Advertisement

European Journal of Pediatrics

, Volume 178, Issue 3, pp 315–322 | Cite as

Inability of Asian risk scoring systems to predict intravenous immunoglobulin resistance and coronary lesions in Kawasaki disease in an Italian cohort

  • Marianna FabiEmail author
  • Laura Andreozzi
  • Elena Corinaldesi
  • Tetyana Bodnar
  • Francesca Lami
  • Cristina Cicero
  • Bertrand Tchana
  • Chiara Landini
  • Monica Sprocati
  • Barbara Bigucci
  • Claudia Balsamo
  • Paola Sogno Valin
  • Giorgia Di Fazzio
  • Lorenzo Iughetti
  • Enrico Valletta
  • Federico Marchetti
  • Andrea Donti
  • Marcello Lanari
Original Article
  • 141 Downloads

Abstract

Since resistance to intravenous immunoglobulin (IVIG) is associated with coronary lesions (CALs) in Kawasaki disease (KD), it is crucial to identify patients at risk to protect them from coronary involvement. The available risk scores to predict IVIG resistance were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. The aim of this study is to evaluate the ability of the Kobayashi, Egami, and Formosa risk scores to predict IVIG resistance and CALs in Italian patients with KD. A multicenter retrospective analysis involving children with KD diagnosed between 2000 and 2015 was carried out: 257 patients were enrolled (57.9% boys, 89.9% Caucasian); 43 patients were IVIG resistant (16.7%). The scores have low sensitivity and specificity in predicting IVIG resistance: respectively, KS 64% and 62.5%, ES 41.4% and 77.4%, and FS 70.8% and 44.9%. The predictive value of the 3 scores for predicting CALs was also poor.

Conclusion: Kobayashi, Egami, and Formosa Scores are ineffective in predicting IVIG resistance and coronary involvement in a predominantly Caucasian cohort. A specific score system for mostly Caucasian children with KD is needed enable the early identification of those at risk for CALs who could benefit from intensified treatment.

What is Known:

• There are several risk scores developed in the Asian population to early identify patients with KD at risk for immunoglobulin-resistance and thus for coronary lesions.

• Data are scarce on their effectiveness in non-Asian children.

What is New:

• We present a comprehensive analysis of the ability of 3 Asian risk scores in a cohort of mostly Caucasian children to predict immunoglobulin resistance and coronary involvement.

• Low sensitivity and specificity of the Asian scores for immunoglobulin-resistance and coronary lesions suggest the need for criteria specific for different ethnicities.

Keywords

Kawasaki disease Caucasian Risk-scoring systems IVIG resistance Coronary artery lesions 

Abbreviations

AHA

American Heart Association

ALT

Alanine aminotransferase

ASA

Acetylsalicylic acid

AST

Aspartate aminotransferase

CALs

Coronary artery lesions

CRP

C-reactive protein

ES

Egami score

ESR

Erythrocyte sedimentation rate

FS

Formosa score

Hb

Hemoglobin

IVIG

Intravenous immunoglobulin

KS

Kobayashi score

LDH

Lactate dehydrogenase

Na

Sodium

PLT

Platelet count

RBC

Red blood cells

SD

Standard deviation

WBC

White blood cells

Notes

Authors’ contributions

Marianna Fabi conceptualized and designed the study and the data collection instruments, drafted the initial manuscript, and supervised the reviewed literature.

Laura Andreozzi carried out the statistical analysis and contributed to the collection of data, and to write the initial draft.

Elena Corinaldesi contributed to the collection of data and supervised the reviewed literature.

Tetyana Bodnar coordinated and supervised data collection, contributed to the critical revision of literature, and critically reviewed the manuscript.

Francesca Lami coordinated and supervised data collection, contributed to the critical revision of literature, and critically reviewed the manuscript.

Andrea Donti coordinated and supervised data collection, contributed to the critical revision of literature, and critically reviewed the manuscript.

Chiara Landini contributed to data acquisition and critically revised the manuscript.

Cristina Cicero contributed to data acquisition and critically revised the manuscript.

Monica Sprocati contributed to data acquisition and critically revised the manuscript.

Barbara Bigucci contributed to data acquisition and critically revised the manuscript.

Claudia Balsamo contributed to data acquisition and critically revised the manuscript.

Giorgia Di Fazzio contributed to data acquisition and critically revised the manuscript.

Federico Marchetti helped to draft the manuscript, contributed to the critical revision of literature, and reviewed the manuscript.

Bertrand Tchana helped to draft the manuscript, contributed to the critical revision of literature, and reviewed the manuscript.

Paola Sogno Valin helped to draft the manuscript, contributed to the critical revision of literature, and reviewed the manuscript.

Enrico Valletta helped to draft the manuscript, contributed to the critical revision of literature, and reviewed the manuscript.

Lorenzo Iughetti helped to draft the manuscript, contributed to the critical revision of literature, and reviewed the manuscript.

Marcello Lanari supervised the reviewed literature, contributed to the interpretation of data, and critically reviewed the manuscript for important content.

All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Central Review Board.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E, American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention (2017) Diagnosis, treatment, and long-term Management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation 135:e927–e999.  https://doi.org/10.1161/CIR.0000000000000484 CrossRefGoogle Scholar
  2. 2.
    Eleftheriou D, Levin M, Shingadia D, Tulloh R, Klein NJ, Brogan PA (2014) Management of Kawasaki disease. Arch Dis Child 99:74–83.  https://doi.org/10.1136/archdischild-2012-302841 CrossRefGoogle Scholar
  3. 3.
    Bar-Meir M, Kalisky I, Schwartz A, Somekh E, Tasher D, Israeli Kawasaki Group (2018) Prediction of resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatric Infect Dis Soc 7:25–29.  https://doi.org/10.1093/jpids/piw075 CrossRefGoogle Scholar
  4. 4.
    Hwang JY, Lee KY, Rhim JW, Youn YS, Oh JH, Han JW, Lee JS, Burgner D (2011) Assessment of intravenous immunoglobulin non-responders in Kawasaki disease. Arch Dis Child 96:1088–1090.  https://doi.org/10.1136/adc.2010.184101 CrossRefGoogle Scholar
  5. 5.
    Wei M, Huang M, Chen S, Huang G, Huang M, Qiu D, Guo Z, Jiang J, Zhou X, Yu Q, Guo Y, Fu L, Gao W, Li F (2015) A multicenter study of intravenous immunoglobulin non-response in Kawasaki disease. Pediatr Cardiol 36:1166–1172.  https://doi.org/10.1007/s00246-015-1138-0 CrossRefGoogle Scholar
  6. 6.
    Singh S, Vignesh P, Burgner D (2015) The epidemiology of Kawasaki disease: a global update. Arch Dis Child 100:1084–1088.  https://doi.org/10.1136/archdischild-2014-307536 CrossRefGoogle Scholar
  7. 7.
    Holman RC, Belay ED, Christensen KY, Folkema AM, Steiner CA, Schonberger LB (2016) Hospitalizations for Kawasaki syndrome among children in the United States, 1997–2007. Pediatr Infect Dis J 29:483–488.  https://doi.org/10.1097/INF.0b013e3181cf8705 Google Scholar
  8. 8.
    Onouchi Y, Ozaki K, Burns JC, Shimizu C, Terai M, Hamada H, Honda T, Suzuki H, Suenaga T, Takeuchi T et al (2012) A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat Genet 44:517–521.  https://doi.org/10.1038/ng.2220 CrossRefGoogle Scholar
  9. 9.
    Lee YC, Kuo HC, Chang JS, Chang LY, Huang LM, Chen MR, Liang CD, Chi H, Huang FY, Lee ML, Huang YC, Hwang B, Chiu NC, Hwang KP, Lee PC, Chang LC, Liu YM, Chen YJ, Chen CH, Alliance TPID, Chen YT, Tsai FJ, Wu JY (2012) Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. Nat Genet 44:522–525.  https://doi.org/10.1038/ng.2227 CrossRefGoogle Scholar
  10. 10.
    Chang CJ, Kuo HC, Chang JS, Lee JK, Tsai FJ, Khor CC, Chang LC, Chen SP, Ko TM, Liu YM, Chen YJ, Hong YM, Jang GY, Hibberd ML, Kuijpers T, Burgner D, Levin M, Burns JC, Davila S, International Kawasaki Disease Genetics Consortium¶, Korean Kawasaki Disease Genetics Consortium¶, Taiwan Kawasaki Disease Genetics Consortium¶, Chen YT, Chen CH, Wu JY, Lee YC (2013) Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility. PLoS One 8:e72037.  https://doi.org/10.1371/journal.pone.0072037 CrossRefPubMedCentralGoogle Scholar
  11. 11.
    Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T, Kobayashi T, Morikawa A (2006) Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation 113:2606–2612.  https://doi.org/10.1161/CIRCULATIONAHA.105.592865 CrossRefGoogle Scholar
  12. 12.
    Egami K, Muta H, Ishii M, Suda K, Sugahara Y, Iemura M, Matuishi T (2006) Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr 149:237–240.  https://doi.org/10.1016/j.jpeds.2006.03.050 CrossRefGoogle Scholar
  13. 13.
    Sano T, Kurotobi S, Matsuzaki K, Yamamoto T, Maki I, Miki K, Kogaki S, Hara J (2007) Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment. Eur J Pediatr 166:131–137.  https://doi.org/10.1007/s00431-006-0223-z CrossRefGoogle Scholar
  14. 14.
    Lin MT, Chang CH, Sun LC, Liu HM, Chang HW, Chen CA, Chiu SN, Lu CW, Chang LY, Wang JK, Wu MH (2016) Risk factors and derived formosa score for intravenous immunoglobulin unresponsiveness in Taiwanese children with Kawasaki disease. J Formos Med Assoc 115:350–355.  https://doi.org/10.1016/j.jfma.2015.03.012 CrossRefGoogle Scholar
  15. 15.
    Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, Martin DD, Newburger JW, Burns JC (2008) Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 153:117–121.  https://doi.org/10.1016/j.jpeds.2007.12.021 CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Sleeper LA, Minich LL, McCrindle BM, Li JS, Mason W, Colan SD, Atz AM, Printz BF, Baker A, Vetter VL, Newburger JW, Pediatric Heart Network Investigators (2011) Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr 158:831–835.  https://doi.org/10.1016/j.jpeds.2010.10.031 CrossRefGoogle Scholar
  17. 17.
    Kobayashi T, Saji T, Otani T, Takeuchi K, Nakamura T, Arakawa H, Kato T, Hara T, Hamaoka K, Ogawa S, Miura M, Nomura Y, Fuse S, Ichida F, Seki M, Fukazawa R, Ogawa C, Furuno K, Tokunaga H, Takatsuki S, Hara S, Morikawa A (2012) Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet 379:1613–1620.  https://doi.org/10.1016/S0140-6736(11)61930-2 CrossRefGoogle Scholar
  18. 18.
    Sánchez-Manubens J, Antón J, Bou R, Iglesias E, Calzada-Hernandez J, Borlan S, Gimenez-Roca C, Rivera J, Kawasaki Disease in Catalonia Working Group (2016) Role of the Egami score to predict immunoglobulin resistance in Kawasaki disease among a Western Mediterranean population. Rheumatol Int 36:905–910.  https://doi.org/10.1007/s00296-016-3499-y CrossRefGoogle Scholar
  19. 19.
    Loomba RS, Raskin A, Gudausky TM, Kirkpatrick E (2016) Role of the Egami score in predicting intravenous immunoglobulin resistance in Kawasaki disease among different ethnicities. Am J Ther 23:e1293–e1299.  https://doi.org/10.1097/MJT.0000000000000045 CrossRefGoogle Scholar
  20. 20.
    Davies S, Sutton N, Blackstock S, Gormley S, Hoggart CJ, Levin M, Herberg JA (2015) Predicting IVIG resistance in UK Kawasaki disease. Arch Dis Child 100:366–368.  https://doi.org/10.1136/archdischild-2014-307397 CrossRefGoogle Scholar
  21. 21.
    Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA, Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association, American Academy of Pediatrics (2004) 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 110:2747–2771.  https://doi.org/10.1161/01.CIR.0000145143.19711.78 CrossRefGoogle Scholar
  22. 22.
    Ebato T, Ogata S, Ogihara Y, Fujimoto M, Kitagawa A, Takanashi M, Ishii M (2017) The clinical utility and safety of a new strategy for the treatment of refractory Kawasaki disease. J Pediatr 191:140–144.  https://doi.org/10.1016/j.jpeds.2017.08.076 CrossRefGoogle Scholar
  23. 23.
    Jakob A, Horstmann J, Hufnagel M, Stiller B, Berner R, Schachinger E, Meyer K, Obermeier V (2018) Failure to predict high-risk Kawasaki disease patients in a population-based study cohort in Germany. Pediatr Infect Dis J:1.  https://doi.org/10.1097/INF.0000000000001923
  24. 24.
    Chen S, Dong Y, Kiuchi MG, Wang J, Li R, Ling Z, Zhou T, Wang Z, Martinek M, Pürerfellner H, Liu S, Krucoff MW (2016) Coronary artery complication in Kawasaki disease and the importance of early intervention: a systematic review and meta-analysis. JAMA Pediatr 170:1156–1163.  https://doi.org/10.1001/jamapediatrics.2016.2055 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Marianna Fabi
    • 1
    Email author
  • Laura Andreozzi
    • 1
  • Elena Corinaldesi
    • 2
  • Tetyana Bodnar
    • 1
  • Francesca Lami
    • 3
  • Cristina Cicero
    • 4
  • Bertrand Tchana
    • 5
  • Chiara Landini
    • 6
  • Monica Sprocati
    • 7
  • Barbara Bigucci
    • 8
  • Claudia Balsamo
    • 9
  • Paola Sogno Valin
    • 10
  • Giorgia Di Fazzio
    • 11
  • Lorenzo Iughetti
    • 3
  • Enrico Valletta
    • 12
  • Federico Marchetti
    • 13
  • Andrea Donti
    • 14
  • Marcello Lanari
    • 1
  1. 1.Department of Pediatrics, S.Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly
  2. 2.Department of PediatricsRamazzini HospitalCarpiItaly
  3. 3.Pediatric Unit, Department of Medical and Surgical Sciences for Mothers, Children and AdultsUniversity of Modena and Reggio EmiliaModenaItaly
  4. 4.Department of Pediatrics, AUSLGuglielmo da Saliceto HospitalPiacenzaItaly
  5. 5.Department of Pediatrics, Ospedale dei Bambini BarillaUniversity of ParmaParmaItaly
  6. 6.Department of PediatricsMaggiore HospitalBolognaItaly
  7. 7.Department of PediatricsArcispedale Sant’AnnaFerraraItaly
  8. 8.Department of PediatricsInfermi HospitalRiminiItaly
  9. 9.Department of PediatricsBufalini HospitalCesenaItaly
  10. 10.Department of PediatricsSanta Maria della Scaletta HospitalImolaItaly
  11. 11.Department of Pediatrics, IRCCSArcispedale Santa Maria NuovaReggio EmiliaItaly
  12. 12.Department of Pediatrics, G.B.Morgagni - L. Pierantoni HospitalAUSL della RomagnaForlìItaly
  13. 13.Department of Pediatrics, Santa Maria delle Croci HospitalAUSL della RomagnaRavennaItaly
  14. 14.Pediatric Cardiology and Adult Congenital Unit, S.Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly

Personalised recommendations