Treatment of Hemolytic Uremic Syndrome Associated with Streptococcal Infection
Supportive care with careful fluid management and monitoring for complications is the mainstay of treatment for streptococcal-associated Hemolytic Uremic Syndrome (HUS), with avoidance of antimicrobial therapy in cases where Shiga toxin may be involved.
Diagnosis and Clinical Presentation
Hemolytic Uremic Syndrome (HUS) is characterized by the triad of:
- Microangiopathic hemolytic anemia
- Thrombocytopenia
- Acute kidney injury
While HUS is most commonly associated with Shiga toxin-producing E. coli (STEC), it can rarely be caused by streptococcal infections, particularly Streptococcus pneumoniae (pneumococcal HUS or pHUS) and very rarely Group A Streptococcus.
Diagnostic Workup
- Complete blood count (looking for anemia and thrombocytopenia)
- Peripheral blood smear (to detect schistocytes/fragmented RBCs)
- Renal function tests (BUN, creatinine)
- Urinalysis (proteinuria, hematuria)
- Microbiological cultures (blood, throat, other relevant sites)
- Consider testing for Shiga toxin if diarrhea is present
Treatment Approach
1. Supportive Care (Primary Management)
- Intravenous fluid resuscitation with isotonic fluids (such as lactated Ringer's) to correct dehydration and maintain renal perfusion 1
- Close monitoring of fluid status, electrolytes, and renal function
- Renal replacement therapy (hemodialysis) if indicated for severe acute kidney injury
2. Blood Product Management
- Transfusion with washed red blood cells for significant anemia 2
- Important: Use washed RBCs for pneumococcal HUS to avoid exacerbating the condition
- Platelet transfusions generally avoided unless severe bleeding or invasive procedures are needed
3. Antimicrobial Considerations
- Avoid antibiotics in suspected STEC-associated HUS as they may increase the risk of HUS development 1
- For confirmed streptococcal infections (particularly pneumococcal):
- Appropriate antibiotic therapy should be administered based on susceptibility
- For Group A Streptococcus, penicillin remains the drug of choice
4. Additional Therapies
- Plasma exchange with 5% albumin replacement may be beneficial in pneumococcal HUS 2
- Glucocorticoids have been used successfully in some cases 3
- Blood pressure management for hypertension
5. Monitoring and Follow-up
- Frequent monitoring of hemoglobin, platelet count, electrolytes, BUN, and creatinine 1
- Examination of peripheral blood smear for red blood cell fragmentation
- Long-term follow-up for potential chronic kidney disease
Special Considerations
Pneumococcal HUS (pHUS)
- Accounts for approximately 5% of all HUS cases 2
- May be underdiagnosed and appears to be increasing in incidence
- Often associated with pneumonia, meningitis, or other invasive pneumococcal disease
- Particularly severe in patients with underlying conditions such as nephrotic syndrome 4
Group A Streptococcal HUS
- Extremely rare association 5
- May present with hemorrhagic colitis
- Requires supportive management similar to other forms of HUS
Prevention
- Implement appropriate infection control measures including proper hand hygiene 1
- Consider pneumococcal vaccination in high-risk patients
Pitfalls and Caveats
- Misdiagnosis is common due to the rarity of streptococcal-associated HUS
- Avoid plasma products containing antibodies that may react with exposed T-antigen on RBCs in pneumococcal HUS
- The clinical picture may overlap with thrombotic thrombocytopenic purpura (TTP) or disseminated intravascular coagulation (DIC)
- Early recognition is critical to improve outcomes
While eculizumab (complement inhibitor) has been used in atypical HUS, there is limited evidence for its use in streptococcal-associated HUS, and supportive management remains the mainstay of treatment 3.