What is the role of steroids in the management of hemolytic‑uremic syndrome (HUS)?

Steroids Are Generally Not Recommended for Hemolytic Uremic Syndrome

Steroids have no established role in the routine management of typical (Shiga toxin-associated) HUS and should be avoided, while in atypical HUS, complement blockade with eculizumab is the standard of care, though steroids may have a limited role in rare, select cases with documented steroid-responsive mutations.

Typical (Shiga Toxin-Associated) HUS

Standard Management

• Supportive care remains the cornerstone of treatment for typical HUS, including appropriate fluid and electrolyte management, antihypertensive therapy, and renal replacement therapy when indicated 1
• Approximately two-thirds of children with typical HUS require dialysis, while one-third have milder disease 1
• Steroids are not part of the standard treatment protocol for Shiga toxin-producing E. coli (STEC)-associated HUS 2

What to Avoid

• Antidiarrheal drugs should be avoided in typical HUS 1
• Antibiotic therapy should possibly be avoided, as it may increase toxin release 1
• There is no evidence supporting immunosuppression with steroids in typical HUS 2

Atypical HUS (Complement-Mediated)

First-Line Treatment

• Eculizumab (complement C5 blocker) is the established standard of care for atypical HUS, preventing generation of inflammatory peptide C5a and cytotoxic membrane-attack complex C5b-9 1, 3
• Plasma exchange or fresh frozen plasma infusion may be used when eculizumab is unavailable, as FFP contains factor H at physiological concentrations 1

Limited Role for Steroids

• Steroids are NOT standard therapy for atypical HUS and should only be considered in exceptional circumstances 3
• Isolated case reports describe steroid-responsive atypical HUS in patients with specific mutations (e.g., membrane cofactor protein mutations) who failed plasmapheresis 4
• One case series reported response to steroids and IVIG in a patient with complement pathway mutation, avoiding plasma exchange 5

When Steroids Might Be Considered (Rare Exceptions)

• Only after failure of standard therapies (eculizumab or plasma exchange) in documented atypical HUS 4
• When specific complement mutations are identified that may be steroid-responsive (e.g., MCP mutations) 4
• High-dose corticosteroids (e.g., methylprednisolone 1-2 mg/kg/day) would be the regimen if attempted 4
• This approach is anecdotal and not guideline-supported 5, 4

Critical Pitfalls to Avoid

Diagnostic Errors

• Do not assume all HUS is the same—distinguish typical (diarrhea-associated, Shiga toxin) from atypical (complement-mediated) HUS, as management differs fundamentally 1, 3
• Obtain ADAMTS13 activity levels to exclude thrombotic thrombocytopenic purpura (TTP), which requires plasma exchange 6
• Test for complement pathway mutations (factor H, factor I, MCP) when atypical HUS is suspected 1

Treatment Errors

• Do not delay eculizumab in confirmed atypical HUS while attempting steroids—complement blockade is life-saving and prevents progression to end-stage renal disease 3
• Do not use steroids empirically in typical HUS, as there is no evidence of benefit and potential for harm 1, 2
• Streptococcus pneumoniae-associated HUS has particularly severe outcomes and higher mortality; steroids are not indicated 1

Practical Algorithm

1. Confirm HUS diagnosis: microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury 1
2. Determine HUS type:
   • Diarrhea prodrome + Shiga toxin positive = Typical HUS → supportive care only, no steroids 1, 2
   • No diarrhea + negative Shiga toxin = Atypical HUS → initiate eculizumab immediately 3
3. If eculizumab unavailable: plasma exchange with FFP 1
4. Steroids only considered if: atypical HUS + failure of eculizumab/plasma exchange + documented complement mutation + case-by-case decision 5, 4