DOI: https://doi.org/10.21203/rs.3.rs-359141/v1
Background: Kawasaki disease (KD)is an acute autoimmune systemic vasculitis disease that mainly occurs in infancy and younger children. It has the potential to cause coronary artery lesions (CALs) develop in up to 20-25% of patients with untreated KD caused morbidity and mortality in children worldwide especially in Asia.
Objective: To determine the predictive factors of IVIG resistant Kawasaki disease in Thailand
Method: A retrospective descriptive study. Patient charts of all patients who had newly diagnosed of KD in Bhumibol Adulyadej Hospital, Thailand between January 2010 and December 2020 were reviewed. The protocol was approved by the ethic review committee.
Results: A total of 102 subjects met the inclusion criteria and were enrolled into the study, including 17 cases of IVIG resistant (17/97, 28.5%) and 80 cases of IVIG responder (80/97, 71.4%).Demographic and laboratory characteristics were obtained. Male gender has greater in number in IVIG resistant group. Average age is 27 months and IVIG resistant tends to have age below 6 months old. Two variables were significantly lower in IVIG-resistant group than IVIG-responder group, including serum albumin (3.01±0.51vs 3.48±0.49 g/dL, p-value = 0 . 01) and serum sodium (133.24±3.43 vs 135.79±3.19 mEq/L, p-value = 0.01) meanwhile age at time of diagnosis less than 6 months (29.4% vs 8.75%, p-value = 0.02) and serum ALT (78.29±74.19 versus 71.01±80.19 IU/L, p-value = 0.02) were significantly higher in IVIG-resistant group than IVIG-responder group.
Conclusion: The predictive factors of our study by univariate analysis included age below 6 months, serum albumin <3.5g/dL, serum sodium <135mmol / L and high serum ALT≥45 IU/L. The principal findings in our predictive model is the scoring system for predicting IVIG-resistant patients in Thai population, the scoring system includes total peripheral WBC count >18,000 mm 3 . (1 point), serum albumin < 3.5 g/dl (1 point) and serum ALT ≥ 45 IU/L (1.5 points), and a total score equal 2 points and higher yielded a sensitivity and a specificity of 82.35% and 62.50%, respectively for IVIG resistance prediction, who require more close monitoring which may help physicians make more rational decisions regarding an initial treatment of KD and be the candidates for additional therapies. Our study is similar to previous studies in Japan, a risk scoring system prior to administrate IVIG.
Table 1.
Baseline demographic characteristics among responder (n=80) and resistant (n=17) to intravascular immunoglobulin (IVIG)
Characteristics |
IVIG responder N=80 |
IVIG resistant N=17 |
p-value |
Mean age (months) |
28.5±24.9 |
21±26.1 |
0.308 |
Age less than 6 months |
7 (8.7) |
5(29.4) |
0.027 |
Male gender |
46 (57.5) |
14 (82.3) |
0.067 |
Hematocrit (< 35%) |
65 (81.2) |
16(94.1) |
0.222 |
Hemoglobin (<10g/dL) |
31(38.7) |
8(47.0) |
0.527 |
WBC (> 18,000cell/mm3) |
26(32.5) |
9(52.9) |
0.117 |
Neutrophil (≥80%) |
8(10.0) |
2(11.7) |
0.828 |
Platelet (≤350,000cell/mm3) |
28(35.0) |
7(41.1) |
0.631 |
Albumin (<3.5g/dL) |
36(45.0) |
14(82.3) |
0.010 |
Total bilirubin (≥0.7mg/dL) |
14(17.5) |
3(17.6) |
0.988 |
AST (≥80IU/L) |
12(15.0) |
4(23.5) |
0.394 |
ALT (≥45IU/L) |
36(45.0) |
13(76.4) |
0.025 |
Sodium (<135mmol/L) |
30(37.5) |
12(70.58) |
0.017 |
Chloride (<96mmol/L) |
34(42.5) |
4(23.5) |
0.154 |
ESR (≥40mm/hr) |
53 (66.3) |
11 (64.7) |
0.903 |
CRP (≥60mg/dL) |
49(61.2) |
14(82.3) |
0.109 |
CALծbefore treatment |
29(36.3) |
13(76.4) |
0.005 |
Table 2.
Univariate analysis for predictive values among responder (n = 80) and resistant (n = 17) to intravascular immunoglobulin (IVIG)
Characteristics |
Odds Ratio |
95 % Confidence Interval |
p-value |
Mean age (months) |
0.99 |
(0.96 - 1.01) |
0.308 |
Age less than 6 months |
4.35 |
(1.18 - 15.94) |
0.027 |
Male gender |
3.45 |
(0.92 - 12.96) |
0.067 |
Hematocrit (< 35%) |
3.69 |
(0.45 - 30.06) |
0.222 |
Hemoglobin(< 10 g/dL) |
1.41 |
(0.49 - 4.03) |
0.527 |
WBC (> 18,000 cell/mm3) |
2.34 |
(0.81 - 6.75) |
0.117 |
Neutrophil (≥ 80%) |
1.20 |
(0.23 - 6.23) |
0.828 |
Platelet (≤ 350,000 cell/mm3) |
1.30 |
(0.45 - 3.79) |
0.631 |
Albumin (< 3.5 g/dL) |
5.70 |
(1.52 - 21.4) |
0.010 |
Total bilirubin (≥ 0.7 mg/dL) |
1.01 |
(0.26 - 3.99) |
0.988 |
AST (≥ 80 IU/L) |
1.74 |
(0.49 - 6.26) |
0.394 |
ALT (≥ 45 IU/L) |
3.97 |
(1.19 - 13.24) |
0.025 |
Sodium (<135 mmol/L) |
4.00 |
(1.28 - 12.47) |
0.017 |
Chloride (< 96 mmol/L) |
0.42 |
(0.12 -1 .39) |
0.154 |
ESR (≥ 40 mm/hr) |
0.93 |
(0.31 - 2.80) |
0.903 |
CRP (≥ 60 mg/dL) |
2.95 |
(0.78 - 11.11) |
0.109 |
CALծbefore treatment |
5.72 |
(1.7 - 19.16) |
0.005 |
Table 3. Risk factors for predicting IVIG-resistant by multivariate analysis.
Risk factors |
Intravascular immunoglobulin (IVIG) |
Multiple Analysis |
Coefficient |
Risk score |
||
|
Responder |
Resistant |
Adj OR |
p-value |
||
WBC |
26 (32.5) |
9 (52.9) |
2.34 |
0.117 |
1.35 |
1 |
Serum albumin |
36 (45.0) |
14 (82.3) |
5.70 |
0.010 |
1.63 |
1 |
Serum ALT |
36 (45.0) |
13 (76.4) |
3.97 |
0.025 |
1.76 |
1.5 |
Table 4. Risk scoring for predict IVIG resistant group
Risk score |
Intravascular immunoglobulin (IVIG) |
Total |
|
Responder |
Resistant |
||
< 2 |
50 (62.5) |
3 (17.6) |
53 (54.6) |
≥ 2 |
30 (37.5) |
14 (82.4) |
44 (45.4) |
Total |
80 |
17 |
97 (100.0) |
Table 5. Risk scoring differences among the clinical studies
Predictive factors |
Egami |
Kobayashi |
Sano |
Our study |
CRP*(mg/dL) |
> 8 |
>10 |
> 7 |
|
Age (month) |
< 6 |
>12 |
|
|
BILIծ (mg/dL) |
|
|
> 0.9 |
|
AST (IU/L) |
|
|
> 200 |
|
ALT (IU/L) |
≥ 80 |
≥ 100 |
|
≥ 45 |
Sodium (mmol/L) |
|
≤ 133 |
|
|
Platelet counts (cell/mm3) |
≤ 300,000 |
|
|
|
Percentage of neutrophils (%) |
|
≥ 80 |
|
|
Albumin (g/dL) |
|
|
|
< 3.5 |
WBC (cell/mm3) |
|
|
|
> 18,000 |
*C-reactive protein, ծBilirubin |
Table 6. Predictive validity for resistant to intravascular immunoglobulin (IVIG)
Predictive validity |
|
Sensitivity |
82.35 (74.77 - 89.94) |
Specificity |
62.50 (52.87 - 72.13) |
Positive predictive value |
31.82 (22.55 - 41.09) |
Negative predictive value |
94.34 (89.74 - 98.94) |
Likelihood ratio (+) |
2.20 (1.53 - 3.14) |
Likelihood ratio (-) |
0.28 (0.10 - 0.80) |
Accuracy |
65.97 (55.66 - 0.75) |
AUROC |
0.79 (0.69 - 0.89) |