What Is Reye’s Syndrome?

This article outlines a potentially deadly adverse effect from an ordinary, store-bought drug, aspirin. Many people are aware that aspirin use has its dangers, but to the majority of the population, the specific mechanisms of these dangers remain unknown. 

Reye’s syndrome is relatively unknown to the general public due to its rarity and specific causes. It almost exclusively affects children and young adults, causing serious damage to both the liver and brain. The disease is serious and children should be treated in a hospital, admitted to intensive care for the best chance of survival. Whilst treatments are available for Reye’s syndrome, the chances of survival are around 30%, with a third of survivors continuing life with brain damage. 

This article will outline the known causes, mechanisms and treatments for Reye’s syndrome, helping you to spot signs of the disease and learn the dangers of aspirin use.


In 1962, two Australian doctors, Douglas Reye and Graeme Morgan, unknowingly changed the way we view aspirin forever. Over 11 years, they studied 21 children, noting that they had a disease which caused their similar symptoms of nausea, disturbed consciousness and fever. They discovered that the children sustained serious liver and brain damage but could not find a cause.1 Over the years, this disease would come to be known as Reye’s syndrome.

Two years later, in 1964, an influenza outbreak in North Carolina led the doctor George Johnson to discover the same symptoms as Reye and Morgan in some of his child patients, but he could not find the cause either.2 It took until 1979 for a case study to finally link this disease to aspirin use in young children.3

Reye’s syndrome, also known as Reye-Johnson Syndrome, is a rare disease which causes serious brain and liver damage. It almost exclusively affects people under the age of 20 and is linked to the use of aspirin to treat viral infections.4

Symptoms of the syndrome begin 1-4 days after recovering from a viral infection and include vomiting, lethargy, seizures and fever.4 It is described as a type of encephalopathy, which is a general term for diseases that alter brain function. To avoid permanent brain or liver damage, it is vital that children with Reye’s syndrome are treated as quickly as possible in a hospital.

The exact mechanism (how a disease develops) and cause of this syndrome remains unknown; however, it is inexplicably linked to the use of aspirin to treat young children with viral infections. Around 90% of all historical cases of Reye’s syndrome are associated with this.5

Cases rose in the 1950s and rapidly decreased in the 1980’s, most likely due to the decreased use of aspirin to treat children. In 2023, Reye’s syndrome affects fewer than one in a million children each year, with the majority of cases being linked to aspirin use in Kawasaki’s disease.5

Causes of reye’s syndrome

The specific cause of Reye’s syndrome is unknown. This is due to the disease’s recent discovery and rarity, as well as ethical issues surrounding the investigation and biopsy of children. Furthermore, research on the disease has generally slowed since cases dropped by over 90% in the 1980s.

It is thought that the disease interferes with mitochondria (which generate energy inside cells), particularly within the liver. Liver failure and hepatotoxicity causes the buildup of toxic chemicals within the blood, leading to brain damage and swelling.5

Does aspirin use in young children cause reye’s syndrome?

Reye’s syndrome is the reason over-the-counter aspirin now comes with a warning against using it to treat children. With over 90% of cases linked to aspirin use, it is generally agreed that the drug and the disease are related.5

Multiple studies across the UK and USA provide evidence for a link between aspirin and Reye’s, with over 3000 cases being reviewed to support the claim.6 In the 1980s, aspirin use in children declined as a result of these studies and, following this, Reye’s syndrome itself began to disappear. In 1999, the New England Journal of Medicine hailed the identification and near-elimination of Reye’s syndrome as a ‘public health triumph’.7

There are some studies that oppose the correlation of Reye’s syndrome and aspirin use in children. The majority of these studies note that case numbers also declined in countries that halted aspirin use as well as countries that did not. They counter-propose that Reye’s syndrome was actually a viral mutation that spontaneously disappeared over time.8 Whilst medical professionals agree this is possible, it is not the popular opinion. 

Signs and symptoms of reye’s syndrome

Typically, symptoms will begin to appear between one and four days following a viral infection in a child. Examples of common viruses in children include the common cold or chickenpox. Reye’s syndrome is generally caused by using aspirin to treat the original virus.

The syndrome moves through five phases, each with their own distinct symptoms. In the early, stages, symptoms include:

Stage I

  • Repeatedly being sick
  • Tiredness
  • Unpredictable changes in mood
  • Confusion
  • Headaches

Stage II

  • Disorientation
  • Aggressive behaviour
  • Hyperventilation
  • Slow reflex responses

In the later stages, the symptoms become life threatening.

Stage III

  • Extremely lethargic
  • Increased mood swings and aggressive behaviour

Stage IV

  • Coma
  • Full delirium
  • Seizures
  • Breathing difficulty

Stage V

  • Frequent seizures
  • Struggling to breathe
  • Paralysis
  • Deep coma
  • Death

Regardless of the use of aspirin to treat the infection, if your child is experiencing increased tiredness, sickness and unusual mood swings, take them to see a doctor as soon as possible. If your child is experiencing a seizure or has lost consciousness, take them to a hospital immediately.

Management and treatment of reye's syndrome

Management of Reye’s syndrome is often swift and invasive to prevent further damage. Patients may be fitted with a catheter, a ventilator (to help with breathing) and IV access (to receive drugs rapidly).9

There is no specific cure for Reye’s syndrome. Much of the treatment is supportive, meaning that it aims to reduce symptoms rather than tackling the underlying conditions.9 Supportive treatments include, but are not limited to:

  • Electrolytes and fluids – to maintain stability in the blood
  • Diuretics and mannitol – to reduce pressure on the brain, lowering risk of damage10
  • Ventilation – to ensure lung function is maintained

The sooner the symptoms are treated and managed, the lower the risk of permanent organ damage following recovery.

Diagnosis of reye's syndrome

Reye’s syndrome is incredibly rare, therefore, any other diseases or conditions that may be causing the symptoms should be ruled out first.4 These include:

  • Meningitis
  • Encephalitis
  • Metabolic disorders

Liver functionality will be measured, and tests for brain swelling will be carried out. Reye’s syndrome is often only diagnosed as a last resort. Normally, at this point in the diagnosis, this conclusion is irrelevant as the syndrome has no cure and treatment focuses on the symptoms, which the child is most likely already receiving treatment for.9

Risk factors

The largest suspected risk factor for contracting Reye’s syndrome is the use of aspirin in children. Genetically inheriting mitochondrial diseases may also predispose someone to the syndrome.6


Modern supportive care means that majority of patients with Reye’s syndrome will survive with minimal long-term damage.4

Most of the complications associated with the disease are related to the potential brain damage that occurs if the swelling and inflammation are not brought under control. These complications are typically seen in children; the older the patient, the higher the likelihood of a full recovery.4,6

Possible complications include:

  • Loss of memory/attention span
  • Loss of vision
  • Issues with motor function
  • Learning difficulties 


How can I prevent reye's syndrome?

Reye’s syndrome cannot be directly prevented; however, it is important to avoid using aspirin to treat viral or bacterial infections in children.

How common is reye's syndrome?

Reye’s syndrome is incredibly uncommon, almost always occurring in conjunction with aspirin treatment. Fewer than one in every million children develop Reye’s syndrome each year.

When should I see a doctor?

If your child is experiencing increased tiredness, sickness and unusual mood swings, take them to see a doctor as soon as possible. If your child is experiencing a seizure or has lost consciousness, take them to a hospital immediately.


For the vast majority of the world, Reye’s syndrome is a disease of the past. Whilst the symptoms can be life threatening and the disease remains under-researched, an understanding of the risks associated with aspirin as well as strong modern supportive treatment allow Reye’s syndrome to be avoided and treated.


  1. Reye RDK, Morgan G, Baral J. Encephalopathy and fatty degeneration of the viscera a disease entity in childhood. The Lancet [Internet]. 1963 Oct [cited 2023 May 2];282(7311):749–52. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673663905543 
  2. Johnson GM, Scurletis TD, Carroll NB. A study of sixteen fatal cases of encephalitis- like disease in North Carolina children. N C Med J. 1963 Oct;24:464–73.
  3. Starko KM, Ray CG, Dominguez LB, Stromberg WL, Woodall DF. Reye’s syndrome and salicylate use. Pediatrics [Internet]. 1980 Dec 1 [cited 2023 May 2];66(6):859–64. Available from: https://publications.aap.org/pediatrics/article/66/6/859/79117/Reye-s-Syndrome-and-Salicylate-Use 
  4. Reye’s syndrome [Internet]. NHS. 2017 [cited 2023 May 2]. Available from: https://www.nhs.uk/conditions/reyes-syndrome/ 
  5. Pugliese A, Beltramo T, Torre D. Reye’s and Reye’s-like syndromes. Cell Biochem Funct [Internet]. 2008 Oct [cited 2023 May 2];26(7):741–6. Available from: https://onlinelibrary.wiley.com/doi/10.1002/cbf.1465 
  6. Glasgow JFT. Reye syndrome---insights on causation and prognosis. Archives of Disease in Childhood [Internet]. 2001 Nov 1 [cited 2023 May 2];85(5):351–3. Available from: https://adc.bmj.com/lookup/doi/10.1136/adc.85.5.351 
  7. Monto AS. The disappearance of Reye’s syndrome — a public health triumph. N Engl J Med [Internet]. 1999 May 6 [cited 2023 May 2];340(18):1423–4. Available from: http://www.nejm.org/doi/abs/10.1056/NEJM199905063401809 
  8. Orlowski JP, Hanhan UA, Fiallos MR. Is aspirin a cause of Reye’s syndrome?: a case against. Drug Safety [Internet]. 2002 [cited 2023 May 2];25(4):225–31. Available from: http://link.springer.com/10.2165/00002018-200225040-00001 
  9. Chapman J, Arnold JK. Reye syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 May 2]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK526101/ 10. Tenny S, Patel R, Thorell W. Mannitol. In:
  10. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 May 2]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470392/
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Alex Wan

Master of Science in Drug Discovery and Pharmaceutical Sciences, University of Nottingham

Alex is a graduate from Nottingham working in drug discovery for a startup pharmaceutical company in London. Following a bachelors degree in medicinal chemistry, Alex embarked on on a neuroscience project studying the effectiveness of various animal models for Alzheimer’s disease. Since then, he has developed his interests in small molecule drug discovery, and is currently involved in research isolating antibacterial compounds from natural sources.

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