Hemolytic-uremic Syndrome
Disease Details
Family Health Simplified
- Description
- Hemolytic-uremic syndrome (HUS) is a condition characterized by the simultaneous occurrence of hemolytic anemia, acute kidney injury, and a low platelet count, often resulting from infection with Shiga toxin-producing bacteria like E. coli.
- Type
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Hemolytic-uremic syndrome (HUS) can be categorized into two main types: typical HUS and atypical HUS. Typical HUS, which is more common, usually follows an infection with Shiga toxin-producing Escherichia coli (STEC). Atypical HUS (aHUS) is less common and often linked to genetic mutations.
The genetic transmission of atypical HUS is primarily autosomal dominant, although there are cases with autosomal recessive inheritance. Genetic mutations in complement regulatory proteins are frequently involved in aHUS. - Signs And Symptoms
- After eating contaminated food, the first symptoms of infection can emerge anywhere from 1 to 10 days later, but usually after 3 to 4 days. These early symptoms can include diarrhea (which is often bloody), stomach cramps, mild fever, or vomiting that results in dehydration and reduced urine. HUS typically develops about 5–10 days after the first symptoms, but can take up to 3 weeks to manifest, and occurs at a time when the diarrhea is improving. Related symptoms and signs include lethargy, decreased urine output, blood in the urine, kidney failure, low platelets, (which are needed for blood clotting), and destruction of red blood cells (microangiopathic hemolytic anemia). High blood pressure, jaundice (a yellow tinge in skin and the whites of the eyes), seizures, and bleeding into the skin can also occur. In some cases, there are prominent neurologic changes.People with HUS commonly exhibit the symptoms of thrombotic microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, (an enzyme released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) anemia (low red blood cell count), schistocytes (damaged red blood cells), elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally), proteinuria (indicative of kidney injury), confusion, fatigue, swelling, nausea/vomiting, and diarrhea. Additionally, patients with aHUS typically present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, and coma. Failure of neurologic, cardiac, renal, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression.
- Prognosis
- Acute renal failure occurs in 55–70% of people with STEC-HUS, although up to 70–85% recover renal function. With aggressive treatment, more than 90% of patients survive the acute phase of HUS, and only about 9% may develop ESRD. Roughly one-third of persons with HUS have abnormal kidney function many years later, and a few require long-term dialysis. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed. STEC-HUS is associated with a 3% mortality rate among young children and a 20% mortality rate in middle age or older adults. 15-20% of children infected with STEC develop HUS, with the highest risk being in children younger than 5 years old.Patients with aHUS generally have poor outcomes, with up to 50% progressing to end-stage renal disease (ESRD) or irreversible brain damage; as many as 25% die during the acute phase.
- Onset
- Hemolytic-uremic syndrome (HUS) typically has an acute onset. It often follows a gastrointestinal infection, particularly one caused by Escherichia coli O157:H7 or other Shiga toxin-producing bacteria. The syndrome usually manifests a few days to a week after the initial infection. Symptoms may include diarrhea (which can be bloody), abdominal pain, vomiting, and later signs of hemolysis (destruction of red blood cells), kidney failure, and thrombocytopenia (low platelet count). Early medical intervention is crucial to managing this condition.
- Prevalence
- Hemolytic-uremic syndrome (HUS) has a prevalence that varies based on geographic location and specific population demographics. In developed countries, it is estimated to affect about 2 per 100,000 children annually, making it a relatively rare condition. The incidence is higher in areas with frequent outbreaks of E. coli O157:H7, which is a common cause of HUS.
- Epidemiology
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The country with the highest incidence of HUS is Argentina and it performs a key role in the research of this condition.
In the United States, the overall incidence of HUS is estimated at 2.1 cases per 100,000 persons/year, with a peak incidence between six months and four years of age.HUS and the E. coli infections that cause it have been the source of much negative publicity for the FDA, meat industries, and fast-food restaurants since the 1990s, especially in the contaminations linked to Jack in the Box restaurants. In 2006, an epidemic of harmful E. coli emerged in the United States due to contaminated spinach. In June 2009, Nestlé Toll House cookie dough was linked to an outbreak of E. coli O157:H7 in the United States, which sickened 70 people in 30 states.In May 2011 an epidemic of bloody diarrhea caused by E. coli O104:H4-contaminated fenugreek seeds hit Germany. Tracing the epidemic revealed more than 3,800 cases, with HUS developing in more than 800 of the cases, including 36 fatal cases. Nearly 90% of the HUS cases were in adults.
== References == - Intractability
- Hemolytic-uremic syndrome (HUS) can be challenging to manage but is not considered inherently intractable. The severity and outcomes depend on various factors, including the underlying cause and promptness of treatment. HUS typically requires hospitalization with supportive care, such as fluid replacement, blood transfusions, and sometimes dialysis. In many cases, particularly those related to infections like E. coli, patients can recover with appropriate medical intervention. However, some forms, particularly atypical HUS (aHUS) related to genetic factors, may be more difficult to manage and may require long-term treatment, including medications like eculizumab. Early diagnosis and treatment are crucial for improving the prognosis.
- Disease Severity
- Hemolytic-uremic syndrome (HUS) severity can vary significantly. It ranges from mild to life-threatening. The condition may lead to complications such as acute renal failure, neurological abnormalities, and in severe cases, death. Prompt and appropriate medical treatment is crucial to manage the condition and improve outcomes.
- Healthcare Professionals
- Disease Ontology ID - DOID:12554
- Pathophysiology
- Hemolytic-uremic syndrome (HUS) involves the destruction of red blood cells, leading to kidney failure. It is characterized by three main features: microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The pathophysiology typically includes endothelial cell damage, often initiated by infection with Shiga toxin-producing bacteria such as E. coli O157:H7. The toxin binds to endothelial cells, causing inflammation and clot formation in small blood vessels, particularly in the kidneys. This results in reduced blood flow, hemolysis, and kidney damage.
- Carrier Status
- Hemolytic uremic syndrome (HUS) is not typically associated with a carrier status. It is a condition that primarily occurs due to infections, often caused by certain strains of E. coli bacteria. There are also atypical forms of HUS that may have a genetic component; in these cases, mutations in certain genes related to the complement system can be inherited. However, in most cases, there is no carrier status like in classic hereditary diseases.
- Mechanism
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Hemolytic-uremic syndrome (HUS) is primarily caused by microvascular damage leading to the formation of blood clots in small blood vessels, particularly in the kidneys. This results in hemolytic anemia (destruction of red blood cells), thrombocytopenia (low platelet count), and renal failure.
**Molecular Mechanisms:**
1. **Shiga toxin-producing Escherichia coli (STEC-HUS):** The most common form of HUS is triggered by Shiga toxin-producing bacteria, primarily *Escherichia coli* O157:H7. The Shiga toxin binds to globotriaosylceramide (Gb3) receptors on endothelial cells, particularly in the kidney, leading to cellular damage, inflammation, and apoptosis.
2. **Complement-mediated HUS (atypical HUS or aHUS):** This form involves dysregulation of the complement system, part of the immune system. Mutations in genes encoding complement regulatory proteins (such as CFH, CFI, MCP, C3, and CFB) cause uncontrolled activation of the complement pathway, leading to endothelial injury, platelet activation, and thrombus formation.
In both forms, the endothelial cell damage and resulting microthrombi formation result in the characteristic triad of hemolytic anemia, thrombocytopenia, and acute kidney injury. - Treatment
- Treatment involves supportive care and may include dialysis, steroids, blood transfusions, and plasmapheresis. Early IV fluid hydration is associated with better outcomes including shorter hospital stays and reducing the risk of dialysis.Empiric antibiotics are not indicated in those who are immunocompetent, and may worsen the HUS. Antidiarrheals and narcotic medications to slow the gut are not recommended as they are associated with worsening symptoms, increased risk of HUS in those with STEC infection, and adverse neurologic reactions. Platelet transfusions should not be used as the may drive the process of microangiopathy leading to worsening TTP.While eculizumab is being used to treat atypical hemolytic uremic syndrome, no evidence as of 2018 supports its use in the main forms of HUS. Scientists are trying to understand how useful it would be to immunize humans or cattle.
- Compassionate Use Treatment
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Hemolytic-uremic syndrome (HUS) is a serious condition mostly triggered by infection with certain strains of Escherichia coli (E. coli) producing Shiga toxins. Here are some key points about compassionate use treatments and off-label or experimental treatments for HUS:
1. **Eculizumab (Soliris)**: This monoclonal antibody, originally approved for conditions like atypical HUS and paroxysmal nocturnal hemoglobinuria, has been used off-label for HUS, particularly in severe or refractory cases. Eculizumab works by inhibiting the complement pathway, thus preventing the destruction of red blood cells.
2. **Plasma Exchange or Infusion**: For certain types of HUS, such as atypical HUS not related to Shiga toxin, plasma exchange (plasmapheresis) or plasma infusion is considered a standard therapy. This treatment is aimed at removing and replacing abnormal proteins that can lead to clotting problems.
3. **Immune Modulating Therapies**: Experimental treatments may include immune-modulating therapies, though clinical evidence varies, and their use is typically reserved for refractory or severe cases where traditional treatments have failed.
Always consult medical professionals or specialists for advice tailored to individual clinical situations or for access to these treatments under compassionate use protocols. - Lifestyle Recommendations
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Hemolytic-uremic syndrome (HUS) is a serious condition that often requires medical treatment and hospitalization. While lifestyle changes alone cannot treat HUS, certain recommendations can support overall health and recovery:
1. **Hydration:** Maintain adequate fluid intake to support kidney function and prevent dehydration.
2. **Diet:** Follow any dietary recommendations provided by healthcare providers, which may involve reducing intake of foods high in potassium or phosphorus if kidney function is impaired.
3. **Hygiene:** Practice good hygiene, particularly handwashing, to prevent infections that could trigger HUS, especially if caused by certain strains of E. coli.
4. **Monitoring:** Regularly monitor blood pressure and kidney function as advised by healthcare professionals.
Always follow the specific instructions and treatment plans provided by healthcare specialists. - Medication
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Hemolytic-uremic syndrome (HUS) often requires supportive care rather than specific medications. Treatments may include:
1. **Fluid and electrolyte management:** To maintain fluid balance and correct electrolyte disturbances.
2. **Blood transfusions:** To address severe anemia.
3. **Dialysis:** For kidney failure management.
4. **Plasma exchange:** In certain cases, particularly with atypical HUS.
5. **Eculizumab:** For atypical HUS, as it inhibits the complement system.
Antibiotics are typically avoided, especially in cases related to Shiga toxin-producing E. coli, to prevent worsening the condition. Always consult a doctor for personalized medical advice. - Repurposable Drugs
- Currently, there are limited repurposable drugs specifically identified for Hemolytic Uremic Syndrome (HUS). Management often focuses on supportive care, such as maintaining fluid and electrolyte balance, managing hypertension, and dialysis if needed. Antibiotics and antidiarrheal medications are generally avoided in Shiga toxin-producing E. coli (STEC)-HUS, as they might increase toxin release. In some cases, eculizumab, a monoclonal antibody initially used for atypical HUS, has been considered as a treatment option.
- Metabolites
- In hemolytic-uremic syndrome (HUS), key metabolites to be aware of include elevated levels of blood urea nitrogen (BUN) and serum creatinine due to kidney dysfunction, as well as decreased levels of hemoglobin and platelets caused by hemolysis and thrombocytopenia.
- Nutraceuticals
- Nutraceuticals are not a standard treatment for hemolytic-uremic syndrome (HUS). Management typically includes supportive care such as fluid management, blood transfusions, and dialysis if needed. Nutritional support is important but should be guided by healthcare professionals.
- Peptides
- Hemolytic-uremic syndrome (HUS) does not have a direct treatment involving specific peptides. The standard treatment for HUS focuses on managing complications such as kidney failure and includes supportive care like hydration, blood transfusions, and dialysis if necessary. Use of monoclonal antibodies like eculizumab has been explored for certain atypical HUS but is not considered a peptide-based therapy.