A 4-year-old boy presents to his pediatrician because of swelling over the face, malaise, fatigue, and decreased appetite. On further questioning, his parents state that he appears pale and has reduced urine output. He recently finished a course of antibiotics for bloody diarrhea. On exam, he is found to be hypertensive and pale and has anasarca. Initial laboratory studies show a hemoglobin of 7 g/dL, platelet count of 44,000/mm³, blood urea nitrogen of 39 mg/dL and creatinine of 2.9 mg/dL. Peripheral smear shows the presence of schistocytes and a paucity of platelets (Figures 69-1 and 69-2). He is admitted to the pediatric intensive care unit for hemolytic uremic syndrome. He is treated conservatively with close attention to fluid intake and output, restriction of sodium and fluid intake, and antihypertensive medications as needed. A stool culture obtained at the onset of his bloody diarrhea grows Escherichia coli and is identified as serotype 0157:H7. Hemoglobin declines to 5.2 g/dL for which he is transfused packed red blood cells. Platelet count decreases over the next few days and then improves. He has no evidence of bleeding. Azotemia and oliguria improve over a week, appetite improves and anasarca resolves. He is discharged home with an excellent prognosis for full recovery.

The hemolytic uremic syndrome (HUS) was first described in 1955 by Gasser et al.¹ HUS is a thrombotic microangiopathy characterized by a triad of hemolytic anemia, thrombocytopenia and acute kidney injury.

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  Typical HUS is also known as D(+) HUS, Shiga toxin-producing Escherichia coli (STEC) HUS, verocytotoxin producing Escherichia coli (VTEC) HUS, or Shiga-like toxin associated (Stx) HUS.

  
  
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  Atypical HUS is also referred to as D(–) HUS and non-Shiga-like toxin associated (non-Stx) HUS.

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  It is the most common cause of renal failure in childhood.²

  
  
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  Worldwide, the incidence is 0.2 to 4 cases per 100,000 per year.³

  
  
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  It is more common in children under 5 years with an incidence of approximately 6 cases per 100,000 per year.⁴

  
  
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  There is also a geographical variation, with the highest incidence reported in Argentina.⁵

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  In 2006, the European Study Group for HUS proposed a classification for HUS, thrombotic thrombocytopenic purpura (TTP) and related disorders, which is summarized in Table 69-1.⁶

  
  
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  The underlying histological lesion in HUS is thrombotic microangiopathy, characterized by thickening of arteriole and capillary walls, with prominent endothelial damage (swelling and detachment), subendothelial accumulation of proteins and cell debris, and fibrin and platelet-rich thrombi obstructing vessel lumina.

  
  
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  In practice, HUS can be distinguished in a “typical” variety or diarrheal-associated form, termed as D(+) HUS, primarily triggered by preceding diarrheal illness with Shiga toxin-producing Ecoli, mostly serotype O157:H7. This form accounts for 90 percent of all cases of HUS.⁷

  
  
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  Ten percent of cases of HUS fall into the “atypical” category known as atypical HUS or D(–) HUS. It occurs in a familial as well as in a sporadic form.

  
  
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  Atypical HUS (aHUS) is a heterogeneous group of disorders caused by defective complement regulation in the majority of cases.^7,8 Mutations have been identified in genes encoding the regulatory proteins of the complement alternative pathway, complement factor H (CFH), membrane cofactor protein (MCP or CD46), complement factor I (CFI) and complement factor H-related proteins (CFHR) as well as complement activators, complement factor B (CFB) and C3 as well as thrombomodulin (THBD). Inhibitory autoantibodies to CFH account for an additional 5 to 10 percent of cases and can occur in isolation or in association with these mutations.⁷

  
  
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  Atypical HUS has an equal incidence in boys and girls.⁹ Seventy percent of children have the first episode before the age of 2 years and approximately 25 percent before the age of 6 months.⁹

  
  
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  In contrast, less than 5 percent of D(+) HUS occurs in children below the age of 6 months.⁹

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  Only 10 to 15 percent of children who are infected with E coli O157:H7 develop HUS.^10,11

  
  
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  Higher initial leukocyte counts, vomiting, and use of antibiotics are associated with subsequent development of HUS.¹¹

  
  
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  About 80 percent of cases of aHUS are also triggered by infections, either upper respiratory tract infections or gastroenteritis.⁹ Other triggers reported are varicella, H1N1 influenza and, interestingly, Shigatoxin associated diarrheal illness.⁹