Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab

Abstract

BackgroundAn outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin-secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all patients were treated with the monoclonal anti-C5 antibody, eculizumab.MethodsThe diagnosis of HUS was made based on haemolytic anaemia, low platelet count and acute kidney injury. Data were obtained from initial gastrointestinal symptoms to the end of follow-up 10 weeks after the start of eculizumab.ResultsAmong 24 cases of STEC gastroenteritis, HUS developed in nine patients (eight adults and one child), 6 (median; range 3–12) days after digestive symptoms begun. The median (range) highest or lowest biological values were platelet count 26 (range 14–93) G/L; haemoglobin 6.6 (range 5–10.7) g/dL; LDH 1520 (range 510–2568) IU/L; creatinine 152 (range 48–797) µmol/L. All patients had extra-renal complications (liver 9, pancreas 5, brain 3 and heart 3). Two patients were dialysed, and one was ventilated. After failure of plasma exchange to increase platelets in the first three patients, eculizumab was administered in all nine patients, 0–4 days after HUS diagnosis (median 1 day). One patient with very severe neurological HUS received immunoadsorption. Outcome was favourable in all patients, with rapid normalization of haemoglobin, platelets, LDH levels, renal function and neurological improvement. There were no deaths and no serious adverse events related to eculizumab.ConclusionsEarly treatment of O104:H4 STEC-HUS by eculizumab was associated with a rapid and efficient recovery. Controlled prospective evaluation of eculizumab in STEC-HUS is warranted.

Shiga Toxin Associated Hemolytic Uremic Syndrome

“…43,49 Therefore, administering eculizumab earlier may be more effective at modifying the disease pathogenesis and have a greater influence on patient outcome, possibly explaining the positive results from Delmas and colleagues. 71 A randomized controlled trial is needed to address this issue.…”

“…In contrast, a French group used eculizumab earlier within 0 to 4 days of HUS caused by E coli O104 HUS. 71 The group studied 9 patients. Six had not received prior plasma therapy.…”

Compromiso cerebrovascular agudo en síndrome hemolítico urémico: descripción de dos casos pediátricos

“…Los resultados de este tratamiento en niños con compromiso neurológico severo por SHU+D aún son inciertos, por lo que es necesario evaluar crí-ticamente los resultados de los estudios que se llevan a cabo en la actualidad antes de recomendar su uso [7][8][9][10]22 .…”

“…Todos deben detectarse y tratarse precozmente incluyendo diálisis en falla renal aguda. No obstante, la plasmaféresis y el uso de antagonistas de proteínas del complemento podrían ser alternativas frente al compromiso severo del SNC [7][8][9][10] .…”

The Glomerulus

“…Activation of complement leads to perturbation of otherwise thromboresistant renal endothelial cells with resultant local damage and an influx of inflammatory cells. Although the most common form of HUS-diarrheal HUS, caused by Shiga toxin-has not been clearly linked to complement dysregulation, several small series have demonstrated benefit from complement inhibition in patients during a recent large outbreak of diarrheal HUS in Germany (51,52). These data raise the intriguing possibility that complement dysregulation is responsible for renal injury in common forms of HUS as well.…”