Reye Syndrome

What is Reye Syndrome?

Reye syndrome is a rare and potentially deadly disease that affects children. It involves acute (sudden onset) neurological problems, like confusion (termed noninflammatory encephalopathy) and a damaged liver that stores too much fat (fatty liver failure). This syndrome was first documented by R.D.K. Reye, an Australian pathologist, in 1963.

In the early 1970s, the United States began monitoring Reye syndrome, which led to serious warnings about using aspirin in children. Children with Reye syndrome typically start vomiting and becoming confused, which can quickly lead to a coma and possibly death.

The disease often shows up a few days after a child recovers from a viral illness where aspirin was given for treatment. Certain metabolic disorders (especially those involving fatty acid metabolism), reactions to medications, and exposure to toxins can also make a child more likely, or predispose them, to develop Reye syndrome.

Doctors diagnose Reye syndrome based on symptoms and lab tests, but there’s no specific test for this disease.

What Causes Reye Syndrome?

Reye syndrome is often triggered by viral infections such as the flu (influenza A and B) and chickenpox (varicella). Data from the Centers for Disease Control and Prevention (CDC) shows that between 1980 and 1997, about 73% of Reye syndrome cases were preceded by the flu, 21% by chickenpox, and 14% by infections causing stomach upset or diarrhea (gastroenteritis). Salicylate, a compound found in aspirin, was detectable in the blood of 82% of these cases.

Less commonly, Reye syndrome has been associated with other viruses like coxsackie, parainfluenza, Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus, and hepatitis. Bacteria like Chlamydia, Bordetella pertussis, Mycoplasma, and Shigella have also been linked to Reye syndrome.

Studies have linked the use of salicylate, or aspirin, to the development of Reye syndrome. While it’s true that less than 0.1% of children who took aspirin developed Reye syndrome, more than 80% of children diagnosed with Reye syndrome had taken aspirin in the three weeks prior to their diagnosis. This led to the recommendation in 1980 that children should not use aspirin. After this warning was widely publicized, the number of Reye syndrome cases reported decreased dramatically.

Risk Factors and Frequency for Reye Syndrome

Reye syndrome is a rare disease, with less than 2 cases reported each year since 1994. It’s important to note that the actual total may be higher because the obligation to report cases to the Centers for Disease Control and Prevention (CDC) has been removed. This illness primarily affects children between 5 and 14 years old, but babies under one year of age can also get it. The syndrome does not favor any particular gender, and most reports come from December to April each year.

The CDC started monitoring Reye syndrome in 1973.
Between 1979 and 1980, 555 cases were reported.
From December 1980 to November 1997, there were 1207 cases in the U.S.
In 1985 and 1986, an average of 100 cases were reported annually, but this fell to an average of 36 cases per year from 1987 to 1993.
Between 1991 and 1994, the incidents dropped dramatically to just 0.2 to 1.1 cases per million in the U.S.

Warnings about using aspirin in children were given in the U.S. in 1980, which resulted in a significant drop in Reye syndrome cases. The U.K. saw a similar fall in incidence after issuing their own warnings about aspirin use in 1986. In fact, their incident rates fell from 0.63 cases per 100,000 in 1983-1984 to 0.11 cases per 100,000 in 1990-1991. France reported comparable declines in cases.

Still, it’s important to note that aspirin is a key treatment for Kawasaki disease in children. For those in long-term salicylate therapy, it’s crucial to watch for signs and symptoms of Reye syndrome.

Signs and Symptoms of Reye Syndrome

Reye syndrome is a rare condition that usually develops within 12 hours to 3 weeks after recovering from a viral illness like the common cold or stomach flu. It’s important to catch this disease early, so doctors must keep a high level of suspicion based on the patient’s medical history, current signs and symptoms, and lab test results. Common early signs include throwing up a lot and feeling sleepy or confused a few days after a viral illness. The Centers for Disease Control and Prevention (CDC) have divided the progression of Reye syndrome into five stages.

Stage 1: Constant severe vomiting, feeling unusually sleepy or having nightmares, and confusion
Stage 2: Feeling unaware or restless, experiencing delusions, overactive reflexes, a positive Babinski sign (where your big toe bends up and back while the other toes fan out), an unresponsive reaction to pain, pupils in the eyes that are large and slow to respond, rapid breathing and heart rate
Stage 3: Becoming unresponsive or entering a state of coma, abnormal stiffness in the body
Stage 4: Eyes that are slow to react or don’t react at all to light, loss of control over eye movements with temperature changes, deeper coma, more severe body stiffness
Stage 5: Seizures, loss of muscle tone, lack of response in the pupils of the eyes, inability to breathe, death

Due to the severity of these symptoms, it’s crucial to catch and treat Reye syndrome early, and not to give aspirin to children without a doctor’s advice.

Testing for Reye Syndrome

The Centers for Disease Control and Prevention (CDC) has outlined criteria needed to identify Reye’s syndrome, a rare but severe condition that causes swelling in the liver and brain. This disease is diagnosed based on two main criteria:

Proof of acute, non-inflammatory brain disease: This is established by noticing a change in the patient’s consciousness or, if possible, checking the patient’s cerebrospinal fluid (the fluid around the brain and spinal cord), which will contain 8 or fewer white blood cells per cubic millimeter. Additionally, any surgical or post-mortem brain tissue samples must show signs of general brain swelling without signs of inflammation around brain vessels or membranes.
Signs of liver disease: This is established by either conducting a liver biopsy or post-mortem exam that shows the characteristics of Reye’s syndrome, or by finding an increase of three times or more in certain liver enzymes (specifically, serum glutamic-oxaloacetic transaminase or serum glutamic-pyruvic transaminase) or ammonia in the blood.

Moreover, there should be no other reasonable explanations for any brain and liver abnormalities for a diagnosis of Reye syndrome.

Lab tests for Reye syndrome usually show increased liver function (as evidenced by high ALT, AST, bilirubin), higher levels of ammonia in the blood, irregularities in blood clotting tests, increased levels of amylase and lipase (enzymes related to digestion), decreased bicarbonate in the blood, and other indicators of dehydration. The most common lab finding is an increase in blood ammonia levels which usually happens within 1 to 2 days of the changes in mental status. If the doctor performs a lumbar puncture to acquire cerebrospinal fluid, there should be fewer than 8 white blood cells per cubic millimeter. Any increase in the pressure within the solids and fluids of the brain and spinal cord is typically seen in the later stages of the disease and may remain stable early on.

Treatment Options for Reye Syndrome

Reye syndrome is a serious disease that can quickly get worse. As such, it may require early medical interventions to keep the patient’s heart stable and to ensure proper lung function. Some of these interventions could include inserting a central venous access (a tube placed in a large vein to give medications and fluids), intubation (a tube in the windpipe to help with breathing), and putting in a Foley catheter to check urine flow. In some cases, the doctor might perform a liver biopsy (a procedure to remove a small piece of the liver for examination) or monitor the pressure inside the skull.

Treatments for Reye syndrome aim to relieve symptoms and are usually done in an intensive care unit where the doctors can closely track multiple health indicators. In severe cases, the doctor may need to correct certain abnormalities in the blood:

* Hypoglycemia, or low blood sugar, might be treated with fluids that contain dextrose, a type of sugar.
* Acidosis, or an excess amount of acid in body fluids, might be treated with sodium bicarbonate (baking soda), and by adjusting the patient’s breathing.
* Hyperammonemia, or too much ammonia in the blood, might be treated with specialized medications, but might also require a procedure called hemodialysis (cleaning the blood with a machine) if the ammonia level is extremely high.
* Coagulopathy, a condition where the blood doesn’t clot properly, might be treated using different types of blood products or Vitamin K, especially before invasive procedures or if there’s significant bleeding.

If the pressure inside the patient’s skull increases, the treatment could involve:

* Raising the head of the bed to 30 degrees.
* Controlling any fevers to prevent increased brain activity and shaking.
* Monitoring the pressure inside the skull.
* Giving Lasix, a diuretic to remove excess fluid in the body.
* Carefully managing fluid intake to avoid overhydration.
* Providing sedation (medications for relaxation) and pain relief.
* Administering mannitol or hypertonic saline – specialized treatments to reduce brain swelling.
* Treating any seizures and providing preventive treatment for future seizures.

When a person is showing symptoms, the doctor must consider all possible causes to determine an accurate diagnosis. These could include:

Drug toxicity
Low blood sugar (Hypoglycemia)
Brain inflammation (Encephalitis)
Inflammation of the protective membranes covering the brain and spinal cord (Meningitis)
Poisoning from lead or other heavy metals
Bleeding within the brain (Intracranial bleeding)
Poisonous mushrooms (Mushroom toxicity)

Possible Complications When Diagnosed with Reye Syndrome

These are some potential medical complications:

Seizures: sudden, uncontrolled disturbances in the brain’s electrical activity
Cerebral herniation: when parts of the brain get pushed out of their normal positions
Aspiration pneumonia: a lung infection that occurs after inhaling food, liquid, vomit, or mucus into the lungs
Cardiac arrhythmias: irregular heart rhythms
Cardiovascular collapse: a severe and sometimes fatal medical emergency, often from a sudden drop in blood flow throughout the body
Pancreatitis: inflammation of the pancreas, an organ in the abdomen
Gastrointestinal bleeding: bleeding in the digestive tract
Respiratory failure: when the lungs can’t adequately oxygenate your blood or remove carbon dioxide from your blood
Renal failure: when the kidneys can’t properly clean the body’s blood
Sepsis: a potentially life-threatening bodily response to an infection
Death: the cessation of all vital bodily functions

Frequently asked questions

The prognosis for Reye syndrome can be serious and potentially deadly. It can quickly lead to a coma and possibly death. However, with early diagnosis and appropriate treatment, the prognosis can be improved.

Reye syndrome is often triggered by viral infections such as the flu (influenza A and B) and chickenpox (varicella). It can also be associated with other viruses like coxsackie, parainfluenza, Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus, and hepatitis. Bacteria like Chlamydia, Bordetella pertussis, Mycoplasma, and Shigella have also been linked to Reye syndrome.

The signs and symptoms of Reye Syndrome include: - Constant severe vomiting - Feeling unusually sleepy or having nightmares - Confusion - Feeling unaware or restless - Experiencing delusions - Overactive reflexes - Positive Babinski sign (where your big toe bends up and back while the other toes fan out) - Unresponsive reaction to pain - Pupils in the eyes that are large and slow to respond - Rapid breathing and heart rate - Becoming unresponsive or entering a state of coma - Abnormal stiffness in the body - Eyes that are slow to react or don't react at all to light - Loss of control over eye movements with temperature changes - Deeper coma - More severe body stiffness - Seizures - Loss of muscle tone - Lack of response in the pupils of the eyes - Inability to breathe - Death It is important to note that these symptoms can progress through the five stages of Reye Syndrome, with each stage becoming more severe. Therefore, it is crucial to catch and treat Reye Syndrome early. Additionally, it is advised not to give aspirin to children without a doctor's advice, as it can increase the risk of developing Reye Syndrome.

The types of tests needed for Reye Syndrome include: - Checking the patient's cerebrospinal fluid for 8 or fewer white blood cells per cubic millimeter - Conducting a liver biopsy or post-mortem exam to show signs of Reye's syndrome - Finding an increase of three times or more in certain liver enzymes or ammonia in the blood - Lab tests to show increased liver function, higher levels of ammonia in the blood, irregularities in blood clotting tests, increased levels of amylase and lipase, decreased bicarbonate in the blood, and other indicators of dehydration - Lumbar puncture to acquire cerebrospinal fluid with fewer than 8 white blood cells per cubic millimeter - Monitoring the pressure inside the skull - In some cases, performing a liver biopsy to remove a small piece of the liver for examination

The other conditions that a doctor needs to rule out when diagnosing Reye Syndrome are: 1. Drug toxicity 2. Low blood sugar (Hypoglycemia) 3. Brain inflammation (Encephalitis) 4. Inflammation of the protective membranes covering the brain and spinal cord (Meningitis) 5. Poisoning from lead or other heavy metals 6. Bleeding within the brain (Intracranial bleeding) 7. Poisonous mushrooms (Mushroom toxicity)

When treating Reye Syndrome, there can be several side effects or potential complications. These include: - Seizures: sudden, uncontrolled disturbances in the brain's electrical activity. - Cerebral herniation: when parts of the brain get pushed out of their normal positions. - Aspiration pneumonia: a lung infection that occurs after inhaling food, liquid, vomit, or mucus into the lungs. - Cardiac arrhythmias: irregular heart rhythms. - Cardiovascular collapse: a severe and sometimes fatal medical emergency, often from a sudden drop in blood flow throughout the body. - Pancreatitis: inflammation of the pancreas, an organ in the abdomen. - Gastrointestinal bleeding: bleeding in the digestive tract. - Respiratory failure: when the lungs can't adequately oxygenate your blood or remove carbon dioxide from your blood. - Renal failure: when the kidneys can't properly clean the body's blood. - Sepsis: a potentially life-threatening bodily response to an infection. - Death: the cessation of all vital bodily functions.

A pediatrician or a specialist in pediatric neurology or hepatology.

Reye syndrome is a rare disease, with less than 2 cases reported each year since 1994.

Reye Syndrome is treated through a combination of interventions and medications. Medical interventions may include inserting a central venous access, intubation, putting in a Foley catheter, performing a liver biopsy, or monitoring the pressure inside the skull. Treatments aim to relieve symptoms and are usually done in an intensive care unit where doctors can closely monitor the patient's health. Specific treatments depend on the abnormalities present in the patient's blood, such as hypoglycemia, acidosis, hyperammonemia, or coagulopathy. Additionally, if the pressure inside the patient's skull increases, treatments may involve raising the head of the bed, controlling fevers, monitoring pressure, giving diuretics, managing fluid intake, providing sedation and pain relief, and administering specialized treatments to reduce brain swelling and treat seizures.

Reye Syndrome is a rare and potentially deadly disease that affects children. It involves acute neurological problems, like confusion, and a damaged liver that stores too much fat.