Skip to main content

Advertisement

Log in

Red blood cell distribution width and tumor necrosis factor-α for the early prediction of coronary artery lesion in Kawasaki disease: a retrospective study

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

A Correspondence to this article was published on 29 January 2022

Abstract

We aimed to identify novel risk factors for the early prediction of coronary artery lesion (CAL) in children with Kawasaki disease (KD). We retrospectively analyzed data from hospitalized children newly diagnosed with KD between January 1, 2018, and December 31, 2020, with the following inclusion criteria: (1) diagnosis of KD, (2) first onset of CAL after admission, (3) with complete clinical records. Demographic and laboratory data were collected and analyzed. The independent risk factors of KD combined with CAL were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the efficacy of identified risk factors in predicting KD combined with CAL. Among 241 initially recruited patients, 226 were eligible to be included in the study. Based on echocardiographic indications of CAL, 104 patients (46%) were assigned to the CAL (KD-CAL) group and 122 (54%) patients were assigned to the non-CAL (KD-nCAL) group. The levels of red blood cell count, red blood cell distribution width (RDW), C-reactive protein, tumor necrosis factor-α (TNF-α), and interleukin-6 were significantly higher in the KD-CAL group than those in the KD-nCAL group (all p < 0.05). RDW and TNF-α were found as independent risk factors of CAL occurrence. The sensitivity and specificity of RDW, TNF-α, and RDW + TNF-α in predicting KD with CAL were 67.31% and 79.51%, 74.04% and 73.77%, and 79.81% and 80.33%, respectively.

Conclusion: In conclusion, alterations in RDW and TNF-α levels can be used as novel biomarkers for early prediction of CAL in KD patients, although the differences in their absolute values were small and might not give any added value to echocardiography.

What is Known:

•Known risk factors of CAL in children with KD include male gender and delayed use of intravenous immune globulin.

What is New:

•Our current study identified that red blood cell distribution width (RDW) and tumor necrosis factor-α (TNF-α) are novel independent risk factors for predicting CAL combined with KD among patients.

•The combination of these RDW and TNF-α together shows higher sensitivity and specificity than either one used alone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Availability of data and materials

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Code availability

Not applicable.

Abbreviations

CAL:

Coronary artery lesion

KD:

Kawasaki disease

TNF-α:

Tumor necrosis factor-α

WBC:

White blood cell count

NEUT#:

Absolute neutrophil count

LYMPH#:

Absolute lymphocyte count

MONO#:

Absolute monocyte count

RBC:

Red blood cell count

HGB:

Hemoglobin

RDW:

Red blood cell distribution width

PLT:

Platelet count

PDW:

Platelet distribution width

MPV:

Mean platelet volume

CRP:

C-reactive protein

IL-6:

Interleukin-6

ESR:

Erythrocyte sedimentation rate

ALT:

Alanine transaminase

ALP:

Alkaline phosphatase

TBIL:

Total bilirubin

ALB:

Albumin

CREA:

Creatinine

Na:

Blood sodium

K:

Blood potassium

References

  1. Kawasaki T, Kosaki F, Okawa S, Shigematsu I, Yanagawa H (1974) A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 54:271–276

    Article  CAS  Google Scholar 

  2. Sundel RP (2015) Kawasaki disease. Rheum Dis Clin North Am 41:63–73, viii

  3. Kuo HC (2017) Preventing coronary artery lesions in Kawasaki disease. Biomed J 40:141–146

    Article  Google Scholar 

  4. Makino N, Nakamura Y, Yashiro M, Ae R, Tsuboi S, Aoyama Y, Kojo T, Uehara R, Kotani K, Yanagawa H (2015) Descriptive epidemiology of Kawasaki disease in Japan, 2011–2012: from the results of the 22nd nationwide survey. J Epidemiol 25:239–245

    Article  Google Scholar 

  5. Wu MH, Chen HC, Yeh SJ, Lin MT, Huang SC, Huang SK (2012) Prevalence and the long-term coronary risks of patients with Kawasaki disease in a general population <40 years: a national database study. Circ Cardiovasc Qual Outcomes 5:566–570

    Article  Google Scholar 

  6. Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, Glode MP, Mason WH, Reddy V, Sanders SP et al (1986) The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 315:341–347

    Article  CAS  Google Scholar 

  7. Duan J, Jiang H, Lu M (2020) Risk factors for coronary artery lesions in children with Kawasaki disease. Arch Argent Pediatr 118:327–331

    PubMed  Google Scholar 

  8. 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 E, Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Y, Council on C, Stroke N, Council on Cardiovascular S, Anesthesia, Council on E, 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

    Article  Google Scholar 

  9. Organization WH (2018) ICD purpose and uses. Classification. Available online at: http://www.who.int/classifications/icd/en/. Accessed 20 Jun 2018

  10. Agarwal S, Agrawal DK (2017) Kawasaki disease: etiopathogenesis and novel treatment strategies. Expert Rev Clin Immunol 13:247–258

    Article  CAS  Google Scholar 

  11. Kuo HC, Yang KD, Chang WC, Ger LP, Hsieh KS (2012) Kawasaki disease: an update on diagnosis and treatment. Pediatr Neonatol 53:4–11

    Article  Google Scholar 

  12. Chang LY, Lu CY, Shao PL, Lee PI, Lin MT, Fan TY, Cheng AL, Lee WL, Hu JJ, Yeh SJ, Chang CC, Chiang BL, Wu MH, Huang LM (2014) Viral infections associated with Kawasaki disease. J Formos Med Assoc 113:148–154

    Article  Google Scholar 

  13. Guo MM, Tseng WN, Ko CH, Pan HM, Hsieh KS, Kuo HC (2015) Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease. Allergy 70:310–318

    Article  CAS  Google Scholar 

  14. Kuo HC, Hsu YW, Wu MS, Chien SC, Liu SF, Chang WC (2016) Intravenous immunoglobulin, pharmacogenomics, and Kawasaki disease. J Microbiol Immunol Infect 49:1–7

    Article  CAS  Google Scholar 

  15. Zhang CRC, Nix D, Gregory M, Ciorba MA, Ostrander EL, Newberry RD, Spencer DH, Challen GA (2019) Inflammatory cytokines promote clonal hematopoiesis with specific mutations in ulcerative colitis patients. Exp Hematol 80:36–41 e33

  16. Bazzi W, Cattenoz PB, Delaporte C, Dasari V, Sakr R, Yuasa Y, Giangrande A (2018) Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila. Elife 7

  17. Fraenkel PG (2017) Anemia of inflammation: a review. Med Clin North Am 101:285–296

    Article  Google Scholar 

  18. Almizraq RJ, Norris PJ, Inglis H, Menocha S, Wirtz MR, Juffermans N, Pandey S, Spinella PC, Acker JP, Muszynski JA (2018) Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity. Blood Adv 2:2296–2306

    Article  CAS  Google Scholar 

  19. Poz D, De Falco E, Pisano C, Madonna R, Ferdinandy P, Balistreri CR (2019) Diagnostic and prognostic relevance of red blood cell distribution width for vascular aging and cardiovascular diseases. Rejuvenation Res 22:146–162

    Article  Google Scholar 

  20. Martin SL, Desai S, Nanavati R, Colah RB, Ghosh K, Mukherjee MB (2019) Red cell distribution width and its association with mortality in neonatal sepsis. J Matern Fetal Neonatal Med 32:1925–1930

    Article  Google Scholar 

  21. Korkmaz MF, Tutanc M, Bostanci M, Korkmaz M, Salihoglu TE (2019) Red blood cell distribution width as a useful marker for severity in pediatric acute gastroenteritis. Pediatr Int 61:1109–1113

    Article  CAS  Google Scholar 

  22. Zuk M, Migdal A, Dominczak J, Brzezinska-Rajszys G (2019) Usefulness of red cell width distribution (RDW) in the assessment of children with pulmonary arterial hypertension (PAH). Pediatr Cardiol 40:820–826

    Article  Google Scholar 

  23. Zhang Q, Li Y, Liao Y, Du J (2017) Significance of red cell distribution width in the differential diagnosis between neurally mediated syncope and arrhythmic syncope in children. Cardiol Young 27:691–696

    Article  Google Scholar 

  24. Okazaki K, Matsui K, Takahashi N, Miura M, Kondo M (2018) Kawasaki disease in a preterm neonate: case report and cytokine profile. Pediatr Int 60:1037–1039

    Article  Google Scholar 

  25. Nagai K, Hosono S, Nonaka K, Hirakubo Y, Ichihashi K (2019) Rhabdomyolysis with Kawasaki disease and a family history of rhabdomyolysis. Pediatr Int 61:622–623

    Article  Google Scholar 

  26. Takahashi K, Oharaseki T, Yokouchi Y (2014) Update on etio and immunopathogenesis of Kawasaki disease. Curr Opin Rheumatol 26:31–36

    Article  CAS  Google Scholar 

  27. Yu J-S, Jin J, Li Y-Y (2020) The Physiological functions of IKK-selective substrate identification and their critical roles in diseases. STEMedicine 1:e49

    Article  Google Scholar 

  28. Bai L, Feng T, Yang L, Zhang Y, Jiang X, Liao J, Chen L, Feng X, Rong Y, Li Y, Qin Z, Qiao J (2017) Retrospective analysis of risk factors associated with Kawasaki disease in China. Oncotarget 8:54357–54363

    Article  Google Scholar 

Download references

Funding

This work was funded by the Shanghai Municipal Science and Technology Commission (18411966600).

Author information

Authors and Affiliations

Authors

Contributions

Jie Li, Dong-e Li, Man Hu, Heyu Huang, Shanshan Xu, and Huajun Li conceived and designed the experiments; Jie Li, Dong-e Li, Man Hu, Heyu Huang, Shanshan Xu, and Huajun Li performed the experiments; Jie Li, Dong-e Li, Shanshan Xu, and Huajun Li analyzed and interpreted the data and contributed reagents, materials, analysis tools, or data; and Jie Li and Huajun Li wrote the paper.

Corresponding author

Correspondence to Huajun Li.

Ethics declarations

Ethical approval

This study was approved by the Ethical Committee of The First Affiliated Hospital of USTC. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to participate

All participants gave their written consent to participate.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Nicole Ritz

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 115 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Li, De., Hu, M. et al. Red blood cell distribution width and tumor necrosis factor-α for the early prediction of coronary artery lesion in Kawasaki disease: a retrospective study. Eur J Pediatr 181, 903–909 (2022). https://doi.org/10.1007/s00431-021-04252-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-021-04252-3

Keywords

Navigation