Usefulness of an Initial Single Intravenous Immunoglobulin Infusion with Delayed Use of Aspirin against Kawasaki Disease Relapse: A Single-Center Retrospective Study

Keywords: Coronary Artery Lesions, Intravenous Immunoglobulin Therapy, Kawasaki Disease, Relapse, Treatment

Abstract

Background: Kawasaki Disease (KD) relapse is a risk factor for Coronary Artery Lesion (CAL) development. However, the frequency and outcomes of patients with relapse remain unclear.

Objective: To determine the frequency and outcomes of patients with KD relapse and to ascertain the usefulness of treatment with initial single intravenous immunoglobulin (IVIG) therapy (2g/kg) with delayed use of aspirin (DUA).

Materials and Methods: The outcomes of 207 patients who underwent initial single IVIG therapy at 2 g/ kg/ dose with DUA for KD were analyzed retrospectively. The patient data were divided according to whether the patients had relapses (relapse group, n=5) or not (non-relapse group, n=202). KD presentations were considered as relapses when a second episode appeared within 2 months of the first one. Stat Flex version 6 for Windows was used for all statistical analyses. Chi-square, Fisher’s exact, and Mann-Whitney U tests were used as appropriate, with sample size considerations.

Results: The frequency of patients with disease relapse was 2.4%. The five patients who experienced relapses (two boys and three girls; median age, 10 months; range, 3 months to 3 years 11 months) received initial IVIG therapy at 5 days of illness. The median day of illness for the relapse was 16 (range, 12-29). No patients with disease relapse developed CAL. The rate of incomplete type, IVIG resistance and CAL, and timing of initial IVIG therapy with regard to the days of illness were similar between the relapse group and the non-relapse group. Three parameters, including serum C-reactive protein, albumin values, and Neutrophil-to-Lymphocyte ratio (NLR) before and after initial IVIG, were similar between the two groups. Although not statistically significant (P=0.055), the median NLR after initial IVIG therapy of the relapse group was higher than that of the non-relapse group (2.48 vs. 0.84).

Conclusion: An initial single IVIG therapy (2g/ kg/ dose) with DUA for KD may lead to a low KD relapse frequency and to favorable patient outcomes.

References

Burns JC, Glod é MP. Kawasaki syndrome. Lancet 2004; 364 (9433): 533-544.

Nakada T. Background factors associated with the complications of coronary artery lesions caused by Kawasaki disease. Clinical Medicine Research 2015; 4: 127-131.

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): 40-44.

Yang HM, Du ZD, Fu PP. Clinical features of recurrent Kawasaki disease and its risk factors. Eur J Pediatr 2013;

(12): 1641–1647.

Maddox RA, Holman RC, Uehara R et al. Recurrent Kawasaki disease: USA and Japan. Pediatr Int 2015;

(6): 1116-1120.

Nakada T. Clinical features of patients with recurrent Kawasaki disease. Nihon Rinsho 2008; 66(2): 296-300.

Nakada T. Different subgroups regarding the absence of rescue therapy in intravenous

mmunoglobulinresistant Kawasaki disease. IOSR Journal of Pharmacy 2016; 6(8): 40-47.

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; 135: e927-99.

McCrindle BW, Tierney ESS. Acute treatment for Kawasaki disease: challenges for current and future therapies. J Pediatr. 2017; 184: 7-10.

Kuo HC, Guo MM, Lo MH et al. 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(1): 200.

Nakada T. Effects of anti-inflammatory drugs on intravenous immunoglobulin therapy in the acute phase of Kawasaki disease. Pediatr Cardiol 2015; 36: 335-339.

Lau AC, Duong TT, Ito S et al. Intravenous immunoglobulin and salicylate differentially modulate pathogenic

processes leading to vascular damage in a model of Kawasaki disease. Arthritis Rheum 2009; 60: 2131-2141.

Cho HJ, Bak SY, Kim SY et al. High neutrophil: lymphocyte ratio is associated with refractory Kawasaki disease.

Pediatr Int 2017; 59: 669-674. 14. Nakada T. Acute phase treatment for prevention of coronary artery stenosis caused in Kawasaki disease: a single center retrospective study. J Adv Res Med 2018; 5(4): 1-7.

Ayusawa M, Sonobe T, Uemura S et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th

revised edition). Pediatr Int 2005; 47: 232-234.

Egami K, Muta H, Ishii M et al. Prediction of resistance to intravenous immunoglobulin treatment in patients

with Kawasaki disease. J Pediatr 2006; 149: 237-240.

Kobayashi T, Inoue Y, Takeuchi K et al. Prediction of intravenous immunoglobulin unresponsiveness in

patients with Kawasaki disease. Circulation 2006; 113: 2606-2612.

Muta H, Ishii M, Egami K et al. Early intravenous gamma-globulin treatment for Kawasaki disease: the

nationwide surveys in Japan. J Pediatr 2004; 144: 496-499.

Ho CL, Fu YC, Lin MC et al. Early Immunoglobulin Therapy and Outcomes in Kawasaki Disease A Nationwide

Cohort Study. Medicine (Baltimore) 2015; 94: e1544.

Abrams JY, Belay ED, Uehara R et al. Cardiac complications, earlier treatment and initial disease

severity in Kawasaki disease. J Pediatr 2017; 188: 64-66.

Shiozawa Y, Inuzuka R, Shindo T et al. Effect of i.v. immunoglobulin in the first 4 days of illness in Kawasaki

disease. Pediatr Int 2018; 60: 334-341.

Nanishi E, Nishio H, Takada H et al. Clarithromycin plus intravenous immunoglobulin therapy can reduce the

relapse rate of Kawasaki Disease: a phase 2, open-label, randomized control study. J Am Heart Assoc 2017;

(7): pii: e005370.

Zahorec R. Ratio of neutrophil to lymphocyte counts–rapid and simple parameters of systemic inflammation

and stress in critically ill. Bratisl Lek Listy 2001; 102: 5-14.

Azab B, Zaher M, Weiserbs KF et al. Usefulness of neutrophil to lymphocyte ratio in predicting short- and

long-term mortality after non-ST-elevation myocardial infarction. Am J Cardiol 2010; 106: 470-476.

Ha KS, Lee J, Jang GY et al. Value of neutrophil lymphocyte ratio in predicting outcomes in Kawasaki

disease. Am J Cardiol 2015; 116: 301-306.

Demir F, Karadeniz C, Ó¦zdemir R et al. Usefulness of neutrophil to lymphocyte ratio in predicting of coronary

artery lesions in patients with Kawasaki disease. Balkan Med J 2015; 32: 371-376.

Nakada T. Outcomes of older children with Kawasaki disease who received intravenous immunoglobulin

therapy with delayed use of anti-inflammatory drugs. Journal of Advances in Medicine and Medical Research 2017; 22: 1-7.

Published
2019-12-24