Efficacy of the Delayed Use of Low-dose Aspirin in Intravenous Immunoglobulin Therapy for Acute-phase Kawasaki Disease

Efficacy of the Delayed Use of Low-dose Aspirin in Intravenous Immunoglobulin Therapy for Acute-phase Kawasaki Disease



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The mainstay of current standard therapy for acute-phase Kawasaki disease (KD) is intravenous immunoglobulin (IVIG) therapy at 2 g/kg. However, the efficacy of combining medium- or high-dose aspirin with IVIG therapy at 2 g/kg has not been fully investigated. Some studies suggested that aspirin may inhibit coronary artery lesion (CAL) prevention in IVIG therapy and that the delayed use of aspirin in IVIG therapy may be beneficial for the suppression of CALs and prevention of coronary artery stenosis in patients with KD. The efficacy of the delayed use of low-dose aspirin in IVIG therapy for acute-phase KD remains unclear. Therefore, this retrospective study aimed to assess the efficacy of the delayed use of low-dose aspirin, when combined with IVIG therapy for acute-phase KD. Data were obtained from 193 KD patients who underwent acute-phase treatment from January 2009 to October 2020 and IVIG therapy at 2 g/kg with the delayed use of aspirin/flurbiprofen. The patients were divided into three groups: (1) low-dose group, in which 40 patients received low-dose aspirin (5 mg/kg/day); (2) medium-dose group, in which 90 patients received medium-dose aspirin (30 mg/kg/day); and (3) flurbiprofen group, in which 63 patients received flurbiprofen (3–5 mg/kg/day). KD patients with liver damage or those present during influenza season underwent flurbiprofen therapy between January 2009 and November 2017. All patients except one received low-dose aspirin after December 2017. The serum albumin level (median 3.40 vs. 3.30 g/dL, P = 0.026) and Egami score (median 1.0 vs. 2.0, P < 0.001) before the initial treatment were significantly different between the medium-dose group and the flurbiprofen group. The rates of initial IVIG therapy resistance (25.0% vs. 18.9% vs. 25.4%, P = 0.790), rescue therapy (17.5% vs. 8.9% vs. 17.5%, P = 0.721), and CALs (5.0% vs. 0.0% vs. 4.8%, P = 0.713) were similar among the low-dose, medium-dose, and flurbiprofen groups. Overall, the efficacy of the delayed use of low-dose aspirin was similar to that of the delayed use of medium-dose aspirin/flurbiprofen in IVIG therapy for acute-phase KD.

Keywords: aspirin, coronary artery lesions, flurbiprofen, intravenous immunoglobulin therapy, Kawasaki disease
  1. Kawasaki T, Kosaki F, Okawa S, Shigematsu I, Yanagawa H. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 1974; 54: 271–6.
    DOI
     Google Scholar 
  2. Fukazawa R, Kobayashi J, Ayusawa M, Hamada H, Miura M, Mitani Y, et al. JCS/JSCS 2020 Guideline on Diagnosis and Management of Cardiovascular Sequelae in Kawasaki Disease. Circ J 2020; 84: 1348–407. doi:10.1253/circj.CJ-19-1094.
    DOI
     Google Scholar 
  3. Rearch 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; 56: 135–58. https://doi.org/10.1111/ped.12317.
    DOI
     Google Scholar 
  4. McCrindle BW, Tierney ESS. Acute treatment for Kawasaki disease: challenges for current and future therapies. J Pediatr 2017; 184: 7–10. DOI: 10.1016/j.jpeds.2017.01.072.
    DOI
     Google Scholar 
  5. Kuo HC, Guo MM, Lo MH, Hsieh KS, Huang YH. Effectiveness of intravenous immunoglobulin alone and intravenous immunoglobulin combined with high-dose aspirin in the acute stage of Kawasaki disease: study protocol for a randomized controlled trial. BMC Pediatr. 2018; 18: 200. https://doi.org/10.1186/s12887-018-1180-1.
    DOI
     Google Scholar 
  6. Nakada T. Effects of anti-inflammatory drugs on intravenous immunoglobulin therapy in the acute phase of Kawasaki disease. Pediatr Cardiol 2015; 36: 335–9. DOI 10.1007/s00246-014-1010-7.
    DOI
     Google Scholar 
  7. Lau AC, Duong TT, Ito S, Yeung RS. Intravenous immunoglobulin and salicylate differentially modulate pathogenic processes leading to vascular damage in a model of Kawasaki disease. Arthritis Rheum 2009; 60: 2131–41. https://doi.org/10.1002/art.24660
    DOI
     Google Scholar 
  8. Cho HJ, Bak SY, Kim SY, Yoo R, Baek HS, Yang S, et al. High neutrophil: lymphocyte ratio is associated with refractory Kawasaki disease. Pediatr Int 2017; 59: 669–74. https://doi.org/10.1111/ped.13240|.
    DOI
     Google Scholar 
  9. Nakada T. Acute phase treatment for prevention of coronary artery stenosis caused in Kawasaki disease: a single center retrospective study. Journal of Advanced Research in Medicine 2018; 5(4): 1–7. https://doi.org/10.24321/2349.7181.201818.
    DOI
     Google Scholar 
  10. Nakada T. Acute Phase Treatment and Medium-Term Outcomes in Kawasaki Disease. European Journal of Medical and Health Sciences 2020; 2 (4), August: 1–7. http://dx.doi.org/10.24018/ejmed.2020.2.4.419.
    DOI
     Google Scholar 
  11. Kwon JE, Roh DE, Kim YH. The Impact of Moderate-Dose Acetylsalicylic Acid in the Reduction of Inflammatory Cytokine and Prevention of Complication in Acute Phase of Kawasaki Disease: The Benefit of Moderate-Dose Acetylsalicylic Acid. Children 2020, 7, 185; doi:10.3390/children7100185.
    DOI
     Google Scholar 
  12. Jia X, Du X, Bie S, Li X, Bao Y, Jiang M. What dose of aspirin should be used in the initial treatment of Kawasaki disease? A meta-analysis. Rheumatology 2020; 59 (8): 1826–33. https://doi.org/10.1093/rheumatology/keaa050.
    DOI
     Google Scholar 
  13. Dallaire F, Fortier-Morissette Z, Blais S, Dhanrajani A, Basodan D, Renaud C, et al. Aspirin Dose and Prevention of Coronary Abnormalities in Kawasaki Disease. Pediatrics 2017; 139: pii: e20170098.
    DOI
     Google Scholar 
  14. Zheng X, Yue P, Liu L, Tang C, Ma F, Zhang Y, et al. Efficacy between low and high dose aspirin for the initial treatment of Kawasaki disease: Current evidence based on a meta-analysis. PLoS ONE 2019; 14(5): e0217274. https://doi.org/10.1371/journal.pone.0217274.
    DOI
     Google Scholar 
  15. Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int 2005; 47: 232–4. https://doi.org/10.1111/j.1442-200x.2005.02033.
    DOI
     Google Scholar 
  16. Hirata S, Nakamura Y, Yanagawa H. Incidence rate of recurrent Kawasaki disease and related risk factors: from the results of nationwide surveys of Kawasaki disease in Japan. Acta Paediatr 2001; 90(1): 40-4.
    DOI
     Google Scholar 
  17. Nakada T. Usefulness of an initial single intravenous immunoglobulin infusion with delayed use of aspirin against Kawasaki disease relapse: a single-center retrospective study. Journal of Advanced Research in Medicine 2019; 6 (1): 18–24. https://doi.org/10.24321/2349.7181.201905.
    DOI
     Google Scholar 
  18. Egami K, Muta H, Ishii M, Suda K, Sugahara Y, Iemura M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease, J Pediatr 2006; 149: 237–40.
    DOI
     Google Scholar 
  19. Kobayashi T, Inoue Y, Takeuchi K, OkadaY, Tamura K, Tomomasa T, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation 2006; 113: 2606–12. http://www.circulationaha.org DOI:10.1161/CIRCULATIONAHA.105.592865.
    DOI
     Google Scholar 
  20. Huang X, Huang P, Zhang L, Xie X, Xia S, Gong F, et al. Is aspirin necessary in the acute phase of Kawasaki disease? J Paediatr Child Health 2018; 54(6): 661–4. doi: 10.1111/jpc.13816.
    DOI
     Google Scholar 
  21. Kim GB, Yu JJ, Yoon KL, Jeong SI, Song YH, Han JW, et al. Medium- or Higher Acetylsalicylic Acid for Acute Kawasaki disease and Patient Outcomes. J Pediatr 2017; 184: 125-9.
    DOI
     Google Scholar 
  22. Dhanrajani A, Chan M, Pau S, Ellsworth J, Petty R, Guzman J. Aspirin dose in Kawasaki disease–the ongoing battle. Arthritis Care Res (Hoboken). 2018; 70(10):1536–40. https://doi.org/10.1002/acr.23504 PMID: 29287309.
    DOI
     Google Scholar 
  23. Rahbarimanesh A, Taghavi-Goodarzi M, Mohammadinejad P, Zoughi J, Amiri J, Moridpour K. Comparison of high-dose versus low-dose aspirin in the management of Kawasaki disease. Indian J Pediatr. 2014; 81(12):1403. https://doi.org/10.1007/s12098-014-1437-0 PMID: 24710712.
    DOI
     Google Scholar 
  24. Amarilyo G, Koren Y, Brik Simon D, Bar-Meir M, Bahat H, Helou MH, et al. High-dose aspirin for Kawasaki disease: outdated myth or effective aid? Clin Exp Rheumatol. 2017; 35 Suppl 103(1):209–12. PMID: 28079513.
     Google Scholar 
  25. Lee G, Lee SE, Hong YM, Sohn S. Is high-dose aspirin necessary in the acute phase of kawasaki disease? Korean Circ J. 2013; 43(3):182–6. https://doi.org/10.4070/kcj.2013.43.3.182 PMID: 23613695.
    DOI
     Google Scholar 
  26. Chiang MH, Liu HE, Wang JL. Low-dose or no aspirin administration in acute-phase Kawasaki disease: a meta-analysis and systematic review. Archives of Disease in Children 2019. http://dx.doi.org/10.1136/archdischild-2019-318245.
    DOI
     Google Scholar 
  27. Tsujii N, Nogami K, Yoshizawa H, Fukuda K, Ishiguro A, Shima M, et al. Assessment of Platelet Thrombus Formation under Flow Conditions in Patients with Acute Kawasaki Disease. J Pediatr 2020; 226: 266–73. https://doi.org/10.1016/j.jpeds.2020.06.025.
    DOI
     Google Scholar 
  28. Branchford BR, Neeves K. New Insights into Platelet Dysfunction in Kawasaki Disease Using a Microfluidic Model of Thrombosis. J Pediatr 2020; 226: 10–1. https://doi.org/10.1016/j.jpeds.2020.08.016
    DOI
     Google Scholar 
  29. Wei CM, Chen HL, Lee PI, Chen CM, Ma CY, Hwu WL. Reye’s syndrome developing in an infant on treatment of Kawasaki syndrome.J Paediatr Child Health. 2005;41(5-6):303-4. doi:10.1111/j.1440-1754.2005.00617.x.
    DOI
     Google Scholar 
  30. Matsubara T, Mason W, Kashani IA, Kligerman M, Burns JC. Gastrointestinal hemorrhage complicating aspirin therapy in acute Kawasaki disease.J Pediatr. 1996;128(5, pt 1):701-3. doi:10.1016/S0022-3476(96)80140-5.
    DOI
     Google Scholar 
  31. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz MG, et al. Diagnosis, treatment, and long-term management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation 2017; 135: e927–99. DOI:10.1161/CIR.0000000000000484.
    DOI
     Google Scholar 
  32. Platt B, Belarski E, Manaloor J, Ofner S, Carroll AE, John CC, et al. Comparison of Risk of Recrudescent Fever in Children With Kawasaki Disease Treated With Intravenous Immunoglobulin and Low-Dose vs High-Dose Aspirin. JAMA Network Open. 2020;3(1):e1918565. doi:10.1001/jamanetworkopen.2019.18565.
    DOI
     Google Scholar 
  33. Sakulchit T, Benseler SM, Goldman RD. Acetylsalicylic acid for children with Kawasaki disease. Canadian Family Physician 2017; 63: 607-9.
     Google Scholar 
  34. Kuo HC, Lo MH, Hsieh KS, Guo MM, Huang YH. High-dose aspirin is associated with anemia and does not confer benefit to disease outcomes in Kawasaki disease. PLoS One. 2015; 10(12):e0144603. https://doi.org/10.1371/journal.pone.0144603 PMID: 26658843.
    DOI
     Google Scholar 
  35. Hsieh KS, Weng KP, Lin CC, Huang TC, Lee CL, Huang SM. Treatment of acute Kawasaki disease: aspirin’s role in the febrile stage revisited. Pediatrics. 2004; 114(6):e689–93. https://doi.org/10.1542/peds.2004-1037 PMID: 15545617.
    DOI
     Google Scholar 
  36. Nakada T. Risk stratification after initial therapy for intravenous immunoglobulin-resistant Kawasaki disease. Research Journal of Life Sciences, Bioinformatics, Pharmaceutical and Chemical Sciences 2019; 5 (5): 1–13. DOI: 10.26479/2019.0505.01.
    DOI
     Google Scholar 
  37. Nakada T. Background factors associated with the complications of coronary artery lesions caused by Kawasaki disease. Clinical Medicine Research 2015;4: 127–31.
    DOI
     Google Scholar 
  38. Bertino Jr JS, Willis ED, Reed MD, Speck WT. Salicylate hepatitis: a complication of the treatment of Kawasaki's disease. Case Reports Am J Hosp Pharm 1981; 38(8):1171–2.
    DOI
     Google Scholar 
  39. Japanese Circulation Society Joint Research Group. Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease, Pediatr Int, 47, 2005, 711–32.
    DOI
     Google Scholar 
  40. Liu MY, Liu HM, Wu CH, Chang CH, Huang GJ, Chen CA, et al Risk factors and implications of progressive coronary dilatation in children with Kawasaki disease. BMC Pediatrics 2017; 17: 139.
    DOI
     Google Scholar 
  41. Nakada T: Inhibitory Effect of Anti-Inflammatory Drugs on the Initial Intravenous Immunoglobulin Therapy (2 g/kg/dose) in Kawasaki Disease. International Journal of Advances in Medical Sciences 2018; 3 (5): 1-10. www.kibanresearchpublications.com.
    DOI
     Google Scholar 

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How to Cite

Nakada, T. (2021). Efficacy of the Delayed Use of Low-dose Aspirin in Intravenous Immunoglobulin Therapy for Acute-phase Kawasaki Disease. European Journal of Medical and Health Sciences, 3(1), 121–126. https://doi.org/10.24018/ejmed.2021.3.1.691

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