Review Question - QID 100981

This patient's presentation is consistent with hemolytic uremic syndrome (HUS). HUS is most frequently due to infection with Shiga-like toxin-producing Escherichia coli O157:H7 following ingestion of contaminated hamburger meat which likely occurred at the family barbecue mentioned in this question.

HUS is the most common cause of acute renal failure in children with peak incidence between ages 5-10 years. Children with HUS often present following a diarrheal illness. The triad of HUS is nonimmune microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Renal failure in HUS is caused by enteric Shiga toxin-producing Escherichia coli (STEC) infection. Shiga-like toxin binds to glycosphingolipid globotriaosylceramide which is found on renal glomerular endothelial, mesangial and tubular epithelial cells. Shiga-like toxin inhibits the 60S ribosomal subunit leading to endothelial cell damage. This endothelial cell damage exposes von Willebrand's factor which then binds to GPIB on platelets causing clots to form in the vasculature. These clots can occlude blood vessels partially and shear any passing red blood cells producing schistocytes leading to a microangiopathic anemia. In addition, these formed clots also decrease the platelet count; however, it is important to note that only the platelet count is decreased and that clotting factors are not used, thus the PT and PTT are normal. Contrast this to the clots formed in disseminated intravascular coagulation (DIC) which utilize platelets and clotting factors which results in a decreased platelet count and an increased PT/PTT.

Razzaq et al. describe the classic features of HUS including microangiopathic anemia, thrombotic thrombocytopenia, and renal failure. Complications from HUS can include intussusception, chronic renal failure, and seizures in severe cases.

Filler et al. reviews the common causes of acute renal failure in children including HUS, acute tubular necrosis secondary to various causes (such as congestive heart failure and sepsis), and glomerulonephritis and urinary tract obstruction.

Illustration A depicts the pathogenesis of HUS. Illustration B is a peripheral blood smear of a patient with HUS showing the characteristic schistocytes.

Incorrect Answers:
Answer 1: Hypothalamic dysfunction in children is most commonly caused by a craniopharyngioma. Symptoms due to tumor mass may include headaches or loss of vision. Other symptoms may result from an absence or decrease in hypothalamic hormone production such as cold intolerance, fatigue, or amenorrhea.
Answer 2: Surreptitious laxative abuse may be suspected in individuals with chronic, watery diarrhea that has eludes diagnosis after a thorough investigation, particularly in individuals with depressive symptoms. This is not consistent with the above clinical vignette.
Answer 3: Toxic shock syndrome, or gram-positive "septic" shock, often presents with vomiting and diarrhea and may progress rapidly to severe and intractable hypotension and multisystem dysfunction.
Answer 4: Shigella infection can present very similarly to EHEC infection and discriminating between EHEC and Shigella can be difficult. This case presentation however is a better description for EHEC: young child, beef consumption (barbecue) followed by HUS. Though both EHEC and Shigella can cause bloody diarrhea Shigella is more commonly associated with a bloody diarrhea as well which was not mentioned.