first report of drug-induced esophagitis by deferasirox
TRANSCRIPT
CASE REPORT
First report of drug-induced esophagitis by deferasirox
Takeshi Yoshikawa • Takeshi Hara •
Hiroshi Araki • Hisashi Tsurumi • Masami Oyama •
Hisataka Moriwaki
Received: 18 June 2011 / Revised: 13 March 2012 / Accepted: 14 March 2012 / Published online: 1 May 2012
� The Japanese Society of Hematology 2012
Abstract Deferasirox is a new oral iron chelator used to
treat transfusional iron overload. We describe a case of a
79-year-old man with myelodysplastic syndrome (MDS)
who developed esophagitis induced by deferasirox. He
repeatedly received multiple red blood cell transfusions after
a diagnosis of MDS. Two years after starting red blood cell
transfusions, he was diagnosed with iron overload, and was
then started on deferasirox at 1 g/day with about 400 ml of
water. He was admitted to our institution because he was
unable to swallow his own saliva 1 month after starting
deferasirox. Esophagogastroendoscopy revealed white-
coated mucosa covering the entire esophagus. A component
analysis of biopsy specimens using high-performance liquid
chromatography identified deferasirox. Symptoms resolved
within about 2 weeks after discontinuing deferasirox, and
repeated endoscopy showed marked improvement of
esophagitis after 1 month. Re-administration of deferasirox
was not attempted. Unfortunately, the patient died due to
pneumonia 6 months after administration of deferasirox was
started. This is the first report of drug-induced esophagitis
associated with deferasirox.
Keywords Drug-induced esophagitis � Deferasirox
Introduction
Iron overload due to red blood cell transfusions represents
an important problem around the world for patients with
thalassemia, myelodysplastic syndrome (MDS), or severe
aplastic anemia. Desferrioxamine has been available as an
iron-chelating agent since the early 1960s, resulting in
increased survival for these patients [1]. In addition, two
oral iron chelators have been developed. Deferiprone was
approved for use in India in 1995 and in Europe in 1999
[2], while deferasirox was approved in the United States in
2005 and in Japan in 2008. Deferasirox is thus the only oral
iron chelator available in these two countries [2]. The main
adverse events of deferasirox in the initial clinical trials
were transient gastrointestinal complaints [3, 4], but no
reports have described esophagitis. We report herein a case
of drug-induced esophagitis in a patient treated with
deferasirox for MDS.
Case report
A 79-year-old man was diagnosed with refractory cytopenia
with unilineage dysplasia (RCUD) and subsequently
received multiple red blood cell transfusions at another
institution. A total of 48 U of red blood cell transfusions
were administered, the serum ferritin level was 1480 lg/L,
and a diagnosis of iron overload was made. He was then
started on deferasirox at 1 g/day with about 400 ml of water
2 years after starting red blood cell transfusions. Progres-
sion of anemia led to general fatigue, resulting in admission
to our institution 1 month after starting deferasirox. Repeat
bone marrow aspiration showed MDS, and the serum fer-
ritin level was 1606 lg/L. On presentation, he was unable to
swallow his own saliva. Laboratory studies showed
T. Yoshikawa � M. Oyama
Department of Internal Medicine,
Kisogawa Municipal Hospital, Aichi, Japan
T. Hara � H. Araki � H. Tsurumi (&) � H. Moriwaki
First Department of Internal Medicine,
Gifu University Graduate School of Medicine,
1-1 Yanagido, Gifu 501-1194, Japan
e-mail: [email protected]
123
Int J Hematol (2012) 95:689–691
DOI 10.1007/s12185-012-1060-7
leukocytosis (31400/mm3) and an elevated C-reactive pro-
tein (4.8 mg/dL), while b-D glucan was within the normal
range. Liver and kidney functions were normal. Negative
results were obtained for bacterial cultures of a blood
sample obtained on admission. Esophagogastroendoscopy
revealed white-coated mucosa covering the entire esopha-
gus (Fig. 1), with no abnormal findings in the stomach.
Standard histological and microbiological investigations
showed no evidence of esophageal candidiasis. A compo-
nent analysis of biopsy specimens using high-performance
liquid chromatography identified the presence of deferasi-
rox (Fig. 2). A diagnosis of deferasirox-induced esophagitis
was therefore made. Deferasirox was discontinued, and
nearly all symptoms resolved within 2 weeks. No other
treatment was required for esophagitis. Repeat endoscopy
performed 1 month later showed marked improvement of
the esophagitis. Re-administration of deferasirox was not
attempted. Unfortunately, the patient died due to pneumo-
nia 6 months after administration of deferasirox was
started.
Discussion
Causes of esophagitis include reflux esophagitis, infectious
microbes such as Candida albicans, and drug-induced
esophagitis. Candida species are the most common cause
of esophagitis and, after the oropharynx, the esophagus is
the most common site of gastrointestinal candidiasis. The
prevalence of esophageal candidiasis has increased mainly
because of the high frequency of this complication in
AIDS. Approximately 10–15 % of patients with AIDS will
suffer from this disorder during their lifetime [5, 6],
although a reliable diagnosis can only be made based on
histological evidence of tissue invasion in biopsy material.
The etiology of drug-induced esophagitis includes
impaired motility of the esophagus by pharmaceuticals or
Fig. 1 Endoscopic image of the esophagus on admission. White-
coated mucosa is apparent throughout the esophagus on gastrointes-
tinal endoscopy
Fig. 2 High-pressure liquid chromatogram of esophageal biopsy specimens. Positive control (deferosirax) is shown in the left panel, and the
sample is shown in the right panel
690 T. Yoshikawa et al.
123
corrosive esophagitis from alkaline or acidic drugs. Injury
to the esophageal mucosa caused by drugs passing through
the esophagus is a rare but well-known clinical condition,
as recognized by terms such as ‘‘pill-esophagitis’’ [7].
Esophageal mucosal injury caused by reflux of gastric
contents is a common condition. Much less common is
esophagitis from injurious agents passing down the
esophagus, seen most typically in cases after the ingestion
(usually accidental) of a caustic alkali. The potential of
medications such as quinidine, potassium, and tetracycline
derivatives to cause esophagitis or discrete ulcers has
recently been recognized. This effect usually results from
prolonged contact of the drug with the esophageal mucosa
and the ability of the drug to alter local conditions, such as
the production of acidic conditions by tetracycline. How-
ever, adverse effects of deferasirox involving the esopha-
gus occurred in only a small number of patients in the
initial clinical trials [3, 4]. We hypothesized that prolonged
direct contact of deferasirox with the mucosa caused
esophagitis. The present patient was elderly and tended to
sleep for longer periods. We suspected that such factors
contributed to esophagitis. We directed the patient to take
deferasirox with more water, but this did not prevent
esophagitis. Bed-ridden elderly patients require particular
attention in terms of the risk of such adverse effects.
Treatment for deferasirox-induced esophagitis is very
important. In this patient, no drugs were used to treat the
esophagitis; in fact, discontinuation of deferasirox was
sufficient. Stopping the drug might be enough for this type
of esophagitis, and no other treatment may be required.
In summary, this is the first report of deferasirox-
induced esophagitis. Knowledge of the potential for drug-
induced esophagitis is important, as the incidence of MDS
is increasing, and MDS patients are living longer. The use
of iron-chelating agents is thus also likely to increase.
Deferasirox-induced esophagitis must be considered as a
potential complication in elderly patients.
Conflict of interest None.
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