Carolinas Research Day 2021

The Impact of Early Intravenous Immunoglobulin Treatment on Coronary Artery Disease in Children with Kawasaki Disease MacKenzie LeMay, OMS IV 1 ; Ning Cheng, PhD 1 ; Jessica Resnick, OMS III 1 ; Lucas Hooks, OMS III 1 ; Hanna S. Sahhar, MD, FAAP, FACOP 1,2 1 Edward Via College of Osteopathic Medicine, Spartanburg, SC 2 Spartanburg Regional Medical Center, Spartanburg, SC Introduction Results Discussion

CLIN-6

Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown cause that has an affinity for negatively impacting the coronary arteries of infants and young children. Common cardiac complications include coronary artery aneurysms, depressed myocardial contractility and heart failure may develop. If left untreated, about 25% of patients will develop coronary artery disease (CAD) or coronary lesions. Intravenous immunoglobulin (IVIG) treatment reduces morbidity and mortality related to cardiac involvement, however, how quickly results are seen is unknown. In the first phase of this study, there was CAD found in about half the patients studied and had 1 year follow up echocardiograms. In this larger scope of patients we found less CAD at presentation so have taken a closer look at IVIG dosing and antibiotic usage.

Our subject population has shown no statistical significance in developing CAD if given before the accepted 10-day window or given after. This could mean the recommendation for IVIG intervention before day 10 can be less of a hard line and allow for more flexibility of treatment. This does support our hypothesis that we would have no significant increase in CAD between our two groups. Obviously, earlier intervention produces better results but in some rural communities around the hospital there are barriers to care that have previously prevented immediate diagnosis and referral to the PICU. A future direction could look at how translatable these findings are over a larger patient population or in a different geographical location (more urban, more racial representation). An interesting point that became evident during data collection was the number of patients who were given antibiotics. Kawasaki disease has no established bacterial component currently. We saw that 38.9% of our population were given antibiotics from community physicians or ER physicians prior to arriving in the community hospital PICU. Current antibiotic stewardship guidelines suggest antibiotics shouldn’t be given before day 5-10 because it is typically viral before that point. 27.8% of our subjects were given antibiotics in the appropriate fever timing, but 63.9% were given before guideline recommendation. However, there was no statistical difference between these two groups. This is important because it means there was not significantly more antibiotic usage in a disease process with no appropriate use of antibiotics or outside of stewardship guidelines. This still ultimately refutes our hypothesis that there would be no antibiotic usage in this patient population. Even though it did not reach statistical significance, this would still be a good jumping off point for a future Quality Improvement project in antibiotic stewardship for the local pediatrics community.

Of our 36 subject patients pool, 1 was Asian (2.8%), 21 were Black or African American (58.3%), 1 was Native Hawaiian or other Pacific Islander (2.8%), 11 were Caucasian (30.6%), and 2 were listed as Other (5.6%). 7 identified as Hispanic or Latino (19.4%). 7 had sequelae of coronary artery disease (19.4%). (see Table 2)

Table 2 .

Demographics Hispanic/Latino Not Hispanic/Latino

Frequency

Percent

7

19.4% 80.6% 2.8% 58.3% 2.8% 30.6% 5.6%

29

Asian

1

Black or African American Native Hawaiian or Other Pacific Islander

21

1

Caucasian

11

Other

2

31 were given intravenous immunoglobulin before day 10 (86.1%), 4 were given after day 10 (11.1%), and 1 did not have any IVIG documented in their chart (2.8%). Of the group who were given IVIG on or before day 10, 6 developed CAD (19.4%). Of the group given IVIG after day 10, 1 subject developed CAD. There was no statistical significance between these two groups (p= 1). (see Table 3)

Table 3 .

IVIG Day < 10 days >10 days

CAD+

CAD-

Total

6 1 0 7

25

31

3 1

4 1

Conclusions

N/A

Total

29

36

Our consecutive case series has confirmed previous medical literature that early IVIG intervention helps to prevent CAD in KD patients. However, this protective benefit extended beyond the typical 5-10 day window that has been established in guidelines. Our study also revealed inappropriate use of antibiotics in this disease process prior to diagnosis. Prompt diagnosis and treatment of KD is crucial for reducing risk of CAD and overuse of antibiotics.

14 were given one or more antibiotic prior to presentation (38.9%), 21 were not given any antibiotics during their course (58.3%), and 1 did not have full documentation. 23 of the subjects presented before day 7 of their fever (63.9%), 10 presented after day 7 (27.8%). 3 of our patients were missing documentation on when their fever started (8.3%). Of the group presenting before day 7, 9 were given one or more antibiotic (39.1%). Of the group presenting after day 7, 4 were given one or more antibiotic (40%). There was no significant difference between these two groups (p= 0.641). (See Table 4)

Methods

References

Retrospective chart review of thirty-six consecutive pediatric patients admitted to a community-based hospital in South Carolina with diagnosis of KD over a thirteen and a half-year period from September 20, 2006 to March 31, 2020. Institutional Review Board review was exempted for this study. We did descriptive analyses on patients' demographic characteristics (age, Ethnicity (Hispanic or Latino or not), race (White, Black or African American, Asian, Native American or Pacific Islander, and other), geographic area (by zip code). We used Chi-square-test to compare patients' risk of developing CAD (yes or no) in IVIG treatment groups (<=10 days vs >10 days). We also used Chi- square-test to compare whether patients having antibody treatment (yes or no) within recommended treatment time (<=7 days vs >7 days).

[1] Coustasse A, Larry J, Lee D. “Can Kawasaki Disease be Managed?”. Perm J . 2012; 16(2): 70-72. [2] Newburger JW, Takahashi M, Gerber MA, et al. “Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart”. Circulation. 2004; 110: 2747-2771. [3] Holman RC, Cums AT, Belay ED, Steiner CA, Schonberger LB. Kawasaki syndrome hospitalizations in the United States,1997 and 2000. Pediatrics . 2003; 112:495–501 [4] Chang RK. The incidence of Kawasaki disease in the United States did not increase between 1988 and 1997. Pediatrics. 2003; 111:1124–1125 [5] Yanagawa H, Yashiro M, Nakamura Y, Kawasaki T, Kato H. Epidemiologic pictures of Kawasaki disease in Japan: from the nationwide incidence survey in 1991 and 1992. Pediatrics . 1995; 95: 475–479 [6] Thiha K, Japan Kawasaki Disease Genome Consortium, Mashimo Y, et al. Investigation of novel variations of orai1 gene and their association with kawasaki disease. Journal of human genetics. 2019;64(6):511-519. doi:10.1038/s10038-019-0588-2 [7] Bums JC, Glode MP. Kawasaki syndrome. The lancet . 2004;9433(9433):533-544. [8] Hirata S, Nakamura Y, Yanagawa H. Incidence of recurrent Kawasaki disease and related risk factors: for the results of nationwide surveys of Kawasaki disease in Japan. Acta Pediatr . 2001; 90: 40–44. [9] Meissner HC and Leung DYM. Superantigens, conventional antigens and the etiology of Kawasaki syndrome . Pediatr Infect Dis J. 2000; 19: 91–94. [10] Leung DYM, Meissner C, Shulman ST, et al. Prevalence of superantigen-secreting bacteria in patients with Kawasaki disease. J Pediatr . 2002; 140: 742–46.

Table 4 .

Fever Days

ABX +

ABX -

UNK

Total

< 7 days > 7 days

9 4 1

14

0 1 0 1

23 10

5 2

N/A

3

Total

14

21

36

29

2 0 2 1 R e s e a r c h R e c o g n i t i o n D a y