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Indian Pediatr 2009;46: 585-590 |
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Clinical Characteristics of Kawasaki Disease
According to Age at Diagnosis |
Seong Hyun Kim, Ki Hwan Kim and Dong Soo Kim
From Department of Pediatrics, Severance Children’s
Hospital, Yonsei University College of Medicine, Seoul, Korea.
Correspondence to: Dr Dong Soo Kim, Severance Children’s
Hospital, Yonsei University College of Medicine,
134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea.
Email: [email protected]
Manuscript received: July 21, 2008;
Initial review: September 19, 2008;
Accepted: April 2, 2009.
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Abstract
Objective: We compared the clinical, laboratory
and diagnostic features of Kawasaki disease (KD) in children
£6 mo and
³5 y of age to those in the more
typical age range at diagnosis (6 mo-5 y of age).
Study design: Retrospective analysis.
Setting: Severeance Children Hospital attached to
a Medical School, Korea.
Methods: All children with a discharge diagnosis
of KD at Severance Children’s Hospital (2006-2007) were retro-spectively
reviewed and grouped according to age at presentation in 3 groups: <6
mo, 6 mo-5 y and ³5 years. Clinical,
hematological, and biochemical features and involvement of coronary
artery and proportion of Classic vs. Incomplete KD were compared
between the 3 groups.
Results: A total of 185 children were identified.
Complete KD was found in 63 (34%) children and Incomplete KD in 122
(66%). There was 22(12%) children below 6 months of age, 131 (71%)
between 6 months to 5 years) and 32 (17%) above 5 years of age.
Clinical, hematological and biochemical features were comparable between
the three age groups. Overall, coronary artery lesions occurred in 9%
children without any preference for age. The proportion of Classical
vs. Incomplete KD was also similar in the three age categories.
Conclusion: The clinical and laboratory phenotype
of KD does not vary significantly with age.
Key Words: Age, Clinical features, Kawasaki disease, Korea.
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Kawasaki disease (KD) is an acute,
self-limited systemic vasculitis of unknown etiology that occurs
predominantly in infants and young children and was first described in
1967 by Tomisaku Kawasaki(1-3). Though its incidence varies among
countries, higher rates of KD have been reported in Asian countries such
as Japan and Korea(5-7). According to a recent nationwide epidemiologic
study, the number of Korean children with KD has steadily increased each
year with an annual incidence of 105/100,000 children, which is second
only to Japan(8).
KD is the leading cause of acquired heart disease in
childhood, causing overt damage in up to 15-25% of untreated children and
2-4% of those who receive appropriate treatment, and may lead to
myocardial infarction, sudden death, or ischemic heart disease(2,4,9-12).
Prompt diagnosis using intra-venous immunoglobulin (IVIG) can reduce the
incidence of coronary artery abnormalities from 20-25% to 5%(13,14).
Reported risk factors for coronary artery lesions include delayed
diagno-sis(15,16) and an age of onset outside the typical age
distribution(17,18). Some studies have shown that risk factors for delayed
diagnosis include an age of < 6 mo and incomplete KD(16). In addition,
more patients are being diagnosed who do not meet the classic diagnostic
criteria(19). It has been reported that in incomplete KD and younger
children, the clinical features are fewer and more subtle and
consequently, diagnosis may be more difficult and delayed(16).
Although conventional diagnostic criteria are useful in
preventing overdiagnosis, some studies suggest that these should be
revised to include guidelines that recognize incomplete forms of KD(2,20),
and a revision of new diagnostic guidelines has been attempted(21,22).
General pediatricians may hesitate to make an early diagnosis and treat
those outside the typical age range (£6
mo and ³5
y of age) and those who do not fully meet the classic criteria. This may
delay diagnosis and prompt treatment, and worsen outcome, as discussed
above(23). In this study the clinical features, laboratory findings and
outcome were compared in patients with KD within and outside the typical
age range.
Methods
A total of 198 patients with KD were treated at
Severance Children’s Hospital of Yonsei University College of Medicine,
Seoul, Korea, between 2006 and 2007. Thirteen cases of recurrent KD were
excluded. To investigate age-related differences in clinical
characteristics, a retrospective analysis of 185 KD children with a
discharge diagnosis of KD was performed after seeking approval from the
Institute’s Ethics Committee. Diagnosis of KD was made as per AHA
Guidelines(2). Subjects were also evaluated to determine whether they
satisfied the classic diagnostic criteria. Incomplete KD was defined as
meeting less than 4 clinical criteria, irrespective of echocardiography
findings(2,24,25). Overall, there were 63 (34%) cases with classic KD and
122 cases with incomplete KD (66%). Subjects were categorized by age in
Group A (22 cases, £5 mo
of age), Group B (131 cases, 6 mo-4 y of age) and group C (32 cases,
³5 y
of age).
All children were treated with IVIG at a dose of 2 g/kg
and a high dose of aspirin (100 mg/kg) during the febrile period, in
keeping with current consensus guidelines(3,4). Additional IVIG (2 g/kg)
was given when fever persisted for more than 48 h, even after the initial
IVIG infusion.
Echocardiography was performed within 2 wk of the onset
of illness, during the 4th wk, and subsequently repeated depending on the
initial findings. Coronary artery lesion (CAL) was defined as an internal
lumen diameter >3 mm in children <5 y of age or >4 mm in children
³5
y of age, if the internal diameter of a segment measured
³1.5
times that of an adjacent segment, or if the lumen was clearly irregular
(the Japanese Ministry of Health criteria)(26). When a coronary artery was
larger than normal (dilated) and without a segmental aneurysm, the vessel
was considered ecstatic(2). All patients underwent laboratory
investigations for leukocyte (WBC) count, hemoglobin, thrombocyte,
C-reactive protein, erythrocyte sedimentation rate, aspartate
aminotransferase, alanine aminotransferase, lactate dehydrogenase,
creatine kinase (CK), CK-MB, N-terminal fragment of B-type natriuretic
peptide (NT-proBNP), and urine WBC, which were performed at admission and
1 day after the initial IVIG infusion, in keeping with normal clinical
practice at our hospital.
Statistical analysis was performed using SPSS 13.0 for
Windows. The three age groups were compared for clinical characteristics
including presence of coronary artery lesions, hematological and
bio-chemical parameters, and for presence of classical or incomplete KD.
The means of the continuous variables in the 3 age groups were compared
using 1-way ANOVA. If there were significant differences among the 3
groups, identification of the 2 groups that showed significant differences
were made by post hoc tests (Scheffe, LSD and Tukey’s). Chi-square
test was used for comparing categorical variables. A probability of
£0.05
was considered statistically significant.
Results
The average age of 185 children with KD was 2.8 year,
with a range of 1 month to 10 years. The clinical features are summarized
in Table I. The most common clinical feature was fever,
followed by red lips and red eyes.Sixty-three of 185 (34%) children
fulfilled the diagnostic criteria for Classical KD and 122 (66%) were
diagnosed with Incomplete KD. Incomplete KD was found in 15 (68%) children
in Group A, 88 (67%) in Group B, and 19 (59%) in Group C (P>0.05).
TABLE I
Clinical Characteristics of Kawasaki Disease According to Age at Diagnosis
|
Group A
≤5 mo (n = 22) |
Group B
6 mo-4 y (n = 131) |
Group C
≥5 y (n = 32) |
P-value
|
Mean age
(mo) |
3.5 |
27 |
78 |
0 |
Male/female |
11/11 |
73/58 |
13/19 |
NS |
Fever
duration(d, mean ± SD) |
4.73 ± 3.14 |
4.91 ± 4.13 |
6.69 ± 5.82 |
NS |
Clinical signs (%) |
Skin rash |
14 (64) |
87 (66) |
17 (53) |
NS |
Cervical nodes |
7 (32) |
47 (36) |
17 (53) |
NS |
Red eyes |
15 (68) |
95 (73) |
23 (72) |
NS |
Red lips |
19 (86) |
103 (79) |
28 (88) |
NS |
Changes in extremities |
8 (36) |
58 (44) |
14 (44) |
NS |
BCG erythema |
16 (73) |
44 (34) |
1 (3) |
0.001
|
Anal desquamation |
1 (5) |
15 (12) |
2 (6) |
NS |
GB
hydrops |
4 (20) |
15 (13) |
2 (8) |
NS |
NS: not significant, GB: gallbladder. |
Laboratory findings between the three age groups are
compared in Table II. Marked leukocytosis and thrombocytosis
on admission were noted more in children <6 months of age. The
incidence of sterile pyuria was 14% (26 cases overall: 2 in group A, 20 in
group B, and 3 in group C) with statistical insignificance between groups
(P=0.16). The incidence of coronary artery lesions was comparable
both at admission and 6 months later, in all age groups (Table
III). The overall recurrence rate was 0.3% with no significant
differences between groups (P=0.5:1 case in group A, 5 in group B,
and none in group C).
TABLE II
Laboratory Findings of Kawasaki Disease Before IVIG Treatment
|
Group A (n = 22) |
Group B (n = 131) |
Group C (n = 32) |
P value |
WBC
(x103/mm3) |
16.1 ± 6.1 |
12.8 ± 5.5 |
10.4 ± 3.9 |
0.001 |
Hemoglobin (g/dL) |
15.5 ± 2.6 |
12.5 ± 0.9 |
11.9 ± 0.9 |
NS |
Platelet
count (x103/mm3) |
511 ± 304 |
385 ± 137 |
331 ± 136 |
0.01 |
ESR
(mm/h) |
47 ± 34.7 |
54 ± 38.4 |
50 ± 35.0 |
NS |
CRP (mg/dL)
|
5.1 ± 4.7 |
5.7 ± 6.4 |
6.1 ± 6.2 |
NS |
AST (IU/L)
|
56 ± 64.5 |
104 ± 209.0 |
48 ± 56.8 |
0.045 |
ALT |
40 ± 42.2 |
99 ± 164.0 |
35 ± 75.3 |
0.09 |
LDH (IU/L)
|
517 ± 88.2 |
615 ± 202.2 |
501 ± 180.1 |
0.03 |
CK (IU/L)
|
77 ± 65.2 |
129 ± 172.3 |
180 ± 326.8 |
NS |
MB (ng/mL)
|
3 ± 1.3 |
4 ± 2.1 |
4 ± 4.1 |
NS |
MB/CK
|
6 ± 3.3 |
5 ± 3.2 |
5 ± 7.5 |
NS |
NT-proBNP
(pg/mL) |
1203 ± 959.6 |
1257 ± 3795.3 |
632 ± 1864.3 |
NS |
Urine WBC
|
0 |
0.02 ± 0.14 |
0.07 ± 0.26 |
NS |
NS: not significant; WBC: White blood cells; ESR: Erythrocyte sedimentation rate;
CRP: C-reactive protein; AST: Aspartate aminotransferase;
ALT: Alanine aminotransferase; LDH: Lactate dehydrogenase; CK: Creatine Kinase;
MB: Creatine kinase - MB components; NT: ProBNB: N-terminal fragment of B-type natriuretic peptide.
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TABLE III
Coronary Artery Lesions in Kawasaki Disease
|
Group A (n = 22) |
Group B (n = 131) |
Group C (n = 32) |
Total |
P value |
Initial
CALs (%) |
3 (1.6%) |
13 (7.0%) |
1 (0.5%) |
17 (9.2%) |
0.74 |
F/U CALs
(%) |
3 (1.6%) |
6 (3.2%) |
1 (0.5%) |
10 (5.4%) |
0.15 |
CALs: coronary artery lesions, F/U:
follow up. |
Discussion
There have been many reports of the different features
of KD outside the typical age range of the disease. In some studies,
patients <6 mo of age were at increased risk for CALs, giant aneurysms,
incomplete KD, and atypical features(17,27). Other studies have shown that
older children and adolescents with KD were predominantly male, had
delayed diagnosis of KD, higher incidence of cervical lymphadenopathy, and
presence of additional symptoms such as abdominal and joint pain as well
as higher rates of CAL(18,23,28,29).
We did not observe any variation in the clinical
presentation of children at various ages, except that the erythema at BCG
site was more pronounced in children <6 months. In laboratory parameters,
leuco-cytosis and thrombocytosis were more prominent in younger infants.
However, the incidence of incomplete Kawasaki disease and coronary artery
lesions remained comparable at all ages. The major strength of this study
is a large sample size analyzed in different age groups. However, most of
the children (66%) had incomplete Kawasaki disease.
While children outside the typical age range (<6 mo and
>5 y) are reported to be at higher risk for CALs in some reports
(23,27,29), CALs occurred equivalently in all age groups in this study,
suggesting that the risk of CAL may not be increased in those who receive
early IVIG therapy. Initially, the incidence of CAL was 9% overall in this
study, which was similar to other reports, but showed a decreased rate of
incidence of 5% on 6-month follow-up echocardiography, as compared to
other studies. This may be due to earlier echocardiography performed
within the first week of disease onset, unlike in other studies.
There were no other cardiac manifestations presenting as heart failure,
which may explain the elevated NT-proBNP. However, we found that 7 (4%)
cases had pericardial effusion on echocardiography, though it is not a CAL
category.
With no specific diagnostic test for KD, phy-sicians
are likely to diagnose it on the basis of clinical findings. Rigorous
application of the classical clinical diagnostic criteria is inappropriate
and may result in missed diagnoses(2).
Since some clinical and laboratory findings are characteristic, they can
help prevent misdiagnosis(20). BCG site change and NT-proBNP may be highly
suggestive markers for acute KD to differentiate from other acute febrile
illnesses and also be useful as additional diagnostic tools(30). Recently
published less stringent diagnostic algorithms may prove particularly
useful, especially in younger age groups(2,22). Further research is needed
to continue the revision of diagnostic criteria of the Kawasaki disease.
Contributors: All authors contributed to the study
design, acquisition of data and its analysis, and writing the report.
Funding: None.
Competing interests: None stated.
What is Already Known?
• Kawasaki disease is associated with coronary
artery lesions; this might be related to the age at which the
disease occurs.
What This Study Adds?
• In 185 children diagnosed with Kawasaki disease
(Classical: 63; imcomplete: 122), there were no major differences in
clinical presentation with respect to age, including the incidence
of coronary artery lesions. |
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