Reye syndrome - Wikipedia, the free encyclopedia

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Reye syndrome
From Wikipedia, the free encyclopedia

Reye syndrome or Reye's syndrome is a rapidly

progressive encephalopathy which usually begins shortly
after recovery from an acute viral illness, especially
influenza and varicella (chickenpox). It is a potentially
fatal syndrome that has numerous detrimental effects on
many organs, especially the brain and liver, as well as
causing hyperammonemia (elevated blood ammonia level)
and low blood sugar.[1] The classic features are a rash,
vomiting, and liver damage. The exact cause is unknown
and, while it has been associated with aspirin consumption
by children with viral illness, it also occurs in the absence
of aspirin use. The disease causes fatty liver with minimal
inflammation and cerebral edema (swelling of the brain).
The liver may become slightly enlarged and firm, and
there is a change in the appearance of the kidneys.
Jaundice is not usually present.[2]
Children of ages 4 to 12 are most commonly afflicted.[3]
Early diagnosis is vital; although most children recover
with supportive therapy, it may lead to severe brain injury
and death. Cases in adults are extremely rare and are
more responsive to treatment. The first description of this
syndrome was probably made by Najib Khan in
Jamshedpur in 1956 (Jamshedpur fever).[4]

Contents
1 Signs and symptoms
2 Causes
2.1 Aspirin
3 Prognosis
4 Differential diagnosis
5 Epidemiology
6 History
7 References
8 External links

Reye syndrome

Histopathology of autopsy liver from child who died

of Reye syndrome. Hepatocytes are pale-staining due
to intracellular fat droplets.
Classification and external resources
Specialty

neurology

ICD-10

G93.7 (http://apps.who.int
/classifications/icd10/browse
/2015/en#/G93.7)

ICD-9-CM

331.81 (http://www.icd9data.com
/getICD9Code.ashx?icd9=331.81)

DiseasesDB 11463
(http://www.diseasesdatabase.com
/ddb11463.htm)
MedlinePlus 001565 (http://www.nlm.nih.gov
/medlineplus/ency/article/001565.htm)
eMedicine

emerg/399
(http://www.emedicine.com/emerg
/topic399.htm)

Patient UK Reye syndrome (http://patient.info

/doctor/reyes-syndrome)
MeSH

D012202 (https://www.nlm.nih.gov
/cgi/mesh/2015/MB_cgi?field=uid&
term=D012202)

Signs and symptoms

Reye syndrome progresses through five stages:[5][6][7]
Stage I
Rash on palms of hands and feet
Persistent, heavy vomiting that is not relieved by not eating
Generalized lethargy
Confusion

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Nightmares
No fever usually present[8]
Headaches
Stage II
Stupor
Hyperventilation
Fatty liver (found by biopsy)
Hyperactive reflexes
Stage III
Continuation of Stage I and II symptoms
Possible coma
Possible cerebral edema
Rarely, respiratory arrest
Stage IV
Deepening coma
Dilated pupils with minimal response to light
Minimal but still present liver dysfunction
Stage V
Very rapid onset following stage IV
Deep coma
Seizures
Multiple organ failure[9]
Flaccidity
Hyperammonemia (above 300 mg/dL of blood)
Death

Causes
The precise mechanism by which Reye syndrome occurs is unknown. This serious condition is described as a
"syndrome" rather than a disease as the clinical features that physicians use to diagnose it are quite broad.

Aspirin
There is an association between taking aspirin for viral illnesses and the development of Reye syndrome.[10]
But no animal model of Reye syndrome has been developed in which aspirin causes the condition.[11]
The serious symptoms of Reye syndrome appear to result from damage to cellular mitochondria,[12] at least
in the liver, and there are a number of ways that aspirin could cause or exacerbate mitochondrial damage. A
potential increased risk of developing Reye syndrome is one of the main reasons that aspirin has not been
recommended for use in children and teenagers, the age group for which the risk of lasting serious effects is
highest. No research has found a definitive cause of Reye syndrome, and association with aspirin has only
been shown through epidemiological studies. The diagnosis of "Reye Syndrome" greatly decreased in the
1980s, when genetic testing for inborn errors of metabolism was becoming available in developed
countries.[11] A retrospective study of 49 survivors of cases diagnosed as "Reye's Syndrome" showed that the
majority of the surviving patients had various metabolic disorders, particularly a fatty-acid oxidation disorder
medium-chain acyl-CoA dehydrogenase deficiency.[13]
In some countries, oral mouthcare product Bonjela (not the form specifically designed for teething) has
labeling cautioning against its use in children, given its salicylate content. There have been no cases of Reye
syndrome following its use, and the measure is a precaution.[14] Other medications containing salicylates are
often similarly labeled as a precaution.
The Centers for Disease Control and Prevention (CDC), the U.S. Surgeon General, the American Academy

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of Pediatrics (AAP) and the Food and Drug Administration (FDA) recommend that aspirin and combination
products containing aspirin not be given to children under 19 years of age during episodes of fever-causing
illnesses. Hence, in the United States, it is advised that the opinion of a doctor or pharmacist should be
obtained before anyone under 19 years of age is given any medication containing aspirin (also known on
some medicine labels as acetylsalicylate, salicylate, acetylsalicylic acid, ASA, or salicylic acid).
Current advice in the United Kingdom by the Committee on Safety of Medicines is that aspirin should not be
given to those under the age of 16 years, unless specifically indicated in Kawasaki disease or in the
prevention of blood clot formation.[15]

Prognosis
Documented cases of Reye syndrome in adults are rare. The recovery of adults with the syndrome is
generally complete, with liver and brain function returning to normal within two weeks of onset. In children,
however, mild to severe permanent brain damage is possible, especially in infants. Over thirty percent of the
cases reported in the United States from 1981 through 1997 resulted in fatality.

Differential diagnosis
Causes for similar symptoms include
Various inborn metabolic disorders
Viral encephalitis
Drug overdose or poisoning
Head trauma
Liver failure due to other causes
Meningitis
Kidney failure
Shaken baby syndrome

Epidemiology
Reye syndrome occurs almost exclusively in children. While a few adult cases have been reported over the
years, these cases do not typically show permanent neural or liver damage. Unlike in the UK, the
surveillance for Reye syndrome in the US is focused on patients under 18 years of age.
In 1980, after the CDC began cautioning physicians and parents about the association between Reye
syndrome and the use of salicylates in children with chickenpox or viruslike illnesses, the incidence of Reye
syndrome in the United States began to decline. However, the decline began prior to the FDA's issue of
warning labels on aspirin in 1986.[11] In the United States between 1980 and 1997, the number of reported
cases of Reye syndrome decreased from 555 cases in 1980 to about 2 cases per year since 1994. During this
time period 93% of reported cases for which racial data were available occurred in whites and the median
age was six years. In 93% of cases a viral illness had occurred in the preceding three-week period. For the
period 1991-1994, the annual rate of hospitalizations due to Reye syndrome in the US was estimated to be
between 0.2 and 1.1 per million population less than 18 years of age.
During the 1980s, a case-control study carried out in the United Kingdom also demonstrated an association
between Reye syndrome and aspirin exposure.[16] In June 1986, the United Kingdom Committee on Safety
of Medicines issued warnings against the use of aspirin in children under 12 years of age and warning labels
on aspirin-containing medications were introduced. UK surveillance for Reye syndrome documented a
decline in the incidence of the illness after 1986. The reported incidence rate of Reye syndrome decreased
from a high of 0.63 per 100,000 population less than 12 years of age in 1983/84 to 0.11 in 1990/91.

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From November 1995 to November 1996 in France, a national survey of pediatric departments for children
under 15 years of age with unexplained encephalopathy and a threefold (or greater) increase in serum
aminotransferase and/or ammonia led to the identification of nine definite cases of Reye syndrome (0.79
cases per million children). Eight of the nine children with Reye syndrome were found to have been exposed
to aspirin. In part because of this survey result, the French Medicines Agency reinforced the international
attention to the relationship between aspirin and Reye syndrome by issuing its own public and professional
warnings about this relationship.[17]

History
The syndrome is named after Dr. Douglas Reye, who, along with fellow physicians Drs. Graeme Morgan and
Jim Baral, published the first study of the syndrome in 1963 in The Lancet.[18] In retrospect, the occurrence
of the syndrome may have first been reported in 1929. Also in 1964, Dr. George Johnson and colleagues
published an investigation of an outbreak of influenza B that described 16 children who developed
neurological problems, four of whom had a profile remarkably similar to Reye syndrome. Some investigators
refer to this disorder as Reye-Johnson syndrome, although it is more commonly called Reye syndrome. In
1979, Dr. Karen Starko and colleagues conducted a case-control study in Phoenix, Arizona and found the
first statistically significant link between aspirin use and Reye syndrome.[19] Studies in Ohio and Michigan
soon confirmed her findings [20] pointing to the use of aspirin during an upper respiratory tract or chickenpox
infection as a possible trigger of the syndrome. Beginning in 1980, the CDC cautioned physicians and
parents about the association between Reye syndrome and the use of salicylates in children and teenagers
with chickenpox or virus-like illnesses. In 1982 the U.S. Surgeon General issued an advisory, and in 1986 the
Food and Drug Administration required a Reye syndrome-related warning label for all aspirin-containing
medications.[21]

References
1. "Reye syndrome (http://web.archive.org
/web/20090616022448/http:
//www.mercksource.com/pp/us
/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs
/us/common/dorlands/dorland/seven
/000092711.htm)" at Dorland's Medical
Dictionary
2. Suchy, FJ, el al.; Sokol, RJ; Balistreri, WF (2007).
Liver Disease in Children. Cambridge: Cambridge
University Press. ISBN 0-521-85657-4.
3. Neil K. Kaneshiro. Reviewed by David Zieve and
Isla Ogilvie (2014-08-30). "Reye syndrome".
MedlinePlus.
4. Ghai Essential pediatrics, 7th edition, page
number:543
5. Knight, J. (2009). "Reye's Syndrome". Healthy
Child Care 12 (4).
6. Boldt, D.W. (February 2003). "Reye Syndrome".
University of Hawaii John A. Burns School of
Medicine.
7. "What is Reye's Syndrome?". National Reye's
Syndrome Foundation.
8. "Reye's Syndrome". KidsHealth.org. Nemour
Foundation. Retrieved 2015-02-06.

9. Ku AS, Chan LT (April 1999). "The first case of

H5N1 avian influenza infection in a human with
complications of adult respiratory distress
syndrome and Reye's syndrome". Journal of
Paediatrics and Child Health 35 (2): 2079.
doi:10.1046/j.1440-1754.1999.t01-1-00329.x.
PMID 10365363.
10. Hurwitz, E. S. (1989). "Reye's syndrome".
Epidemiologic reviews 11: 249253.
PMID 2680560.
11. Orlowski JP, Hanhan UA, Fiallos MR (2002). "Is
aspirin a cause of Reye's syndrome? A case
against". Drug Safety 25 (4): 22531.
doi:10.2165/00002018-200225040-00001.
PMID 11994026.
12. Gosalakkal JA, Kamoji V (September 2008).
"Reye syndrome and reye-like syndrome".
Pediatric Neurology 39 (3): 198200.
doi:10.1016/j.pediatrneurol.2008.06.003.
PMID 18725066.
13. Orlowski JP (August 1999). "Whatever happened
to Reye's syndrome? Did it ever really exist?".
Critical Care Medicine 27 (8): 15827.
doi:10.1097/00003246-199908000-00032.
PMID 10470768.

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14. "New advice on oral salicylate gels in under 16s"

(Press release). Medicines and Healthcare products
Regulatory Agency. 2009-04-23. Retrieved
2009-05-01.
15. "2.9 Antiplatelet drugs". British National
Formulary for Children. British Medical
Association and Royal Pharmaceutical Society of
Great Britain. 2007. p. 151.
16. Hall SM, Plaster PA, Glasgow JF, Hancock P
(1988). "Preadmission antipyretics in Reye's
syndrome". Arch. Dis. Child. 63 (7): 85766.
doi:10.1136/adc.63.7.857. PMC 1779086.
PMID 3415311.
17. Autret-Leca E, Jonville-Bra AP, Llau ME, et al.
(2001). "Incidence of Reye's syndrome in France: a
hospital-based survey". Journal of Clinical
Epidemiology 54 (8): 85762.
doi:10.1016/S0895-4356(00)00366-8.
PMID 11470397.

https://en.wikipedia.org/wiki/Reye_syndrome

18. Reye RD, Morgan G, Baral J (1963).

"Encephalopathy and fatty degeneration of the
viscera. A Disease entity in childhood". Lancet 2
(7311): 74952.
doi:10.1016/S0140-6736(63)90554-3.
PMID 14055046.
19. Starko KM, Ray CG, Dominguez LB, Stromberg
WL, Woodall DF (Dec 1980). "Reye's syndrome
and salicylate use". Pediatrics 66 (6): 859864.
PMID 7454476.
20. Mortimor, Edward A., Jr.; et al. (1 June 1980).
"Reye Syndrome-Ohio, Michigan". Morbidity and
Mortality Weekly Report 69 (29:532): 8102.
PMID 7079050.
21. Associated Press (March 8, 1986). "Aspirin Labels
to Warn About Reye Syndrome". The New York
Times.

External links
reyes_syndrome (http://www.ninds.nih.gov/disorders/reyes_syndrome) at NINDS
FDA Bulletin on Reye-Johnson Syndrome (http://www.fda.gov/bbs/topics/CONSUMER
/CON00034.html)
National Reye's Syndrome Foundation (http://www.reyessyndrome.org/)
Reye Syndrome website at Brigham and Women's Hospital
(http://healthlibrary.brighamandwomens.org/RelatedItems/2,201)
Retrieved from "https://en.wikipedia.org/w/index.php?title=Reye_syndrome&oldid=683796328"
Categories: Pediatrics Toxicology Hepatology Syndromes Ailments of unknown etiology
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