Abstract
Background
Atypical hemolytic uremic syndrome (aHUS) is associated with defective regulation of the complement pathway. Neurological involvement is the most common extrarenal complication and represents a major cause of mortality and morbidity.
Case-diagnosis/treatment
Two girls aged 11 and 6 years, respectively, developed aHUS and were treated immediately with plasma exchange (PE) and fresh frozen plasma infusion (PI). Although initial improvement in renal function was seen in both cases, the first patient showed progressing thrombotic microangiopathy (TMA) despite daily PE, and neurological manifestations (seizures, vision loss, loss of balance, and confusion) developed after 1 month. The second patient developed cerebral TMA (seizures, vision loss, and nystagmus) 6 days after initial presentation and remained unresponsive to PE/PI. Neurological symptoms were similar in both patients, even though they had different complement protein mutations. Treatment with eculizumab achieved complete control of neurological symptoms within 24 h and gradually normalized hematological and renal parameters in both children.
Conclusions
Based on our two cases, we conclude that eculizumab is a rapid-acting, effective, and life-saving treatment for pediatric patients with aHUS and severe neurological involvement, which works by inhibiting complement-mediated TMA in the kidney and other organs, such as the brain.
References
Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, Loirat C, Pecoraro C, Taylor CM, Van de Kar N, Vandewalle J, Zimmerhackl LB, European Paediatric Study Group for HUS (2009) Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 24:687–696
Noris M, Remuzzi G (2009) Atypical hemolytic-uremic syndrome. N Engl J Med 361:1676–1687
Neuhaus TJ, Calonder S, Leumann EP (1997) Heterogeneity of atypical haemolyticuraemic syndromes. Arch Dis Child 76:518–521
Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B, André JL, Takagi N, Cheong HI, Hari P, Le Quintrec M, Niaudet P, Loirat C, Fridman WH, Frémeaux-Bacchi V (2010) Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol 21:2180–2187
Koehl B, Boyer O, Biebuyck-Gougé N, Kossorotoff M, Frémeaux-Bacchi V, Boddaert N, Niaudet P (2010) Neurological involvement in a child with atypical hemolytic uremic syndrome. Pediatr Nephrol 25:2539–2542
Tschumi S, Gugger M, Bucher BS, Riedl M, Simonetti GD (2011) Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatr Nephrol 26:2085–2088
Waters AM, Licht C (2011) aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol 26:41–57
Loirat C, Frémeaux-Bacchi V (2011) Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 6:60
Caprioli J, Noris M, Brioschi S, Pianetti G, Castelletti F, Bettinaglio P, Mele C, Bresin E, Cassis L, Gamba S, Porrati F, Bucchioni S, Monteferrante G, Fang CJ, Liszewski MK, Kavanagh D, Atkinson JP, Remuzzi G, International Registry of Recurrent and Familial HUS/TTP (2006) Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 108:1267–1279
Zuber J, Fakhouri F, Roumenina LT, Loirat C, Frémeaux-Bacchi V (2012) Use of eculizumab for atypical haemolyticuraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 8:643–657
Ohanian M, Cable C, Halka K (2011) Eculizumab safely reverses neurologic impairment and eliminates need for dialysis in severe atypical hemolytic uremic syndrome. Clin Pharmacol 3:5–12
Gruppo RA, Rother RP (2009) Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med 360:544–546
Woodruff TM, Ager RR, Tenner AJ, Noakes PG, Taylor SM (2010) The role of the complement system and the activation fragment C5a in the central nervous system. Neuromolecular Med 12:179–192
Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 102:7227–7232
Vilalta R, Lara E, Madrid A, Chocron S, Muñoz M, Casquero A, Nieto J (2012) Long-term eculizumab improves clinical outcomes in atypical hemolytic uremic syndrome. Pediatr Nephrol 27:2323–2326
Acknowledgments
Assistance with writing this manuscript was provided by Bioscript Stirling Ltd, UK, and funded by Alexion Pharmaceuticals. We give special thanks to Dr. Reyhan Diz Kucukkaya in the Department of Internal Medicine, Division of Hematology at Istanbul Bilim University, Istanbul, Turkey.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gulleroglu, K., Fidan, K., Hançer, V.S. et al. Neurologic involvement in atypical hemolytic uremic syndrome and successful treatment with eculizumab. Pediatr Nephrol 28, 827–830 (2013). https://doi.org/10.1007/s00467-013-2416-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-013-2416-9