HUS with mutations in CFH and STEC infection treated with eculizumab in a 4-year-old girl

Gálvez, Carla; Krall, Paola; Rojas, Alejandro; Oh, Jun; Cano, Francisco

doi:10.1007/s00467-022-05694-z

Cited by 6 publications

(4 citation statements)

References 54 publications

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“…Notably, though, complement activation was transient and self‐limited in STEC‐HUS, irrespective of the presence of variants 38 . Moreover, rare variants were not associated with worse outcomes in STEC‐HUS, 38 overturning previous theories 53,54,60 . Further studies are thus warranted to determine the extent to which complement variants in patients with secondary HUS contribute to the pathogenesis as disease modifiers, and whether their presence calls for targeted therapies, as suggested by a few reports 54 …”

Section: How To Identify Complement‐driven Disease Beyond Atypical Husmentioning

confidence: 93%

“…38 Moreover, rare variants were not associated with worse outcomes in STEC-HUS, 38 overturning previous theories. 53,54,60 Further studies are thus warranted to determine the extent to which complement variants in patients with secondary HUS contribute to the pathogenesis as disease modifiers, and whether their presence calls for targeted therapies, as suggested by a few reports. 54 3.2 | Blurred distinction between primary HUS and secondary HUS…”

Section: Ngs-related Challengesmentioning

confidence: 99%

“…50,51 Importantly, the presence of susceptibility to complementmediated attack might theoretically increase the odds of developing TMA upon environment-mediated endothelial damage and/or worsen its course, as suggested with S. pneumoniae-related HUS 52 and STEC-HUS. 53,54 In fact, features of complement activation were found in 20% of acute gemcitabine-induced TMA, frequently accompanied by complement deposits on renal biopsies. 55,56 Similarly, the level of sC5b-9 was increased in 66% to 100% of STEC-HUS patients at the time of diagnosis, yet rapidly normalized upon HUS resolution.…”

Section: Ngs-related Challengesmentioning

confidence: 99%

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Complement‐driven hemolytic uremic syndrome

Léon

LeStang²,

Sberro-Soussan³

et al. 2023

American J Hematol

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Overactivation of the complement alternative pathway drives the pathogenesis of primary atypical hemolytic uremic syndrome (aHUS). Genetically-determined or acquired dysregulation of the complement is frequently identified in patients with aHUS, pregnancy-related hemolytic uremic syndrome (HUS), and severe hypertensionassociated HUS. In contrast, it is still unclear whether self-limited complement activation, which frequently occurs in other forms of HUS, provides key mechanistic clues or results from endothelial damage. Development of novel biomarkers is underway to firmly establish complement-driven pathogenesis. C5 blockade therapy has revolutionized the management of aHUS patients, resulting in a halving of the subpopulation under chronic dialysis over the course of a few years. On the other hand, the efficacy of C5 blockade in secondary forms of HUS, as assessed by small and uncontrolled case series, is less compelling and should be investigated through properly designed prospective clinical trials. The increased risk of meningococcal infection, related to C5 inhibition, must be rigorously addressed with suitable prophylaxis. Treatment duration should be determined based on an individualized benefit/risk assessment.

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Section: How To Identify Complement‐driven Disease Beyond Atypical Husmentioning

confidence: 93%

Section: Ngs-related Challengesmentioning

confidence: 99%

Section: Ngs-related Challengesmentioning

confidence: 99%

See 1 more Smart Citation

Complement‐driven hemolytic uremic syndrome

Léon

LeStang²,

Sberro-Soussan³

et al. 2023

American J Hematol

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“…Eculizumab is an anti-C5 monoclonal antibody that blocks the activation of the terminal complement pathway and is currently the main treatment for aHUS caused by the genetic defects of the alternative complement pathway ( 2 ). Although some anecdotal studies report the efficacy of eculizumab in STEC-HUS and non-genetic aHUS ( 3 , 4 ), its use in these conditions and the timing of treatment discontinuation remain controversial ( 2 ). Here, we report the efficacy and successful rapid discontinuation of eculizumab in two young adult patients with severe aHUS due to rare infectious and autoimmune etiologies.…”

Section: Introductionmentioning

confidence: 99%

Case report: Short-term eculizumab use in atypical HUS associated with Lemierre's syndrome and post-infectious glomerulonephritis

2023

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Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by genetic abnormalities, infections, autoimmune diseases, drugs, and malignancies. Anti-C5 monoclonal antibody eculizumab is the mainstay of treatment of aHUS caused by the genetic defects of the alternative complement pathway. However, the utility of eculizumab in non-genetic forms of aHUS and the timing of treatment discontinuation remain controversial. Here, we report successful short-term eculizumab use in two young adult patients with aHUS due to rare infectious and autoimmune etiologies: Lemierre's syndrome and post-infectious glomerulonephritis, respectively. Eculizumab was rapidly discontinued in both patients with no aHUS recurrence during long-term follow-up. Considering its favorable safety profile with appropriate meningococcal prophylaxis, eculizumab can be considered as a treatment option for non-genetic aHUS.

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