Elsevier

The Lancet

Volume 378, Issue 9796, 17–23 September 2011, Pages 1089-1093
The Lancet

Articles
Management of an acute outbreak of diarrhoea-associated haemolytic uraemic syndrome with early plasma exchange in adults from southern Denmark: an observational study

https://doi.org/10.1016/S0140-6736(11)61145-8Get rights and content

Summary

Background

Diarrhoea-associated haemolytic uraemic syndrome in adults is a life-threatening, but rare multisystem disorder that is characterised by acute haemolytic anaemia, thrombocytopenia, and renal insufficiency. We aimed to assess the success of management of this disorder with plasma exchange therapy.

Methods

Patients diagnosed with diarrhoea-associated haemolytic uraemic syndrome in southern Denmark were treated with daily plasma exchange by centrifugation and substitution with fresh frozen plasma. Stool culture and serological testing was done to identify the cause of disease, and the success of management with plasma exchange therapy was assessed from change in platelet count, glomerular filtration rate, and lactate dehydrogenase.

Findings

During May 25–28, 2011, five patients with a median age of 62 years (range 44–70) presented with diarrhoea-associated haemolytic uraemic syndrome, which was caused by an unusual Shiga-toxin-producing Escherichia coli serotype O104:H4. Strains of E coli showed a high resistance to third-generation cephalosporins because the strains had extended-spectrum β lactamases. After plasma exchange, median platelet count and glomerular filtration rate increased, median lactate dehydrogenase concentration decreased, and neurological status improved. The time interval from onset of bloody diarrhoea to start of plasma exchange had an inverse correlation with reduction of lactate dehydrogenase concentrations by plasma exchange (p=0·02). All patients were discharged with normal neurological status at 7 days (range 5–8) after starting plasma exchange.

Interpretation

Early plasma exchange might ameliorate the course of diarrhoea-associated haemolytic uraemic syndrome in adults. However, this finding should be verified in randomised controlled trials

Funding

None.

Introduction

Diarrhoea-associated haemolytic uraemic syndrome is a multisystem disorder that is characterised by acute haemolytic anaemia, thrombocytopenia, and renal insufficiency.1 The disorder is very rare in adults (0·5–2·1 cases per 100 000 people per year), but it is recorded more frequently in children (6·1 cases per 100 000 children younger than 5 years per year).2 Most cases of diarrhoea-associated haemolytic uraemic syndrome in childhood and occasional cases in adults are related to enteritis due to a Shiga toxin released by particular types of Escherichia coli (ie, O157:H7, O111, and O104:H4).3, 4 Shiga-toxin-mediated endothelial cell damage causes thrombotic occlusion of capillaries leading to acute renal failure and severe central nervous symptoms, including coma, seizures, or stroke.

Most adults with idiopathic thrombotic thrombocytopenic purpura have reduced activity of von Willebrand factor-cleaving protease (ADAMTS-13).5 In patients with idiopathic thrombotic thrombocytopenic purpura, early start of plasma exchange is recommended, especially in patients with neurological and renal impairment.5, 6 During outbreaks, diarrhoea-associated haemolytic uraemic syndrome is associated with high mortality.2 In a systematic review of 49 studies that were done during 1950–2001 and assessed 3476 patients (aged from 1 month to 18 years) from 18 countries,7 12% (95% CI 10–15) of patients with haemolytic uraemic syndrome died or developed end-stage renal disease. Studies with a higher proportion of patients with central nervous symptoms had a higher proportion of patients that died or developed permanent end-stage renal disease.7 Although mortality could be reduced by plasma exchange, the benefit of this management strategy remains controversial.1, 2, 8, 9, 10 Diarrhoea-associated haemolytic uraemic syndrome induced by Shiga-toxin-producing E coli is a rare disease, therefore it is unlikely that randomised controlled studies could be done to assess the benefit of different treatment options. However, we were able to assess the benefit of plasma exchange in a large outbreak, providing the opportunity to study at least several cases at the same time.

Section snippets

Patients and procedures

Adults presenting with diarrhoea-associated haemolytic uraemic syndrome who were admitted to the Department of Nephrology in Odense University Hospital, Odense, Denmark, were included in the study. We obtained clinical data, including the time interval between initial gastrointestinal symptoms and admission to the nephrology department, the time interval from onset of bloody diarrhoea to start of plasma exchange, and clinical outcomes. To assess the cause of disease, stool culture and

Results

During May 25–28, 2011, five adults (four women and one man) with a median age of 62 years (range 44–70) were admitted to the nephrology department. All patients presented with enteritis, bloody diarrhoea, acute haemolytic anaemia, thrombocytopenia, acute kidney injury, and progressive central nervous dysfunction. The patients were not related to each other. However, about 6–8 days before development of acute enteritic symptoms all patients had separately visited several places in northern

Discussion

We report the successful management of an outbreak of diarrhoea-associated haemolytic uraemic syndrome in five adults from southern Denmark by use of plasma exchange. The strains of E coli had an unusual Shiga-toxin-producing E coli serotype O104:H4 and a high resistance to third-generation cephalosporins because the strains had extended-spectrum β lactamases.

By July 27, 2011, 782 probable and confirmed cases of haemolytic uraemic syndrome associated with bloody diarrhoea (including 29 deaths)

References (17)

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