Prediction of Resistant to Intravenous Immunoglobulin (IVIG) Treatment in Patients with Kawasaki Disease in the Tertiary Care Hospital.

DOI: https://doi.org/10.21203/rs.3.rs-359141/v1

Abstract

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.

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Tables

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
(95 % CI)

p-value

WBC
(> 18,000 cell/mm3)

26 (32.5)

9 (52.9)

2.34
(0.81 - 6.75)

0.117

1.35

1

Serum albumin
(<3.5 g/dL)

36 (45.0)

14 (82.3)

5.70
(1.52 - 21.4)

0.010

1.63

1

Serum ALT
(≥45 IU/L)

36 (45.0)

13 (76.4)

3.97
(1.19 - 13.24)

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)