DISEASES OF THE
• Infectious Esophagitis
• Infectious esophagitis occurs principally, but not
exclusively, in immunocompromised patients, usually
from cancer chemotherapy, post-transplant antirejection
medication, and acquired immunodeficiency syndrome
(AIDS) (especially with CD4 counts <200 mm3) .
• Candida albicans , herpes simplex virus type 1 (HSV-1) ,
and CMV are the most common causes, and coinfection
with more than one agent may occur.
• In AIDS, CMV esophagitis may coexist with CMV retinitis
• Odynophagia is characteristic and may be severe.
• Dysphagia, weight loss, and gastrointestinal bleeding are common.
• Complications are infrequent but may include tracheobronchial
fistula, perforation, and hemorrhage.
• Esophageal candidiasis in AIDS is associated with oral candidiasis
(thrush) in only about two thirds of cases, and HSV esophagitis is
associated with oral herpetic lesions in about a third of cases.
• In an immunocompetent host, infectious esophagitis is primarily due
to HSV or Candida.
• On barium swallow, a ―shaggy‖ mucosa suggests
Candida; numerous small, volcanic-shaped ulcers
suggest HSV; and large, deep linear ulcers suggest
CMV (or HIV).
• Multiple biopsies of ulcerated areas with routine
histologic evaluation provide a definitive diagnosis.
• Candida esophagitis is characterized on endoscopy by
numerous small white-yellow mucosal plaques
containing microorganisms, inflammatory cells, and
necrotic mucosa .
• Positive brushings and biopsy demonstrate Candida
pseudohyphae with periodic acid–Schiff reagent or
special silver stains.
• HSV esophagitis on endoscopy begins as numerous
vesicles that ulcerate to yield small (<2 cm), shallow,
volcano-shaped ulcers .
• A positive biopsy specimen from the ulcer edge
demonstrates the characteristic cytopathic effect of HSV
within squamous epithelial cells—eosinophilic
• CMV esophagitis is characterized by large (>2 cm),
deep, often linear ulcers; a positive biopsy specimen
from the ulcer base demonstrates the characteristic
cytopathic effect of CMV within fibroblasts and
endothelial cells—basophilic intranuclear inclusions.
• In non-AIDS patients, Candida esophagitis may
be treated with oral nystatin, 1 to 3 million units
four times a day, or clotrimazole, 100-mg tablets
dissolved in the mouth three to five times a day,
but patients with AIDS require an azole
antifungal such as oral or intravenous
fluconazole, 100 to 200 mg/day for 10 to 14
• Ketoconazole and itraconazole are also effective
but, unlike fluconazole, require normal gastric
acidity for absorption.
• In resistant cases, intravenous caspofungin, 50
mg/day (after a 70-mg loading dose), or low-
dose intravenous amphotericin, 0.3 to 0.5
mg/kg/day, for 10 to 14 days is effective.
• HSV esophagitis is treated with a nucleoside
analogue such as acyclovir, 200 to 400 mg
orally five times a day or 250 mg/m2
intravenously every 8 hours for 2 weeks.
• Valacyclovir and famciclovir are alternatives; for
resistant cases, intravenous foscarnet, 60 mg/kg
every 8 hours for 2 to 4 weeks, is effective.
• CMV esophagitis is treated with intravenous
ganciclovir, 5 mg/kg every 12 hours for 2 to 4
weeks; for resistant cases, foscarnet is
administered intravenously at 60 mg/kg every 8
hours for 2 to 4 weeks.
• Idiopathic HIV-associated ulcers are treated with
prednisone, 40 mg/day, tapering by 10 mg/wk
for 1 month; thalidomide, 200 mg/day, may also
• Because relapse of all forms of infectious
esophagitis is common in immunocompromised
patients, maintenance therapy may be required.
Alkaline Reflux Esophagitis
• Alkaline reflux esophagitis is an uncommon and
poorly defined clinical entity that develops in the
setting of repeated and prolonged contact of the
esophageal epithelium with nonacidic gastric or
intestinal contents, usually in subjects with a
destroyed pylorus after total gastrectomy or a
Billroth II gastroenterostomy.
• Treatment is with bile salt–binding or mucosal-
coating agents such as cholestyramine,
sucralfate, or colloidal bismuth. Surgical
fundoplication (intact stomach) or creation of a
Roux-en-Y limb (after gastrectomy) is performed
in refractory cases.
• Pill-induced esophagitis commonly develops in patients,
particularly the elderly, who are taking medication
improperly (i.e., while supine or with too little liquid).
• It also occurs in patients with a preexisting abnormality,
such as a stricture, diverticulum, or motor disorder.
• Pills adhere to the esophageal mucosa and cause
necrosis and ulceration by the topical release of caustic
• Among the common offenders are doxycycline,
tetracycline, vitamin C, potassium chloride, nonsteroidal
anti-inflammatory drugs, quinidine, alendronate and
other bisphosphonates , and iron.
• Odynophagia is characteristic and commonly
accompanied by dysphagia.
• Ulceration may lead to hemorrhage, perforation, and
stricture. Upper endoscopy is indicated in nonobvious
cases to exclude infectious esophagitis.
• Discontinuation of the offending medication and
treatment with sucralfate suspension (1 g orally four
times a day for 1 to 2 weeks) or a cocktail (equal parts
viscous lidocaine, antacid, and diphenhydramine )may
control the symptoms.
• Once-a-day PPI therapy is useful to prevent aggravation
• Education about the proper method of taking medication
may prevent recurrence.
• Radiation esophagitis occurs after chest
radiation therapy at dose levels that exceed 30
Gy (3000 rad) .
• At levels higher than 60 Gy, severe esophagitis
and ulceration can develop and lead to
hemorrhage, perforation, or fistula.
• Concomitant chemotherapy with cytotoxic
agents (e.g., doxorubicin [Adriamycin]) can
potentiate radiation injury.
• Substernal pain, odynophagia, and dysphagia
• Barium swallow and endoscopy can
demonstrate the extent and severity of mucosal
inflammation, ulceration, and luminal narrowing;
endoscopy has the added benefit of biopsy for
exclusion of infectious esophagitis.
• A liquid diet or intravenous fluids plus the
treatments described for pill-induced esophagitis
• Strictures may require bougienage for dilation or
even esophagectomy with colonic or jejunal
• Eosinophilic esophagitis is an uncommon,
immunologically mediated entity that is being
recognized with increasing frequency in children
and adults aged 20 to 40 years.
• It has a 3 : 1 male-to-female predominance, and
half the patients have asthma, skin reactions,
and peripheral eosinophilia.
• The disease is due to food allergy and can be
manifested as chest pain or heartburn, but solid
food dysphagia and food impaction are
• Endoscopic findings range from grossly normal
to a corrugated, inflamed, eroded, or fibrotic
esophagus in which a single- or multiple-ringed
esophagus or a stiff, narrowed, noncompliant
organ is often produced.
• Esophageal biopsy is diagnostic with high (>15
to 20 per high-power field) concentrations of
mucosal eosinophils .
• The presence of a dense collagen network
within the lamina propria accounts for the rigidity
and propensity to fracture (tear) on bougienage.
• Skin testing for allergy should be performed to identify
and remove the offending agent or agents—the most
common being seafood, nuts, milk, eggs, and soy.
• Dietary changes or therapy with oral cromolyn (100 to
200 mg four times daily), an H1-antagonist (e.g.,
chlorpheniramine, 4 mg four times daily) plus an H2-
antagonist (e.g., cimetidine, 300 mg four times daily),
glucocorticoids (topical fluticasone propionate, 220 μg
per puff, two puffs swallowed twice to four times daily),
or a leukotriene receptor antagonist (montelukast) may
control symptoms, but relapse is common after cessation
• Monoclonal antibodies to interleukin-5 are being
investigated as therapy because this cytokine mediates
the esophageal eosinophilia.
• Caustic esophagitis occurs from accidental ingestion in
children and from suicidal attempts in adults.
• Among the more common materials ingested are drain
cleaners (sodium hydroxide), bleach (sodium
hypochlorite), detergents (sodium tripolyphosphates),
and disc batteries (sodium hydroxide).
• Sodium hydroxide (lye) produces liquefaction necrosis
on contact with the oropharynx and esophagus and thus
has the potential to cause acute ulceration, perforation,
and later stricture formation.
• When perforation is excluded by contrast (Gastrografin
and, if negative, barium) swallows, endoscopy may be of
value to assess the esophageal injury, but passage of
the scope beyond an area of severe injury is not
recommended to avoid perforation.
• Emergency esophagogastrectomy is indicated for free
perforation and mediastinitis. In the absence of these
complications, esophagitis is treated supportively with
intravenous fluids and prophylactic antibiotics.
• Steroids in tapering dosage are often given but are
without proven efficacy.
• A feeding tube is passed under direct vision to provide
nutrition and a means for later dilation of a tight stricture.
• When strictures are complex and respond poorly to
dilation, intestinal or colonic interposition should be
considered to restore oral intake.
• Esophageal motor disease is characterized by
dysphagia for liquids and solids or chest pain (or
• Although the chest pain may mimic cardiac
disease and be the dominant complaint, careful
questioning should also detect dysphagia.
• Recurrent chest pain without dysphagia is rarely
due to esophageal motor disease.
• Oropharyngeal dysphagia is due to
neuromuscular disorders of the oropharynx and
the skeletal muscle portion of the esophagus,
including stroke, Parkinson's disease,
amyotrophic lateral sclerosis, multiple sclerosis,
myasthenia gravis, polymyositis, and myotonic
• It is characterized by difficulty in bolus transfer
from the mouth to the esophagus and by nasal
regurgitation or coughing (from aspiration) with
• Oropharyngeal dysphagia commonly occurs
amid other signs and symptoms of the
underlying neuromuscular disorder.
• A modified barium swallow with
videofluoroscopy is the procedure of choice.
• The swallows are performed with barium of
different consistencies and with the subject
swallowing in different head and body positions.
• Nutritional support via diet, swallow maneuvers,
feeding tubes, or percutaneous endoscopic
gastrostomy is appropriate, whereas primary
therapy is directed at the neuromuscular
• Esophageal dysphagia is due to disease
of the smooth muscle–lined portion of the
• The dysphagia is not accompanied by
failure of bolus transfer from the mouth to
the esophagus, by nasal regurgitation, or
by coughing with swallowing, and it
characteristically occurs with liquids as
well as solids, thus indicating a lack of
discrimination for bolus size.
• Achalasia and diffuse esophageal spasm are
primary esophageal motor disorders, whereas
scleroderma is the most common secondary
• A barium swallow is valuable as a first test
because it provides evidence to support either a
motor or mechanical cause of dysphagia.
• When motor disease is suggested, esophageal
manometry is often diagnostic and provides both
quantitative and qualitative information about
peristaltic and sphincter function.
• Achalasia is the most common primary
esophageal motor disorder, with a
prevalence of about 10 per 100,000
• Its etiology is unknown, and it can occur at
any age but usually between the ages of
30 and 60 years.
• Achalasia is characterized histopathologically by degeneration of the
nerves in Auerbach's plexus, although changes also occur in the
vagus nerve and swallowing center.
• The consequences of neuronal injury are an increase in LES
pressure, incomplete LES relaxation with swallowing (achalasia
means ―failure to relax‖), and complete (100%) aperistalsis in the
• Failure of the LES to relax produces an obstruction at the
gastroesophageal junction that leads to esophageal retention.
• Dilation of the esophageal body occurs as a result of the increase in
intraluminal pressure and the presence of weak, aperistaltic
• Dysphagia for liquids and solids is the primary complaint.
• Regurgitation is common, and nocturnal cough suggests
aspiration on reclining.
• Atypical chest pain and heartburn occur in about a third
of cases secondary to increased intraesophageal
pressure and stasis-induced mucosal inflammation,
• Weight loss is highly variable and should raise concern
about adenocarcinoma of the esophagus or gastric
• The chest radiograph may show a widened
mediastinum, air-fluid level, and absent gastric air
• Barium swallow characteristically shows a dilated
esophagus, air-fluid level, delayed esophageal emptying,
and a smooth, tapered ―bird's beak‖ deformity at the
• Chagas' disease can mimic achalasia by producing
megaesophagus, but it also produces megaduodenum
and often megaureter and cardiomegaly.
• Confirmation is by esophageal
manometry, which shows the
characteristic incomplete relaxation of the
LES with swallows and complete
aperistalsis in the esophageal body.
• LES pressure may or may not be elevated.
• However, neither radiographic nor
manometric criteria can effectively exclude
pseudoachalasia, or achalasia secondary
to an infiltrating cancer.
• For this reason, endoscopy is performed
to examine the area before treatment; if
findings are suspicious but inconclusive,
biopsy should be performed, followed by
examination of the area by endoscopic
ultrasonography or computed tomography
• A muscle relaxant such as nifedipine, 10 mg
sublingually before meals, may be helpful.
• More effective treatment requires either
endoscopic injection of botulinum toxin into the
LES (20 units per quadrant), pneumatic dilation,
or surgical Heller myotomy.
• The benefits of botulinum toxin are relatively
short lived (3 to 6 months) when compared with
pneumatic dilation, so repeated injections are
necessary for the life of the patient.
• Pneumatic dilation under conscious sedation inflates a
balloon (3 to 4 cm in diameter) placed across the LES to
rupture its musculature; repeated treatment may be
necessary for maximum benefit.
• A surgical Heller myotomy, which involves direct incision
of the LES, is usually performed laparoscopically.
• Both pneumatic dilation and Heller myotomy provide
excellent relief of symptoms for 5 to 10 years in about
85% of subjects.
• The major risk associated with pneumatic dilation is
esophageal perforation (average of ≈3%), and the major
side effect of Heller myotomy is reflux esophagitis
• An antireflux procedure can be combined with a Heller
myotomy to reduce the risk for postoperative GERD.
Diffuse Esophageal Spasm
• Clinical Manifestations
• This uncommon motor disorder is manifested
clinically as intermittent chest pain and
dysphagia—with chest pain often being the
dominant complaint but rarely occurring without
• Like achalasia, diffuse esophageal spasm is
associated with degeneration of the nerves in
Auerbach's plexus and, in rare instances, can
evolve to achalasia.
• On barium swallow, diffuse esophageal
spasm has prominent, spontaneous,
nonpropulsive tertiary contractions that
can give rise to the appearance of a
―corkscrew‖ esophagus .
• This appearance, however, is not
pathognomonic because it is also
observed in asymptomatic elderly patients,
hence the term presbyesophagus.
• On esophageal manometry, more than
30% (but less than 100%) of esophageal
contractions are aperistaltic and
occasionally repetitive, but manometric
findings are not pathognomonic because
the diagnosis of diffuse esophageal spasm
requires exclusion of diseases that
produce similar motor changes, such as
diabetes mellitus , amyloidosis ,
scleroderma , idiopathic pseudo-
obstruction, and reflux esophagitis.
• Therapy is principally supportive and empirical.
• Recommendations include reassurance of the benign
nature of the disease, a trial of smooth muscle relaxants
(e.g., isosorbide, 10 mg, nifedipine, 10 mg, or
dicyclomine , 20 mg before meals) or a trial of an
antidepressant (e.g., amitriptyline, 25 to 50 mg at
bedtime, imipramine, 25 to 50 mg at bedtime, and
trazodone, 50 mg three times a day).
• In some instances, relaxation exercises, biofeedback,
and psychological counseling are helpful adjuncts to
• The esophagus is the gastrointestinal
organ most often affected in scleroderma ,
and it results in a characteristic
manometric pattern of low LES pressure
and weak aperistaltic contractions in the
smooth muscle portion of the esophageal
• UES and skeletal muscle–lined upper
esophageal contractions are normal.
• Esophageal involvement in scleroderma
results in dysphagia, regurgitation, and
• When dysphagia for solids is prominent, it
probably reflects a peptic stricture or
adenocarcinoma in Barrett's esophagus.
• Patients with scleroderma should be
treated prophylactically for GERD .
• Nutcracker esophagus is a term given to a
relatively common manometric pattern found in
patients with noncardiac chest pain.
• This pattern consists of normal peristalsis but
with contractions of very high amplitude
(average >180 mm Hg).
• However, a reduction in contraction amplitude
by calcium-channel blockers has no consistent
effect on chest pain, and chest pain can be
relieved by medications (e.g., trazodone) that
have no effect on amplitude.
• Patients with chest pain and nutcracker
esophagus commonly exhibit symptoms and
signs of depression or anxiety.
• Treatment of these disorders with
• (1) amitriptyline (25 to 75 mg at bedtime),
imipramine (25 to 50 mg at bedtime), and
trazodone (50 mg three times a day) or
• (2) alprazolam (0.25 to 0.5 mg three times a
day) and clonazepam (0.5 to 1 mg twice a day)
may relieve the chest pain.
• Tumors of the esophagus may be benign or
• Benign tumors are uncommon and include
fibrovascular polyps, leiomyomas, papillomas,
lipomas, neurofibromas, and granular cell
• When large, benign tumors can cause
dysphagia or chest pain from obstruction or
• Malignant tumors of the esophagus currently
occur at a rate of about 14,000 cases per year in
the United States and are divided about equally
between squamous cell carcinoma and
• Rare primary malignancies include
leiomyosarcoma, melanoma, lymphoma, and
• Tumors metastatic to the esophagus usually
originate from the breast, lung, or skin
Squamous Cell Carcinoma
• The incidence of squamous cell carcinoma in
the United States is about 2.6 per 100,000, with
men having a three- to fourfold higher risk than
women and blacks a four- to fivefold higher risk
• Regions of high risk also exist in the Transkei of
South Africa, China's Linxian and Yangcheng
provinces, and Kashmir and Bombay in India.
• The risk for squamous cell cancer is higher with
heavy alcohol and tobacco use, papillomavirus
infection, lye ingestion, achalasia, Plummer-
Vinson syndrome, tylosis, celiac disease, and
• The clinical manifestation is typically rapidly
progressive dysphagia for solids, anorexia, and
• Less commonly, squamous cell carcinoma is
accompanied by hypercalcemia
(recurrent laryngeal nerve paralysis), or
• Barium swallow generally reveals a bulky,
eroded, partially obstructing esophageal mass
that is proved to be squamous cell carcinoma by
• Adjacent lymph node invasion is common
because the esophagus lacks a serosal layer.
• Hematogenous metastases usually spread
to the liver, lungs, kidney, heart, and bone.
• Endoscopic ultrasonography or CT, or
both, are used for staging.
• Squamous cell carcinoma is
radiosensitive, and chemoradiation
therapy, with or without subsequent
surgery, can improve the outcome.
• Nonetheless, late-stage diagnosis is the
rule, so the overall 5-year survival rate is
only 20 to 30%.
• Palliation for dysphagia caused by
inoperable, obstructing cancers is better
with brachytherapy than with endoscopic
• Other options include bougienage or tumor
ablation by laser, heater probe, or alcohol
• Adenocarcinomas are equally as common as
squamous cell cancers but, unlike squamous
cancers, arise principally in the distal end of the
esophagus , because the predominant risk for
adenocarcinoma is Barrett's esophagus.
• However, only about 40% of patients with
esophageal adenocarcinoma have a history of
heartburn, and heartburn occurs in an even
smaller percentage of those with Barrett's
• The diagnosis of adenocarcinoma is typically
made at endoscopy in a patient with dysphagia,
anorexia, and weight loss secondary to a lumen-
• Lymphatic spread is common.
• Adenocarcinomas are radioinsensitive; although
chemoradiation therapy and surgery may
improve survival, 5-year survival rates are less
• Palliation is the same as for inoperable
squamous cell carcinoma.
• Oral bisphosphonates have been linked to esophageal
adenocarcinoma and squamous cell carcinoma
according to a post-marketing Food and Drug
Administration (FDA) lette.
• The reasons why they should increase the risk are not
understood, although crystalline material similar to
alendronate has been identified in biopsies of patients
with erosive esophagitis suggesting a potential for
• At present, the FDA recommends that oral
bisphosphonates not be used in patients with Barrett's