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Clinical manifestations and diagnosis of Shiga toxin associated (typical) hemolytic uremic syndrome in children

INTRODUCTION

The hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury [1]. It is one of the main causes of acute renal injury in children under the age of three years.

This disorder is divided by whether or not there is an association with bacteria that produce a Shiga toxin [2].

  • Shiga toxin associated HUS – Shiga toxin (Stx) associated HUS is the most common form of HUS in children accounting for 90 percent of all cases. It usually occurs after a prodromal episode of diarrhea that is frequently bloody. In the majority of cases, typical HUS is associated with strains of Escherichia coli that produce a Shiga toxin [3-6]. This form is also referred to as typical, classical, or diarrhea-associated HUS, D+ HUS, or Shiga toxin-associated HUS.

    Cases of HUS in children due to Shiga toxin-producing Escherichia coli (E. coli) infections other than colitis (eg, urinary tract infections) can occur [7,8]. Although these cases are not associated with diarrhea, the clinical course and pathophysiology are the same as the D+ HUS and will be included in the discussion on Stx HUS. In addition, D+ HUS associated with Shigella dysenteriae serotype 1 will be included in the discussion of Stx HUS [9,10].
  • Non-Shiga toxin associated HUS – Non-Shiga toxin (NStx) associated HUS is a heterogeneous group of disorders distinguished clinically by the absence of diarrhea or Shiga toxin-producing E. coli infection [11,12]. This disorder is also referred to as atypical, nondiarrhea-associated HUS, D- HUS, or sporadic HUS. Complement disorders involving factors H, I, and membrane cofactor protein and Streptococcus pneumoniae infection have been associated with cases of NStx HUS. The clinical manifestations, diagnosis, treatment, and prognosis of NStx HUS are presented separately. (See "Atypical hemolytic uremic syndrome in children".)

The clinical manifestations and diagnosis of Stx HUS in children are presented in this topic review. The treatment and prognosis of this disorder are presented separately. (See "Treatment and prognosis of Shiga toxin associated (typical) hemolytic uremic syndrome in children".)

Stx HUS is also a different disorder from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) in adults. This is discussed in detail separately. (See "Causes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults".)

                

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Literature review current through: Apr 2013. | This topic last updated: Mar 14, 2013.
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References
Top
  1. Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16:1035.
  2. Boyer O, Niaudet P. Hemolytic uremic syndrome: new developments in pathogenesis and treatment. Int J Nephrol 2011; 2011:908407.
  3. Repetto HA. Epidemic hemolytic-uremic syndrome in children. Kidney Int 1997; 52:1708.
  4. Yukioka H, Kurita S. Escherichia coli O157 infection disaster in Japan, 1996. Eur J Emerg Med 1997; 4:165.
  5. Slutsker L, Ries AA, Greene KD, et al. Escherichia coli O157:H7 diarrhea in the United States: clinical and epidemiologic features. Ann Intern Med 1997; 126:505.
  6. Gerber A, Karch H, Allerberger F, et al. Clinical course and the role of shiga toxin-producing Escherichia coli infection in the hemolytic-uremic syndrome in pediatric patients, 1997-2000, in Germany and Austria: a prospective study. J Infect Dis 2002; 186:493.
  7. Starr M, Bennett-Wood V, Bigham AK, et al. Hemolytic-uremic syndrome following urinary tract infection with enterohemorrhagic Escherichia coli: case report and review. Clin Infect Dis 1998; 27:310.
  8. Hogan MC, Gloor JM, Uhl JR, et al. Two cases of non-O157:H7 Escherichia coli hemolytic uremic syndrome caused by urinary tract infection. Am J Kidney Dis 2001; 38:E22.
  9. Houdouin V, Doit C, Mariani P, et al. A pediatric cluster of Shigella dysenteriae serotype 1 diarrhea with hemolytic uremic syndrome in 2 families from France. Clin Infect Dis 2004; 38:e96.
  10. Bhimma R, Rollins NC, Coovadia HM, Adhikari M. Post-dysenteric hemolytic uremic syndrome in children during an epidemic of Shigella dysentery in Kwazulu/Natal. Pediatr Nephrol 1997; 11:560.
  11. Constantinescu AR, Bitzan M, Weiss LS, et al. Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis 2004; 43:976.
  12. Neuhaus TJ, Calonder S, Leumann EP. Heterogeneity of atypical haemolytic uraemic syndromes. Arch Dis Child 1997; 76:518.
  13. Fitzpatrick M. Haemolytic uraemic syndrome and E coli O157. BMJ 1999; 318:684.
  14. Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365:1073.
  15. van de Kar NC, Roelofs HG, Muytjens HL, et al. Verocytotoxin-producing Escherichia coli infection in hemolytic uremic syndrome in part of western Europe. Eur J Pediatr 1996; 155:592.
  16. Banatvala N, Griffin PM, Greene KD, et al. The United States National Prospective Hemolytic Uremic Syndrome Study: microbiologic, serologic, clinical, and epidemiologic findings. J Infect Dis 2001; 183:1063.
  17. Mody RK, Luna-Gierke RE, Jones TF, et al. Infections in pediatric postdiarrheal hemolytic uremic syndrome: factors associated with identifying shiga toxin-producing Escherichia coli. Arch Pediatr Adolesc Med 2012; 166:902.
  18. www.rki.de/EN/Home/homepage__node.html (Accessed on June 02, 2011).
  19. www.cdc.gov/media/releases/2011/s0601_ecoligermany.html?s_cid=2011_s0601_ecoligermany (Accessed on June 02, 2011).
  20. www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19878 (Accessed on June 02, 2011).
  21. Kemper MJ. Outbreak of hemolytic uremic syndrome caused by E. coli O104:H4 in Germany: a pediatric perspective. Pediatr Nephrol 2012; 27:161.
  22. Loos S, Ahlenstiel T, Kranz B, et al. 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 2012; 55:753.
  23. Centers for Disease Control and Prevention (CDC). Community outbreak of hemolytic uremic syndrome attributable to Escherichia coli O111:NM--South Australia 1995. MMWR Morb Mortal Wkly Rep 1995; 44:550.
  24. Elliott EJ, Robins-Browne RM, O'Loughlin EV, et al. Nationwide study of haemolytic uraemic syndrome: clinical, microbiological, and epidemiological features. Arch Dis Child 2001; 85:125.
  25. Piercefield EW, Bradley KK, Coffman RL, Mallonee SM. Hemolytic Uremic Syndrome After an Escherichia coli O111 Outbreak. Arch Intern Med 2010; 170:1656.
  26. Tozzi AE, Caprioli A, Minelli F, et al. Shiga toxin-producing Escherichia coli infections associated with hemolytic uremic syndrome, Italy, 1988-2000. Emerg Infect Dis 2003; 9:106.
  27. Boyce TG, Swerdlow DL, Griffin PM. Escherichia coli O157:H7 and the hemolytic-uremic syndrome. N Engl J Med 1995; 333:364.
  28. Bell BP, Goldoft M, Griffin PM, et al. A multistate outbreak of Escherichia coli O157:H7-associated bloody diarrhea and hemolytic uremic syndrome from hamburgers. The Washington experience. JAMA 1994; 272:1349.
  29. Espié E, Grimont F, Mariani-Kurkdjian P, et al. Surveillance of hemolytic uremic syndrome in children less than 15 years of age, a system to monitor O157 and non-O157 Shiga toxin-producing Escherichia coli infections in France, 1996-2006. Pediatr Infect Dis J 2008; 27:595.
  30. Vaillant V, Espié E, de Valk H, et al. Undercooked ground beef and person-to-person transmission as major risk factors for sporadic hemolytic uremic syndrome related to Shiga-toxin producing Escherchia coli infections in children in France. Pediatr Infect Dis J 2009; 28:650.
  31. Stritt A, Tschumi S, Kottanattu L, et al. Neonatal hemolytic uremic syndrome after mother-to-child transmission of a low-pathogenic stx2b harboring shiga toxin-producing Escherichia coli. Clin Infect Dis 2013; 56:114.
  32. Su C, Brandt LJ. Escherichia coli O157:H7 infection in humans. Ann Intern Med 1995; 123:698.
  33. Siegler RL. Spectrum of extrarenal involvement in postdiarrheal hemolytic-uremic syndrome. J Pediatr 1994; 125:511.
  34. Nathanson S, Kwon T, Elmaleh M, et al. Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 2010; 5:1218.
  35. Jeong YK, Kim IO, Kim WS, et al. Hemolytic uremic syndrome: MR findings of CNS complications. Pediatr Radiol 1994; 24:585.
  36. de Buys Roessingh AS, de Lagausie P, Baudoin V, et al. Gastrointestinal complications of post-diarrheal hemolytic uremic syndrome. Eur J Pediatr Surg 2007; 17:328.
  37. Rahman RC, Cobeñas CJ, Drut R, et al. Hemorrhagic colitis in postdiarrheal hemolytic uremic syndrome: retrospective analysis of 54 children. Pediatr Nephrol 2012; 27:229.
  38. Siegler RL, Pavia AT, Christofferson RD, Milligan MK. A 20-year population-based study of postdiarrheal hemolytic uremic syndrome in Utah. Pediatrics 1994; 94:35.
  39. Ludwig K, Bitzan M, Bobrowski C, Müller-Wiefel DE. Escherichia coli O157 fails to induce a long-lasting lipopolysaccharide-specific, measurable humoral immune response in children with hemolytic-uremic syndrome. J Infect Dis 2002; 186:566.
  40. Habib R, Levy M, Gagnadoux M, et al. Prognosis of the hemolytic uremic syndrome in children. Adv Nephrol Necker Hosp 1982; 11:99.
  41. Habib R. Pathology of the hemolytic and uremic syndrome. In: Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura, Kaplan BS, Trompeter R, Moake J (Eds), Dekker, New York 1992. p.315.
  42. Loirat C, Taylor CM. Hemolytic Uremic Syndromes. In: Pediatric Nephrology, 4th ed, Avner ED, Harmon WE, Niaudet P (Eds), Lippincott, Williams & Wilkins, Baltimore 2004. p.887.
  43. Marder VJ, Martin SE, Francis CW, Colman RW. Consumptive thrombo-hemorrhagic disorders. In: emostasis and Thrombosis: Basic Principles and Clinical Practice, 2nd ed, Colman RW, Hirsh J, Marder VJ, Salzman EW (Eds), Lippincott, Philadelphia 1987. p.975.
  44. Neame PB, Hirsh J, Browman G, et al. Thrombotic thrombocytopenic purpura: a syndrome of intravascular platelet consumption. Can Med Assoc J 1976; 114:1108.