BACKGROUND: In May 2011, an outbreak of Shiga toxin-producing enterohaemorrhagic E coli O104:H4 in northern Germany led to a high proportion of patients developing post-enteritis haemolytic uraemic syndrome and thrombotic microangiopathy that were unresponsive to therapeutic plasma exchange or complement-blocking antibody (eculizumab). Some patients needed ventilatory support due to severe neurological complications, which arose 1 week after onset of enteritis, suggesting an antibody-mediated mechanism. Therefore, we aimed to assess immunoadsorption as rescue therapy. METHODS: In our prospective non-controlled trial, we enrolled patients with severe neurological symptoms and confirmed recent E coli O104:H4 infection without other acute bacterial infection or raised procalcitonin concentrations. We did IgG immunoadsorption processing of 12 L plasma volumes on 2 consecutive days, followed by IgG replacement (0·5 g/kg intravenous IgG). We calculated a composite neurological symptom score (lowest score was best) every day and assessed changes before and after immunoadsorption. FINDINGS: We enrolled 12 patients who initially presented with enteritis and subsequent renal failure; 10 (83%) of 12 patients needed renal replacement therapy by a median of 8·0 days (range 5-12). Neurological complications (delirium, stimulus sensitive myoclonus, aphasia, and epileptic seizures in 50% of patients) occurred at a median of 8·0 days (range 5-15) and mandated mechanical ventilation in nine patients. Composite neurological symptom scores increased in the 3 days before immunoadsorption to 3·0 (SD 1·1, p=0·038), and improved to 1·0 (1·2, p=0·0006) 3 days after immunoadsorption. In non-intubated patients, improvement was apparent during immunoadsorption (eg, disappearance of aphasia). Five patients who were intubated were weaned within 48 h, two within 4 days, and two patients needed continued ventilation for respiratory problems. All 12 patients survived and ten had complete neurological and renal function recovery. INTERPRETATION: Antibodies are probably involved in the pathogenesis of severe neurological symptoms in patients with E coli O104:H4-induced haemolytic uraemic syndrome. Immunoadsorption can safely be used to rapidly ameliorate these severe neurological complications. FUNDING: Greifswald University and Hannover Medical School.
BACKGROUND: In May 2011, an outbreak of Shiga toxin-producing enterohaemorrhagic E coli O104:H4 in northern Germany led to a high proportion of patients developing post-enteritis haemolytic uraemic syndrome and thrombotic microangiopathy that were unresponsive to therapeutic plasma exchange or complement-blocking antibody (eculizumab). Some patients needed ventilatory support due to severe neurological complications, which arose 1 week after onset of enteritis, suggesting an antibody-mediated mechanism. Therefore, we aimed to assess immunoadsorption as rescue therapy. METHODS: In our prospective non-controlled trial, we enrolled patients with severe neurological symptoms and confirmed recent E coli O104:H4infection without other acute bacterial infection or raised procalcitonin concentrations. We did IgG immunoadsorption processing of 12 L plasma volumes on 2 consecutive days, followed by IgG replacement (0·5 g/kg intravenous IgG). We calculated a composite neurological symptom score (lowest score was best) every day and assessed changes before and after immunoadsorption. FINDINGS: We enrolled 12 patients who initially presented with enteritis and subsequent renal failure; 10 (83%) of 12 patients needed renal replacement therapy by a median of 8·0 days (range 5-12). Neurological complications (delirium, stimulus sensitive myoclonus, aphasia, and epilepticseizures in 50% of patients) occurred at a median of 8·0 days (range 5-15) and mandated mechanical ventilation in nine patients. Composite neurological symptom scores increased in the 3 days before immunoadsorption to 3·0 (SD 1·1, p=0·038), and improved to 1·0 (1·2, p=0·0006) 3 days after immunoadsorption. In non-intubated patients, improvement was apparent during immunoadsorption (eg, disappearance of aphasia). Five patients who were intubated were weaned within 48 h, two within 4 days, and two patients needed continued ventilation for respiratory problems. All 12 patients survived and ten had complete neurological and renal function recovery. INTERPRETATION: Antibodies are probably involved in the pathogenesis of severe neurological symptoms in patients with E coli O104:H4-induced haemolytic uraemic syndrome. Immunoadsorption can safely be used to rapidly ameliorate these severe neurological complications. FUNDING: Greifswald University and Hannover Medical School.
Authors: Dakshina M Jandhyala; Vijay Vanguri; Erik J Boll; Yushuan Lai; Beth A McCormick; John M Leong Journal: Infect Dis Clin North Am Date: 2013-07-24 Impact factor: 5.982