2. definition
Hemolytic uremic syndrome (HUS), a disease that destroys red blood cells,
is the most common cause of sudden, short-term acute kidney failure in
children.
It is a triad of:
Micro-angiopathic hemolytic anemia
Thrombocytopenia.
Acute kidney injury (acute renal failure)
3. epidemology
Hemolytic uremic syndrome (HUS) is a rare disorder with an annual
incidence of 6.1 cases per 100,000 children aged under 5 years (compared
with an overall incidence of 1 to 2 cases per 100,000).
Over 90% of cases in children are secondary to infection. Approximately
15% of cases of E. coli O157 infection will develop HUS. The development
of HUS may occur up to two weeks after the initial onset of symptoms, and
may develop after apparent recovery from the initial acute illness. Cases
may be sporadic or occur as part of larger outbreaks. The largest
documented outbreak in England occurred in Cumbria in 1999, and was
associated with pasteurized milk.
About 10% of HUS cases are atypical and are not caused by Shiga toxin-
producing bacteria or streptococci.
4. Types of hus
Classified into 2 main categories, depending on whether it is associated with Shiga-like
toxin or not.
1. TYPICAL HUS:
Typical HUS follows a diarrheal infection often caused by E. coli OH157:H7. Infection
related Shiga toxin producing E.coli/Shigella Pneumococcal infection HIV Typical
Other viral or bacterial infections. Only the diarrheal form of HUS is considered to be
typical HUS and is usually a disease of infants and children younger than 3 years of
age
2. ATYPICAL HUS
caused by exposure to certain medications (eg ciclosporin, tacrolimus), genetic
mutations in the complement pathway[4] and systemic conditions, including lupus,
cancer and pregnancy.
5. Pathogenesis
Specifically, E coli serotype O157:H7 has been associated with more than 80% of
infections leading to Hemolytic Uremic Syndrome.
The shiga-like toxin affects endothelial cells and initiates intravascular thrombo-
genesis. After entering the circulation via the gastrointestinal mucosa, the toxin
preferentially localizes to the kidneys, inhibiting protein synthesis and eventually
leading to cell necrosis or apoptosis.
Endothelial cell damage subsequently potentiates renal microvascular thrombosis by
promoting activation of the blood coagulation cascade.
Platelet aggregation results in a consumptive thrombocytopenia. Microangiopathic
hemolytic anemia results from mechanical damage to red blood cells circulating
through partially occluded microcirculation.
6. causes
Hemolytic-uremic syndrome (HUS) predominantly occurs in infants and children after
prodromal diarrhea. In summer epidemics, the disease may be related to infectious causes.
BACTERIAL INFECTIONS :
S dysenteriae
E coli
Salmonella typhi
Campylobacter jejuni
Yersinia pseudotuberculosis
Neisseria meningitidis
S pneumoniae
Legionella pneumophila
Mycoplasma species
9. Signs & symptoms
HUS develops about 5-10 days after onset of diarrhea
EARLY SYMPTOMS:
• Blood in the stools
Irritability
Fever
Lethargy
Vomiting and diarrhea
Weakness
10. LATER SYMPTOMS:
• Bruising
Decreased consciousness
Low urine output
No urine output
Pallor
Seizures -- rare
Skin rash that looks like fine red spots (petechiae)
Yellow skin (jaundice)
11. DIAGNOSIS
Findings of hemolysis and thrombocytopenia on a complete blood count are required to establish the
diagnosis.
Anemia: invariable finding and usually severe
Thrombocytopenia: Platelet survival time is shortened in HUS.
The peripheral blood smear reveals fragmented RBCs (e.g., schistocytes, spherocytes, segmented RBCs)
Reticulocytosis (proportional to hemolysis) and circulating free hemoglobin may be found
Increased serum thrombo-modulin levels may be found and are a marker for endothelial injury in HUS.
Leukocytosis: moderate leukocytosis in post diarrheal cases indicates renal failure due epithelial injury
disseminated intravascular coagulopathy (elevated fibrin split products, prolongation of the activated
partial thromboplastin time, and low anti-thrombin III levels)
12. Healthy red blood cells (left) are smooth and round. In hemolytic uremic
syndrome, toxins destroy red blood cells (right). These misshapen cells
may clog the tiny blood vessels in the kidneys.
14. A bloody diarrhea is followed in a few days by renal failure caused by
endothelial injury from the toxin, leading to the characteristic fibrin
thrombi in glomerular and interstitial capillaries.
15. Because of intravascular hemolysis, direct bilirubin values are elevated with elevated
serum lactate dehydrogenase (LDH) level
Renal function and electrolytes: a rise in urea and creatinine may be due to
dehydration
Azotemia
Elevated C-reactive protein level
Negative Coombs’ test
Stool culture positive for Shiga toxin–roducing Escherichia coli O157:H7
Hematuria on urinalysis
18. TREATMENT & MANAGEMENT
Hemolytic uremic syndrome requires treatment in the hospital. To ease immediate signs and
symptoms and prevent further problems, hemolytic uremic syndrome treatment may include:
FLUID REPLACEMENT: The key treatment for HUS is fluid replacement. This treatment replaces
electrolytes that the body needs to function. Fluid replacement also increases blood flow through
the kidneys. The extra fluids help offset the impaired blood flow that occurs due to the breakdown of
red blood cells.
KIDNEY DIALYSIS
PLASMA EXCHANGE
PLATELET TRANSFUSIONS
RED BLOOD CELL TRANSFUSIONS: Low RBCs result in chills, fatigue, short of breath, rapid heart rate,
yellow skin and dark urine. Transfusions (IV) can relieve these symptoms.
19. Antibiotics and antimotility agents are not recommended as treatments for hemolytic uremic
syndrome during the diarrheal stage of the disease. Some children who were diagnosed with
Shigella dysenteriae type 1 and treated with ampicillin developed hemolytic uremic
syndrome.
Use of monoclonal antibodies which block complement activity. Case reports of experimental
treatments with eculizumab is used to treat congenital atypical hemolytic uremic syndrome,
as well as severe shiga-toxin associated hemolytic uremic syndrome.
These have shown promising results. Eculizumab was approved by the U.S. Food and Drug
Administration on September 23, 2011 for the treatment of atypical hemolytic uremic
syndrome (aHUS) It was approved by the European Medicines Agency on November 29, 2011
for the treatment of aHUS.
Trials of gamma globulin are under way, with promising preliminary results. Findings suggest
the possibility of some benefit in children.
Azathioprine and vincristine are potent drugs with potential benefit in the management of
HUS.
20. PROGNOSIS
Typical hemolytic uremic syndrome (HUS) with a diarrheal prodrome usually
has a good prognosis. The two British Pediatric Surveillance Unit prospective
surveys in the UK and Ireland (1985-1988 and 1997-2001) of HUS in children
under 16 years reported a mortality rate of HUS in the first of these surveys to
be 5.6% and this had decreased to 1.8% in the second survey.
Death due to HUS is nearly always associated with severe extra-renal disease,
including severe central nervous system involvement.
Fatality is highest in infants, small children and the elderly.
Whilst renal recovery is the norm, there have been permanent and serious
renal sequelae (hypertension, proteinuria, diminishing glomerular filtration
rate) found in 5-25% of HUS patients.
Atypical HUS often has a poorer prognosis, with death rates reportedly as high
as 25%, and progression to end-stage renal disease in 50%.
21. prevention
The organism is very common in cattle and a low level of infection causes clinical disease. Prevention
is based on reducing fecal contamination during slaughtering and processing.
Good personal hygiene measures, e.g. hand-washing before and after food-handling and eating,
after toilet use and after contact with farm animals.
Increased public awareness about good food hygiene, eg cook meat and meat products well,
especially where minced or in burger form; avoid cross-contamination between raw and cooked
food.
Early diagnosis enables early supportive treatment and better ultimate prognosis. Similarly, early
identification of an outbreak enables public health measures to be put in place to prevent further
cases. Separating known cases from their younger siblings may also be an appropriate measure.
Conjugate vaccines against E. coli O157 are in development - phase 3 trials are awaited.
