John is a four-year-old child who goes with his family on a trip to visit a farm. During the trip, he drinks a glass of raw (unpasteurized) milk fresh from the cow. His father objects, but his mother, noting that the farm is “organic,” encourages him to drink. Late in the next day John complains to his mother that he feels warm. She notes an oral temperature of 102°F (38.9°C) and treats him with acetaminophen. John develops diarrhea and complains of stomach pain. His pediatrician diagnosis gastroenteritis (believing it to be reovirus, which was currently affecting children in John’s day care) and suggests food restriction, fluid replacement, and alternating ibuprofen and acetaminophen for fever control. John’s parents become increasing concerned. There are traces of blood in the child’s stool, and he is becoming lethargic. On day four of John’s illness, his parents note that he is pale, his face has become puffy, and he seems to be urinating very little, if at all (is becoming anuric). Alarmed, John’s pediatrician has him admitted to a local hospital. At the local hospital John is found to be hypertensive, and tests of kidney function disclose acute renal failure with elevated levels of serum creatinine. Blood studies are abnormal with a low platelet count, decreased levels of several coagulation factors including fibrinogen, and elevated levels of fibrin degradation products. A peripheral blood smear shows that several percent of the red cells are schistocytes (fragmented irregular cells). Stool culture shows E. coli O157:H7. John remains hospitalized for several days, and his blood electrolyte levels, renal function, and platelet count are carefully monitored. His hydration status is checked to maintain normal fluid volume. He is treated with an antihypertensive drug (a calcium channel blocker). Renal dialysis is considered, but John slowly begins to recover renal function. He is discharged with frequent follow-up visits to monitor his continuing renal function.
Discussion
The case is a classic presentation of Shiga toxin producing E. coli induced hemolytic uremic syndrome (STEC-HUS), predominantly a pediatric disease usually occurring in children between one and four years of age. This is most frequently caused by E. coli 0157:H7, an enterohemorrhagic strain of the bacteria that produces an enterotoxin (a bacterial secreted toxin that targets the gastrointestinal tract). A similar toxin is produced by the Shigella species of bacteria responsible for types of bacterial dysentery (hence the term “shiga toxin”). The bacteria E. coli 0157:H7 is very resistant and may contaminate the environment for months. Most cases of STEC-HUS are related to meat or milk products contaminated with animal waste, and cattle are the major reservoir. Contaminated raw milk would be a likely source in this case. About 10 percent of children infected with E. coli 0157:H7 will develop STEC-HUS. The disease presents with three sets of abnormalities: (1) microangiopathic anemia, a type of anemia related to mechanical damage of red cells as they pass through thrombosed or otherwise damaged small blood vessels, (2) thrombocytopenia, and (3) acute renal failure. The abnormalities are all related to the effect of the Shiga toxins produced by the bacteria. The toxin is produced by bacteria that adhere to the gut wall and is absorbed from the inflamed colon. Subsequently, the toxin binds to vascular endothelial cells predominantly in the gut and kidney. The toxin damaged endothelial cells become prothrombotic, leading to platelet adhesion and aggregation and the formation of microthrombi within the vasculature of the kidney. The damaged endothelium and adherent fibrin thrombi shear red cells as they flow through, resulting in the microangiopathc anemia characterized by the presence of damaged red cells (schistocytes). The disseminated intrarenal thrombosis leads to consumption of platelets (hence thrombocytopenia) and also of coagulation factors. Fibrinolysis of the microthrombi leads to the presence of fibrin degradation products. The vascular damage to the kidney results in acute renal failure (FIGURE 14-7).
FIGURE 14-7
Etiology and Pathogenesis
Infection with a shiga toxin producing strain of bacteria E. coli 0157:H7 resulting in STEC hemolytic uremic syndrome. STEC-HUS can be seen as a renal/gut limited form of disseminated intravascular coagulation.
Questions
1. What preventative measures should be undertaken to prevent infection by food-borne enteropathic bacteria?
2. Some advocates suggest that the production of antibiotic-free beef will lower the incidence of E. coli 0157:H7 infections. Do you believe there is any potential validity to the claim?
3. STEC-HUS may be seen as a localized form of DIC. Support this contention.
4. STEC-HUS initially can be diagnosed using a simple blood-based test that can be done in many doctors’ offices. What is the test, and how is it used to make the diagnosis?