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Core concept2 exam ›

Triad: microangiopathic haemolytic anaemia + thrombocytopenia + acute kidney injury
STEC (typical) HUS - ~90% of childhood HUS
- E. coli O157:H7 (also O111, O26, O145) and Shigella dysenteriae type 1
- Source: undercooked mince, unpasteurised milk, contaminated produce, petting zoos, person-to-person
Shiga toxin (Stx1, Stx2) is an AB5 toxin
- B subunit binds globotriaosylceramide (Gb3 / CD77) - densely expressed on glomerular endothelium, podocytes, tubular epithelium, and on cerebral endothelium
  - Gb3 distribution explains the renal and neurological tropism, and why children are more susceptible - Gb3 expression falls with age
- Internalised, retrograde transport to the ER
- A subunit is an N-glycosidase - cleaves a single adenine from 28S rRNA of the 60S subunit
- -> irreversible arrest of protein synthesis -> ribotoxic stress -> apoptosis + endothelial activation
- -> inc von Willebrand factor release, loss of thrombomodulin, platelet-fibrin microthrombi -> mechanical RBC shearing (schistocytes) and platelet consumption
Stx2 is ~1,000x more potent for HUS than Stx1 - Stx2-producing strains predict severity
Complement is also activated on the injured endothelium, but the primary lesion is toxin-mediated, not complement-mediated

Course

Bloody diarrhoea prodrome, afebrile or low-grade -> HUS 5-13 days later, as diarrhoea is settling
- ~15% of children with STEC develop HUS
Coombs-NEGATIVE haemolysis: schistocytes, inc LDH, absent haptoglobin, inc unconjugated bilirubin, reticulocytosis
Thrombocytopenia without coagulopathy - normal PT/APTT and fibrinogen distinguishes it from DIC
AKI often oliguric; ~50% need dialysis acutely
Extra-renal: CNS in ~20-25% (seizures, encephalopathy, stroke - the main cause of acute death), pancreatitis with transient diabetes, colonic necrosis, cardiomyopathy

Diagnosis

Stool for STEC PCR (stx1/stx2) plus culture on sorbitol-MacConkey (O157 is sorbitol non-fermenting)
- Send early - the organism clears quickly and cultures are often negative by the time HUS appears
ADAMTS13 >10% excludes TTP - send before any plasma exchange

The other HUS forms

	Trigger	Discriminator
STEC-HUS	Shiga toxin	Bloody diarrhoea, child, stool PCR
Pneumococcal HUS	Neuraminidase cleaves sialic acid -> exposes Thomsen-Friedenreich (T) antigen	Severe invasive pneumococcal disease, ~30% with meningitis; direct Coombs POSITIVE (preformed anti-T IgM); avoid plasma-containing products - donor plasma contains anti-T
Atypical HUS	Alternative complement dysregulation	No diarrhoea, relapsing, family history, may have nephrotic-range proteinuria
Secondary TMA	Drugs, malignancy, transplant, pregnancy, malignant hypertension, autoimmune	Context

Treatment of STEC-HUS is supportive - careful fluid and electrolyte management, dialysis, transfusion, BP control
- Early IV volume expansion during the diarrhoeal prodrome, before HUS declares, reduces the need for dialysis
*Avoid antibiotics in suspected STEC colitis - antibiotics induce the SOS response and phage-encoded stx expression -> increased HUS risk*
*Avoid anti-motility agents and NSAIDs*
Plasma exchange and eculizumab are not routinely indicated in STEC-HUS; consider eculizumab only in severe neurological involvement (evidence weak)
Platelet transfusion only for bleeding or before a procedure - fuels microthrombi
Prognosis: acute mortality 3-5%; ~25-30% have long-term CKD, proteinuria or hypertension -> lifelong follow-up
Notifiable disease - public health follow-up for outbreak source
Recurrence after renal transplant is rare in STEC-HUS - the discriminator from aHUS, where it is common

4 of 4 sections written · drafted 2026-09-04