Medical Management (based on the case scenario):

1. IVIg (Intravenous Immunoglobulin)

- It is the first line and currently the most effective medical treatment for Kawasaki disease.
Its effectivity in reducing the risk for coronary abnormalities, and reducing fever and
inflammatory markers during the active phase is well established.
- 2 g/kg IVIg be administered before the 10th day of illness, either having persistent fever
of unknown origin/cause or significant elevation of erythrocyte sedimentation rate (ESR),
C-reactive protein (CRP) and serum amyloid-A (SAA).
(Based on the case scenario, the child is having persistent fever for 4 days and has 9.4
mg/dL of CRP).
 Dosage and Route: IVIg is given as a 2 g/kg infusion delivered over 10 to 12
hours, ideally within the first 7 days of the illness. The mechanism of action of
IVIG is unknown, but it appears to have an antiinflammatory effect, which
decreases the inflammation of the coronary arteries and speeds the resolution of
the fever.
- IVIg should be administered if the patient’s diagnosis with Kawasaki disease is missed
earlier or it occurred retrospectively with persistent fever and without any other diagnoses
with persisting lab finding of inflammation.
( The child has inflamed tonsils with yellowish purulent coating as reveled by the
physical examination and has a 4-day history of fever).

2. Aspirin
- Aspirin is used in the acute phase for its antiinflammatory effect as well as for its
antithrombotic effect.
 Dosage: The doses is divided into two phases. During the initial phase, aspirin is
given at 80 to 100 mg/kg/day in four divided doses. High-dose aspirin should be
initiated as soon as Kawasaki disease is suspected and given until the child
remains afebrile for 48 to 72 hours. After the resolution of the fever, the dose of
aspirin is decreased to 3 to 5 mg/kg/day in a single daily dose for 6 to 8 weeks.
After 6 to 8 weeks, if the echocardiogram is normal, the aspirin is discontinued. If
the echocardiogram reveals coronary artery abnormalities, low-dose aspirin
therapy (3 to 5 mg/kg/day) is continued indefinitely.
 Route: PO

- Caution should be observed to children with viral infection. (eg. varicella, influenza) due to risk
of Reye’s syndrome especially in high dose aspirin.

Other Drugs:
1. Anticoagulant
 Warfarin (Caumadin) is given to child who developed giant aneurysms. It is
combined with aspirin to prevent thromboembolism, Myocardial Infarction (MI),
and potential risk of sudden death in patients with giant coronary aneurysms.
Dosage and Route: IV: Initially, 2-5 mg, daily; Maintenance: 2-10 mg daily
 Haparin is used as treatment and prophylaxis of thromboembolic disorders.
Dosage (children): lower IV infusion; Maintenance: continuous IV infusion of 15-
25 u/kg/hr or SC injection of 250/kg/hr
2. Antiplatelet
 Clopidogrel ( Clotisprin) is used for the prevention of ischemic events. May be
potential to patients with allergy to Aspirin otr with concomitant varicella and
influenza infection. However, its efficacy and safety have not been established in
children.
Dosage: 1 cap OD; Acute coronary syndrome maintenance: 1 cap daily.
 Dipyridamole may potentiates the effects of aspirin in platelet aggregation but
should not be given alone; may cause hemorrhage and worsening of angina.
Dosage and Route: PO: 75-100 mg QID in combination with warfarin; PO: 1 cap
BID in morning and evening for Dipyridamole 200 mg and aspirin 25 mg; max:
ASA 50 mg and dipyridamole 400 mg

 Ticlopidine is given in combination with Aspirin to prevent coronary ischemia

and thrombus formation.
Dosage: 250 mg BID for 4 days
3. Flurbiprofen (Strepsils Maxpro) for oral ulceration and inflammation
 It is the potential alternative to Aspirin in patients with severe hepatic impairment.
However, further studies are needed to establish its efficacy on acute Kawasaki
disease.
Preparation: dissolve 1 loz every 3-6 hours ; Maximum: 5 loz/24 hr for maximum
of 3 days
4. Corticosteroids
 It decreases inflammation by suppression of leukocytes and reversal of increased
capillary permeability. It suppressed immune system by reducing the activity and
volume of lymphatic system.
 Treatment should be restricted in patients in whom ≥2 infusions of IVIg have
been ineffective in alleviating fever and acute inflammation.
 It reduces fever but effects on coronary artery abnormalities are uncertain. High
incidence of giant aneurysms and coronary artery rupture have been reported.
Dosage and Route: IV: 30 mg/kg 24 hourly for 3 consecutive days
5. Tumor Necrosis Factor (TNF) Inhibitors
  Infliximab has been shown to be successful in patients refractory to IVIg and
corticosteroids. It reverses the clinical signs of Kawasaki disease.
 It may be used in patients with severe coronary artery disease, without substantial
effects. However, further studies are needed to establish its effect in reducing the
prevalence of Coronary Artery aneurysms.
Dose and Route: IV infusion: Initially 3 mg/kg, followed with additional similar
doses at 2 and 6 week after the first infusion, then every 8 weeks thereafter. Dose
may be adjusted to 10 mg/kg or treating as often as every 4 weeks, given with
methotrexate.
6. Immunosuppressant
 May be used in patients refractory to IVIg, infliximab or corticosteroid therapy as
third line treatment. Studies have shown that treatment with Cyclosporine A
(immunosuppressant) effectively reduces fever. However, more studies are needed
to establish its efficacy.
Dose and Route: IV: 12 mg² q3mo; max lifetime dose: 140 mg/m² IV; PO: 120 mg
BID for 7 days, then, 240 mg BID; max: 480 mg/d
7. Beta Blocker
 It is widely used in the treatment of coronary artery disease due to their well-
proven anti-hypertensive and anti-ischemic effects. In KD, BB therapy is
recommended but not required.
Dosage and Route: PO: Initially 25-50 mg/d; may increase to 100 mg/d after 7-14
days; maximum: 100 mg/d
8. Angiotensin – Converting Enzyme (ACE) Inhibitor
 It is used as a treatment for cardiovascular protection and Kawasaki disease, and
ACE inhibitor is reported to have direct inhibiting effect on matrix
metalloproteinase – 9 (MMP-9), which is responsible for activating chemikines
and cytokines.
Dosage and Route: PO: initially 10 mg/d; maintenance: 20-40 mg/d in 1-2 divided
doses; max: 80 mg/dl

References:
1. Chao B, Wang X, Wu L, et al. Diagnostic value of dual-source CT in Kawasaki disease.
Chin Med J. 2010 Mar;123(6):670-674. PMID: 20368084

2. De Rosa G, Pardeo M, Rigante D. Current recommendations for the pharmacologic

therapy in Kawasaki syndrome and management of its cardiovascular complications. Eur
Rev Med Pharmacol Sci. 2007 Mar;11(5):301-308. http://
www.ncbi.nlm.nih.gov/pubmed/?term=18074939 PMID: 18074939
3. Freeman AF, Shulman ST. Kawasaki disease: summary of the American Heart
Association guidelines. Am Fam Physician. 2006 Oct;74(7):1141-1148. PMID: 17039750

4. Falcini F, Capannini S, Rigante D. Kawasaki syndrome: an intriguing disease with

numerous unsolved dilemmas. Pediatr Rheumatol Online J. 2011 Jul;9:17. Doi:
10.1186/1546-0096-9-17. PMID: 21774801

5. Kim DS. Kawasaki Disease. Yonsei Medl J. 2006 Dec;47(6):759-772. PMID: 17191303

6. JCS Joint Working Group. Guidelines for diagnosis and management of cardiovascular
sequelae in Kawasaki disease (JCS 2008) [digest version]. Aug 18, 2010. Circ J. 2010
Sep;74(9):1989-2020. https://www.jstage.jst.go
.jp/article/circj/74/9/74_CJ-10-74-0903/_pdf. PMID: 20724794

7. 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 Association. Circulation. 2004
Oct;110(17):2747-2771. http://circ.ahajournals .org/content/110/17/2747.full.pdf. PMID:
15505111

8. Yellen ES, Gauvreau K, Takahashi M, et al. Performance of 2004 American Heart

Association recommendations for treatment of Kawasaki disease. Jan 25, 2010.
Pediatrics. 2010 Feb;125(2):e234-e241. http://www.ncbi
.nlm.nih.gov/pmc/articles/PMC2896313/pdf /nihms209849.pdf. PMID: 20100771
9. Son MB, Newburger JW. Kawasaki disease. In: Kliegman RM, Stanton BF, St Geme JW
III, et al, eds. Nelson textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders, Elsevier;
2011.

10. MedWormhttp://www.medworm.com/rss/index
.php/Pediatrics/33/http://www.medworm.com
/rss/medicalfeeds/specialities/Pediatrics.xml

11. Sundel R. Kawasaki disease: initial treatment and prognosis. UpToDate.

http://www.uptodate.com. Feb 2023. Accessed 09 Jul 2013.

12. Sundel R. Treatment of refractory Kawasaki disease. UptoDate Web Site.

http://www.uptodate .com/contents/treatment-of-refractory-kawasaki -disease. Jun 2013.
Accessed 09 Jul 2013.

13. JCS Joint Working Group. Guidelines for diagnosis and management of cardiovascular
sequelae in kawasaki disease (JCS 2013). Circ J. 2014 Sep;78(10):2521-2562.
https://www.jstage .jst.go.jp/article/circj/78/10/78_CJ-66-0096/_pdf PMID: 25241888

14. Research Committee of the Japanese Society of Pediatric Cardiology; Cardiac Surgery
Committee for Development of Guidelines for Medical Treatment of Acute Kawasaki
Disease. Guidelines for medical treatment of acute Kawasaki disease: report of the
Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac
Surgery (2012 revised version). Pediatr Int. 2014 Apr;56(2):135-158. Doi: 10.1111/
ped.12317. Accessed 15 Oct 2014. PMID: 24730626

15. Eleftheriou D, Levin M, Shingadia D, et al. Management of Kawasaki disease. Arch Dis
Child. 2014 Jan;99(1):74-83. Doi: 10.1136/ archdischild-2012-302841. PMID: 24162006
16. Fukazawa R, Kobayashi J, Ayusawa M, et al. JCS/JSCS 2020 Guideline on diagnosis and
management of cardiovascular sequelae in Kawasaki disease. Circ J. 2020
Jul;84(8):1348-1407. Doi: 10.1253/ circj.CJ-19-1094. PMID: 32641591

17. Gorelik M, Chung SA, Ardalan K, et al. 2021 American College of

Rheumatology/Vasculitis Foundation guideline for the management of Kawasaki disease.
Arthritis Rheumatol. 2022 Apr;74(4):586-596. Doi: 10.1002/art.42041. PMID: 35257501

18. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term
management of Kawasaki disease: a scientific statement for health professionals from the
American Heart Association. Circulation. 2017 Apr;135(17):e927-e999. Doi: 10.1161/
CIR.0000000000000484. PMID: 28356445

19. Newburger JW, Ferranti SD, Fulton DR. Cardiovascular sequelae of Kawasaki disease:
clinical features and evaluation. UpToDate. https://www.uptodate.com/. Feb 2023.

20. Newburger JW, Ferranti SD, Fulton DR. Cardiovascular sequelae of Kawasaki disease:
management and prognosis. UpToDate. https://www.uptodate.com/. Feb 2022.

21. Son MB, Newburger JW. Kawasaki disease. In: Kliegman RM, St. Geme III JW, Blum
NJ, et al. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier Inc;
2019:1310-1316.

22. Scuccimarri R, Yeung RS. Kawasaki disease: high index of suspicion needed in a febrile
child. Paediatr Child Health. 2014 May;19(5):239-40.doi: 10.1093/pch/19.5.239. PMID:
24855425

23. Sundel R. Incomplete (atypical) Kawasaki disease. UpToDate.

https://www.uptodate.com/.Feb 2022.
 24. Sundel R. Kawasaki disease: clinical features and diagnosis. UpToDate.
https://www.uptodate.com/.Feb 2022.

25. Sundel R. Kawasaki disease: complications. UpToDate. https://www.uptodate.com/. Jan

2023.

26. Sundel R. Kawasaki disease: epidemiology and etiology. UpToDate.

https://www.uptodate.com/. Jan 2023.

27. Sundel R. Refractory Kawasaki disease. UpToDate. https://www.uptodate.com/. Aug

2022.

28. The Royal Children’s Hospital (RCH) Melbourne. Kawasaki disease. RCH.
https://www.rch.org.au/. Jan 2021.

29. Zhu F, Ang JY. 2021 Update on the clinical management and diagnosis of Kawasaki
disease. Curr Infect Dis Rep. 2021;23(3):3. Doi: 10.1007/ s11908-021-00746-1. PMID:
35194409

30. Sundel R. Kawasaki disease: initial treatment and prognosis. UpToDate.

https://www.uptodate.com/ Feb 2023.
1. Chao B, Wang X, Wu L, et al. Diagnostic value of dual-source CT in Kawasaki disease. Chin
Med J. 2010 Mar;123(6):670-674. PMID: 20368084
2. De Rosa G, Pardeo M, Rigante D. Current recommendations for the pharmacologic therapy in
Kawasaki syndrome and management of its cardiovascular complications. Eur Rev Med
Pharmacol Sci. 2007 Mar;11(5):301-308. http:// www.ncbi.nlm.nih.gov/pubmed/?
term=18074939 PMID: 18074939
3. Freeman AF, Shulman ST. Kawasaki disease: summary of the American Heart Association
guidelines. Am Fam Physician. 2006 Oct;74(7):1141-1148. PMID: 17039750
4. Falcini F, Capannini S, Rigante D. Kawasaki syndrome: an intriguing disease with numerous
unsolved dilemmas. Pediatr Rheumatol Online J. 2011 Jul;9:17. Doi: 10.1186/1546-0096-9-17.
PMID: 21774801
5. Kim DS. Kawasaki Disease. Yonsei Medl J. 2006 Dec;47(6):759-772. PMID: 17191303
6. JCS Joint Working Group. Guidelines for diagnosis and management of cardiovascular
sequelae in Kawasaki disease (JCS 2008) [digest version]. Aug 18, 2010. Circ J. 2010
Sep;74(9):1989-2020. https://www.jstage.jst.go .jp/article/circj/74/9/74_CJ-10-74-0903/_pdf.
PMID: 20724794
7. 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 Association. Circulation. 2004 Oct;110(17):2747-2771.
http://circ.ahajournals .org/content/110/17/2747.full.pdf. PMID: 15505111
8. Yellen ES, Gauvreau K, Takahashi M, et al. Performance of 2004 American Heart Association
recommendations for treatment of Kawasaki disease. Jan 25, 2010. Pediatrics. 2010
Feb;125(2):e234-e241. http://www.ncbi .nlm.nih.gov/pmc/articles/PMC2896313/pdf
/nihms209849.pdf. PMID: 20100771
9. Son MB, Newburger JW. Kawasaki disease. In: Kliegman RM, Stanton BF, St Geme JW III, et
al, eds. Nelson textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders, Elsevier; 2011.
10. MedWormhttp://www.medworm.com/rss/index
.php/Pediatrics/33/http://www.medworm.com /rss/medicalfeeds/specialities/Pediatrics.xml
11. Sundel R. Kawasaki disease: initial treatment and prognosis. UpToDate.
http://www.uptodate.com. Feb 2023. Accessed 09 Jul 2013.
12. Sundel R. Treatment of refractory Kawasaki disease. UptoDate Web Site.
http://www.uptodate .com/contents/treatment-of-refractory-kawasaki -disease. Jun 2013.
Accessed 09 Jul 2013.
13. JCS Joint Working Group. Guidelines for diagnosis and management of cardiovascular
sequelae in kawasaki disease (JCS 2013). Circ J. 2014 Sep;78(10):2521-2562. https://www.jstage
.jst.go.jp/article/circj/78/10/78_CJ-66-0096/_pdf PMID: 25241888
14. Research Committee of the Japanese Society of Pediatric Cardiology; Cardiac Surgery
Committee for Development of Guidelines for Medical Treatment of Acute Kawasaki Disease.
Guidelines for medical treatment of acute Kawasaki disease: report of the Research Committee
of the Japanese Society of Pediatric Cardiology and Cardiac Surgery (2012 revised version).
Pediatr Int. 2014 Apr;56(2):135-158. Doi: 10.1111/ ped.12317. Accessed 15 Oct 2014. PMID:
24730626
15. Eleftheriou D, Levin M, Shingadia D, et al. Management of Kawasaki disease. Arch Dis
Child. 2014 Jan;99(1):74-83. Doi: 10.1136/ archdischild-2012-302841. PMID: 24162006
16. Fukazawa R, Kobayashi J, Ayusawa M, et al. JCS/JSCS 2020 Guideline on diagnosis and
management of cardiovascular sequelae in Kawasaki disease. Circ J. 2020 Jul;84(8):1348-1407.
Doi: 10.1253/ circj.CJ-19-1094. PMID: 32641591
17. Gorelik M, Chung SA, Ardalan K, et al. 2021 American College of Rheumatology/Vasculitis
Foundation guideline for the management of Kawasaki disease. Arthritis Rheumatol. 2022
Apr;74(4):586-596. Doi: 10.1002/art.42041. PMID: 35257501
18. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term
management of Kawasaki disease: a scientific statement for health professionals from the
American Heart Association. Circulation. 2017 Apr;135(17):e927-e999. Doi: 10.1161/
CIR.0000000000000484. PMID: 28356445
19. Newburger JW, Ferranti SD, Fulton DR. Cardiovascular sequelae of Kawasaki disease:
clinical features and evaluation. UpToDate. https://www.uptodate.com/. Feb 2023.
20. Newburger JW, Ferranti SD, Fulton DR. Cardiovascular sequelae of Kawasaki disease:
management and prognosis. UpToDate. https://www.uptodate.com/. Feb 2022.
21. Son MB, Newburger JW. Kawasaki disease. In: Kliegman RM, St. Geme III JW, Blum NJ, et
al. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier Inc; 2019:1310-1316.
22. Scuccimarri R, Yeung RS. Kawasaki disease: high index of suspicion needed in a febrile
child. Paediatr Child Health. 2014 May;19(5):239-40.doi: 10.1093/pch/19.5.239. PMID:
24855425
23. Sundel R. Incomplete (atypical) Kawasaki disease. UpToDate.
https://www.uptodate.com/.Feb 2022.
24. Sundel R. Kawasaki disease: clinical features and diagnosis. UpToDate.
https://www.uptodate.com/.Feb 2022.
25. Sundel R. Kawasaki disease: complications. UpToDate. https://www.uptodate.com/. Jan
2023.
26. Sundel R. Kawasaki disease: epidemiology and etiology. UpToDate.
https://www.uptodate.com/. Jan 2023.
27. Sundel R. Refractory Kawasaki disease. UpToDate. https://www.uptodate.com/. Aug 2022.
28. The Royal Children’s Hospital (RCH) Melbourne. Kawasaki disease. RCH.
https://www.rch.org.au/. Jan 2021.
29. Zhu F, Ang JY. 2021 Update on the clinical management and diagnosis of Kawasaki disease.
Curr Infect Dis Rep. 2021;23(3):3. Doi: 10.1007/ s11908-021-00746-1. PMID: 35194409
30. Sundel R. Kawasaki disease: initial treatment and prognosis. UpToDate.
https://www.uptodate.com/ Feb 2023.
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