Esophageal Disorders Caused by Medications, Trauma, and Infection

Mechanisms

Medications cause esophageal injury through several mechanisms. These can initially be divided into those that cause direct injury to esophageal mucosa because of their caustic nature or by facilitation of injury through other mechanisms such as induction of acid reflux (e.g., calcium channel antagonists). Medications directly damage the esophageal mucosa through 1 of 4 known mechanisms: (1) production of a caustic acidic solution (e.g., ascorbic acid and ferrous sulfate); (2) production of a caustic alkaline solution (e.g., alendronate); (3) creation of a hyperosmolar solution in contact with esophageal mucosa (e.g., potassium chloride); and (4) direct drug toxicity to the esophageal mucosa (e.g., tetracycline). For many medications, the mechanism of esophageal injury does not fall into any of these known categories. Other factors may influence the toxicity of the pill, particularly contact time, pills coated with gelatinous material, sustained-release formulations, and a wax matrix form of the drug. Cellulose fiber and guar gum pills may swell and lodge in the esophagus, causing complete obstruction because of their water-absorbing capacity. Finally, medications may cause esophageal injury through induction of a systemic reaction that affects the esophagus.

It is commonly assumed that a predisposition to medication-induced esophageal injury is due to an anatomic or motility disorder of the esophagus or that the medication was taken incorrectly, in either case allowing for prolonged exposure of the medication to esophageal mucosa. For example, studies have shown that patients with left atrial enlargement, esophageal strictures, esophageal dysmotility, and esophageal diverticula (either Zenker or epiphrenic diverticula) have greater risk of pill-induced injury. Similarly, in the patient with normal esophageal function, the site of drug-induced injury most commonly occurs where there are areas of normal hypomotility or extrinsic compression, such as in the trough zone of the esophagus (where the smooth and skeletal muscle overlap) or at the level of the aortic or left bronchial impression on the esophagus. These locations of relative stasis allow for a pill, when taken incorrectly, to cause injury. However, any part of the esophagus may be involved. Methods of taking a medication incorrectly that predispose to injury include ingesting a pill without enough water or assuming a recumbent position or sleeping immediately after pill ingestion, or both. The latter 2 factors are particularly problematic, by eliminating the help of gravity in esophageal transit and by reducing saliva production and frequent swallowing, which occur normally while awake. Importantly, however, many, if not most, patients who suffer pill-induced esophageal injury presumably have normal esophageal function and do not necessarily ingest their medication in a faulty manner. That pill-induced esophageal injury can occur under “normal” conditions is supported by data demonstrating prolonged radiographic retention of capsules in the esophagus by normal subjects even when taken with water in the upright position. Capsules may have longer esophageal retention times than tablets.

Clinical Features and Diagnosis

Patients typically note an acute onset of chest pain, which may radiate over the central chest and to the back. The pain is commonly accentuated with inspiration and may be accompanied by severe odynophagia, even to small sips of liquids. Some patients may complain of a severe acute onset of heartburn-type symptoms. This set of symptoms associated with ingestion of a potentially injurious medication taken incorrectly (particularly just before bedtime without enough water) strongly suggests the diagnosis. If objective confirmation of the diagnosis is necessary, endoscopy or radiography can be used, although endoscopy is considered more sensitive. Findings range from discrete ulcers to diffuse severe esophagitis with pseudomembranes, as may be seen with bisphosphonates or with sodium polystyrene sulfonate suspension (Kayexalate), mimicking candidal esophagitis. A diffuse sloughing appearance of the mucosa, also known as esophageal dissecans superficialis , may also be identified. Occasionally, severe inflammatory reactions causing stenoses and tumor-like appearances occur. Similar findings may be seen radiographically, particularly when double-contrast radiography is used. The range of findings described on esophagography may also include solitary or multiple ulcers; small or large ulcerations; ulcers with punctate, ovoid, linear, serpiginous, or stellate collections of barium; confluent ulcers; or areas of normal-appearing mucosa separating ulcers ( Fig. 45.1 ). The occurrence of multiple esophageal septa has also been described. Rarely, severe complications of medication-induced injury occur such as esophagorespiratory fistula, esophageal perforation, hemorrhage secondary to ulceration, and chronic stricture formation. Pathologically, esophageal biopsies in affected areas reveal dilated intercellular spaces and a predominance of T lymphocytes and eosinophils in a pattern different from other causes of esophagitis.

Prevention, Treatment, and Clinical Course

No specific treatments have been shown to be beneficial in altering the course of medication-induced injury. Treatment is aimed at symptom control, prevention of superimposed injury from acid reflux, maintenance of adequate hydration, and removal of the offending medication. Symptom control may be achieved topically by local anesthetics such as viscous lidocaine solution. Occasionally, narcotics are necessary. Prevention of superimposed reflux is best achieved with a twice-daily PPI, although no data show that prevention of acid reflux hastens symptomatic or pathologic improvement of pill-induced injury. For patients who have severe odynophagia prohibiting adequate oral intake, IV hydration may be necessary for a few days. Removal of the cause of injury is self-evident, although this is not always easily achieved. This is particularly true in clinical situations in which there may not be an adequate substitute such as in aspirin prophylaxis for cardiovascular disease, bisphosphonates for severe osteoporosis, or high-dose NSAIDs for pain from chronic inflammatory arthritides. No data address the question of whether rechallenge with a pill that induced prior esophagitis poses higher risk of recurrent injury if the pill is taken with better caution, with the possible exception of bisphosphonates. It is also unclear if patients with a theoretical underlying risk (e.g., esophageal dysmotility) have a greater risk of esophagitis with rechallenge. In the absence of stricture formation or catastrophic presentation, most patients have clinical resolution of symptoms within 2 to 3 weeks, and radiographic resolution has been described in 7 to 10 days.

Because no treatment has been proved effective, it is hoped that proper administration of potentially injurious medications will help avoid occurrence of esophageal injury. On the basis of the sometimes normally slow transit of medications through the esophagus, particularly for gelatin capsules and larger tablets, the following recommendations are made: (1) medications should be swallowed with at least 8 ounces of a clear liquid; (2) patients should remain upright for at least 30 minutes following ingestion of the medication; and (3) in patients with potential underlying increased risk for pill-induced injury (e.g., inability to follow the previous instructions, poor esophageal motility, anatomic compromise of the esophageal lumen), one should search for alternative safer medications or carefully weigh the risks and benefits of this medication against the disease for which this medication is necessary.

Specific Medications

Several broad categories of medication types cause esophageal injury. These include antibiotics, antivirals, NSAIDs, specific antiarrhythmic drugs, vitamins, and miscellaneous isolated drugs from varied categories .