Hemolytic Uremic Syndrome from Shiga-Toxin Producing E. coli
December 6, 2023
By Laura Murphy
This article provides a review of hemolytic-uremic syndrome (HUS) associated with Shiga toxin-producing Escherichia coli (STEC) infection. This condition, which disproportionately impacts children under five, is defined by thrombocytopenia, non-immune hemolytic anemia, and azotemia caused by thrombotic microangiopathy.
More than just dehydration…
Of E. coli serotypes, those that produce Shiga toxin 2 (rather than Shiga toxin 1) cause almost all cases of diarrhea-associated HUS. Of these high-risk serotypes, O157:H7 is the best characterized (84% of HUS cases in the US). Incidence peaks in summer and fall. Pathogenesis of HUS is related to activation of microvascular endothelium; mucosal injury in the colon leads to diarrhea and abdominal pain; translocation of the toxin causes systemic circulation of Shiga toxin, causing organ-specific microvascular injury and associated thrombotic response.
Course of illness typically starts with nonspecific symptoms such as abdominal pain, vomiting, and fever followed by diarrhea, which becomes bloody within 1-3 days. Early diagnosis of STEC infection by stool sample (or rectal swab) to identify case clusters as well as high-risk individuals for HUS is important. Sensitivity is best early in the course of the illness. High-risk patients include those with Shiga toxin 2 detected, unknown Shiga toxin genotype with bloody diarrhea, or E coli O157 on bacterial culture or nucleic acid amplification. Risk factors for development of HUS include age (<5 or >75), presence of bloody diarrhea, absence of Shiga toxin 1, elevated WBC count, low platelet count, hemoconcentration or hyponatremia.
HUS develops in 15-20% of children infected with high-risk STEC, and risk is highest under the age of 5; it typically manifests between days 5 and 14 of illness. In patients with suspected STEC infection, lab evaluation for HUS including CBC, BMP, peripheral smear should be obtained and monitored through illness (if high-risk STEC infection). Rapidly progressive thrombocytopenia is the sentinel and universal hematologic abnormality; other lab findings include anemia, azotemia, hemoglobinuria, elevated lactate dehydrogenase (LDH), and low haptoglobin levels.
For patients with STEC infection, avoid antibiotic administration, which is associated with increased risk of HUS, as well as opioid and antimotility drugs, which prolong symptoms and increase risk for HUS and neurologic complications. NSAIDs can cause acute kidney injury during GI illness and should also be avoided. Oral rehydration is important, and administration of IV isotonic fluids can reduce incidence of anuria and shorten hospitalization. Several studies have demonstrated that aggressive fluid administration can reduce need for renal replacement therapy, but caution should be taken to avoid fluid overload.
Oligo-anuria occurs in 50-60% and typically requires renal replacement therapy. Chronic kidney disease is associated with duration of anuria, need for kidney-replacement therapy, or both. Case-fatality rate is around 3% in children and up to 20% in middle-aged or older adults; death is typically related to complications such as seizures, coma, stroke. Other complications include hypertension, cardiac (ischemia, arrhythmia, cardiomyopathy, effusion), intestinal events, pancreatitis, cholestasis, respiratory distress syndrome, pulmonary hemorrhage, volume overload, disseminated intravascular coagulation. Many patients require packed red blood cell transfusion, but platelet infusions should be limited to those with hemodynamically significant bleeding since complications of HUS are associated with thrombotic injury.
How will this change my practice?
I will perform early testing for STEC infection in children with bloody diarrhea or at high-risk for STEC by stool studies or rectal swab, with close monitoring for patients with high-risk STEC infections. I’ll avoid of potentially harmful interventions (including antibiotics, antidiarrheals) and use aggressive hydration for patients with high risk for HUS.
Shiga Toxin-Producing Escherichia coli and the Hemolytic-Uremic Syndrome. N Engl J Med. 2023 Oct 12;389(15):1402-1414. doi: 10.1056/NEJMra2108739.