MRCEM Notes

Haemolytic uraemic syndrome (HUS)

Pathology
On this page
Haemolytic uraemic syndrome (HUS) is a severe thrombotic microangiopathy characterised by the classic triad of:
  • Acute kidney injury
  • Microangiopathic haemolytic anaemia (Coombs' test negative)
  • Thrombocytopenia.
HUS is the most common cause of acute kidney injury in children and represents a medical emergency requiring prompt recognition and management.

Classification
HUS is broadly classified into two main types:

Typical (STEC) HUSAtypical HUS (aHUS)
  • STEC-HUS: Shiga toxin-producing Escherichia coli HUS
  • Most commonly caused by E. coli O157:H7 producing Shiga toxin (verotoxin)
  • Alternative names: Shiga toxin-producing E. coli (STEC) or verotoxin-producing E. coli (VTEC)
  • Two types of Shiga toxins: Stx1 and Stx2 (Stx2, particularly subtype stx2a, more likely to cause HUS)
  • Usually preceded by bloody diarrhoea
  • About 10% of cases
  • Not caused by Shiga toxin-producing bacteria
  • Causes include:
    • - Genetic mutations in complement pathway
    - Medications (ciclosporin, tacrolimus, some chemotherapy agents)
    - Systemic conditions (lupus, cancer, pregnancy)
    - Other infections (Streptococcus pneumoniae, HIV, Coxsackievirus)

    Epidemiology

    • Incidence: 6.1 cases per 100,000 children aged under 5 years (overall incidence 1-2 per 100,000)
    • Peak age: Children less than 5 years (most susceptible age group)
    • Gender: No significant gender predominance in children
    • Seasonality: More common in warmer summer months (June-September)
    • Geographic variation: Scotland has one of the highest incidences of VTEC outbreaks worldwide
    • Progression: One-fifth of STEC cases progress to HUS; highest odds in girls aged 1-4 years

    Pathophysiology
    • Trigger (e.g. Shiga toxin) causes endothelial damage and triggers thrombin and fibrin deposition in microvasculature
    • Erythrocytes are damaged passing through partially occluded vessels, causing haemolysis
    • Platelets are sequestered without triggering coagulation cascade (unlike DIC)
    • Incubation period: 2-4 days for STEC; HUS develops within 7-14 days of exposure

    Pathophysiology in simple terms:
    endothelial injury → platelet activation → microvascular thrombosis → MAHA + thrombocytopenia.

    Kidneys are particularly affected with AKI, haematuria and proteinuria typical

    Risk Factors:

    • Rural populations > urban populations
    • Young age (6 months to 5 years)
    • Contact with farm animals
    • Consumption of contaminated food/water
    • Known community outbreaks
    • Immunocompromised status

    Clinical Presentation

    Phase/SystemClinical features
    Prodromal Phase (STEC-HUS)Profuse diarrhoea becoming bloody after 1-3 days (80-90% develop blood in stool)
    Fever (50% have history, most afebrile on admission)
    Severe abdominal pain (more marked than other bacterial enteritis)
    Vomiting
    Painful defecation
    HaematologicalPallor and jaundice (haemolytic anaemia)
    Petechiae, purpura, bruising (thrombocytopenia)
    Bleeding tendency
    RenalOliguria
    Fluid retention and oedema
    Hypertension
    NeurologicalAltered consciousness
    Seizures
    Headache
    Irritability
    CardiovascularHypertension
    Signs of fluid overload
    Tachycardia
    GastrointestinalBloody diarrhoea
    Abdominal tenderness
    Signs of colitis
    GeneralDehydration or fluid overload
    Fatigue and weakness
    Reduced urine output

    Investigations

    TestExpected findings
    Full blood count and film - Anaemia with schistocytes (fragmented red cells)
    - Thrombocytopenia
    - Elevated white cell count (early indicator)
    Renal function
    • Elevated urea and creatinine
    Haemolysis markers - Elevated LDH (early indicator)
    - Elevated indirect bilirubin
    - Reduced/absent haptoglobin
    - Elevated reticulocyte count
    Coagulation screen
    • Usually normal (differentiates from DIC)
    Urinalysis
    • Haematuria
    • Proteinuria
    Microbiological Investigations
    • Stool testing: culture on sorbitol-MacConkey agar & PCR for Shiga toxin
    • Blood cultures
    • Urine culture
    Additional tests for atypical HUS
    • Complement gene mutation analysis
    • ADAMTS13 activity levels
    • Autoimmune markers

    Management
    HUS is a medical emergency requiring immediate supportive care and specialist input.

    1. Fluid Management:
    • Hypovolaemia: 10 mL/kg isotonic solution bolus, evaluate response, repeat cautiously
    • Euvolaemia: Fluid restriction to insensible losses (300 mL/m²/24h) plus measured output
    • Fluid overload: Further restriction; consider furosemide (1-5 mg/kg IV, max 20 mg/dose)
    • Caution: High risk of pulmonary/cerebral oedema in oligo-anuric patients

    2. Renal Support:
    • Monitor for hyperkalaemia and treat promptly
    • Dialysis indications as for any acute kidney injury
    • Early nephrology consultation essential

    3. Hypertension Management:
    • Target: Systolic BP <95th centile for age
    • May require short-acting calcium channel blockers

    4. Haematological Management:
    • Red cell transfusion: If active bleeding or compromised oxygen-carrying capacity
    • Platelet transfusion: Only if active bleeding or high-risk intervention
    • Avoid unnecessary transfusions: May worsen HUS course

    5. Medication Considerations:
    • Antibiotics:
    • Contraindications: NSAIDs, antimotility agents
    • Consider need for dose adjustment due to renal impairment

    Antibiotic use
    • Antibiotics are NOT routinely recommended in STEC-HUS as may increase toxin release.
    • Antibiotics arr used in suspected sepsis or non-STEC bacterial infections

    Specific Treatments:

    Atypical HUS:
    • Plasma exchange: Early intervention to remove mutant complement proteins
    • Eculizumab: Monoclonal antibody blocking complement activity
    • Factor H concentrate: For specific complement deficiencies
    • Liver/kidney transplantation: For severe cases

    Complications

    SystemComplications
    Renal
    • Acute kidney injury (most common)
    • Hypertension
    • Fluid overload/pulmonary oedema
    • Electrolyte imbalances (hyperkalaemia)
    Neurological
    • Altered consciousness
    • Seizures
    • Cerebral oedema
    • Stroke
    Cardiovascular
    • Hypertensive cardiomyopathy
    • Myocardial injury/myocarditis
    • Pericardial effusion
    Gastrointestinal
    • Severe colitis with bleeding risk
    • Intestinal perforation/necrosis
    • Pancreatitis
    • Intussusception

    Prognosis

    Typical (STEC) HUS:
    • Generally good prognosis with supportive care
    • Mortality: Very low (only one death reported in 2018 PHE data)
    • Long-term sequelae: 5-25% develop permanent renal complications (hypertension, proteinuria, reduced GFR)
    • Recovery: Most children recover completely with appropriate supportive care

    Atypical HUS:
    • Poorer prognosis than typical HUS
    • Mortality: Up to 25%
    • End-stage renal disease: 50% progression rate
    • Requires aggressive treatment with complement inhibition

    Factors Associated with Poor Outcomes:
    • Severe extrarenal disease (especially CNS involvement)
    • Extremes of age (infants and elderly)
    • Delayed recognition and treatment
    • Atypical HUS subtype

    Prevention and Public Health

    Primary Prevention:
    • Food safety: Proper cooking of meat, especially minced products
    • Hand hygiene: Before/after food handling, after toilet use, after animal contact
    • Avoid cross-contamination between raw and cooked foods
    • Water safety: Avoid contaminated water sources

    Infection Control:
    • Isolation: Contact precautions for hospitalized patients
    • School/nursery exclusion: Until two negative stool tests
    • Sibling separation: May be appropriate to prevent household transmission
    • Public health notification: Mandatory reporting of STEC/HUS cases
    Full-size image