What disease states can cause Hemolytic Uremic Syndrome (HUS)?

Disease States Associated with Hemolytic Uremic Syndrome (HUS)

Hemolytic uremic syndrome (HUS) primarily occurs in two major disease states: Shiga toxin-producing infections (typical HUS) and complement-mediated disorders (atypical HUS), with several other secondary causes also recognized.

Primary Classifications of HUS

1. Typical HUS (Shiga Toxin-Associated)

• Shiga toxin-producing Escherichia coli (STEC) infections

  • Most commonly E. coli O157:H7 1
  • Other important non-O157 STEC serogroups: O26, O45, O103, O111, O121, O145 1
  • Characterized by prodromal bloody diarrhea followed by HUS development 4-5 days after diarrhea onset 2
  • Accounts for approximately 90% of pediatric HUS cases 3

• Shigella dysenteriae type 1 infection (also produces Shiga toxin) 2

2. Atypical HUS (aHUS)

• Complement-mediated disorders
  • Genetic mutations in complement regulatory proteins (identified in ~60% of cases) 4
  • Deficiencies in:
    • Factor H
    • Membrane cofactor protein
    • Von Willebrand factor-cleaving protease (ADAMTS 13)
    • Intracellular vitamin B12 metabolism 3
  • Both autosomal recessive and dominant inheritance patterns 3

Secondary Causes of HUS

3. Infection-Associated (Non-STEC)

• Streptococcus pneumoniae infections 3
• HIV infections 3

4. Drug-Induced HUS

• Calcineurin inhibitors (post-transplantation) 3
• Other medications that can trigger HUS include certain chemotherapeutic agents and immunosuppressants

5. Autoimmune Disease-Associated HUS

• Systemic lupus erythematosus 3
• Catastrophic antiphospholipid syndrome 3

Clinical Presentation and Diagnosis

HUS is characterized by the classic triad of:

1. Microangiopathic hemolytic anemia
2. Thrombocytopenia
3. Acute renal injury 5

Diagnostic criteria include:

• Anemia with microangiopathic changes (schistocytes, burr cells, helmet cells)
• Renal injury with hematuria, proteinuria, or elevated creatinine
• Low platelet count (usually detected early but may normalize) 2

Key Distinctions Between Types

• Typical HUS (STEC-associated):

  • Usually follows bloody diarrhea
  • More common in children
  • Generally better prognosis with supportive care 4

• Atypical HUS:

  • Often no preceding diarrhea (D-HUS)
  • Relapsing course

  • 50% progress to end-stage renal disease

  • Higher mortality rate 4

Management Considerations

• Supportive care remains the mainstay of treatment for typical HUS 5
• Antibiotics are generally avoided in STEC infections as they may increase HUS risk 1
• For atypical HUS, therapy is directed toward the underlying cause 3
• Complement blockade therapy is being studied for atypical HUS, though evidence for STEC-HUS is lacking 5

Prevention

Prevention of typical HUS focuses on preventing primary STEC infection through:

• Proper cooking of ground meats
• Consuming only pasteurized dairy products and juices
• Proper hand hygiene
• Preventing cross-contamination during food preparation 1

Early recognition and prompt diagnosis are essential for optimal management of all forms of HUS to reduce morbidity and mortality.