An evaluation of children with Kawasaki disease in Istanbul: a retrospective follow-up study.
ABSTRACT Kawasaki disease (KD) is an acute, self-limiting vasculitis of unknown etiology. The incidence of KD is increasing world wide. However, the epidemiological data for KD in Turkey has not been well described.
To describe the demographic, clinical, and laboratory features of children with KD who were diagnosed and managed in the American Hospital, Istanbul, Turkey.
Patients with KD were retrospectively identified from the hospital discharge records between 2002 and 2010. Atypical cases of KD were excluded. A standardized form was used to collect demographic data, clinical information, echocardiography and laboratory results.
Thirty-five patients with KD, with a mean age of 2.5 + 1.9 years, were identified. Eighty-five point seven per cent of patients were under 5 years of age. A seasonal pattern favouring the winter months was noticed. In addition to fever and bilateral conjunctival injection, changes in the oral cavity and lips were the most commonly detected clinical signs in our cases. Coronary artery abnormalities were detected in nine patients. The majority of our patients had started treatment with intravenous immunoglobulin in the first 10 days of the onset of fever, and only one patient required systemic steroids for intravenous immunoglobulin-resistant KD. The coronary artery abnormalities resolved in all nine patients within 8 months.
This study is the most comprehensive series of children from Turkey with KD included in Medline. As adult-onset ischemic heart disease may be due to KD in childhood, further prospective clinical investigations are needed to understand the epidemiology, management and long-term follow-up of the disease.
- Kawasaki disease: an overview. 263-70..
An evaluation of children with Kawasaki disease in
Istanbul: a retrospective follow-up study
Sinan Mahir Kayiran, Aygu ¨n Dindar, Berkan Gurakan
American Hospital - Department of Pediatrics, Istanbul, Turkey.
BACKGROUND: Kawasaki disease (KD) is an acute, self-limiting vasculitis of unknown etiology. The incidence of KD
is increasing world wide. However, the epidemiological data for KD in Turkey has not been well described.
OBJECTIVE: To describe the demographic, clinical, and laboratory features of children with KD who were diagnosed
and managed in the American Hospital, Istanbul, Turkey.
METHOD: Patients with KD were retrospectively identified from the hospital discharge records between 2002 and
2010. Atypical cases of KD were excluded. A standardized form was used to collect demographic data, clinical
information, echocardiography and laboratory results.
RESULTS: Thirty-five patients with KD, with a mean age of 2.5¡1.9 years, were identified. Eighty-five point seven
per cent of patients were under 5 years of age. A seasonal pattern favouring the winter months was noticed. In
addition to fever and bilateral conjunctival injection, changes in the oral cavity and lips were the most commonly
detected clinical signs in our cases. Coronary artery abnormalities were detected in nine patients. The majority of
our patients had started treatment with intravenous immunoglobulin in the first 10 days of the onset of fever, and
only one patient required systemic steroids for intravenous immunoglobulin-resistant KD. The coronary artery
abnormalities resolved in all nine patients within 8 months.
CONCLUSION: This study is the most comprehensive series of children from Turkey with KD included in Medline. As
adult-onset ischemic heart disease may be due to KD in childhood, further prospective clinical investigations are
needed to understand the epidemiology, management and long-term follow-up of the disease.
KEYWORDS: Kawasaki disease; Coronary artery disease; Echocardiography; Steroids.
Kayiran SM, Dindar A, Gurakan B. An evaluation of children with Kawasaki disease in Istanbul: a retrospective follow-up study. Clinics. 2010;65(12):
Received for publication on August 13, 2010; First review completed on August 28, 2010; Accepted for publication on September 08, 2010
Tel.: + 90 532 238 0466
Kawasaki disease (KD) is an acute, self-limiting systemic
aged ,5 years. It was first described by Tomisaku Kawasaki
in 1967 in Japan.1KD has now replaced rheumatic fever as
the leading cause of acquired heart disease in childhood in
the developed world, and is the second most common
childhood vasculitis.2,3Although the incidence of KD varies
among countries, it is much higher in children from Asian
countries.4,5The clinical signs of KD are similar to those of
many other childhood illnesses. The disease is often com-
plicated by coronary artery abnormalities (CAA), including
dilatation and/or aneurysms, and thus is a leading cause
of acquired heart disease in children.6,7Some clinical fea-
tures other than the classic diagnostic criteria are intense
irritability, cough, diarrhea, sterile pyuria, arthritis, arthral-
gia, redness and induration at the site of a Bacille–Calmette–
Guerin (BCG) scar. Patients with prolonged fever and fewer
than four of the other principal criteria are diagnosed as
atypical or incomplete KD if CAA are present.8
The incentive for this research came from the remarkable
lack of knowledge about the epidemiology and features of
KD in Turkey. In this article we present the demographic,
clinical and laboratory features of children with KD, who
were diagnosed and managed in our hospital.
MATERIAL AND METHODS
Patients with KD were identified from hospital discharge
records between 2002 and 2010. All the children were being
followed up routinely at an outpatient clinic of the
American Hospital, Istanbul, Turkey—a private hospital,
generally relying on a high socioeconomic population from
Istanbul. Diagnosis of KD was made according to American
Heart Association guidelines.9Table 1 shows the standard
diagnostic criteria for KD. Medical charts of patients with
KD were reviewed using a standardized form to collect
Copyright ? 2010 CLINICS – This is an Open Access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License (http://
creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-
commercial use, distribution, and reproduction in any medium, provided the
original work is properly cited.
demographic data, clinical information, and laboratory test
results, retrospectively. All children diagnosed with aty-
pical KD were excluded. Echocardiography was performed
during hospitalization and follow-up in all patients.
Definitions of CAA were based on the following criteria:
for children aged ,5 years, an internal lumen diameter
(ILD) #3 mm was considered normal and for children aged
$5 years, an ILD #4 mm was considered normal. An ILD of
a coronary artery segment enlarged to ,1.5 times the
normal upper limit was defined as a dilatation, and an ILD
enlarged to $1.5 times the normal upper limit was defined
as an aneurysm. When a coronary artery was larger than
normal (dilated) and without a segmental aneurysm, the
vessel was considered ectasic.9
usually repeated within 2 weeks of the onset of illness,
during the fourth week, and thereafter depending on the
initial findings. All patients underwent laboratory investi-
gations for platelets, leukocyte (white blood cell) count,
hemoglobin (Hb), C-reactive protein (CRP), erythrocyte
sedimentation rate (ESR), aspartate aminotransferase, ala-
nine aminotransferase and underwent urine analysis.
Qualitative data are presented as frequencies with
percentages and quantitative data as means with standard
Thirty-five patients with KD were treated in the Istanbul
American Hospital during the 8-year period. The mean age
of the patients was 2.5¡1.9 years (range 2 months to
7 years). Eighty per cent of the cases were diagnosed within
the first 10 days, with the longest time to diagnosis being
15 days. The demographic and clinical characteristics of
patients are summarized in Table 2. Eighty six per cent (30
cases) of patients were aged ,5 years and 14% (five cases) of
patients were aged .5 years at the time of diagnosis. Fever
was the main clinical sign in all patients and mean body
temperature was 39.4¡0.9˚C at diagnosis. Although intense
irritability is not part of the classic diagnostic criteria, it was
present in all patients. In one patient there was redness and
induration at the site of the BCG scar. Three patients had
arthritis and one patient had abdominal pain and diarrhea.
Laboratory findings showed that anemia (Hb ,11 g/dl) was
present in 14 (40%) patients who were all a year old.
Elevated serum transaminases were detected in 10 (28.6%)
patients. Laboratory values of the patients at diagnosis are
shown in Table 3. No positive culture (blood, urine and
throat) was found in our patients. Sterile pyuria was present
in two patients.
Patients were receiving antibiotic therapy at diagnosis,
with the exception of two patients. During the 8-year period,
the monthly number of cases was lowest between July and
September and peaked in the winter months (Fig 1). The
highest incidence was seen in February, with seven patients.
CAA were detected in nine (25.7%) cases (six males, three
female). One patient had ectasia in the right coronary artery
and two patients in the left coronary artery. Six children had
coronary artery aneurysms (one in both right and left
coronary arteries with pericardial effusion, three had left
coronary artery aneurysms and two had right coronary
artery aneurysms with mitral valve regurgitation). All
children were treated with intravenous immunoglobulin
(IVIg) at a dose of 2 g/kg for a period of 10–12 h in addition
to high-dose aspirin (100 mg/kg) during the febrile period,
according to current consensus guidelines.10In one patient,
after a second infusion of IVIg, high-dose (30 mg/kg)
methylprednisolone pulse therapy was carried out for a
period of 2 h. Symptoms resolved in this child after two
intravenous doses of steroids. There was no recurrence in
KD is an acute febrile vasculitis that has been reported
with increasing incidence among all racial ethnic groups.
Table 1 - Diagnostic criteria for Kawasaki disease.
Fever for 5 days or more
Presence of at least four of the following five conditions:
(1)Bilateral (non-purulent) conjunctivitis
(3)Changes in the lips and mouth
reddened, dry or cracked lips
diffuse erythema of oral or pharyngeal mucosa
(4) Changes in the extremities
erythema of palms or soles
indurative edema of hands or feet
desquamation of skin of hand, feet and perineum
(5) Cervical lymphadenopathy
more than 1.5 cm in diameter
Differential diagnosis with a similar presentation:
Staphylococcal infection (such as scalded skin syndrome, toxic shock
syndrome), streptococcal infection (such as scarlet fever, toxic shock-
like syndrome, carriage of group A streptococcus does not exclude the
possibility of Kawasaki disease), measles and other viral exanthems
(including rubella, enterovirus, Epstein–Barr virus, cytomegalovirus,
human herpes virus 6, parvovirus), mycoplasma, Stevens–Johnson
syndrome, drug reaction, juvenile rheumatoid arthritis.
Table 2 - Demographic and clinical characteristics of
patients at diagnosis.
- Age (months) 30.4¡22.4 (2–84)
- Male (%)
- Female (%)
- Duration of fever (days)
- Clinical features (%)
Changes in oral cavity and lips
Bilateral conjuctival injection
Changes in extremities
Data are presented as mean ¡ SD (range) or number (%).
Table 3 - Laboratory values of patients at diagnosis.
ValueMean ¡ SD (range)
Platelet count (/mm3)
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-
reactive protein; ESR. erythocyte sedimentation rate; Hb, hemoglobin;
WBV, white blood cell count.
Children with Kawasaki disease in Istanbul
Kayiran SM et al.
While Japan has the highest and increasing annual
incidence in the world (184.6 per 100,000 children aged
,5 years between 2005 and 2006), the epidemiology of KD
in Europe has not been well described.11,12Likewise, the
epidemiology of KD in Turkey is also not well known. A
nationwide survey found that KD had an incidence of 9% of
There are many unconfirmed hypotheses about the cause
of KD. Although clinical, laboratory and epidemiologic
features strongly suggest an infectious cause, the etiology of
KD still remains unknown. One possibility is that a viral
repiratory infection (represented by a seasonal pattern),
juxtaposed with a subsequent secondary bacterial coloniza-
tion, precipitates a cascade of events that result in an
exaggerated immunologic response.14,15Our study confirms
the winter peak of KD (Figure 1), but no clear relationship
with respiratory pathogens was shown as virologic and
immunologic data were lacking. KD is more common in boys
than girls and 85% of cases occur in children aged ,5 years.11
In our study, we detected a male predominance and age
distribution resembling that of previous studies.16Studies
from the United States also show that KD is more common
duringthe winterand that76%ofchildrenare,5 yearsold.17
In KD, the fever is typically high-spiking and remittent,
with peak temperatures of .39˚C and, in many cases,
.40˚C.18Our patients’ fever pattern was consistent with this
classicfinding, witha mean
39.4¡0.9˚C at diagnosis. In addition to fever, bilateral
conjunctival injection and changes in the oral cavity and
lips were the most commonly detected clinical signs in our
cases, as found in other studies from Turkey and other parts
of the world.19-22The occurrence of cervical lymphadeno-
pathy in KD is variable. It is seen in only 50–75% of patients,
whereas most of the other features are seen in approxi-
mately 90%.23It is usually unilateral and confined to the
anterior cervical triangle, and its classic criteria include $1
lymph node that is .1.5 cm in diameter.18In our study,
cervical lymphadenopathy was the least common of the
principal clinical features (48.6%). The lymphadenopathies
in our patients were typically classic, except for one patient
who presented with massive cervical node enlargement.
Multiple clinical findings may be observed in patients
with KD. Arthritis or arthralgia can occur in the first week of
the illness and tends to affect multiple joints, including the
small interphalangeal joints and large weight-bearing
joints.18In our series, two patients had arthritis in their
knees and one patient had arthritis in his ankle.
Children with KD are often more irritable than the
children with other febrile ilnesses,18and all the patients
in this study were irritable. Gastrointestinal complaints,
including diarrhea, vomiting and abdominal pain, occur in
about one-third of patients.24Rarely, KD can present as an
acute surgical abdomen.24Contrary to previous studies,
only one of our 35 patients had abdominal pain and
diarrhea. Erythema and induration at the site of BCG
vaccination is common in Japan, where BCG is used
widely.25As in Japan, BCG is routinely performed in
Turkey, but only one patient had redness and induration at
the site of the BCG scar.
KD is mainly a clinical diagnosis and there are no
pathognomonic laboratory tests or findings. However,
leukocytosis is typical during the acute stage of KD.
Approximately 50% of patients had white blood cell counts
.15,000/mm3.18Similar to other reports,8,10,22the mean
leukocyte count of our study group was 15,896¡6,383/
mm3. Normocytic anemia may develop, particularly with
Figure 1 - Monthly hospital admission of patients during 2002–2010.
CLINICS 2010;65(12):1261-1265 Children with Kawasaki disease in Istanbul
Kayiran SM et al.
Marked anemia (Hb ,11 g/dl) on admission was noted in
14 (40%) patients who were all over 1 year old and who had
prolonged fever for more than 7 days. Thrombocytosis is a
characteristic feature of the later phases of the illness. It is
rarely present in the first week of the illness, usually
appearing in the second week, and peaking in the third
week with a gradual return to normal by 4–8 weeks after
onset in uncomplicated cases. Platelet counts are usually
.450,000/mm3in patients evaluated after day 7 of illness.18
In our series most of the patients were diagnosed in the
second week and the mean platelet count was 496,889¡
208,503/mm3, which is consistent with other studies.18
Elevations of CRP and ESR are almost universal in KD,
usually returning to normal values by 6–10 weeks after the
onset of illness.18Mean values of CRP and ESR were high in
our patients. Burns et al.26reported mild to moderate
elevations in serum transaminases in #40% of patients.
Although the mean values of transaminases were not high
in our study group, the ratio of patients with high levels
(28.6%) was consistent with this multicenter study.
Urine analysis showed intermittent mild to moderate
sterile pyuria in approximately 33% of patients, suggesting
urethritis.18Urine cultures of two patients with sterile
pyuria were normal.
As the principal clinical findings that fulfill the diagnostic
criteria are not specific for KD, patients with other diseases
(Table 1) with similar clinical features were excluded from
The major sequelae of KD are related to the cardiovascular,
and more specifically, the coronary arterial system. Therefore
cardiac imaging by echocardiography is a critical part of the
evaluation of all patients with suspected KD. For uncompli-
cated cases, echocardiography is recommended at the time of
diagnosis, at 2 weeks, and at 6–8 weeks after the onset of
disease.27We followed the above recommendations and also
repeated the echocardiography beyond 8 weeks for all
patients with previously normal findings, as other abnorm-
alities in the coronary artery vasculature (aneurysms) and
aortic root (dilatation with or without regurgitation) may
develop, even among patients with normal baseline echo-
cardiograms.27,28Additionally, echocardiography was per-
formed with higher frequency for patients with pericardial
effusion,mitralvalveregurgitationandIVIg-resistant KD, for
closer evaluation and follow-up. None of our patients with
normal baseline echocardiography was shown to develop
CAA on follow-up echocardiograms beyond the 8 weeks.
CAA developin approximately 15–25% of untreated children
with the disease and may lead to ischemic heart disease,
myocardial infarction or sudden death.18In our patients,
CAAwere detectedin nine(25.7%)cases.Noneof themledto
myocardial infarction or ischemic heart disease. A recent
study from Turkey reported the CAA rate as 33.3% in 24
children with KD.22Burns et al. described the emergence of
the peak mortality as 15–45 days after the onset of fever; and
during this time, well-established coronary vasculitis occurs
concomitantly with a marked elevation of the platelet count
and a hypercoagulable state.28The mean duration of fever in
our cases was 7.8¡2.8 days (range 4–15). Our patients had
fewer adverse sequelae, as all were treated before the peak
mortality days, thus suggesting the importance of early
diagnosis and treatment. The opportunity for early manage-
ment occurred as the patients were being routinely followed
up in our outpatient clinic.
The current medical management of KD is IVIg and high-
dose aspirin. IVIg is very effective when given in the first ten
days of illness. It reduces the risk of CAA from 20–25% to 1–
2%.6,9A subgroup of patients with KD will be resistant to IVIg
therapy; these patients are at greatest risk of developing
coronary artery aneurysms and long-term sequelae of the
disease.29Data have demonstrated the usefulness and safety of
majority of our patients were given IVIg before the tenth day
and only one patient was IVIg resistant, who was successfully
treated with pulse methylprednisolone. Newburger et al.
reported that 50–67% of aneurysms resolve within 1–2 years.31
our study was normal within 8 months (three within 6 months,
four within 7 months, and two within 8 months). All patients
are alive and receiving annual echocardiographic follow-up.
In summary, it is our belief that KD is not a rare disease in
Turkey. This study is the most comprehensive series of
children from Turkey with KD included in Medline. As
adult-onset ischemic heart disease may be due to KD in
childhood,9,18,28further prospective clinical investigations
are needed to understand the epidemiology, management
and long-term follow-up the disease in Turkey.
Conflict of interest
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CLINICS 2010;65(12):1261-1265Children with Kawasaki disease in Istanbul
Kayiran SM et al.