Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children
- Patrick Niaudet, MD
Patrick Niaudet, MD
- Section Editor — Pediatric Nephrology
- Professor of Pediatrics
- Hôpital Necker-Enfants Malades, Paris, France
- Section Editors
- Tej K Mattoo, MD, DCH, FRCP
Tej K Mattoo, MD, DCH, FRCP
- Section Editor — Pediatric Nephrology
- Professor of Pediatrics
- Wayne State University School of Medicine
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
The hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury . The most common cause of HUS is Shiga toxin-producing Escherichia coli (STEC), and it is one of the main causes of acute kidney injury in children under the age of three years.
The clinical manifestations and diagnosis of STEC HUS in children are presented in this topic review. The treatment and prognosis of this disorder and other causes of HUS are presented separately. (See "Treatment and prognosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children" and "Overview of hemolytic uremic syndrome in children" and "Complement-mediated hemolytic uremic syndrome".)
Traditionally, HUS had been divided into diarrhea-positive and diarrhea-negative HUS. The former, also referred to as typical HUS, primarily resulted from STEC infections, and less frequently from Shigella dysenteriae type 1 infection. All other causes of HUS were referred to as atypical HUS or assigned to the diarrhea-negative HUS, even though some patients with non-STEC-associated HUS also presented with diarrhea.
The following classification is now preferred, based on a better understanding of the various causes of HUS (see "Overview of hemolytic uremic syndrome in children"):
●Primary causes without coexisting disease; such as cases due to complement dysregulation (also referred to as atypical HUS) 
- Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16:1035.
- Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2016; 31:15.
- 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.
- Fitzpatrick M. Haemolytic uraemic syndrome and E coli O157. BMJ 1999; 318:684.
- Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365:1073.
- 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.
- 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.
- 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.
- Hashimoto H, Mizukoshi K, Nishi M, et al. Epidemic of gastrointestinal tract infection including hemorrhagic colitis attributable to Shiga toxin 1-producing Escherichia coli O118:H2 at a junior high school in Japan. Pediatrics 1999; 103:E2.
- Voss E, Paton AW, Manning PA, Paton JC. Molecular analysis of Shiga toxigenic Escherichia coli O111:H- proteins which react with sera from patients with hemolytic-uremic syndrome. Infect Immun 1998; 66:1467.
- www.rki.de/EN/Home/homepage__node.html (Accessed on June 02, 2011).
- www.cdc.gov/media/releases/2011/s0601_ecoligermany.html?s_cid=2011_s0601_ecoligermany (Accessed on June 02, 2011).
- www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19878 (Accessed on June 02, 2011).
- Kemper MJ. Outbreak of hemolytic uremic syndrome caused by E. coli O104:H4 in Germany: a pediatric perspective. Pediatr Nephrol 2012; 27:161.
- 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.
- 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.
- 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.
- Piercefield EW, Bradley KK, Coffman RL, Mallonee SM. Hemolytic Uremic Syndrome After an Escherichia coli O111 Outbreak. Arch Intern Med 2010; 170:1656.
- 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.
- Boyce TG, Swerdlow DL, Griffin PM. Escherichia coli O157:H7 and the hemolytic-uremic syndrome. N Engl J Med 1995; 333:364.
- 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.
- 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.
- 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.
- 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.
- 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.
- Su C, Brandt LJ. Escherichia coli O157:H7 infection in humans. Ann Intern Med 1995; 123:698.
- 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.
- Balestracci A, Martin SM, Toledo I, et al. Dehydration at admission increased the need for dialysis in hemolytic uremic syndrome children. Pediatr Nephrol 2012; 27:1407.
- Siegler RL. Spectrum of extrarenal involvement in postdiarrheal hemolytic-uremic syndrome. J Pediatr 1994; 125:511.
- 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.
- Bauer A, Loos S, Wehrmann C, et al. Neurological involvement in children with E. coli O104:H4-induced hemolytic uremic syndrome. Pediatr Nephrol 2014; 29:1607.
- Jeong YK, Kim IO, Kim WS, et al. Hemolytic uremic syndrome: MR findings of CNS complications. Pediatr Radiol 1994; 24:585.
- 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.
- 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.
- Masumoto K, Nishimoto Y, Taguchi T, et al. Colonic stricture secondary to hemolytic uremic syndrome caused by Escherichia coli O-157. Pediatr Nephrol 2005; 20:1496.
- Askiti V, Hendrickson K, Fish AJ, et al. Troponin I levels in a hemolytic uremic syndrome patient with severe cardiac failure. Pediatr Nephrol 2004; 19:345.
- Thayu M, Chandler WL, Jelacic S, et al. Cardiac ischemia during hemolytic uremic syndrome. Pediatr Nephrol 2003; 18:286.
- Andreoli S, Bergstein J. Exocrine and endocrine pancreatic insufficiency and calcinosis after hemolytic uremic syndrome. J Pediatr 1987; 110:816.
- Nesmith JD, Ellis E. Childhood hemolytic uremic syndrome is associated with adolescent-onset diabetes mellitus. Pediatr Nephrol 2007; 22:294.
- 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.
- Habib R, Levy M, Gagnadoux M, et al. Prognosis of the hemolytic uremic syndrome in children. Adv Nephrol Necker Hosp 1982; 11:99.
- 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.
- 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.
- Marder VJ, Martin SE, Francis CW, Colman RW. Consumptive thrombo-hemorrhagic disorders. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 2nd ed, Colman RW, Hirsh J, Marder VJ, Salzman EW (Eds), Lippincott, Philadelphia 1987. p.975.
- Keir LS, Saleem MA. Current evidence for the role of complement in the pathogenesis of Shiga toxin haemolytic uraemic syndrome. Pediatr Nephrol 2014; 29:1895.
- Poolpol K, Orth-Höller D, Speth C, et al. Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. Mol Immunol 2014; 58:77.
- Fremeaux-Bacchi V, Fakhouri F, Garnier A, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 2013; 8:554.
- Enterohemorrhagic E. coli
- CLINICAL AND LABORATORY MANIFESTATIONS
- Microangiopathic hemolytic anemia
- Acute kidney injury (AKI)
- Other organ involvement
- Evidence of STEC infection
- DIFFERENTIAL DIAGNOSIS
- SUMMARY AND RECOMMENDATIONS