GU - Haemolytic Uraemic Syndrome

Question 1

Defintion

Answer 1

Triad:
- microangiopathic haemolytic anaemia,
- thrombocytopenia,
- acute kidney injury (AKI) .

Question 2

Secondary typical HUS

Answer 2

MC type of HUS + typically triggered by Shiga toxin-producing E.coli 0157:H7 (STEC) through exposure to undercooked meat.
The toxin causes endothelial damage leading to microvascular thrombosis. This process consumes platelets, resulting in thrombocytopenia . These thrombi shear red blood cells, which causes microangiopathic haemolytic anaemia and leads to end-organ damage, particularly renal failure .

Question 3

Primary ‘atypical’ HUS

Answer 3

Rare and associated with complement dysregulation

Question 4

Epidemiology

Answer 4

• Age < 5 years (but can occur any age even adults)
• Exposure to Escherichia coli (STEC) 0157:H7 : particularly due to ingestion of undercooked meat; responsible for 90% of cases in children
• Primary ‘atypical’ HUS : complement dysregulation associated with familial syndromes
• Secondary ‘typical’ HUS : E. coli 0157:H7, pneumococcal infection, HIV, and other rare causes such as SLE , drugs (e.g. cyclosporin) and cancer

Question 5

Signs

Answer 5

Dehydrated
- Cap refil > 2 seconds
- Tachycardic/hypotensive
- Mottled skin
Pyrexic
Pallor: due to anaemia

Question 6

Symptoms

Answer 6

Symptoms usually occur after 3-4 days of ingestion for contaminated food, whist HUS MC develops about 5-10 days after initial symptoms
Bloody diarrhoea
Fever
Abdominal pain
Vomiting
Reduced urine output

Question 7

Diagnosis

Answer 7

Haemolysis screen:
- FBC: anaemia, thrombocytopenia
- Blood film: schistocytes due to microangiopathic haemolysis; fragmented
- LDH: raised as haemolysis releases lactate dehydrogenase (LDH)
- Haptoglobin: decreased as haptoglobin binds free haemoglobin
- Liver function: haemoglobin is broken down to bilirubin

Urinalysis: microscopic haematuria and proteinuria

U&Es: raised creatinine and reduced eGFR (AKI), often with associated hyperkalaemia

Stool culture: E.coli 0157:H7

PCR Shiga toxin

Question 8

Treatment

Answer 8

Supportive:
- IV fluids: as with any gastroenteritis, repleting fluid losses is crucial
- Red cell transfusion: indicated if significant anaemia or reduced haematocrit
- Dialysis: indicated if there is refractory acidosis, hyperkalaemia , fluid overload or oliguria

Second line:
- Antibiotics: avoid in HUS due to E.coli 0157:H7 as they can exacerbate symptoms. Antibiotics may be used in non-E. coli causes, such as streptococcal-induced HUS.
- Plasma exchange: indications are complex but typically used for severe cases of HUS not associated with diarrhoea
- Eculizumab : a C5 inhibitor monoclonal antibody typically used in the treatment of adult atypical HUS, with greater efficacy than plasma exchange alone

Question 9

Complications

Answer 9

Neurological: encephalopathy, seizures and strokes (25%)
Renal: significant risk of renal failure which may require dialysis