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 Abstract
Esophageal ulceration occasionally occurs in patients taking doxycycline
capsules or tablets. We report two
patients who develop acute esophageal
ulceration after ingestion of
doxycycline capsules for Acne vulgaris.
Despite extensive investigation, no
evidence of other causes was found. The
ulcers are postulated to result from
close contact between the capsules and
the esophageal mucosa. We show the
endoscopic image of the lesion,
symptomatology, diagnosis, treatment,
and prevention of doxycycline-induced
esophageal lesions.
Key words: Esophagitis, doxycycline,
esophageal ulcer.
Introduction
Three decades after the first report of
drug-induced esophageal injury (DIEI)
induced by potassium therapy(1),
approximately 1,000 cases of DIEI caused
by almost 100 different drugs, have been
reported in the world literature.
Antibiotics have contributed to almost
50% and doxycycline alone to 27 % of all
cases(2). Doxycycline is often used for
treatment of Acne vulgaris. It can
induce esophageal abnormalities via both
systemic and local actions. Examples of
systemic effects include gastro
esophageal reflux promoted by smooth
muscle relaxants, and medication-induced
compromise of the immune system,
resulting in infectious complications.
The types of medication causing direct
esophageal injury can be roughly divided
into antibiotics, anti-inflammatory
agents, and others. We describe two
cases of Tetracycline-induced
esophagitis with endoscopic images.
Dysphagia or odynophagia with
retrosternal pain were the main
presenting symptoms in both cases.
Symptoms started 7-15 days after
medication used.
Case Report
Case 1
A 19-years old male Qatari admitted to
the hospital complaining of retrosternal
chest pain starting five days prior to
admission, sharp in nature, aggravated
by food and not associated with nausea
or vomiting. The complaint started 15
days after the initiation of doxycycline
capsules for acne. On direct questioning
he mentioned taking the medication at
bed time with a little amount of fluid.
Apart from acne vulgaris on his face,
the clinical examination was
unremarkable. Investigations including
hemoglobin, platelets, leukocyte count,
blood chemistry and liver function tests
were normal. Electrocardiography tracing
was normal. Upper gastrointestinal
endoscopy revealed superficial
ulceration (Figure 1).
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As a result, Doxycycline was stopped and proton pump
inhibitors with antacid were initiated.
In the following days, the pain subsided
and the patient was discharged.
Case 2
A 33-years old Jordanian female had
history of acne vulgaris and was started
on Doxycycline capsules, 10-days later
she developed dysphagia & retrosternal
chest pain without nausea or vomiting.
On direct questioning she mentioned
taking the medication at bed time with a
little amount of fluid. Clinical
examination was unremarkable.
Investigations including hemoglobin,
platelets, leukocyte count, blood
chemistry and liver function tests were
normal.
Electrocardiography tracing was normal. Endoscopy showed linear ulcer in
the esophagus
(Figure 2).
As a result, Doxycycline was
stopped and proton pump inhibitors with
antacid were initiated. In the following
days, both the pain and dysphagia
subsided and the patient was discharged.
Discussion
The reported DIEI approximate
incidence of 4/100 000 is probably
underestimated. The actual incidence is
apparently much higher because of
increase in drugs prescription and
failure of reporting (2,3). History has
been considered sufficient for assuming
a clinical diagnosis(4,5). Retrosternal
pain and sudden odynophagia with or
without dysphagia are suspicious of the
diagnosis(2). History of medication,
time of drug intake and amount of
concurrent fluid ingested are important
(6,7). Upper gastrointestinal endoscopy
is almost always abnormal and it has
been considered as the method of choice
to confirm DIEI (2). The clinical course
is usually uneventful and DIEI may heal
after withdrawal of the offending drugs
(5-8). Approximately 100 types of drugs
have been incriminated in the etiology
of around 1,000 cases of DIEI. The
precise mechanism is not well explained.
However, multiple factors, including
increasing age, decreased esophageal
peristalsis and external compression
predispose to DIEI(2). Furthermore,
drugs that have a large size and sticky
surface are retained longer in the
esophagus(2,7,9). A clinical and
experimental study has shown that
doxycycline capsules remain three times
longer in the esophagus than doxycycline
tablets(10). Elderly patients are more
prone to develop DIEI due to their
altered esophageal motility and
decreased saliva production. In
addition, they more frequently suffer
from cardiac disease, require more
cardiovascular medication and remain
longer in a recumbent position(7,11,12).
In younger patients, DIEI is mainly
caused by antibiotics(2,5,6). Our
patients were young and the only
incriminated drug was doxycycline. Both
patients took doxycycline capsules and
shared the same risk factor by taking
the medication at bed time with a little
amount of fluid. None of them suffered
from a cardiac or a pre-existing
esophageal disease. The mechanism of
esophageal mucosal injury induced by
doxycycline capsules may be explained by
their acidic reaction, gelatinous sticky
capsules, increased mucosal
concentration and intracellular
toxicity(2,13,14). The presence of a
hiatus hernia in patients receiving
indomethacin or doxycycline is
associated with an increased risk of
developing DIEI. The symptoms of DIEI
usually manifest within a few hours up
to ten days after exposure in the form
of chest pain, odynophagia and dysphagia,
ranked according to their frequency(7).
In our patients, odynophagia,
retrostemal burning pain and dysphagia
were the commonest symptoms. Although
the typical history is sufficient to
establish the diagnosis, endoscopy
remains the method of choice for
detecting DIEI(3). Findings on
endoscopic biopsy material are non
specific(6,15). In the majority of
patient, DIEI symptoms resolved within
one week. Discontinuation of the
offending drug is the main treatment. It
is not clear whether specific therapy is
required, or even effective, in treating
the acute lesion. Antacids, histamine H2
receptor blockers, proton pump
inhibitors, sucralfate, and even local
anesthetic agents are often prescribed,
but their value is unsubstantiated. Even
potent acid suppressing drugs seem
unlikely to offer any real advantage,
unless gastroesophageal reflux is
believed to be exacerbating or
perpetuating the injury. In conclusion,
physicians must be aware of doxycycline
induced esophageal ulcers where
discontinuation of the antibiotic is the
main treatment. They must, therefore,
encourage their patients to take the
pills with enough liquid, in an upright
position and pay special attention to
the elderly and those with esophageal
disease.
References
Other
Topics:
Case Report # 1
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