Stec-Triggered Deap-Hus in a Toddler: Successful Management with Eculizumab and Mycophenolate Mofetil Without Corticosteroids

Technical Summary: Stec-Triggered DEAP-HUS in a Toddler

Problem Statement
Hemolytic uremic syndrome (HUS) is typically classified into two distinct categories: typical HUS, caused by Shiga toxin–producing Escherichia coli (STEC) infection, and atypical HUS (aHUS), resulting from genetic dysregulation of the alternative complement pathway. A rare autoimmune subtype of aHUS, known as DEAP-HUS (deficiency of CFHR proteins and autoantibody-positive HUS), is characterized by homozygous deletions of CFHR1 and/or CFHR3 genes and the presence of autoantibodies against complement factor H (anti-FH).

The clinical challenge addressed in this paper is the diagnostic and therapeutic dilemma presented when a patient presents with severe HUS symptoms alongside confirmed STEC infection. Conventional diagnostic algorithms often treat STEC positivity as sufficient to diagnose typical HUS, thereby excluding complement investigations and delaying the identification of underlying autoimmune predispositions. This paper investigates a case where a severe clinical course necessitated a re-evaluation of this paradigm, revealing a coexistence of STEC infection and DEAP-HUS.

Methodology
The study employs a detailed retrospective case report of a 30-month-old child admitted to the pediatric intensive care unit in April 2025. The methodology involves:

1. Clinical Assessment: Evaluation of acute kidney injury (AKI), hemolytic anemia, thrombocytopenia, and neurological manifestations (seizures, MRI findings).
2. Diagnostic Workup:
   • Confirmation of STEC infection via stool PCR (Stx1 and Stx2 positive).
   • Exclusion of thrombotic thrombocytopenic purpura (normal ADAMTS13 activity).
   • Comprehensive complement profiling at a national reference laboratory, including CH50, C3, C4, Factor H, Factor I, and anti-FH antibody titers.
   • Genetic testing for CFHR1 and CFHR3 deletions.
3. Therapeutic Intervention:
   • Initiation of eculizumab (a terminal complement inhibitor) due to multiorgan dysfunction and neurological involvement.
   • Deliberate omission of high-dose corticosteroids, attributed to the active STEC infection.
   • Introduction of mycophenolate mofetil (MMF) at month 5.
   • Discontinuation of eculizumab at month 9, transitioning to MMF monotherapy.
4. Follow-up: Monitoring of clinical status, renal function (Schwartz eGFR), and anti-FH antibody titers for 12 months.

Key Results

• Reclassification: Despite confirmed STEC positivity, the patient was reclassified as having DEAP-HUS based on markedly elevated anti-FH antibody titers (686 UA) and a homozygous CFHR1–CFHR3 deletion.
• Clinical Course: The patient required 29 days of continuous kidney replacement therapy and experienced neurological complications (encephalopathy) and extrarenal involvement (hepatic cytolysis, troponin elevation).
• Treatment Efficacy:
  • Eculizumab successfully managed the acute phase without the use of high-dose corticosteroids.
  • MMF was introduced at month 5.
  • Eculizumab was successfully discontinued at month 9.
  • At the 12-month follow-up, the patient remained in clinical and biological remission with no relapse.
  • Renal function showed partial recovery (eGFR improved from 11 to 80 mL/min/1.73 m²).
• Antibody Dynamics: Anti-FH antibody titers remained stable and markedly elevated throughout the follow-up period under MMF monotherapy, despite the absence of clinical relapse.

Key Contributions

1. Diagnostic Paradigm Shift: The paper demonstrates that STEC positivity does not exclude complement-mediated disease. It argues that severe presentations of STEC-HUS warrant complement investigation to identify underlying autoimmune predispositions like DEAP-HUS.
2. Therapeutic Strategy without Corticosteroids: The case provides evidence that high-dose corticosteroids, historically part of DEAP-HUS induction therapy, may not be an absolute prerequisite for remission, particularly when contraindicated by active infection.
3. MMF Monotherapy for Maintenance: The study documents a successful transition from complement blockade (eculizumab) to MMF monotherapy. It suggests that MMF provides sufficient immunological stabilization to prevent relapse, even in the absence of a significant reduction in anti-FH antibody titers.
4. Extended Follow-up Data: Unlike previous reports with shorter follow-ups, this case provides a documented 12-month outcome under MMF monotherapy after eculizumab discontinuation in a STEC-triggered DEAP-HUS context.

Significance and Claims
The authors claim that this case highlights the limitations of relying solely on STEC positivity to rule out complement-mediated HUS. They posit that an infectious trigger can unmask a latent autoimmune predisposition (the "two-hit" model: genetic deletion + infection).

The paper asserts that:

• STEC-triggered DEAP-HUS is a distinct entity requiring specific management different from typical STEC-HUS.
• Eculizumab can be safely discontinued in DEAP-HUS patients under MMF monotherapy, even without high-dose corticosteroids.
• Clinical remission can be sustained without the normalization of anti-FH antibody titers, suggesting that complement blockade is the primary driver of short-term remission while MMF ensures long-term immunological stability.

The authors conclude that while their findings are promising, prospective multicenter registries are necessary to better characterize the natural history and optimal immunosuppressive strategies for this rare association. They remain modest regarding the long-term risk of relapse and the potential for MMF to eventually reduce antibody titers, noting that longer-term follow-up is required.