Eculizumab treatment of child with hemolytic-uremic syndrome associated with Escherichia coli infection – case report

Czech version

Authors: P. Konopásek; J. David; F. Fencl; J. Zieg
Authors‘ workplace: Pediatrická klinika 2. LF UK a FN Motol, Praha
Published in: Čes-slov Pediat 2020; 75 (8): 479-483.
Category: Case Report

Overview

Hemolytic-uremic syndrome (HUS) is one of the various kinds of so-called thrombotic microangiopathy (TMA) characterized by thrombocytopenia, hemolytic anemia and other organ manifestations. Apart from the TMA symptoms, HUS further manifests itself by acute kidney injury (AKI). HUS is in fact the most common cause of AKI in the pediatric population. Eculizumab, the inhibitor of the C5 complement component, is indicated mainly in case of atypical HUS forms where the efficiency has been clearly demonstrated. On the other hand, using it for treating patients with Shiga-toxin-producing E. coli (STEC)-HUS is controversial.

We present a case report of a three-year-old boy with STEC-HUS treated with eculizumab.

Keywords:

Hemolytic-uremic syndrome – STEC-HUS – eculizumab – children

Sources

1. Talarico V, Aloe M, Monzani A, et al. Hemolytic uremic syndome in children. Minerva Pediatr 2016; 68 (6): 441–455.

2. Canpolat N. Hemolytic uremic syndrome. Türk Pediatri Arş 2015; 50 (2): 73–81.

3. Sheerin NS, Glover E. Haemolytic uremic syndrome: diagnosis and management. F1000 2009; 8.

4. Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365 (9464): 1073–1086.

5. Orth-Holler D, Riedl M, Wurzner R. Inhibition of terminal complement activation in severe Shiga toxin-associated HUS – perfect example for a fast track from bench to bedside. EMBO Mol Med 2011; 3 (11): 617–619.

6. Thurman JM, Marians R, Emlen W, et al. Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 2009; 4 (12): 1920–1924.

7. Arvidsson I, Stahl A, Manea Hedstrom M, et al. Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in hemolytic uremic syndrome. J Immunol 2015; 194 (5): 2309–2318.

8. Brady TM, Pruette C, Loeffler LF, et al. Typical HUS: Evidence of acute phase complement activation from a daycare outbreak. J Clin Exp Nephrol 2016; 1 (2): 11.

9. Ahlenstiel-Grunow T, Hachmeister S, Bange FC, et al. Systemic complement activation and complement gene analysis in enterohaemorrhagic Escherichia coli - associated paediatric haemolytic uraemic syndrome. Nephrol Dial Transplant 2016; 31 (7): 1114–1121.

10. Karnisova L, Hradsky O, Blahova K, et al. Complement activation is associated with more severe course of diarrhea-associated hemolytic uremic syndrome, a preliminary study. Eur J Pediatr 2018; 177 (12): 1837–1844.

11. Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS. Long-term outcomes of Shiga toxin hemolytic uremic syndrome. Pediatr Nephrol 2013; 28 (11): 2097–2105.

12. Monet-Didailler C, Godron-Dubrasquet A, Madden I, et al. Long-term outcome of diarrhea-associated hemolytic uremic syndrome is poorly related to markers of kidney injury at 1-year follow-up in a population-based cohort. Pediatr Nephrol 2019; 34 (4): 657–662.

13. Nester CM, Brophy PD. Eculizumab in the treatment of atypical haemolytic uraemic syndrome and other complement-mediated renal diseases. Curr Opin Pediatr 2013; 25 (2): 225–231.

14. Percheron L, Gramada R, Tellier S, et al. Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study. Pediatr Nephrol 2018; 33 (8): 1385–1394.

15. Pape L, Hartmann H, Bange FC, et al. Eculizumab in typical hemolytic uremic syndrome (HUS) with neurological involvement. Medicine (Baltimore) 2015; 94 (24): e1000.

16. Walsh PR, Johnson S. Eculizumab in the treatment of Shiga toxin hae-molytic uraemic syndrome. Pediatr Nephrol 2019; 34 (9): 1485–1492.

17. Freedman SB, Xie J, Neufeld MS, et al. Shiga toxin-producing Escherichia coli infection, antibiotics, and risk of developing hemolytic uremic syndrome: A meta-analysis. Clin Infect Dis 2016; 62 (10): 1251–1258.

18. Michael M, Elliott EJ, Craig JC, et al. Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: A systematic review of randomized controlled trials. Am J Kidney Dis 2009; 53 (2): 259–272.

19. Bitzan M, Schaefer F, Reymond D. Treatment of typical (enteropathic) hemolytic uremic syndrome. Semin Thromb Hemost 2010; 36 (6): 594–610.

20. Lapeyraque AL, Malina M, Fremeaux-Bacchi V, et al. Eculizumab in severe Shiga-toxin–associated HUS. N Engl J Med 2011; 364 (26): 2561–2563.

21. Loos S, Oh J, Kemper MJ. Eculizumab in STEC-HUS: need for a proper randomized controlled trial. Pediatr Nephrol 2018; 33 (8): 1277–1281.

22. Dinh A, Anathasayanan A, Rubin LM. Safe and effective use of eculizumab in the treatment of severe Shiga toxin Escherichia coli-associated hemolytic uremic syndrome. Am J Health Syst Pharm 2015; 72 (2): 117–120.

23. Giordano P, Netti GS, Santangelo L, et al. A pediatric neurologic assessment score may drive the eculizumab-based treatment of Escherichia coli-related hemolytic uremic syndrome with neurological involvement. Pediatr Nephrol 2019; 34 (3): 517–527.

24. Agbas A, Goknar N, Akinci N, et al. Outbreak of Shiga toxin-producing Escherichia-coli-associated hemolytic uremic syndrome in Istanbul in 2015: outcome and experience with eculizumab. Pediatr Nephrol 2018; 33 (12): 2371–2381.

25. Kielstein JT, Beutel G, Fleig S, et al. Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin--producing E. coli O104: H4 induced haemolytic-uraemic syndrome. Nephrol Dial Transplant 2012; 27 (10): 3807–3815.

26. Menne J, Nitschke M, Stingele R, et al. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104: H4 induced haemolytic uraemic syndrome. BMJ 2012; 345 (191): e4565–e4565.

27. Monet-Didailler C, Chevallier A, Godron-Dubrasquet A, et al. Outcome of children with Shiga toxin-associated haemolytic uraemic syndrome treated with eculizumab: a matched cohort study. Nephrol Dial Transplant 2019; 158.

28. Aldridge A, Burke J. Follow-up of children with infection-associated haemolytic uraemic syndrome 1979–1995: Would eculizumab have improved prognosis? J Paediatr Child Health 2019.

29. Keenswijk W, Raes A, Vande Walle J. Is eculizumab efficacious in Shigatoxin-associated hemolytic uremic syndrome? A narrative review of current evidence. Eur J Pediatr 2018; 177 (3): 311–318.

30. Mahat U, Matar RB, Rotz SJ. Use of complement monoclonal antibody eculizumab in Shiga toxin producing Escherichia coli associated hemolytic uremic syndrome: A review of current evidence. Pediatr Blood Cancer 2019; 66 (11): e27913.