E. coli is the name of a common family of bacteria, most members of which do not cause human disease. E. coli O157:H7 is a specific member of this family that can cause bloody diarrhea (hemorrhagic colitis) in man. In the eighteen years since E. coli O157:H7 was first identified as a cause of diarrhea, this bacterium has established a reputation as a significant public health hazard.
After a susceptible individual ingests a sufficient quantity of E. coli O157:H7, the bacteria attach to the inside surface of the large intestine and initiate an inflammatory reaction. This reaction is believed to be due to chemicals secreted by the bacteria, and results in the bloody diarrhea and abdominal cramps characteristic of the intestinal illness. The incubation period is usually about 3 to 8 days, but slightly more or less is common. A wide spectrum of disease is possible from mild diarrhea without blood, to life-threatening and severe bloody diarrhea with excruciating abdominal pain. In most infected individuals the intestinal illness lasts about a week and resolves without any long-term sequelae. Antibiotics do not improve the illness and some believe these medications might even increase the risk of complications. Apart from good supportive care, which should include close attention to hydration and nutrition, there is no specific therapy. About 5 to 10% of individuals go on to develop hemolytic uremic syndrome (HUS), a severe life-threatening complication of the intestinal illness.
HUS was first described in 1955 and is recognized as the most common cause of kidney failure in childhood. E. coli O157:H7 is responsible for over 90% of the cases of HUS that develop in North America. When HUS follows a diarrhea illness the correct terminology is diarrhea-associated HUS (D+HUS) to distinguish the disease from a less common variety of HUS that occurs as a familial, recurrent, or isolated form associated with other clinical situations.
D+HUS is believed to develop when the E. coli O157:H7 enters into the circulation through the inflamed bowel wall and releases a specific chemical known as shiga-like toxin (SLT). SLT, and most likely other chemical mediators, attach to receptors on the inside surface of blood vessel cells (endothelial cells) and initiate an inflammatory reaction that damages the organs supplied by these tiny arteries. Some organs seem more susceptible, perhaps due to the presence of increased numbers of receptors (kidney, pancreas, and brain). Red blood cells and platelets are also damaged, either directly by the SLT or secondarily due to the clotting process in damaged blood vessels. By definition, when fully expressed, D+ HUS presents with the triad of hemolytic anemia (red blood cells break down), thrombocytopenia (low platelet count), and acute renal failure (loss of the filter function of the kidney).
There is no known therapy to halt the progression of D+HUS. The active stage of the disease usually lasts one to two weeks during which a variety of complications are possible. D+HUS is a frightening illness that even in the best American centers has a mortality rate of about 5%. By comparison, the mortality rate in the developing world is over 75%. About 50% of patients require dialysis due to kidney failure, 25% develop pancreatitis, 25% experience seizures, and 5% suffer from diabetes mellitus. The majority requires transfusion of blood products and develops complications common to the critically ill. The illness is a living nightmare for the patients and families, and leaves a painful memory that lingers long after the acute illness.
Among survivors, about 5% will eventually develop end stage kidney disease with the resultant need for dialysis or transplantation, and another 5 to 10% will develop neurological or pancreatic problems which significantly impair quality of life. Since the longest available follow-up studies of D+HUS are about 20 years, an accurate lifetime prognosis is not available, and as such, lifetime medical follow-up is indicated for even the mildest affected.
1.Tonshoff B., Sammet A., Sanden I., Mehls O., Waldherr R., Scharer K., Outcome and prognostic determinants in the hemolytic uremic syndrome of children.
“The rate of recovery correlated with the degree of oligoanuria…. The proportion of patients who recovered was lower in the presence of severe hypertension during the acute phase…. The degree of CNS involvement was a strong predictor of [bad] outcome.”
2.De Jong M., Monnens L. Haemolytic-uremic syndrome: A 10 year follow-up study of 73 patients.
“All six patients belonging to the third group (oliguria for more than 14 days or anuria for more than 7 days) had late sequelae: two started dialysis more than 10 years after the initial phase; three had decreased GFR and concentrating capacity.”
3.Gagnadoux MF., Habib R. Long-term prognosis of childhood HUS.
“after follow up of 15 to 20 years, about 25% of patients affected with typical HUS in their childhood present with some degree of renal impairment. 10% being in advanced renal failure.”
4.Kelles A., VanDyck M., Proesman W. Childhood HUS: long-term outcome and prognostic features.
“severe hypertension, anuria lasting more than 7 days and central nervous system involvment have all been said to be associated with poor outcome that means early death and end-stage renal failure.”
5.Tonshoff B., Sammet A., et al. Outcome and prognostic determinats in the HUS of Children.
“The degree of CNS involvement was a strong predictor of [bad] outcome…. The most important difference in the rate of recovery of our patients was the degree of oligoanuria.”
6.Siegler R., Pavia A., et al. At 20 year population based study of post-diarrheal HUS in Utah.
“severe disease was significantly associated with… prodromal anuria and white blood cell count greater than 20,000…. Seizures or other neurological findings during the acute illness were also strongly associated with bad outcome.”
7.Gianantonio CA., Vitacco M., et al. The hemolytic uremic syndrome.
“One peculiar feature of the HUS is the striking association of severe renal damage and erthrocyte destruction with notable neurologic abnormalities…. Anuria of more than 4 days duration is also a sign of poor prognosis.”
8.Rowe PC. Epidemiology of HUS in Canadian children from 1986 to 1988.
“all patients with oliguria exceeding 15 days or anuria persisting for more than 8 days were left with chronic disease…. None of our patients with oliguria that lasted more than approximately 2 weeks or anuria that persisted more than approximately 1 week escaped chronic disease.”
9.Sprizzirri, Francisco D, Rahman, Ricardo C., Bibiloni, Norma, Ruscasso, Javier D., Amoreo, Oscar R. Childhood hemolytic uremic syndrome in Argentina: long-term follow-up and prognostic features.
“the severity of acute renal failure – as determined by the days of anuria – and the presence of proteinuria one year after the acute phase, were the most useful prognostic indicators [of bad outcome].”
10.Caletti, Maria G., Gallo, Guillermo, and Gianantonio, Carlos. Development of focal segmental sclerosis and hyalinosis in hemolytic uremic syndrome.
“These observations also confirm that prolonged oligoanuria during the acute stage of HUS frequently results
in an unfavorable long-term prognosis…. The severe form was defined as anuria more than 7 days…. Proteinuria appeared after a proteinuria-free interval…
11.Schlieper, A., et al. Sequelae of haemolytic uraemic syndrome.
“HUS patients had numerically lower cognitive and achievement scores and higher behavioural problems ratings than their controls on every measure…. The results of this investigation provides preliminary indications of a post-HUS deficit in verbal intelligence and in the verbally based skills of reading comprehension and vocabulary use, as well as behaviour.”
12.Orme, S., Clark, E., Siegler, R.L., Neuropsychological sequele of post-diarrheal hemolytic uremic syndrome encephalopathy.
“HUS subjects consistently scored lower than controls on verbal intelligence, reading comprehension and vocabulary and behavior…. the data suggests that children who suffer from encephalopathy during HUS may have persistent cognitive problems…. The present data show a pattern of relative weakness in problem solving, visual-spatial reasoning, motor speed, memory, mathematical reasoning and spelling.”
13.Robson, Wm. Lane M. M.D., F.R.C.P., Leung, Alexander K.C. M.D., F.R.C.P. Kaplan, Bernard, S. M.B., B.Ch. Hemolytic-Uremic Syndrome.
“The following factors are reported to be associated with a poor prognosis in D+ HUS: Elevated WBC count, Prolonged anuria, Severe prodromal illness, Severe hemorrahagic colitis, Severe multisystem involvement…. The longer the duration of anuria, the less the recovery in GFR that can be expected.”
14.Thomson, Peter D. HUS in Johannesburg, South Africa: Epidemiology and Long-term Follow-up.
“We recommend that all severely affected cases of HUS should be followed for up to 20 years.”
15.Lopez, Eduardo L., Gianantonio, Carlos A., Cleary, Thomas G. The Hemolytic Uremic Syndrome in Argentina.
“A poor prognosis has been associated with oliguria of more than 3 weeks duration and/or anuria of more that 4 days duration.”