Other Esophagitides

PATHOGENESIS

The type and degree of injury in drug-induced esophagitis depend not only on the properties of the offending medication but also on the manner of ingestion. Affected individuals often swallow the pills or capsules with little or no water before going to bed. ^, The pills can then lodge in the midesophagus (where it is compressed by the aortic arch or left main bronchus), causing direct mucosal injury. When the esophagus is compressed by an enlarged heart, injury can also result from retained medication in the esophagus above this level. Occasionally, drug-induced esophagitis may be caused by abnormal esophageal motility or preexisting strictures that delay pill transit. ^,

Causative Agents

CLINICAL FINDINGS

Most patients with drug-induced esophagitis present with acute onset of severe odynophagia. Symptoms usually develop hours to days after taking the medication and often resolve rapidly after withdrawal of the offending agent. Some patients subsequently experience dysphagia because of developing strictures. ^,

RADIOGRAPHIC FINDINGS

The radiographic findings in drug-induced esophagitis depend on the nature of the offending agent. Tetracycline and doxycycline cause superficial injury of the mucosa, manifested on double-contrast esophagrams by a solitary ulcer ( Fig. 10.1A ), several small, discrete ulcers ( Fig. 10.1B ), or a cluster of tiny ulcers in the upper or midesophagus. ^, These ulcers are so shallow that they almost always heal without scarring or fibrosis, and affected individuals almost never develop strictures.

Drug-induced esophagitis from NSAIDs, potassium chloride, and quinidine may be manifested on barium studies by small ulcers indistinguishable from those caused by tetracycline or doxycycline ( Fig. 10.1C ). In other patients, however, NSAID-induced esophagitis may produce a giant, flat ulcer ( Fig. 10.2 ), whereas drug-induced esophagitis from potassium chloride and quinidine may produce a large, deep ulcer with considerable surrounding edema, sometimes mimicking an ulcerated esophageal carcinoma ( Fig. 10.3A ). ^{, ,} Alendronate sodium may also cause marked esophagitis with extensive ulceration, predominantly in the distal esophagus. In patients with severe esophagitis from any of these agents, subsequent scarring and fibrosis can lead to segmental strictures, mainly in the upper or midesophagus ( Fig. 10.3B ). ^{, , , ,}

DIFFERENTIAL DIAGNOSIS

Herpes esophagitis is the major consideration in the differential diagnosis for small, discrete ulcers in the upper or midesophagus, but this condition primarily occurs in patients who are immunocompromised. Reflux esophagitis is a more common cause of small ulcers, but the ulcers are almost always located in the distal esophagus. Mediastinal irradiation and caustic ingestion are other causes of ulceration, but the correct diagnosis is usually suggested on clinical grounds. Occasionally, Crohn’s disease may be manifested by aphthoid ulcers in the esophagus, but these patients almost always have concomitant Crohn’s disease in the small bowel or colon. Finally, giant drug-induced ulcers may resemble ulcerated esophageal carcinomas (see Fig. 10.3A ) or giant cytomegalovirus or human immunodeficiency virus (HIV) ulcers in patients with AIDS (see Fig. 10.2 ).

Because drug-induced esophageal strictures are usually located in the upper or midesophagus, they should be differentiated from high strictures caused by Barrett’s esophagus, eosinophilic esophagitis, mediastinal irradiation, and caustic ingestion.

PATHOGENESIS

High-dose mediastinal irradiation is thought to cause acute, self-limited esophagitis 1 to 3 weeks after the onset of therapy. ^, In contrast, chronic radiation injury is characterized by progressive scarring and stricture formation 4 to 8 months after completion of radiation therapy at doses of 30 to 50 Gy, and 3 to 4 months after therapy at doses of more than 60 Gy.

CLINICAL FINDINGS

Acute radiation esophagitis, which typically develops 1 to 3 weeks after the onset of mediastinal irradiation, is characterized by severe substernal burning, odynophagia, and/or dysphagia. The symptoms usually subside in 24 to 48 hours but occasionally persist for several weeks. Because these patients are immunocompromised, infectious esophagitis may be suspected, but the correct diagnosis should be suggested by a temporal relationship between the onset of radiation therapy and the development of symptoms. Acute radiation esophagitis is self-limited, so affected individuals usually undergo empirical treatment without the need for diagnostic testing.

Radiation-induced esophageal dysmotility or strictures may cause dysphagia several months or more after completion of radiation therapy. ^, The strictures can often be successfully dilated, but tight strictures sometimes necessitate feeding tube placement or other palliative measures. Rarely, radiation-induced esophageal injury may cause life-threatening complications such as an esophageal-airway fistula or esophageal perforation.

RADIOGRAPHIC FINDINGS

Most patients with acute radiation esophagitis are treated empirically, but, if performed, barium studies may reveal small, discrete ulcers or, even more commonly, mucosal granularity and decreased distensibility due to edema and inflammation of the irradiated esophagus ( Figs. 10.4A and 10.5 ). With more severe disease, the esophagus may have an irregular, serrated contour due to larger ulcers and mucosal sloughing, and the extent of esophagitis conforms to the radiation portal.

Radiation-induced esophageal dysmotility is characterized on barium studies by weakened or absent primary peristalsis and numerous nonperistaltic contractions within the radiation portal. ^, Radiation strictures typically appear as smooth, tapered areas of concentric narrowing in the upper or midesophagus because of the location of the radiation portal ( Fig. 10.4B ). ^, Esophageal-airway fistulas (most commonly left-sided esophagobronchial fistulas) are potentially life-threatening complications of mediastinal irradiation. Such fistulas are usually caused by radiation necrosis with erosion of tumor from the esophagus into the adjacent airway. When an esophageal-airway fistula is suspected, the fluoroscopic study should be performed with barium sulfate because a water-soluble contrast agent may cause severe pulmonary edema if it enters the lungs via a fistula.

DIFFERENTIAL DIAGNOSIS

When acute odynophagia or dysphagia develops shortly after mediastinal irradiation, the major diagnostic considerations are acute radiation esophagitis versus infectious esophagitis in an immunocompromised patient. Candida esophagitis should be suggested on barium studies by mucosal plaques, whereas herpes esophagitis should be suggested by small, discrete ulcers. In contrast, radiation esophagitis is more commonly manifested by a granular appearance, and the area of involvement conforms to a known radiation portal (see Fig. 10.4A ).

The major considerations for an upper or midesophageal stricture after mediastinal irradiation should be a radiation stricture versus esophageal involvement by mediastinal tumor (see Chapter 13). A concentric area of smooth, tapered narrowing should favor a radiation stricture, whereas irregular, eccentric narrowing and extrinsic mass effect should favor malignant tumor. When the radiographic findings are equivocal, computed tomography (CT) may help differentiate a radiation stricture from recurrent tumor.

PATHOGENESIS

Caustic injury to the esophagus may be caused by ingestion of alkali, acids, ammonium chloride, phenols, silver nitrate, and other common household products. Children usually ingest these agents accidentally, whereas adults take them intentionally to commit suicide. The degree of injury depends on the nature, concentration, and volume of the corrosive agent as well as the duration of tissue contact. In the United States, most patients swallow liquid lye (concentrated sodium hydroxide), which causes severe esophageal injury by liquefaction necrosis. ^, In contrast, ingested acids cause tissue damage by coagulative necrosis, forming a protective eschar that limits tissue penetration. ^, Nevertheless, acidic agents may produce severe esophagitis and strictures comparable to those caused by lye.

Caustic esophagitis is characterized by three phases of injury: (1) acute necrosis; (2) ulceration and granulation; and (3) cicatrization and scarring. The initial phase of acute cellular necrosis begins immediately after caustic ingestion and lasts 1 to 4 days. The ulceration-granulation phase begins 3 to 5 days after caustic ingestion and is characterized by edema, ulceration, and sloughing of necrotic mucosa. During the next 7 to 14 days, granulation tissue forms in areas of mucosal sloughing; the esophagus is thought to be most vulnerable to perforation during this period. The final phase of cicatrization begins 3 to 4 weeks after caustic ingestion, often leading to severe scarring and stricture formation.

CLINICAL FINDINGS

Patients with caustic esophagitis may present with odynophagia, chest pain, drooling, vomiting, and/or hematemesis. ^{, ,} Severe substernal pain, fever, and shock usually indicate esophageal perforation and mediastinitis. ^, Associated gastric perforation can lead to peritonitis. If patients survive the acute illness, they may be asymptomatic for weeks before developing intractable dysphagia due to progressive stricture formation 1 to 3 months after the initial injury. ^{, ,}

DIAGNOSIS AND TREATMENT

When caustic ingestion is suspected, examination of the mouth and oropharynx sometimes reveals extensive mucosal injury and ulceration. Liquid corrosives may be swallowed rapidly, however, so caustic esophagitis often occurs without associated oropharyngeal injury. ^{, ,} Direct esophageal visualization is therefore required for a definitive diagnosis. A limited fluoroscopic study may be performed with a water-soluble contrast agent to detect esophageal or gastric perforation or other gross signs of caustic injury. In the absence of signs of perforation, however, early endoscopy is advocated to assess the severity and extent of injury. ^{, ,}

Treatment of caustic esophagitis is aimed at preventing stricture formation. Administration of steroids and antibiotics and prophylactic esophageal bougienage are often recommended to inhibit collagen formation and decrease stricture formation. ^, Nevertheless, 10% to 40% of patients with caustic esophagitis develop strictures. ^, If these strictures are too severe or extensive to be dilated endoscopically, an esophageal bypass operation such as a colonic interposition may be required (see Chapter 16). When strictures develop after caustic ingestion, barium studies are often performed to determine the degree and extent of stricture formation. Patients with lye strictures are also thought to have a substantially increased risk of developing esophageal carcinoma 20 to 40 years after the initial caustic injury (see Chapter 12). ^,