A catch in the Reye

Twenty-six cases of Reye syndrome from The Children's Hospital, Camperdown, Australia, occurring between 1973 and 1982 were reviewed. Of these, 20 cases met the US Public Health Service Centers for Disease Control criteria for the diagnosis of Reye syndrome. Aspirin or salicylate ingestion had occurred in only one of the 20 cases (5%), and paracetamol (acetaminophen) had been administered in only six of the cases (30%). Pathologic confirmation of the diagnosis of Reye syndrome was accomplished in 90% of the cases. The incidence of Reye syndrome in New South Wales, Australia, is estimated from this study to be approximately nine cases per 1 million children compared with recent US data of ten to 20 cases per 1 million children and three to seven cases per 1 million children in Great Britain. The mortality for these Reye syndrome cases in Australia was 45% as compared with a 32% case-fatality rate in the United States. In Australia, the pediatric usage of aspirin has been extremely low for the past 25 years (less than 1% of total dosage units sold), with paracetamol (acetaminophen) dominating the pediatric analgesic and antipyretic market. Reye syndrome may be disappearing from Australia despite a total lack of association with salicylates or aspirin ingestion, since there were no cases found at The Children's Hospital in 1983, 1984, or 1985.     

Changing epidemiology of Reye syndrome in the United States

The average annual incidence of Reye syndrome reported through national surveillance was lower during 1981 to 1984 than during the previous five surveillance years. This is accounted for by a decrease in cases among children younger than 10 years of age; the number of cases in 10- to 19-year-old persons remained relatively stable during this period. The overall decline in incidence and the differing age-specific incidence trends are apparent for both varicella-associated cases and for nonvaricella-associated cases. During 1985, the incidence has been much lower than during any previous year since surveillance was initiated; this most recent decrease includes children 10 to 19 years of age. Independently conducted surveys suggest that the prevalence of salicylate use for viral illnesses has decreased among children in recent years, particularly among children younger than 10 years of age. The changing epidemiology of Reye syndrome may reflect, in part, the declining use of salicylates among children and teenagers in the United States.     

Reye syndrome associated with aspirin therapy for systemic lupus erythematosus

A 14-year-old girl in whom Reye syndrome developed during aspirin therapy for an inflammatory disorder proven to be systemic lupus erythematosus is reported. This case and similar cases of Reye syndrome in patients with juvenile rheumatoid arthritis suggest that an etiologic relationship exists between salicylate therapy and Reye syndrome in children with collagen vascular disorders.     

The changing clinical pattern of Reye's syndrome 1982-1990.

OBJECTIVE: To describe trends in the clinical pattern of Reye''s syndrome in the British Isles between 1982 and 1990; and to determine the relation between any changes and the June 1986 warnings against the use of aspirin in children. DESIGN: Development, and application to reported cases, of a scoring system designed such that patients showing the typical clinical and pathological features of ''classical'' Reye''s syndrome scored highly. The relations between ''Reye scores'' and a number of explanatory variables were explored using multivariable analysis. SETTING: British Isles. SUBJECTS: 445 cases fulfilling the Reye''s syndrome case definition reported to the surveillance scheme between January 1982 and December 1990. MAIN OUTCOME MEASURE: Individual ''Reye score''. RESULTS: Cases with high scores were more likely to have occurred in the 4 1/2 year period before June 1986 compared with the subsequent period (p < 0.006). Numbers of cases in the low and intermediate score categories declined by about 50% after June 1986, whereas those in the high category fell by 79%. High scorers were more likely to have received aspirin (p < 0.0001) and were older than intermediate and low scorers (p < 0.008). No relation was identified between score and season of onset. CONCLUSIONS: The decline in Reye''s syndrome after the aspirin warnings cannot be explained entirely, as has been proposed, by improved diagnosis of ''Reye-like'' inherited metabolic and other disorders: this would not account for the greater decline of the high scoring subgroup which also contained those cases most likely to resemble ''classical'' Reye''s syndrome and to have received aspirin. This study provides further evidence for the role of aspirin in a subset of cases meeting the standard diagnostic criteria for Reye''s syndrome and supports the need to consider this disorder as a heterogeneous group of conditions including Reye-like inherited metabolic disorders.     

Reye syndrome: the Indian experience

All articles reporting cases of Reye syndrome in India were studied. The total number of reported cases is 71. Of these 54 are well-described and have been analysed with reference to their epidemiological, clinical and investigative features. The seasonal prevalence is early summer to the monsoon. Clinical and investigative features were similar to cases reported elsewhere. Mortality is high (87%). None of the patients had taken aspirin. The importance of Reye syndrome as a health problem and the need for wider surveillance of outbreaks of certain viral illnesses is dicussed.     

Severe Reye syndrome: report of 14 cases managed in a pediatric intensive care unit over 11 years]

Idiopathic Reye syndrome is a rare disease revealed by unexplained encephalopathy and microvesicular liver steatosis. Some clinical and epidemiological studies mainly performed in English speaking countries questioned the reality of Reye syndrome because numerous know inherited metabolic diseases, and some of them unrecognized, could mimick this disorder. We focused in our study on severe forms of Reye syndrome admitted to a pediatric intensive care unit. METHODS: Retrospective study over the last eleven years (1991-2001) included all the pediatric patients admitted to our tertiary referral center with the classical American Reye syndrome criteria (e.g. CDC). Extensive metabolic screening was performed in all cases, except for the ultimately dead patients. RESULT: Fourteen patients (mean age 52 months) were included. Fever always occurred before their admission and aspirin (n = 12) or acetaminophen (n = 7) was prescribed. Median Glasgow scale was 7 on admission. Mean amoniac plasma level was 320 mumol/L and alanine-aminotransferase peak plasma level 1475 +/- 1387 IU/L. Mechanical ventilation was started in ten children and six of them underwent continuous venovenous hemofiltration. Three patients ultimately died and 11 survived with a mean five years follow-up without relapses or neurological impairment. Any of them demonstrated inherited metabolic disease except for one infant with hereditary fructose intolerance. CONCLUSION: Unlike widespread opinion, severe Reye syndrome without identified metabolic disorders seems to not disappear in our country. Reye syndrome remains a potentially life threatening disease and raises for aggressive treatment of brain edema. If aspirin and Reye syndrome association are not formally documented in France, cautiousness must be kept in mind and all the aspirin adverse effects notifications should be addressed to the public drugs survey network.     

The changing clinical pattern of Reye's syndrome 1982-1990

OBJECTIVE: To describe trends in the clinical pattern of Reye's syndrome in the British Isles between 1982 and 1990; and to determine the relation between any changes and the June 1986 warnings against the use of aspirin in children. DESIGN: Development, and application to reported cases, of a scoring system designed such that patients showing the typical clinical and pathological features of 'classical' Reye's syndrome scored highly. The relations between 'Reye scores' and a number of explanatory variables were explored using multivariable analysis. SETTING: British Isles. SUBJECTS: 445 cases fulfilling the Reye's syndrome case definition reported to the surveillance scheme between January 1982 and December 1990. MAIN OUTCOME MEASURE: Individual 'Reye score'. RESULTS: Cases with high scores were more likely to have occurred in the 4 1/2 year period before June 1986 compared with the subsequent period (p < 0.006). Numbers of cases in the low and intermediate score categories declined by about 50% after June 1986, whereas those in the high category fell by 79%. High scorers were more likely to have received aspirin (p < 0.0001) and were older than intermediate and low scorers (p < 0.008). No relation was identified between score and season of onset. CONCLUSIONS: The decline in Reye's syndrome after the aspirin warnings cannot be explained entirely, as has been proposed, by improved diagnosis of 'Reye-like' inherited metabolic and other disorders: this would not account for the greater decline of the high scoring subgroup which also contained those cases most likely to resemble 'classical' Reye's syndrome and to have received aspirin. This study provides further evidence for the role of aspirin in a subset of cases meeting the standard diagnostic criteria for Reye's syndrome and supports the need to consider this disorder as a heterogeneous group of conditions including Reye-like inherited metabolic disorders.     

Antipyretic use among children during the 1983 influenza season

We conducted a telephone survey in Houston in March 1983 to assess the level of aspirin use among children during the influenza season. We completed interviews of 200 households with 346 children aged 12 years or younger. Fifty-two percent of the 346 children experienced at least one acute illness in the preceding three months. Fever was measured with a thermometer in 114 ill children, 103 of whom had at least one measured temperature of 37.7 degrees C or greater. Fourteen percent of these 103 children received aspirin only, 61% received acetaminophen only, and 20% received both. Among a subgroup of 44 children with temperatures of at least 39.4 degrees C, 11% received aspirin only, 59% received acetaminophen only, and 27% received both. Only 60% of the 200 parents interviewed had heard of Reye's syndrome. Forty-two percent knew of the association between Reye's syndrome and aspirin use. The survey suggests that acetaminophen has replaced aspirin as the major antipyretic used by children in Houston. If the decline in aspirin use in Houston is representative of the population in the United States, and if aspirin is causally related to Reye's syndrome, the incidence of Reye's syndrome may decline.     

Reye syndrome and juvenile rheumatoid arthritis in Michigan

Reye syndrome (RS) is believed to occur infrequently among children receiving long-term aspirin therapy. We reviewed all cases of RS reported to the Michigan Department of Public Health during 1982 and 1983. Three of the 36 patients were receiving aspirin for the treatment of juvenile rheumatoid arthritis. All three patients had clinical courses characteristic of RS and two had supportive histologic findings on liver biopsy. The incidence of RS among children with juvenile rheumatoid arthritis is significantly greater than the incidence of RS among children who do not have juvenile rheumatoid arthritis. These findings support previous studies that showed that the use of aspirin during the antecedent illness may be a risk factor for the development of RS. Physicians should be aware of the potential for the development of RS among children who are receiving long-term aspirin therapy for the treatment of systemic inflammatory illnesses.     

Trends in the incidence of Reye's syndrome and the use of aspirin.

In 1986 there was a public warning in the United Kingdom about a link between the consumption of aspirin and Reye''s syndrome. To find out if the use of aspirin and paracetamol in children had altered, and whether the incidence of Reye''s syndrome had changed since a previous study, parents were interviewed in Belfast and London, and the British Reye''s Syndrome Surveillance System data were reviewed. Children with febrile illnesses were 17 times more likely to have received aspirin before admission to hospital in 1985/6 compared with 1988/9. Only 21 Belfast parents (40%) and 13 London parents (27%) had heard of Reye''s syndrome and only 12 in Belfast (23%) and seven in London (15%) knew of its association with aspirin, suggesting a continuing need for public education. Cases of Reye''s syndrome declined both in numbers (from a peak of 79 in 1983/4 to 19 in 1988/9) and in median age. Of the 418 reported cases, the diagnosis was subsequently revised in 89, most often (in 31 of 89, 36%) to ''inborn errors of metabolism''.     

Reye syndrome or side-effects of anti-emetics?

By analysing two patients initially diagnosed as Reye syndrome evidence is given that in some patients considered as having Reye syndrome, the syndrome is an escalation of symptoms due to viral disease and to unrecognized drug-induced encephalopathy, mainly by anti-emetics. A detailed drug history, considering all medication — not exclusively aspirin — taken during the full course of the illness is essential to differentiate between Reye syndrome and drug-induced symptoms. In addition, a critical analysis is presented of the four main case-control surveys that have lead to the proposal that salicylates are primary causative agents of Reye syndrome. In these surveys, medications given during the prodromal illness were adequately recorded, but other drugs given after the onset of vomiting have been overlooked or deliberately excluded. New epidemiological studies are needed, recording all drugs given to the patients throughout the full course of their illness until the moment of admission, in order to elucidate the mystery of Reye syndrome.     

Reye's syndrome: review and update

Reye's syndrome is a rare but potentially fatal disease that affects all organs of the body, with an especially devastating attack upon the liver and brain. It is characterized by encephalopathy with severe edema of the brain, increased intracranial pressure, hypoglycemia, and fatty infiltration of the liver. It is a two-phase illness, almost always associated with a previous viral infection. Studies strongly support a link between the use of aspirin and Reye's syndrome. Reported cases are on the decline. Recent epidemiologic studies show the incidence for children 10 to 19 years old to be stable, but reduced for younger children. Special attention needs to be directed toward educating adolescents and parents of older children about Reye's syndrome and cautioning against the use of aspirin to treat influenza, upper respiratory infections, or varicella.     

Increasing patient knowledge, satisfaction, and involvement: randomized trial of a communication intervention

A brief educational intervention to promote effective communication between physicians, children, and parents during pediatric office visits was designed and tested. A randomized clinical trial involving 141 children (5- to 15-year-olds) tested the effectiveness of the intervention to improve the process and outcome of medical care. The intervention was contained in three brief videotapes (one each for parents, physicians, and patients) and in accompanying written materials. Materials were designed to build skills and motivation for increased child competence and participation during pediatric medical visits. Control subjects saw health education videotapes and received materials comparable in length with those of experimental subjects. Postintervention medical visit process was analyzed using videotapes of visits. Visit outcomes, assessed with standardized instruments and interviews, included children's rapport with physicians, children's anxiety, children's preference for an active health role, children's recall of information, parents' satisfaction with the medical visit, and physician satisfaction. Results indicated that physicians in the intervention group, compared with their counterparts in the control group, more often included children in discussions of medical recommendations (50% vs 29%, t = 2.39, P less than .05); that children in the intervention group, compared with control children, recalled more medication recommendations (77% vs 47%, P less than .01) and reported greater satisfaction and preference for an active health role; and that the intervention and control groups did not differ in parent satisfaction, physician satisfaction, or child anxiety. The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children's preference for an active role in health and their acquisition of medical information.     

National Reye syndrome surveillance, 1982

Despite the fact that influenza B was the primary influenza virus strain during the winter of 1981-1982, only 213 cases of Reye syndrome were reported to the Centers for Disease Control (CDC) between Dec 1, 1981 and Nov 30, 1982. This national reported incidence of 0.33 cases per 100,000 children less than 18 years of age is the lowest reported incidence since the Centers for Disease Control began surveillance in 1973. This relatively low incidence probably reflected, at least in part, the fact the influenza B activity was spotty and the illness relatively mild the winter of 1981-1982. The 213 cases were reported from 43 states; and in 56% of the patients, Reye syndrome occurred following a respiratory illness. The mean age of the children was 7.0 years; there were equal numbers of girls and boys; and 93% were white. Of the ten black patients, 80% were less than 1 year of age compared with 9% of the white patients. Of the 208 patients with reported admission stage, 45% were admitted in stage I or 0, a slightly lower proportion than that observed in the previous 2 years. Salicylate levels were obtained in 55% of the patients and were reported as "detectable" in 81% compared with 96% in 1981 (P = .003, chi 2). Of the 200 patients with known outcome, 70 patients died (a case fatality ratio of 35%).     

Encephalopathy and fatty metamorphosis of the liver associated with cold-agglutinin autoimmune hemolytic anemia.

Three patients with encephalopathy clinically indistinguishable from Reye syndrome but associated with elevated cold-agglutinin titers and antiglobulin-I autoimmune hemolytic anemia are reported. The patients were treated with exchange transfusions, dexamethasone, controlled hyperventilation, and intracranial pressure monitoring. Liver biopsy specimens in two of the three patients showed fatty infiltration of the hepatocytes, but the light microscopic and electron microscopic appearance of the liver was not typical for Reye syndrome. These patients are reported to alert physicians to a metabolic encephalopathy in children which mimics Reye syndrome, but is distinctly different in clinical course and complicated by cold agglutinins and an autoimmune hemolytic anemia.     

Trends in sepsis-related neonatal mortality in the United States, 1985-1998

BACKGROUND: In the United States, bacterial sepsis affects up to 32,000 live births annually. In the 1990s, intrapartum antibiotic prophylaxis (IAP) was recommended to prevent maternal-infant transmission of group B Streptococcus (GBS), a leading cause of sepsis occurring in the first week of life (early onset sepsis). Since IAP has been used, early onset GBS disease declined 70%; however, increased antibiotic use associated with IAP might lead to more severe or antimicrobial resistant etiologies of sepsis. To understand the influence of IAP on neonatal sepsis, in general, we evaluated neonatal mortality from sepsis before and after IAP recommendations were issued. METHODS: Using the National Center for Health Statistics Linked Birth/Infant Death Datasets, we compared trends in sepsis-related early neonatal mortality (<7 days) and late neonatal mortality (7-27 days) among singleton United States births from 1985 through 1991 to 1995 through 1998 [data beyond 1998 not included because of International Classification of Diseases (ICD)-10/ICD-9 coding differences]. We compared trends in mortality between the 2 time periods by estimating the average annual percent change in mortality using log linear regression and stratified by gestational age. RESULTS: Combined early and late neonatal mortality from sepsis averaged 39.6/100,000 live births from 1985 through 1991 and 31.8/100,000 live births from 1995 through 1998. Early neonatal mortality from sepsis averaged 24.9/100,000 live births from 1985 through 1991 and 15.6 from 1995 through 1998; late neonatal mortality averaged 14.8/100,000 live births from 1985 through 1991 and 16.2 from 1995 through 1998. Early neonatal mortality declined more steeply after IAP recommendations were issued, 5.0% annually from 1995 through 1998 versus 3.0% annually from 1985 through 1991. Late neonatal mortality increased more from 1995 through 1998, 5.0% annually compared with 0.5% from 1985 through 1991. CONCLUSIONS: Lower mortality rates and greater declines in early neonatal mortality from sepsis during 1995-1998 indicate greater survival of infants beyond 7 days of life and suggest an association with GBS disease prevention efforts. Thus these findings provide some evidence for continuing IAP for GBS-colonized women. Our findings of apparent increasing trends in late neonatal mortality from sepsis necessitate follow-up with clinical studies.     

Reye syndrome in Bombay

Ten cases of Reye syndrome are reported. Significant hypoglycemia was present in six cases, with hypoglycorrhachia in four. There was significant elevation of serum transaminases in nine cases. Histological examination of the liver revealed fatty degeneration in all of the cases biopsied. The prognosis was poor; nine children expired within 72 hours of hospitalization.     

Treatment of fever in childhood

Although the need for routine antipyretic therapy in children has often been questioned, there are no data to contra-indicate this. Not all fevers need to be treated but many physicians do so to relieve parental concern. The most commonly used antipyretic drugs are acetylsalicylic acid (ASA), paracetamol (acetaminophen) and dipyrone (metamizol). Paracetamol and ASA have been extensively evaluated but there are few clinical trials on dipyrone. In the last decade a strong statistical association has been observed between salicylates and Reye syndrome. Paracetamol is the most common cause of acute hepatic failure. Dipyrone has been associated with agranulocytosis. In the light of these findings the extensive use of antipyretics drugs has been seriously questioned.