Pill esophagitis: two case reports
CASE REPORTS
Pill Esophagitis: Two Case Reports
Simona Vãlean1, Magda Petrescu2, Adrian Cãtinean1, Romeo Chira1, Petru A. Mircea1
1) 1st Medical Clinic. 2)Department of Pathology, University of Medicine and Pharmacy “Iuliu Haþieganu”, Cluj-Napoca
Abstract
Pill esophagitis is a rare clinical diagnosis. We report a
series of two patients who experienced ulcerative
esophagitis while taking doxycycline (patient 1) and
alendronate (patient 2). Both patients presented with
retrosternal pain, odynophagia and dysphagia. Symptoms
developed after 3 days of treatment with doxycycline in
patient 1 and after 3 months of treatment with alendronate
in patient 2. Endoscopy revealed ulcerative lesions in the
mid-esophagus, sparing the distal esophagus. Biopsies
showed inflammatory infiltrate (patient 1) and ulceration and
hyperplastic cells (patient 2). Patient 1 recovered completely
endoscopically after discontinuation of the antibiotic and a
one month course of sucralfate treatment. Patient 2 did not
accept the discontinuation of alendronate therapy. She also
had a course of one month treatment with sucralfate. At
one, two and even at seven months after the first diagnosis,
endoscopy still showed the persistence of millimetric defects
of epithelisation. She is still under endoscopical survey.
In conclusion, doxycycline and alendronate can cause
chemical esophagitis when taken improperly. In adults and
elderly patients exclusion of esophageal carcinoma by
histology is neccessary. Continuation of treatment with the
offending drug can delay healing. Pill esophagitis is a
preventable cause of morbidity that consists of giving simple
advice of how and when to take medication.
Key words
Pill esophagitis – doxycycline - alendronate
Rezumat
Esofagita post-medicamentoasã este rar diagnosticatã
în clinicã. Raportãm o serie de doi pacienþi care au dezvoltat
esofagitã post-medicamentoasã în cursul unui tratament cu
Romanian Journal of Gastroenterology
June 2005 Vol.14 No.2, 159-163
Address for correspondence: Simona Valean
1st Medical Clinic
Str. Clinicilor, no. 3-5
Cluj-Napoca, Romania
doxyciclinã (pacient 1) ºi alendronate (pacient 2). Ambii
pacienþi au prezentat durere retrosternalã, odinofagie ºi
disfagie. Simptomele au apãrut dupã 3 zile de tratament cu
doxiciclinã la pacientul 1 ºi dupã 3 luni de tratament cu
alendronate la pacientul 2. Endoscopia a evidenþiat leziuni
ulcerative la nivelul treimii medii a esofagului. Esofagul
inferior a fost indemn de leziuni. Examenul histopatologic al
pieselor de biopsie endoscopicã a evidenþiat infiltrat
inflamator (pacient 1) ºi ulceraþie, ºi celule hiperplastice
(pacient 2). La primul pacient, întreruperea antibioticului ºi
un curs de tratament de o lunã cu sucralfate a condus la
remisiunea completã a leziunilor, apreciatã endoscopic.
Pacienta 2 nu a acceptat întreruperea tratamentului cu
alendronate. ªi aceasta a urmat un curs de tratament de o
lunã cu sucralfate. Endoscopia, efectuatã la una ºi la douã
luni a evidenþiat persistenþa unor eroziuni. Chiar ºi la ºapte
luni de la primul diagnostic, endoscopia a evidenþiat
persistenþa unor defecte milimetrice de epitelizare.
În concluzie, doxyciclina ºi alendronate pot induce
esofagite chimice dacã sunt înghiþite impropriu. La adulþi ºi
batrâni este necesarã excluderea carcinomului esofagian prin
biopsii. Continuarea tratamentului cu medicamentul
incriminat poate întârzia cicatrizarea leziunii. Esofagita post-
medicamentoasã este o cauzã de morbititate care poate fi
prevenitã. Prevenirea constã într-un simplu sfat, despre cum
ºi când trebuie luate pastilele.
Introduction
Pill-induced or drug-induced esophagitis is a rare clinical
diagnosis; no more than one thousand cases have been
described in the past 30 years though more than one hun-
dred drugs have been reported to have the potential to induce
esophageal lesions (1,2). We describe the clinics, endo-
scopy, pathology and clinical course of two patients who
experienced pill esophagitis while under a treatment with
doxycycline and alendronate, respectively.
Case reports
Patient 1
A man aged 60 yrs presented with retrosternal pain,
160
odynophagia and dysphagia with sudden clinical onset 24
hours earlier. He had been taking doxycycline for three days.
Endoscopy revealed multiple ulcerations in the mid-
esophagus (Fig.1a). Histology showed inflammatory
infiltrate (Fig.1b). No other abnormalities could be found in
the history, ECG, thoracic radiography, hematology,
biochemistry. The diagnosis of pill esophagitis was retained.
The patient was advised to discontinue doxycycline. He
had a course of sucralfate therapy for one month.
Endoscopic control after one month revealed no more
abnormalities in the esophagus (Fig1c).
Patient 2
A woman aged 54 yrs presented with retrosternal pain,
odynophagia and dysphagia, with sudden onset three hours
before admittance. She had been taking alendronate in a
dose of 10mg per week for three months as a treatment for
prevention of postmenopausal osteoporosis. Endoscopy
revealed a serpiginous ulceration in the mid-esophagus
(Fig.2a). Histology showed inflammatory infiltrate,
ulcerations and hyperplastic cells (Fig.2b). History, ECG,
thoracic radiography, hematology, biochemistry and pH-
metrie revealed no other abnormalities. The diagnosis of
drug-induced esophagitis was retained. The patient did not
accept to discontinue alendronate.
She was advised to be more careful and to respect the
indications of how to take alendronate and to give special
attention to the quantity of water to swallow with the drug.
She also had a one month course of sucralfate therapy.
Endoscopic control after one and two months still revealed
the persistence of some erosions. Even at seven months
after the first diagnosis, endoscopy revealed millimetrical
defects of epithelisation (Fig.2c).
Discussion
In both our patients ulcerative esophagitis was located
in the mid-esophagus, sparing the distal esophagus.
Proximal esophagitis is nearly pathognomonic of pill-
esophagitis in a suggestive clinical setting and effectively
excludes gastroesophageal reflux disease as a cause of
esophagitis (1,2).
The site most frequently affected in pill esophagitis was
presumed to be in the mid-third of the esophagus (1-10).
However, pill esophagitis can be located at any level where
the esophagus is narrowed: the upper sphincter, the aortic
arch, the left main bronchus, and the lower esophageal
sphincter (1,2). Evidence suggests that the highest
incidence of pill esophagitis occurs in the distal, acid
exposed region of the esophagus related to concomitant
acid reflux, as demonstrated by injury from NSAIDs and
other drugs (2,11-13)). The size of the pill appears to influence
the localisation of the lesion, that is proximal in large-sized
pills and distal in small-sized ones. In its distal location, pill
esophagitis is often mistaken for reflux esophagitis (1,2).
The drugs responsible for erosive esophagitis in our
patients were best known to have the potential to induce
Vãlean et al
esophageal injury, i.e. doxycycline and alendronate. In our
patients the main risk factor for pill esophagitis could be
related to the inadequate amount of water taken with the
pill.
Pill esophagitis was first described in 1970 concurrently
in Europe and United States (2-4). Since then, more than
1000 cases have been described and more than 100 drugs
have been reported to have the potential to induce
esophageal abnormalities (1).
The risk of pill esophagitis appears to be related to the
patient (lack of adequate oral water intake following
medication, lying down immediately after ingestion of the
drug), esophageal (dysmotility or narrowing of the
esophagus) and drugs (intrinsic caustic characteristics of
the medication, solubility, sustained-release formulations,
contact time) (1,2).
In 90% of the early reported cases pill esophagitis was
associated with the use of antibiotics, antiviral drugs,
potassium chloride, iron-containing pills, NSAIDs, quinidine
and biphosphonates (1,2). Data suggest that NSAIDs are
actually the most common cause of medication-induced
esophageal injury (2,3,11-14).
Bisphosphonates are widely marketed for the treatment
and prevention of postmenopausal osteoporosis.
Bisphosphonates can cause esophageal (16-22) and gastric
ulcerations (23). It was suggested that their toxicity results
from the disruption of the surface phospholipid layer that
protects the epithelial cells. They differ in their potential to
damage the esophageal and gastric mucosa. Alendronate
(a primary amino bisphosphonate) has been associated with
more esophageal and gastric erosive lesions than
risendronate (a pyridinyl bisphosphonate)(19,21,22).
Tetracycline (and related drugs oxytetracycline,
doxycycline) and other antibiotics accounted for over 50%
of cases of pill esophagitis in an early review of the world
literature (6). Tetracycline’s mechanism of esophageal injury
is caustic, related to its acidic pH upon dissolution and also
related to inhibition of protein synthesis and subsequent
impairment of epithelial repair. Tetracycline has caused
esophagitis in adults and children, in short and long-term
treatments (2,6,24).
NSAIDs are actually the most common cause of medi-
cation-induced esophageal injury (1,2,11-14). The existing
data suggest a cumulative effect of NSAIDs in GERD (11).
NSAIDs have also been associated with an increased risk
of severe esophageal complications versus other agents,
including bleeding, perforation and stricture formation (2,6).
Age was also supposed to be a risk factor for pill eso-
phagitis. The increased risk in the elderly was hypothesized
to be related to more frequent use of high-risk medications
and to increased prevalence of esophageal dysmotility. Data
indicate that anyone, of any age, that takes medication is at
risk of esophageal medication-induced injury and that age
alone confers little if any additional risk (2). Cases have
been reported also in children. Pill esophagitis in children
occurs rarely, in relation to the use of liquid formulations of
drugs at this age (2,24).
Pill esophagitis: two case reports 161

Fig.1a Patient 1. Endoscopy. Erosions of the mid-esophagus. Fig.2a Patient 2. Endoscopy. Serpiginous ulceration of the mid-
esophagus.

Fig.1b Patient 1. Histopathology (HEx10). Diffuse inflammatory Fig.2b Patient 2. Histopathology (HEx10). Inflammatory
infiltrate. infiltrate, ulceration, hyperplastic cells.

Fig.1c Patient 1. Endoscopy after one month. No more erosions. Fig.2c Patient 2. Endoscopy after seven months. Milimetrical
defects of epithelisation.
162
The morphologic lesions recorded in our patients were
represented by ulcerations and inflammation. Macrosco-
pically, a large spectrum of esophageal abnormalities have
been reported in pill esophagitis, ranging from reddened,
edematous mucosa, with small superficial ulcerations, to a
large ulcer with inflamed margins, often with profuse exudate,
resembling carcinoma. Stricture, mass and bleeding have
also been reported (1,2,10). The type of the lesion can differ
in relation to the involved drug (1,2). Biopsy may show
nonspecific inflammatory changes, giant cells. Cytologic
results should be interpreted with caution, as hyperplastic
cells resulting from inflammation can be mistaken for carci-
noma (1). Crystalline material might be seen, representing
drug particles (1,18).
In our patients endoscopy confirmed the diagnosis and
ruled out malignancy by histology. Endoscopy is the method
of choice for the diagnosis of pill esophagitis; even lesions
could also be seen by double-contrast barium x-rays of the
esophagus (1-10). In adults and elderly patients malignancy
mast be ruled out by histology (1-4).
Our patients’ complaints were represented by retroster-
nal pain, odynophagia and dysphagia, a triad of symptoms
classically described in this setting. However, their
relationship with the medication appeared less clear in our
patients, since the medication was started some days before
and some months before, respectively. This association of
symptoms is very suggestive of the esophageal origin. Exa-
minations have been carried out in our patients in order to
confirm/exclude a cardiovascular origin of retrosternal pain.
A clinical diagnosis of pill esophagitis can be raised
when a coincidence between pill taking and the appearance
of esophageal symptoms is discovered in a patient’s history.
The most common symptom is retrosternal pain that
develops after hours of pill taking. But pain can develop
also after days or weeks. Pain is usually continuous,
associated with odynophagia and dysphagia. Dysphagia
may suggest a stricture or large inflammatory mass (1,2)
Discontinuation of doxycycline and sucralfate therapy
were efficient in healing the esophageal lesion in our first
patient. In our second patient, the continuation of
alendronate might have been responsible for the delayed
healing process, since GERD was excluded by pH-metry.
The treatment of pill esophagitis is nonspecific and
empirical. Withdrawal of the offending drug leads to the
healing of the lesion within days to weeks (1,6). Continuation
of the offending drug can delay the healing process.
Sucralfate suspension can be used, but its benefit is
unknown (1). Antisecretory agents are justified when a
concomitant GERD has been documented. Patients with
severe symptoms might require intravenous fluids in order
to avoid dehydration. Dietary modifications in order to
prevent malnutrition are rarely neccessary.
Conclusions
Doxycycline and alendronate can cause chemical eso-
phagitis when taken improperly. In adults and elderly
Vãlean et al
patients exclusion of esophageal carcinoma by histology is
neccessary. Continuation of the treatment with the offending
drug can delay healing.
Pill esophagitis is a preventable cause of morbidity that
consists of giving simple advice of how and when to take
medication.
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