Incomplete Kawasaki disease (iKD) is considered to be a less complete form of Kawasaki disease (cKD), and several differences in the laboratory presentations of iKD and cKD have been noted. We investigated serum procalcitonin levels in patients with iKD, cKD, and other febrile diseases (a control group). Seventy-seven patients with cKD, 24 with iKD, and 41 controls admitted to our hospital from November 2009 to November 2011 were enrolled in the present study. We obtained four measurements of serum procalcitonin levels and those of other inflammatory markers from each patient. Samples were taken for analysis on the day of diagnosis (thus before treatment commenced; D0) and 2 (D2), 14 (D14), and 56 days (D56) after intravenous immunoglobulin infusion. We obtained control group data at D0. The mean D0 serum procalcitonin levels of cKD patients (
Kawasaki disease (KD) is a form of systemic vasculitis, the etiology of which is unknown. No definitive diagnostic laboratory test exists [
Complete KD (cKD) is diagnosed if all diagnostic criteria are fulfilled, whereas incomplete KD (iKD), which occurs in 15–20% of KD patients, is diagnosed when not all clinical features are present provided that several suspicious features are evident, laboratory findings suggest the presence of KD, and alternative diagnoses have been excluded [
Although iKD is considered to be an incomplete form of cKD, because iKD and cKD patient demographic and laboratory findings are similar [
Procalcitonin is a peptide precursor of calcitonin, the level of which increases in response to proinflammatory stimuli, especially those of bacterial origin. Procalcitonin levels >5 ng/mL are closely associated with the presence of severe infection, usually bacteremia [
We enrolled child patients admitted to Chonnam National University Hospital from November 2009 to November 2011. Informed written consent was obtained from the parents of all patients. A total of 101 patients diagnosed with KD were enrolled. Of these, 77 were diagnosed with cKD and 24 with iKD. cKD was diagnosed if all diagnostic criteria were fulfilled [
We performed two-dimensional echocardiography on four occasions on each KD patient: on the day of diagnosis (prior to treatment; D0) and 2 (D2), 14 (D14), and 56 days (D56) after intravenous immunoglobulin (IVIG) infusion. We checked all scans for the presence of pericardial effusion, coronary artery lesions, and mitral regurgitation, and we assessed left ventricular function including the ejection fraction (EF). Both the electrocardiographic rhythm and the heart rate were monitored during each examination. The size of each coronary artery was converted to a
Peripheral venous blood was drawn to measure serum procalcitonin levels in cKD and iKD patients and controls. We also obtained complete blood cell counts and ESRs and measured the levels of CRP, total protein, albumin, sodium, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), ALT, creatine kinase (CK), CK-MB, myoglobin, troponin-I, and N-terminal pro-brain natriuretic peptide (NT-proBNP). We measured serum procalcitonin levels on four occasions in each KD patient: at D0, D2, D14, and D56. Control data were collected only during the acute stage of disease (D0). We compared the D0 values of the cKD, iKD, and control groups and those from cKD and iKD patients gathered at later times. Serum NT-proBNP was analyzed using an electrochemiluminescence immunoassay (Elecsys ProBNP Sandwich Immunoassay; Roche Diagnostics, Basel, Switzerland). Serum procalcitonin levels were quantitated by immunoassay (Elecsys BRAHMS PCT Procalcitonin, Roche). The lower and maximum limits of detection were 0.02 and 100 ng/mL, respectively.
The chi-squared test was used to assess the statistical significance of differences in the values of independent variables, and analysis of variance (ANOVA), followed by application of Tukey’s post hoc test, was employed to compare data among the three groups. Two-way repeated-measures ANOVA followed by use of Tukey’s post hoc test was employed for intragroup analysis. Continuous variables were expressed as means ± standard deviations. A probability of <0.05 was considered to indicate statistical significance. The software package SPSS (version 20.0; SPSS, Chicago, IL) was used for all data analysis.
The present study was approved by the Institutional Review Board of Chonnam National University Hospital (Protocol no. I-2009-09-103). All data were treated confidentially.
Patient demographics are shown in Table
Demographic characteristics of patients with complete Kawasaki disease (cKD), incomplete KD (iKD), and other infectious diseases (controls).
Complete KD |
Incomplete KD |
Control |
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Age (years; mean ± SD) |
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0.451 |
Gender (M/F) | 52/25 | 15/9 | 28/13 | 0.662 |
Duration of fever (days; mean ± SD) |
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0.815 |
Duration of fever prior to admission (days; mean ± SD) |
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0.581 |
KD: Kawasaki disease.
All KD patients (those with either cKD or iKD) were treated with 2 g/kg intravenous immunoglobulin (IVIG) given as a single infusion. All patients were prescribed 30–50 mg/kg oral aspirin during the acute inflammatory stage, and the dose was tapered to 3–5 mg/kg after the acute stage had passed. Twelve patients with cKD and one with iKD who failed to respond to initial IVIG therapy received a second dose of IVIG. Two cKD patients who did not respond to this second dose of IVIG were given infliximab. Eight cKD and six iKD patients yielded positive bacterial blood cultures.
Forty-one patients were enrolled as controls; the male-to-female ratio was 2.15. The mean age was
At admission, of the 77 patients with cKD, 74 (96%) had bilateral bulbar conjunctival infections, 71 (92%) a polymorphous rash, 73 (94%) changes in the oral mucosa, 61 (79%) cervical adenopathy with lymph nodes greater than 1.5 cm in diameter, and 50 (64%) changes in the peripheral extremities. Among 24 patients with iKD, 21 (87%) had bilateral bulbar conjunctival infections, 15 (62%) rash, 18 (75%) changes in the oral mucosa, 7 (29%) cervical adenopathy, and 7 (29%) changes in the peripheral extremities. All clinical features except bilateral bulbar conjunctival infection were significantly more prevalent in cKD than in iKD patients (Table
Clinical features and echocardiographic findings in patients with complete and incomplete Kawasaki disease (KD).
Complete KD |
Incomplete KD |
|
|
---|---|---|---|
Classic clinical presentations | |||
Bilateral bulbar conjunctival infection | 74 (96.0%) | 21 (87.0%) | 0.178 |
Polymorphous rash | 71 (92.0%) | 15 (62.0%) | 0.007 |
Changes in oral mucosa | 73 (94.0%) | 18 (75.0%) | 0.032 |
Cervical adenopathy | 61 (79.0%) | 7 (29.0%) | <0.001 |
Changes in the peripheral extremities | 50 (64.0%) | 7 (29.0%) | 0.002 |
Resistance to first IVIG | 12 (16.0%) | 1 (4.0%) | 0.020 |
Echocardiography | |||
Coronary artery dilatation | 4 (5.2%) | 0 | 0.045 |
Increased perivascular echogenicity | 12 (15.6%) | 4 (16.6%) | 0.696 |
Vascular irregularity | 12 (15.6%) | 2 (8.3%) | 0.464 |
Mitral regurgitation | 7 (9.1%) | 2 (8.3%) | 0.807 |
Pericardial effusion | 1 (1.2%) | 1 (4.2%) | 0.486 |
Data are represented as numbers (percentages).
The basic echocardiographic findings are summarized in Table
Laboratory data obtained at the time of diagnosis are shown in Table
On D0, the WBC (
Laboratory findings at diagnosis in patients with Kawasaki disease (KD) and controls.
Complete KD |
Incomplete KD |
Control |
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White blood cell count (/mm3) |
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Neutrophil proportion (%) |
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Eosinophil proportion (%) |
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Hemoglobin (g/dL) |
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Hematocrit (%) |
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Platelets (103/mm3) |
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Erythrocyte sedimentation rate (mm/h) |
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C-reactive protein (mg/dL) |
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Aspartate aminotransferase (U/L) |
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Alanine aminotransferase (U/L) |
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Total protein (g/dL) |
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Albumin (g/dL) |
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Sodium (mEq/L) |
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Potassium (mEq/L) |
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Chloride (mEq/L) |
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Creatine kinase (IU/L) |
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Creatine kinase-MB (ng/mL) |
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Myoglobin (ng/mL) |
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Troponin I (ng/mL) |
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N-terminal pro BNP (pg/mL) |
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KD: Kawasaki disease. Data are shown as means ± SD.
On D2, the total protein level was significantly higher in the cKD group than in iKD patients or controls (
cKD and iKD patients experienced significant reductions in the WBC and CRP level at D2, D14, and D56, compared to the D0 findings. The NT-proBNP levels of cKD patients at D2 and D14 were significantly lower than those at D0 (Figure
Laboratory data from patients with complete Kawasaki disease (KD), incomplete KD, and other febrile illnesses (controls), collected on the day of diagnosis and 2, 14, and 56 days after intravenous immunoglobulin (IVIG) treatment. (a) White blood cell count, (b) C-reactive protein level, (c) erythrocyte sedimentation rate, and (d) N-terminal pro-brain natriuretic protein (NT-proBNP) level.
Of the 101 KD patients and 41 controls, we measured serum procalcitonin levels of 85 patients (cKD: 64, iKD: 21) and 34 controls at D0. The mean D0 serum procalcitonin levels in cKD patients (
Differences in procalcitonin levels among patients with complete Kawasaki disease (KD), incomplete KD, and other febrile illnesses (controls), on the day of diagnosis and 2, 14, and 56 days after intravenous immunoglobulin (IVIG) treatment.
We measured D2 serum procalcitonin levels in 82 patients (cKD: 65, iKD: 17) and 15 controls (after resolution of fever); D14 levels in 85 patients (cKD: 66, iKD: 19); and D56 levels in 22 patients (cKD: 18, iKD: 4). The mean control procalcitonin level (
cKD patients showed significant reductions in procalcitonin levels at D14 (
In the present study, we have shown the utility of measuring serum procalcitonin levels in patients with cKD, iKD, and other febrile illnesses, at different stages of disease. KD patients had significantly higher WBC and platelet counts and ESR than did those with other febrile illnesses. Also, during the acute stage of disease, cKD patients and those with other febrile illnesses had significantly higher levels of serum procalcitonin than did iKD patients.
Procalcitonin has been suggested to be an acute-phase reactant, because synthesis thereof is thought to be induced by IL-6 or TNF-
In contrast, Chakrabartty and Apong reported that KD patients expressed low levels of procalcitonin [
In our present study, we considered that procalcitonin was an acute-phase reactant and compared the levels thereof in patients with both types of KD and controls with other febrile illnesses. During the acute stage of disease, procalcitonin levels were significantly higher in patients with cKD and other febrile illnesses than in iKD patients, decreased in both types of KD patients to D14 after IVIG treatment, and remained steady thereafter. No statistically significant correlation between the presence of coronary artery disease and procalcitonin level was evident although, as explained above, our analysis may have lacked adequate statistical power. The observed differences in procalcitonin levels may be explained by the fact that cKD patients exhibit more advanced inflammatory reactions than do iKD patients. This pathophysiologic feature of KD requires further study. In the present work, we found that serum procalcitonin levels were relatively low in both cKD (
Several well-known laboratory findings support the diagnosis of either iKD or cKD. Most KD patients have an elevated CRP level or ESR [
In our present study, WBC and platelet count and the ESR were significantly higher in KD patients compared to those with other febrile illnesses, at the time of diagnosis. Also, in the subacute stage, WBC and platelet counts, the ESR, and the CRP level were significantly higher in KD patients than controls. The total protein level was significantly higher in the cKD than in the iKD or control groups and was not correlated with any of IVIG dose, body weight, or body surface area. This finding requires further study. However, none of the WBC, the ESR, or the levels of CRP and NT-proBNP differed significantly between cKD and iKD patients. None of the levels of total protein, albumin, AST, ALT, sodium, or chloride differed significantly among the two KD groups and controls. Only serum potassium level (in the iKD group) was significantly higher than in the cKD group and controls.
One limitation of the present study is that some follow-up data are missing probably because parents refused to permit blood to be drawn as recovering children appeared to be healthy.
In conclusion, this is the first report of serial procalcitonin measurements in patients with both types of KD and controls. The mean D0 serum procalcitonin levels of cKD and controls were significantly higher than those of iKD patients during the acute stage of disease. In contrast, the levels of other inflammatory markers including the WBC, the ESR, and CRP level did not significantly differ between patients with cKD and iKD. Further exploration of differences in procalcitonin levels between cKD and iKD patients is needed to better understand the incomplete presentation of iKD.
The authors have no conflict of interest to disclose.
This study was supported by a Grant (CRI 10-027-1) of the Chonnam National University hospital Research Institute of Clinical Medicine.