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Revising the value of Antistreptolysin O titre in childhood and its interpretation in the diagnostic approach of rheumatic diseases

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Abstract

The burden of group A streptococcus (GAS) infection and its rheumatic sequelae remains dramatically high, especially in low-income countries. Recently, an increased number of Acute Rheumatic Fever (ARF) cases was documented in many regions of Italy. The diagnosis of rheumatic sequelae relies on clinical signs and on the evaluation of the Antistreptolysin O titre (ASO), whose variations are globally reported. To re-examine the standard reference value of ASO titre, by measuring either its upper limit of normal (ULN) in a population of healthy children (HC) or comparing these values with streptococcal antibodies registered in a cohort of patients affected by the rheumatic sequelae of GAS infection. We performed a multicenter retrospective study. We enrolled 125 HC, aged 2–17 years, and a total of 181 patients affected by ARF, acute streptococcal pharyngitis, post-streptococcal arthritis, Henoch-Schönlein purpura and erythema nodosum, divided into four groups. The levels of ASO and anti-deoxyribonuclease B (anti-DNase B) titres were analyzed and compared among the various groups. Moreover, the 80th percentile value was calculated and established as the ULN for ASO titre in HC group. The ULN for ASO titre in overall HC group was 515 IU/mL, resulting in higher than used in the routine investigation. The ASO titre was significantly higher in patients with rheumatic sequelae compared with HC group, with a peak in the age between 5 and 15 years.

   Conclusion: Our study established a new ULN normal value of streptococcal serology in a childhood and adolescent population of Italy, suggesting the need to extend this revaluation to the critical areas, in order to avoid underestimating ARF diagnosis. The correct interpretation of ASO and anti-DNase B values in the context of rheumatic diseases has been discussed.

What is Known:

• The global burden of disease caused by group A streptococcus is not known and remains an important cause of morbidity and mortality. Acute rheumatic fever continues to be a serious worldwide public health problem and a recent recurrence of group A streptococcus infection cases is observed.

• The streptococcal sequelae requires evidence of preceding streptococcal infection, commonly elevated streptococcal antibody titre, but the upper limit for these titres varies considerably based on age group, region, and origin.

What is New:

• This study provides population-specific values for streptococcal antibody titres in Italy.

• Interpret the results of group A streptococcal antibody tests within the clinical context.

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Availability of data and materials

Data supporting the findings of this study are available from the corresponding author, upon reasonable request.

Abbreviations

ARF:

Acute rheumatic fever

ASO:

Antistreptolysin O titre

Anti-DNase B:

Anti-deoxyribonuclease B

GAS:

Group A streptococcus

HC:

Healthy children

RHD:

Rheumatic heart disease

ULN:

Upper limit of normal

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Author information

Authors and Affiliations

  1. Pediatrics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Antonino Maria Quintilio Alberio, Ylenia Biagini, Alessandro Di Gangi & Diego Peroni

  2. Rheumatology Unit, Meyer Children’s Hospital, University of Florence, Florence, Italy

    Ilaria Pagnini & Gabriele Simonini

  3. Section of Clinical and Laboratory Immunology, Pediatrics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, Pisa, 56126, Italy

    Rita Consolini

Authors
  1. Antonino Maria Quintilio Alberio
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  2. Ylenia Biagini
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  3. Alessandro Di Gangi
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  4. Ilaria Pagnini
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  5. Gabriele Simonini
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  6. Diego Peroni
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  7. Rita Consolini
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Contributions

Prof.ssa Consolini conceptualized and designed the study. Dr. Alberio and Dr.ssa Biagini contributed to the data collection and to the review of the literature and drafted the initial manuscript. Dr. Di Gangi contributed to the statistical analysis of data and actively participated in manuscript drafting. Prof. Simonini and Prof. Peroni designed the data collection instruments and actively participated in manuscript drafting. Prof.ssa Consolini and Dr.ssa Pagnini reviewed and critically revised the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rita Consolini.

Ethics declarations

Ethics approval

Data relevant to the study were analysed and reported anonymously. This is an observational and retrospective chart review study design; thus, the ethical research committee approval was waived. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

Informed consent was obtained from all subjects included in the study.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Tobias Tenenbaum

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Alberio, A.M.Q., Biagini, Y., Di Gangi, A. et al. Revising the value of Antistreptolysin O titre in childhood and its interpretation in the diagnostic approach of rheumatic diseases. Eur J Pediatr 183, 835–842 (2024). https://doi.org/10.1007/s00431-023-05269-6

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  • DOI: https://doi.org/10.1007/s00431-023-05269-6

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