Skip to main content

Advertisement

SpringerLink
Log in

Eculizumab in STEC-HUS: a paradigm shift in the management of pediatric patients with neurological involvement

  • Brief Report
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

A Research Letter to this article was published on 30 November 2023

Abstract

Background

Eculizumab for the treatment of atypical hemolytic uremic syndrome (HUS) is a standard of care. Central nervous system (CNS) involvement in Shiga toxin–producing Escherichia coli (STEC)-HUS is associated with increased morbidity and mortality. There is no consensus on the use of plasma exchange and/or eculizumab. We report a series (n = 4) of children with CNS involvement in STEC-HUS with excellent outcomes after treatment with eculizumab only and supportive therapies.

Methods

A retrospective chart review of patients with CNS involvement in STEC-HUS is managed with supportive therapies and eculizumab only.

Results

Four patients (75% female) with a median age of 5 years and 11 months (IQR: 23.5–105.5 months) were admitted to a tertiary pediatric nephrology center with CNS involvement in STEC-HUS. Neurological symptoms presented between days 2 and 7 of illness and included ataxia, altered mental status, visual symptoms, and seizures. All had an abnormal MRI brain. All received two doses of eculizumab, 1 week apart (dosing according to weight). Resolution of neurological symptoms was evident at a mean of 60 h post-administration (range: 24–72 h). All patients have complete kidney and neurological recovery at 12-month follow-up.

Conclusion

We present a case series of four children with STEC-HUS and CNS involvement, managed with eculizumab only, in lieu of plasma exchange (as per our previous policy). The marked improvement in symptoms in our cohort supports the use of eculizumab, rather than plasma exchange in the CNS involvement of STEC-HUS.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AKI:

Acute kidney injury

CNS:

Central nervous system

EEG:

Electroencephalogram

HUS:

Haemolytic uremic syndrome

PCPC:

Pediatric cerebral performance category

PICU:

Pediatric intensive care unit

PLEX:

Plasma exchange

STEC:

Shiga toxin–producing Escherichia coli

References

  1. Noris M, Remuzzi G (2005) Hemolytic uremic syndrome. J Am Soc Nephrol 16:1035–1050

    Article  CAS  PubMed  Google Scholar 

  2. Lynn RM, O’Brien SJ, Taylor CM et al (2005) Childhood hemolytic uremic syndrome, United Kingdom and Ireland. Emerg Infect Dis 11:590–596

    Article  PubMed  PubMed Central  Google Scholar 

  3. Costigan C, Raftery T, Carroll AG et al (2022) Neurological involvement in children with hemolytic uremic syndrome. Eur J Pediatr 181:501–512

    Article  CAS  PubMed  Google Scholar 

  4. Khalid M, Andreoli S (2019) Extrarenal manifestations of the hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli (STEC HUS). Pediatr Nephrol 34:2495–2507

    Article  PubMed  Google Scholar 

  5. Brown CC, Garcia X, Bhakta RT, Sanders E, Prodhan P (2021) Severe acute neurologic involvement in children with hemolytic-uremic syndrome. Pediatrics 147:e2020013631

    Article  PubMed  Google Scholar 

  6. Walsh PR, Johnson S (2019) Eculizumab in the treatment of Shiga toxin haemolytic uraemic syndrome. Pediatr Nephrol 34:1485–1492

    Article  PubMed  Google Scholar 

  7. Rother RP, Rollins SA, Mojcik CF et al (2007) Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 25:1256–1264

    Article  CAS  PubMed  Google Scholar 

  8. Keenswijk W, Raes A, Vande Walle J (2018) Is eculizumab efficacious in Shigatoxin-associated hemolytic uremic syndrome? A narrative review of current evidence. Eur J Pediatr 177:311–318

    Article  CAS  PubMed  Google Scholar 

  9. Lapeyraque AL, Malina M, Fremeaux-Bacchi V et al (2011) Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med 364:2561–2563

    Article  CAS  PubMed  Google Scholar 

  10. Loos S, Ahlenstiel T, Kranz B et al (2012) An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children. Clin Infect Dis 55:753–759

    Article  CAS  PubMed  Google Scholar 

  11. Bauer A, Loos S, Wehrmann C et al (2014) Neurological involvement in children with E. coli O104:H4-induced hemolytic uremic syndrome. Pediatr Nephrol 29:1607–1615

    Article  PubMed  Google Scholar 

  12. Gitiaux C, Krug P, Grevent D et al (2013) Brain magnetic resonance imaging pattern and outcome in children with haemolytic-uraemic syndrome and neurological impairment treated with eculizumab. Dev Med Child Neurol 55:758–765

    Article  PubMed  Google Scholar 

  13. Ekinci Z, Kenan Bek K, Aytac MB, Karadenizli A, Hancer VS (2014) Renal outcome with eculizumab in two diarrhea-associated hemolytic ureamic syndrome cases with severe neurologic involvement. Hong Kong J Nephrol 16:46–49

    Article  Google Scholar 

  14. Saini A, Emke A, Silva MC, Perlman SJ (2015) Response to eculizumab in Escherichia coli O157:H7 induced hemolytic uremic syndrome with severe neurological manifestations. Clin Pediatr (Phila) 54:387–389

    Article  PubMed  Google Scholar 

  15. Pape L, Hartmann H, Bange FC, Suerbaum S, Bueltmann E, Ahlenstiel-Grunow T (2015) Eculizumab in typical hemolytic uremic syndrome (HUS) With neurological involvement. Medicine (Baltimore) 94:e1000

    Article  CAS  PubMed  Google Scholar 

  16. Percheron L, Gramada R, Tellier S et al (2018) Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study. Pediatr Nephrol 33:1385–1394

    Article  PubMed  Google Scholar 

  17. Monet-Didailler C, Chevallier A, Godron-Dubrasquet A et al (2020) Outcome of children with Shiga toxin-associated haemolytic uraemic syndrome treated with eculizumab: a matched cohort study. Nephrol Dial Transplant 35:2147–2153

    Article  CAS  PubMed  Google Scholar 

  18. Weber B, Chan D, Hammer S (2022) Eculizumab use in a temporarily dialysis-dependent patient with Shiga toxin–producing Escherichia coli hemolytic uremic syndrome with neurological complications. J Pediatr Pharmacol Ther 27:90–95

    PubMed  Google Scholar 

  19. HSE Health Protection Surveillance Centre (2019) VTEC infection in Ireland, 2017. HSE HPSC, Dublin

    Google Scholar 

  20. Garnier A, Brochard K, Kwon T et al (2023) Efficacy and safety of eculizumab in pediatric patients affected by Shiga toxin-related hemolytic and uremic syndrome: a randomized, placebo-controlled trial. J Am Soc Nephrol. https://doi.org/10.1681/ASN.0000000000000182

  21. Fiser DH, Tilford JM, Roberson PK (2000) Relationship of illness severity and length of stay to functional outcomes in the pediatric intensive care unit: a multi-institutional study. Crit Care Med 28:1173–1179

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the other members of our research group who were involved with the care of these patients and in the creation of this article (Dr. Niamh Dolan, Prof. Bryan Lynch, Dr. Michael Riordan, and Dr. Maria Stack).

Author information

Author notes

  1. Atif Awan and Kathleen Mary Gorman equally contributed to this study.

Authors and Affiliations

  1. Department of Paediatric Nephrology and Transplantation, Children’s Health Ireland, Dublin, Ireland

    Dermot Michael Wildes, Caoimhe Suzanne Costigan, Clodagh Sweeney & Atif Awan

  2. Department of Paediatric Neurology, Children’s Health Ireland, Dublin, Ireland

    Susan Harvey & Kathleen Mary Gorman

  3. School of Medicine and Medical Science, University College Dublin, Dublin, Ireland

    Susan Harvey, Atif Awan & Kathleen Mary Gorman

  4. Department of Paediatric Radiology, Children’s Health Ireland, Dublin, Ireland

    Éilis Twomey

  5. Department of Paediatrics and Child Health, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland

    Atif Awan

Authors
  1. Dermot Michael Wildes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan Harvey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caoimhe Suzanne Costigan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Clodagh Sweeney
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Éilis Twomey
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Atif Awan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kathleen Mary Gorman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dermot Michael Wildes.

Ethics declarations

Conflict of Interest

Prof. Awan previously served on the medical advisory board of Alexion. All authors have no conflicts, of a financial nature or otherwise, to declare.

Additional information

Publisher's note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wildes, D.M., Harvey, S., Costigan, C.S. et al. Eculizumab in STEC-HUS: a paradigm shift in the management of pediatric patients with neurological involvement. Pediatr Nephrol 39, 315–324 (2024). https://doi.org/10.1007/s00467-023-06102-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-023-06102-w

Keywords

Search

Navigation