2001;84;344-346 Arch. Dis. Child.
P C M S Verhagen, P G J Nikkels and T P V M de Jong
Short report: Eosinophilic cystitis
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P C M S Verhagen, P G J Nikkels, T P V M de Jong
We describe four cases of eosinophilic
cystitis in whom no specific cause could be
found, and review the literature. Com-
plaints at presentation included urgency,
frequency, abdominal pain, and haema-
turia. In three patients the symptoms and
ultrasound pictures suggested a bladder
tumour. One patient was treated with
anticholinergics and corticosteroids with-
out relief of symptoms; a localised eosi-
patient who remained symptom free; and
two patients were managed conservatively
with spontaneous resolution of bladder
pathology and symptoms. One case was
identified by random bladder biopsy in
150 consecutive patients with unexplained
irritable micturition complaints. Eosi-
nophilic cystitis is rare in children. After
biopsy,we consider a wait and see policy is
justified as symptoms tend to disappear
spontaneously. Routine bladder biopsies
in children with unexplained bladder
symptoms is not justifiable.
(Arch Dis Child 2001;84:344–346)
Keywords: eosinophilic cystitis; bladder biopsy
The aetiology and treatment of eosinophilic
cystitis remain poorly understood in spite of
many case reports. Brown is often quoted as
the first to publish on eosinophilic cystitis
owing to his description of eosinophilic granu-
lomas of the bladder wall.1In 1949 Kindall and
Nickels identified eosinophilic leucocytes in
the urine and in the bladder wall of patients
with micturition complaints. These patients
improved after eliminating suspected food
allergens from their diet.2
The pertinent characteristic of the disease is
eosinophilic infiltration as observed in bladder
wall biopsy specimens. The symptoms often
mimic those of urinary tract infection. The
bladder lesions seen by ultrasound and cystos-
copy may be initially interpreted as malignant.
Several drugs have been reported to induce
eosinophilic cystitis in adults: cyclophospha-
mide,3coumadine,4tranilast (an antiallergic
drug),5penicillin, and clometacin.6Intravesical
instillations with mitomycin and thiotepa can
cause eosinophilic infiltration of the bladder
wall.7 8Goble et al found urothelial eosinophilic
infiltration in response to catheterisation.9
Engler et al reported eosinophilic cystitis at the
site of chromic catgut sutures.10
Treatment is empirical.11
removal of any suspected allergen. Cortico-
steroids, anticholinergic drugs, and antiallergic
drugs have been reported to relieve symptoms.
Partial cystectomy has been performed in cases
of circumscribed lesions that show no tendency
to disappear spontaneously.12Many reports
mention the self limiting course of the
disease.13–28Our search of the literature pro-
duced 24 patients under the age of 18 (table 1).
Seventeen presented with a tumour in the
bladder. The symptoms subsided spontane-
ously or during corticosteroid therapy in 20,
including 15 with a bladder mass.
Our study comprises four children with eosi-
nophilic cystitis. Three were suspected of hav-
ing bladder tumours.One was identified by our
previous policy to perform bladder biopsies in
children with severe unexplained micturition
complaints. We assessed retrospectively how
often eosinophilic cystitis was found in this
group of 150 consecutive patients.
It consists of
Patients and results
One patient (patient A) was identified on rou-
tine bladder biopsies in patients with unex-
plained micturition complaints. No specific
pathological diagnosis was established in the
149 other patients biopsied. The symptoms of
Table 1Literature review
Time for symptoms to
Exacerbations > 8
symptoms > 1 year
TUR, transurethral resection.
Arch Dis Child 2001;84:344–346344
Hospital Dijkzigt, PO
Box 2040, 3000 CA
P C M S Verhagen
Dept of Pathology,
Utrecht, PO Box
85090, 3508 AB,
P G J Nikkels
Hospital UMC Utrecht
T P V M de Jong
Dr de Jong
Accepted 22 November 2000
on 27 November 2006 adc.bmj.com Downloaded from
patient A were not remarkably diVerent from
the other biopsied patients. Our other three
patients (B,C,and D) were referred because of
pain and/or haematuria. The clinical suspicion
of a bladder tumour leads to the diagnosis.
Patient A,a boy,became continent night and
day at 3.5 years of age. At 4 he started wetting
day and night, for which he was evaluated else-
where. Both parents had suVered nocturnal
enuresis until the age of 14.At 9 years of age he
became dry during the day, taking oxyphenon-
ium bromide 5 mg three times daily and
imipramine chloride 25 mg twice daily. Physi-
cal examination and laboratory results were
normal except for a modest blood eosinophilia
(0.5 × 109/l). A grade 2 reflux was found at the
right hand side on the micturition cystogram.
Intravenous urography was normal. He pre-
sented to our department at the age of 11
because of persistent nocturnal enuresis and
frequency. He was of normal height and
weight. Blood pressure was 90/60 mm Hg.
White blood cell count (WBC) showed 8.1 ×
109leucocytes/l with 1.5 × 109eosinophils/l.
Repeated urine sediments and cultures were
normal. Analysis of stools revealed no cysts or
worm eggs. Allergic tests were positive for dust
mite, pollen, canary, parrot, and parakeet.
Serum IgE was 2200 IU/ml (normal <100
IU/ml). Cystoscopic examination showed a
hyperaemic mucosa. Random biopsy speci-
mens showed eosinophilic infiltration of the
bladder wall. Oxyphenonium bromide was
continued.He did not improve over six months
Patient B is a 17 year old girl. At the age of 5
bilateral kidney hypoplasia was diagnosed.
Renal function had decreased progressively. At
the age of 16 an arteriovenous shunt was con-
structed for renal dialysis. Shortly after, she
presented at the urologic department because
of pain in the left groin at micturition. Voiding
frequency was eight to 10 times during the day
and two to three times during the night. She
was on the following medication: aluminium
hydroxide 0.5 g twice daily; sodium bicarbo-
nate 1 g four times daily; calcium 500 mg three
times daily; dihydrotachysterol 0.2 mg twice
daily; dipyridamol 25 mg twice daily; dagravit
30 (multivitamin) one tablet daily; lynestrenol
(oral contraceptive) 0.5 mg once daily; and
acenocoumarol according to INR. Her dietary
protein was restricted to 40 g per day. On
physical examination we found her height on
the 5th centile with normal weight for height.
Blood pressure was 107/54 mm Hg.Rectal and
tumour of 5 cm diameter on the left side fixed
to the pelvis. Results of laboratory investiga-
tions were as follows: erythrocyte sedimenta-
tion rate (ESR) 108 mm/h; WBC 8.3 × 109/l;
eosinophilic leucocytes 0.17 × 109/l; haemo-
globin 5.8 mmol/l; haematocrit 0.29; urea 27
mmol/l; and creatinine 990 µmol/l. The urine
sediment contained more than 40 leucocytes
and more than 40 erythrocytes per high power
field. Urine cultures were repeatedly negative
(24 hour urine: volume 2.1 l; Na 77 mmol/l; K
15 mmol/l; urea 67 mmol/l; creatinine 3.2
mmol/l). Amino acid excretion was high for
branched amino acids, iminoacids, citrulline,
and arginine (Fanconi syndrome). Abdominal
ultrasound showed a 45 mm tumour which was
continuous with the bladder wall. At cystos-
copy,this was seen protruding into the bladder.
Biopsy specimens showed severe infiltration
with eosinophilic leucocytes. The tumour was
removed by laparotomy and partial cystectomy.
The sigmoid colon was adherent to the
tumour. Histological analysis showed homoge-
neous eosinophilic infiltration throughout the
swelling. The patient was free of urological
symptoms after this procedure and has re-
mained so for 10 years.
Patient C,an 11 year old boy,was referred to
our department because of terminal haema-
turia and pain during micturition. His voiding
frequency had increased from four to eight
times daily. On physical examination he was of
normal height with weight for height according
to the 75th centile. His blood pressure was
113/58 mm Hg. Abdominal investigation
revealed a slight suprapubic pain. Results of
laboratory investigations were as follows: ESR
3 mm/h; haemoglobin 9.2 mmol/l; WBC 9.5 ×
109/l; eosinophilic leucocytes were within
normal range. Urine sediment contained one
to five leucocytes per high power field. Urine
cultures were negative. Stools showed no cysts
or worm eggs. An abdominal ultrasound
showed normal kidneys. The bladder con-
tained an irregular mass, suspected to be
malignant. Cystoscopy showed severe oedema
of the bladder neck. Biopsy specimens taken
from the oedematous area showed submucosal
eosinophilic infiltration. Symptoms resolved
spontaneously over several days.
Patient D, an 11 year old girl, was referred
because of urgency and haematuria. She was
allergic to pollen and used ketotifen, discontin-
ued shortly before referral. Rectal examination
revealed a mobile 3 cm diameter pelvic mass.
Results of laboratory investigations were as fol-
lows: WBC 7.3 × 109/l; eosinophilic leucocytes
0.07 × 109/l, serum IgE 73 IU/ml (normal).
Abdominal ultrasound showed an irregular
tumour in the bladder. Transurethral bladder
subepithelial connective tissue,predominantly composed of eosinophilic leucocytes.Inset:
Bladder biopsy of patient D,showing an inflammatory infiltrate of the
on 27 November 2006 adc.bmj.comDownloaded from
biopsy specimens of the tumour showed Download full-text
infiltration of the bladder wall by eosinophils
(fig 1). Spontaneous resolution of symptoms
occurred over several days. After three months
the tumour had disappeared.
Eosinophilic cystitis has a variable presentation
and outcome. Two of our four patients were
known to have allergies, an association also
reported in the literature (five of 24 reported
paediatric patients had allergies). However, we
could not identify a cause of the disease in our
patients. Patient D had used ketotifen which
was discontinued shortly before the diagnosis
of eosinophilic cystitis. Ketotifen has not been
reported to induce eosinophilic cystitis but a
variety of diVerent compounds are believed to
cause this.3–8Eosinophilic cystitis may clinically
resemble a bladder tumour. Development of a
secondary malignancy has never been re-
ported. On the contrary, as in our cases, a self
observed.13–27Patient A is our only patient
whose symptoms did not resolve spontane-
ously, possibly due to limited follow up. In ret-
rospect, it is possible that resolution in patient
B might have also been accomplished by more
In children with unexplained micturition
complaints,eosinophilic cystitis is rarely found.
In our patients no other explanation for the
micturition complaints was revealed by the
bladder biopsies. We conclude that routine
bladder biopsy in children with unexplained
urgency is not justifiable.
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