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955
Case
Giant Marc
Esophageal
S. Levine,1
Robin
Ulcer
0. Rothstein,2
Due to Clinoril
and Igor Laufer1
Drug-induced esophagitis is an increasingly frequent cause of acute odynophagia in adults. Affected persons typically have a history of ingesting their medication with little or no water immediately before going to bed. Prolonged exposure of the esophageal mucosa to a variety of capsules or tablets is thought to cause a focal contact esophagitis, manifested by one or more areas of shallow ulceration in the upper or midesophagus. In the past, endoscopy has been advocated as the primary technique for diagnosing this condition. More recently, double-contrast esophagography also has been recognized as a valuable technique for demonstrating these superficial ulcers [1 2]. Occasionally, the length of the ulcers may be several centimeters or more [1 2]. However, we recently encountered a patient in whom double-contrast esophagography showed a giant esophageal ulcer due to ingestion of Chinoril (sulindac), a nonsteroidal antiinflammatory drug (NSAID) that rarely has been implicated as a cause of drug-induced esophagitis. ,
,
Case
Report
A 36-year-old man who had been in good health had acute onset of odynophagia. He denied smoking, drinking, or drug abuse but did indicate that during the past week he had begun treatment with Clinoril for occasional arthralgias. On the night before he became symptomatic, he ingested one Clinoril tablet with only a small amount of water immediately before going to bed. The next morning, he had
Received
substernal chest pain and odynophagia swallow his saliva. Double-contrast
showed
margins.
a giant (7 x 2 cm) esophageal
No
evidence
of a hiatal
was found at fluoroscopy.
hernia
Endoscopic
ulcer below the level of the in relation to the long axis of the ulcer had irregular or gastroesophageal
examination
reflux
1 day later con-
firmed the presence of a giant ulcer in the midesophagus with erythema of the surrounding mucosa. The distal esophagus appeared normal. Biopsy samples from the ulcer margin and brushings from the ulcer base revealed acute and chronic inflammatory cells without evidence of viral inclusions, fungi, or tumor. No organisms (i.e. , herpes or cytomegalovirus) were isolated on viral cultures of specimens from
the esophagus.
Blood tests for antibodies
to human
immunodefi-
ciency virus also were negative. A tentative diagnosis of Clinorilinduced esophagitis was made. The patient was advised to stop taking Clinoril and was treated with cimetidine and sucralfate. He had a dramatic clinical response
and became
asymptomatic
within 3 days of treatment.
Endoscopy
repeated 2 months later showed a residual ulcer in the midesophagus that had decreased significantly in size. Biopsy samples and brushings again revealed acute and chronic inflammatory cells without evidence of viral or fungal infection or tumor. Esophagography re-
peated
4 months
smooth
borders
later showed in the same
a long, shallow
depression
with
as the original ulcer (Fig. 1 B). Because the patient was still asymptomatic, it was uncertain whether this represented an active ulcer or an ulcer scar. Subsequent endoscopy confirmed the presence of a shallow depression in the mid-
location
esophagus with relatively abrupt margins and normal overlying mucosa. Biopsies revealed normal squamous epithelium compatible with a reepithelialized
ulcer scar.
26, 1990; accepted after revision December 27, 1990. 3400 Spruce St., Philadelphia, PA 1 91 04. Address of Medicine, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104.
of Radiology, Hospital of the University of Pennsylvania,
AJR 156:955-956,
so severe that he could barely esophagography 2 days later
carina that had a longitudinal orientation of the esophagus (Fig. 1A). The crater
November
Department
2Department
Report
May 1991 0361 -803X/91 /1 565-0955 © American Roentgen Ray Society
reprint
requests
to M. S. Levine.
LEVINE
956
ET AL.
AJR:156,
Downloaded from www.ajronline.org by NYU Langone Med Ctr-Sch of Med on 06/16/15 from IP address 128.122.253.228. Copyright ARRS. For personal use only; all rights reserved
troesophageal
reflux
disease,
increasing
formation [3, 4]. Whatever the offending
agent,
agography,
esophagitis
the
May 1991
of stricture
risk
on double-contrast esophis usually manifested by a solitary ulcer, several discrete ulcers, or a cluster of tiny ulcers in the midesophagus near the level of the aortic arch or left main bronchus [1 2]. However, our patient had a giant esophageal ulcer approximately 7 cm long (Fig. 1A). Other causes of giant esophageal ulcers include quinidine, nasogastric intubation, Crohn disease, Behcet syndrome, and ulcerative carcinomas. With the worsening worldwide epidemic of AIDS, the possibility of a giant esophageal ulcer due to cytomegalovirus esophagitis in an AIDS patient also should be included in the differential diagnosis [6]. However, endoscopic biopsies, brushings, and cultures for cytomegalovirus and blood tests for antibodies to human immunodeficiency virus were negative in our patient. Ultimately, the correct diagnosis was suggested by the temporal relationship between ingestion of Chinoril and the onset of esophagitis. Thus, NSAIDs should be recognized as another cause of druginduced esophagitis, and, more specifically, ingestion of Clinoril should be included as a possible cause of giant esophageal ulcers. In our patient, esophagography repeated 6 months later showed a long, shallow depression with smooth borders in the same location as the original ulcer (Fig. 1 B). Because the patient was asymptomatic, it was unclear whether this represented an active ulcer or an ulcer scar. However, subsequent endoscopy confirmed the presence of a reepithehiahized pit or depression at the site of the previous ulcer. Radiologists therefore should be aware that healing of a giant esophageal ulcer occasionally may lead to the development of a smooth, well-defined pit or depression that can be mistaken for the crater of an active ulcer. drug-induced
,
Fig. 1.-Giant
esophageal
ulcer due to ingestion
of Clinoril (sulindac).
A, Initial double-contrast esophagogram shows 7 x 2 cm ulcer (arrows) in midesophagus below level of carina. Note irregular margins of ulcer. B, Esophagogram obtained 6 months later shows long, shallow depression with smooth borders (arrows) at site of previous ulcer. Endoscopy showed this was an ulcer scar with a reepithelialized pit or depression.
Discussion Drug-induced esophagitis has become a relatively common entity in today’s pill-oriented society. The medications imphicated in about half the reported cases are antibiotics, usually tetracycline or doxycychine. Other less frequent causes indude potassium chloride, quinidine, emepronium bromide, ferrous sulfate, alprenolol hydrochloride, ascorbic acid, theophylhine, and cromolyn sodium. Although it is well known that aspirin and other NSAIDs can cause erosive gastritis and gastric ulcers, these drugs rarely have been implicated in the development of esophagitis. However, our patient had acute odynophagia due to NSAID-induced esophagitis after ingesting Chinoril (suhindac). On review of the recent literature, we found that esophagitis or even esophageal strictures occasionally may be caused by a variety of NSAIDs, including aspirin, phenylbutazone, Indocin (indomethacin), Motrin (ibuprofen), Naprosyn (naproxen), Feldene (piroxicam), and Clinoril [3-5]. Some authors have postulated that these drugs may exacerbate esophagitis in patients with preexisting gas-
REFERENCES 1 . Creteur V. Laufer by double-contrast
I, Kressel HY, et al. Drug-induced esophagitis radiography. Radiology 1983; 1 47 :365-368
2. Bova JG, Dutton NE, Goldstein
HM, Hoberman
esophagitis: diagnosis by double-contrast 148:731-732 3. Coates AG, Nostrand U, Wislon JAP, caused by nonsteroidal antiinflammatory 1986;79: 1094-1097
detected
U. Medication-induced
esophagography. Elta GH, Agha medication.
AJR
1987;
FP. Esophagitis South Med J
4. Semble EL, Wu WC, Castell DO. Nonsteroidal antiinflammatory drugs and esophageal injury. Semin Arthritis Rheum 1989;19:99-109 5. Heller SR, Fellows 1W, Ogilvie AL, Atkinson M. Non-steroidal anti-inflammatory drugs 167-1 68
and
benign
6. Balthazar EJ, Megibow
oesophageal
stricture.
Br Med
J 1982;285:
AJ, Hulnick D, Cho KC, Berenbaum E. Cytomegalovirus esophagitis in AIDS: radiographic features in 16 patients. AJR
1987;149:919-923
955
Case
Giant Marc
Esophageal
S. Levine,1
Robin
Ulcer
0. Rothstein,2
Due to Clinoril
and Igor Laufer1
Drug-induced esophagitis is an increasingly frequent cause of acute odynophagia in adults. Affected persons typically have a history of ingesting their medication with little or no water immediately before going to bed. Prolonged exposure of the esophageal mucosa to a variety of capsules or tablets is thought to cause a focal contact esophagitis, manifested by one or more areas of shallow ulceration in the upper or midesophagus. In the past, endoscopy has been advocated as the primary technique for diagnosing this condition. More recently, double-contrast esophagography also has been recognized as a valuable technique for demonstrating these superficial ulcers [1 2]. Occasionally, the length of the ulcers may be several centimeters or more [1 2]. However, we recently encountered a patient in whom double-contrast esophagography showed a giant esophageal ulcer due to ingestion of Chinoril (sulindac), a nonsteroidal antiinflammatory drug (NSAID) that rarely has been implicated as a cause of drug-induced esophagitis. ,
,
Case
Report
A 36-year-old man who had been in good health had acute onset of odynophagia. He denied smoking, drinking, or drug abuse but did indicate that during the past week he had begun treatment with Clinoril for occasional arthralgias. On the night before he became symptomatic, he ingested one Clinoril tablet with only a small amount of water immediately before going to bed. The next morning, he had
Received
substernal chest pain and odynophagia swallow his saliva. Double-contrast
showed
margins.
a giant (7 x 2 cm) esophageal
No
evidence
of a hiatal
was found at fluoroscopy.
hernia
Endoscopic
ulcer below the level of the in relation to the long axis of the ulcer had irregular or gastroesophageal
examination
reflux
1 day later con-
firmed the presence of a giant ulcer in the midesophagus with erythema of the surrounding mucosa. The distal esophagus appeared normal. Biopsy samples from the ulcer margin and brushings from the ulcer base revealed acute and chronic inflammatory cells without evidence of viral inclusions, fungi, or tumor. No organisms (i.e. , herpes or cytomegalovirus) were isolated on viral cultures of specimens from
the esophagus.
Blood tests for antibodies
to human
immunodefi-
ciency virus also were negative. A tentative diagnosis of Clinorilinduced esophagitis was made. The patient was advised to stop taking Clinoril and was treated with cimetidine and sucralfate. He had a dramatic clinical response
and became
asymptomatic
within 3 days of treatment.
Endoscopy
repeated 2 months later showed a residual ulcer in the midesophagus that had decreased significantly in size. Biopsy samples and brushings again revealed acute and chronic inflammatory cells without evidence of viral or fungal infection or tumor. Esophagography re-
peated
4 months
smooth
borders
later showed in the same
a long, shallow
depression
with
as the original ulcer (Fig. 1 B). Because the patient was still asymptomatic, it was uncertain whether this represented an active ulcer or an ulcer scar. Subsequent endoscopy confirmed the presence of a shallow depression in the mid-
location
esophagus with relatively abrupt margins and normal overlying mucosa. Biopsies revealed normal squamous epithelium compatible with a reepithelialized
ulcer scar.
26, 1990; accepted after revision December 27, 1990. 3400 Spruce St., Philadelphia, PA 1 91 04. Address of Medicine, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104.
of Radiology, Hospital of the University of Pennsylvania,
AJR 156:955-956,
so severe that he could barely esophagography 2 days later
carina that had a longitudinal orientation of the esophagus (Fig. 1A). The crater
November
Department
2Department
Report
May 1991 0361 -803X/91 /1 565-0955 © American Roentgen Ray Society
reprint
requests
to M. S. Levine.
LEVINE
956
ET AL.
AJR:156,
Downloaded from www.ajronline.org by NYU Langone Med Ctr-Sch of Med on 06/16/15 from IP address 128.122.253.228. Copyright ARRS. For personal use only; all rights reserved
troesophageal
reflux
disease,
increasing
formation [3, 4]. Whatever the offending
agent,
agography,
esophagitis
the
May 1991
of stricture
risk
on double-contrast esophis usually manifested by a solitary ulcer, several discrete ulcers, or a cluster of tiny ulcers in the midesophagus near the level of the aortic arch or left main bronchus [1 2]. However, our patient had a giant esophageal ulcer approximately 7 cm long (Fig. 1A). Other causes of giant esophageal ulcers include quinidine, nasogastric intubation, Crohn disease, Behcet syndrome, and ulcerative carcinomas. With the worsening worldwide epidemic of AIDS, the possibility of a giant esophageal ulcer due to cytomegalovirus esophagitis in an AIDS patient also should be included in the differential diagnosis [6]. However, endoscopic biopsies, brushings, and cultures for cytomegalovirus and blood tests for antibodies to human immunodeficiency virus were negative in our patient. Ultimately, the correct diagnosis was suggested by the temporal relationship between ingestion of Chinoril and the onset of esophagitis. Thus, NSAIDs should be recognized as another cause of druginduced esophagitis, and, more specifically, ingestion of Clinoril should be included as a possible cause of giant esophageal ulcers. In our patient, esophagography repeated 6 months later showed a long, shallow depression with smooth borders in the same location as the original ulcer (Fig. 1 B). Because the patient was asymptomatic, it was unclear whether this represented an active ulcer or an ulcer scar. However, subsequent endoscopy confirmed the presence of a reepithehiahized pit or depression at the site of the previous ulcer. Radiologists therefore should be aware that healing of a giant esophageal ulcer occasionally may lead to the development of a smooth, well-defined pit or depression that can be mistaken for the crater of an active ulcer. drug-induced
,
Fig. 1.-Giant
esophageal
ulcer due to ingestion
of Clinoril (sulindac).
A, Initial double-contrast esophagogram shows 7 x 2 cm ulcer (arrows) in midesophagus below level of carina. Note irregular margins of ulcer. B, Esophagogram obtained 6 months later shows long, shallow depression with smooth borders (arrows) at site of previous ulcer. Endoscopy showed this was an ulcer scar with a reepithelialized pit or depression.
Discussion Drug-induced esophagitis has become a relatively common entity in today’s pill-oriented society. The medications imphicated in about half the reported cases are antibiotics, usually tetracycline or doxycychine. Other less frequent causes indude potassium chloride, quinidine, emepronium bromide, ferrous sulfate, alprenolol hydrochloride, ascorbic acid, theophylhine, and cromolyn sodium. Although it is well known that aspirin and other NSAIDs can cause erosive gastritis and gastric ulcers, these drugs rarely have been implicated in the development of esophagitis. However, our patient had acute odynophagia due to NSAID-induced esophagitis after ingesting Chinoril (suhindac). On review of the recent literature, we found that esophagitis or even esophageal strictures occasionally may be caused by a variety of NSAIDs, including aspirin, phenylbutazone, Indocin (indomethacin), Motrin (ibuprofen), Naprosyn (naproxen), Feldene (piroxicam), and Clinoril [3-5]. Some authors have postulated that these drugs may exacerbate esophagitis in patients with preexisting gas-
REFERENCES 1 . Creteur V. Laufer by double-contrast
I, Kressel HY, et al. Drug-induced esophagitis radiography. Radiology 1983; 1 47 :365-368
2. Bova JG, Dutton NE, Goldstein
HM, Hoberman
esophagitis: diagnosis by double-contrast 148:731-732 3. Coates AG, Nostrand U, Wislon JAP, caused by nonsteroidal antiinflammatory 1986;79: 1094-1097
detected
U. Medication-induced
esophagography. Elta GH, Agha medication.
AJR
1987;
FP. Esophagitis South Med J
4. Semble EL, Wu WC, Castell DO. Nonsteroidal antiinflammatory drugs and esophageal injury. Semin Arthritis Rheum 1989;19:99-109 5. Heller SR, Fellows 1W, Ogilvie AL, Atkinson M. Non-steroidal anti-inflammatory drugs 167-1 68
and
benign
6. Balthazar EJ, Megibow
oesophageal
stricture.
Br Med
J 1982;285:
AJ, Hulnick D, Cho KC, Berenbaum E. Cytomegalovirus esophagitis in AIDS: radiographic features in 16 patients. AJR
1987;149:919-923
