieved with antacids. Significant bleeding from esophagitis or a penetrating esophageal ulcer is unusual, but, when it occurs, it must be distinguished from varices.therefore, endoscopy is indicated. Chronic reflux esophagitis that leads to ulceration ultimately causes scarring that may result in stricture formation. Approximately 10 to 15% of patients with reflux esophagitis develop a stricture. Progressive dysphagia is characteristic, although patients may not always present with a prolonged history of heartburn. Continued acid exposure of the squamous epithelium that lines the esophagus may lead to replacement by metaplastic columnar epithelium, known as Barrett s esophagus. This tends to occur by upward migration of gastric epithelium, although isolated islands of columnar epithelium may be found elsewhere in the esophagus and are believed to be congenital in origin. Barrett s esophagus can be recognized endoscopically by its salmon red appearance. The significance is its association with a 10% incidence of adenocarcinoma, and it is therefore considered to be a premalignant condition. Management includes controlling the underlying reflux and closely monitoring the risk of cancer. OTOLARYNGOLOGIC MANIFESTATIONS Otolaryngologic manifestations of GERD are being recognized with increasing frequency and generally result from spillage of gastric juice into the larynx or pharynx, although some symptoms may relate to secondary spasticity or hypertrophy of the upper esophageal sphincter. SPECIAL CONSIDERATION It has recently been demonstrated that pepsin, and not hydrochloric acid, is the agent largely responsible for the mucosal injury. When there is a prior mucosal injury, such as from intubation, damage from reflux is much more likely to occur.

6 52 INFECTIOUS AND INFLAMMATORY DISORDERS 357 Symptoms that have been linked to acid reflux include hoarseness, chronic cough, chronic throat clearing, globus sensation, dysphagia, otalgia, dysgeusia, and laryngospasm. Recent studies have also suggested an association with laryngeal cancer. In the pediatric patient manifestations include burping, choking, gagging, emesis, failure to thrive, airway obstruction, and sudden infant death syndrome. Many of these patients do not have the classic symptoms normally associated with GERD and esophagitis. Such symptoms have been reported in only 20 to 50% of patients with head and neck manifestations of GERD, and therefore the diagnosis requires a high index of suspicion. PEARL... While not pathognomonic for GERD, erythema and edema of the posterior larynx, referred to as pachydermia laryngitis, is highly suggestive. Other physical findings might include varying degrees of laryngeal and subglottic edema, and even granulation tissue. H 2 blockers are frequently ineffective in this group of patients. Full suppression over a prolonged period with proton pump inhibitors is usually required to achieve mucosal recovery. SUGGESTED READINGS Cote DN, Miller RH. The association of gastroesophageal reflux and otolaryngologic disorders. Compr Ther 1995;21: Kahrilas PJ. Gastroesophageal reflux disease. JAMA 1996;276: Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour ph monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991; 101(suppl):1 64. Olson NR. Laryngopharyngeal manifestations of gastroesophageal reflux disease. Otolaryngol Clin North Am 1991;24: Raufman JP. Esophageal infections. In: Yamada T, Alpers DH, Owyang C, Powell DW, Silverstein FE, eds. Gastroenterology. 2nd ed. Philadelphia: JB Lippincott, 1995: Seiden AM. Esophageal disorders. In: Paparella MM, Shumrick DA, Gluckman JL, Meyerhoff WL, eds. Otolaryngology. 3rd ed. Philadelphia: WB Saunders; 1991: