Gastroenterology and Hepatology Board Review: Pearls of Wisdom, Third Edition

Section II ESOPHAGUS

CHAPTER 11. Esophageal Miscellaneous Inflammatory Diseases

John K. DiBaise, MD

Image A 17-year-old woman with acne but otherwise healthy presents with persistent severe odynophagia. Endoscopy demonstrates the following finding in the mid esophagus. What is the most likely diagnosis.

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Figure 11-1 See also color plate.

Pill esophagitis. This patient recently began taking tetracycline for her acne.

Image How common is pill-induced esophageal injury?

The prevalence is very difficult to determine; however, the incidence is believed to be 3.9 per 100,000 populations per year based on one prospective Swedish study.

Image Which patients are more likely to develop drug-induced esophageal injury?

Most reports reveal predominance in elderly and female patients. The elderly are more prone due to a higher prevalence of esophageal motility disorders and obstructing lesions of the esophagus. In addition, the elderly ingest more drugs in general, produce less saliva, are more likely to forget proper dosing instruction, and spend more time in the recumbent position. Drug-induced injury is about twice as common in females due to greater use of potassium supplements and bisphosphonates.

Image What are the major pathogenic factors contributing to drug-induced esophageal damage?

The chemical content, formulation of the drug, and the manner in which the drug was taken by the patient are the major factors. Most patients with drug-induced esophageal injury have no detectable esophageal dysmotility or structural abnormality.

Image What are the common locations in the esophagus for drug-induced esophageal injury?

The level of the aortic-arch (more prevalent in older patients) and the distal esophagus.

Image What are the most common clinical manifestations of drug-induced esophageal injury?

Retrosternal chest pain is the most common manifestation (61%–72%) followed by odynophagia (50%–74%) and dysphagia (20%–40%). Symptoms can develop within hours to days after starting the medication. In almost all cases, the diagnosis can be determined on the basis of the history.

Image What medications are commonly implicated in drug-induced esophageal injury?

The most common is tetracycline or one of its derivatives. Other medications include nonsteroidal anti-inflammatory drugs, potassium chloride, iron sulfate, quinidine, corticosteroids, pancreatic enzymes, cloxacillin, dicloxacillin, oral contraceptives, and bisphosphonates.

Image What is the best diagnostic modality in drug-induced esophageal injury?

Although not necessary in every patient, endoscopy is the best diagnostic modality with considerable superiority in sensitivity over a barium contrast esophagogram.

Image True/False: In chemotherapy-related esophagitis, esophageal involvement correlates with involvement of oropharyngeal mucosa (ie, presence of mucositis).

True. It is very unusual to have esophageal damage in the absence of oral changes.

Image True/False: The esophagus is the most common segment of the upper gut involved in acute graft versus host disease (GVHD).

False. Acute GVHD of the upper gastrointestinal tract is most often characterized by anorexia, abdominal discomfort, nausea, and vomiting.

Image A 35-year-old man with acute lymphocytic leukemia underwent bone marrow transplantation 120 days ago and now presents with dysphagia and retrosternal pain. Barium swallow reveals a mid-esophageal stricture. What is the most likely etiology?

Chronic graft versus host disease (GVHD) is the most likely etiology and is manifested by webs, rings, and strictures of the upper and mid-esophagus. Esophageal dysmotility also appears to be common. Indeed, the clinical presentation resembles that of progressive systemic sclerosis. Dysphagia may also be precipitated by decreased oral saliva production. Immunosuppressive drugs are commonly employed in this situation and endoscopy with dilatation in selected cases may be helpful.

Image True/False: The finding of esophageal parakeratosis should prompt a careful examination of the esophagus and head and neck for squamous cell cancer.

True, although the clinical significance of the reported association between esophageal parakeratosis and esophageal and head and neck cancers remains unclear. Esophageal parakeratosis appears on endoscopy as whitish, membranous linear plaques that do not turn brown when sprayed with Lugol’s solution. Biopsies reveal epithelial acanthosis, basal hyperplasia, and a dense compact layer of parakeratosis, often featuring cytoplasmic eosinophilia and pyknotic nuclei, covered by an outer layer of nonnucleated squamous cells.

Image What condition is being demonstrated in the endoscopic image?

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Figure 11-2 See also color plate.

Esophagitis dissecans superficialis. This is a rare condition characterized by sloughing of the esophageal mucosa, in severe cases appearing as tubular cast within or tethered to the esophagus. It has been seen in association with desquamating skin diseases such as pemphigus vulgaris.

Image What is “black esophagus”?

Acute esophageal necrosis is also referred to as black esophagus or necrotizing esophagitis. Patients typically present with upper gastrointestinal bleeding and usually have an underlying predisposing condition, most commonly, hypotension or gastric outlet obstruction. Its occurrence is in the absence of caustic or other injurious topical agents.

Image True/False: The mortality rate in “black esophagus” approaches 90%.

False. Most patients recover; however, mortality due to the underlying cause ranges from 25% to 30%.

Image A 37-year-old otherwise healthy man presents to the emergency department with a persistent esophageal food bolus impaction. Following endoscopic removal, the following endoscopic images are obtained and biopsies are taken. What is the diagnosis?

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Figure 11-3 See also color plate.

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Figure 11-4 See also color plate.

Eosinophilic esophagitis. The diagnosis is based on symptoms, endoscopic appearance, and histological findings. Eosinophilic esophagitis should be considered in adults with a history of food impaction, chronic solid dysphagia, or with gastroesophageal reflux disease that fails to respond to medical therapy. In children, symptoms vary by age and include feeding disorders, vomiting, abdominal pain, dysphagia, and food impaction.

Image True/False: Eosinophilic esophagitis (EoE) is more common in middle-aged women.

False. It appears to be most common in young men. The pathogenesis of EoE is incompletely understood but includes both environmental and genetic factors. In particular, adaptive T-cell immunity driven by Th2 cells involving IL-13, IL-5, and IL-15 expression appears to play a major role.

Image True/False: There is a strong association of EoE with allergic conditions such as food allergies, environmental allergies, asthma, and atopic dermatitis.

True.

Image Describe some endoscopic findings in EoE.

Stacked circular rings (“feline” esophagus), linear furrowing that may extend the entire length of the esophagus, whitish papules representing eosinophil microabscesses, and a small caliber, poorly compliant esophagus. Importantly, the sensitivity and specificity of these findings is not good and often the endoscopic appearance is normal, reinforcing the need to biopsy when this condition is suspected.

Image True/False: Biopsies of the distal esophagus are important in the diagnosis of EoE.

False. Increased numbers of eosinophils in the distal esophagus may be due to gastroesophageal reflux. Biopsies for EoE should be taken from the mid- and proximal esophagus. A threshold of 15 eosinophils per high-power field is generally required for the diagnosis.

Image True/False: Peripheral eosinophilia is present in about 10% of patients with EoE.

False. Peripheral eosinophilia, usually mild, is seen in up to 40%–50%.

Image Which one of the following has not been recommended for the treatment of EoE: swallowed fluticasone, inhaled fluticasone, swallowed viscous budesonide, elimination diet, proton pump inhibitor, and esophageal dilation?

Inhaled fluticasone.

Image True/False: Esophageal dilation in EoE is associated with a higher risk of mucosal tears and esophageal perforation.

True. Indeed, endoscopy without dilation also appears to be at higher risk of tears and perforation.

Image True/False: Esophageal lichen planus (ELP) is more common in middle-aged women.

True. ELP is a rare manifestation of lichen planus, which is a common disease typically involving the scalp, nails, skin, and mucosa. Most patients with ELP will complain of dysphagia and will also have oral involvement. A recent review found that 87% of cases in the literature were women with a mean age of 62 years.

Image True/False: Endoscopy with esophageal brushing/cytology is the diagnostic test of choice in suspected ELP.

False. Mucosal biopsy at the time of endoscopy is needed. Endoscopy should be performed in all persons with mucocutaneous lichen planus who complain of esophageal symptoms and/or weight loss.

Image True/False: Endoscopic findings in ELP are most commonly confined to the distal esophagus.

False. The proximal and mid-esophagus are most commonly affected. The sparing of the distal esophageal may be a clue to the presence of ELP. Classical endoscopic findings include peeling tissue paper-like pseudomembranes. Friability of the mucosa is also common. Lacy white plaques, ulcerations, webs, and strictures have also been described.

Image True/False: ELP is associated with an increased risk of esophageal adenocarcinoma.

False. Malignant transformation of ELP to squamous cell cancer has been reported; however, its status as a premalignant condition remains unclear.

Image What treatments are useful in the management of ELP?

Systemic treatments are generally required and are usually effective. Systemic corticosteroids given over 4 to 6 weeks seem to be most effective. Cyclosporine, azathioprine, systemic retinoids, and biologic immunomodulators have also demonstrated benefit. Esophageal dilation(s) may also be needed, particularly once strictures have formed. Maintenance therapy with one of these agents in conjunction with an antisecretory agent has been recommended.

• • • SUGGESTED READINGS • • •

Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128(1):3-20.

Fox LP, Lightdale CJ, Grossman ME. Lichen planus of the esophagus: what dermatologists need to know. J Am Acad Dermatol. 2011;65:175-183.

Carpenter PA. Late effects of chronic graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21(2):309-331.

Kikendall JW. Pill esophagitis. J Clin Gastroenterol. 1999;28(4):298-305.