Cases Of Reye's Syndrome Research Articles

Острая токсическая энцефалогепатопатия. Синдром Рейе

В статье описан нетипичный клинический случай синдрома Рейе у девочки 10 лет, возникший на фоне ОКИ, приведший к летальному исходу. На основании клинических и лабораторных данных, а также анамнеза жизни ребенка проведена краткая дифференциальная диагностика синдрома Рейе, эпилепсии и энцефалита, а также состояний, сопровождающихся нарушением функции нервной системы и печени: фульминантной печеночной недостаточности, панкреатической энцефалопатии, менингита, врожденных ошибок метаболизма.

Spectrum of significant liver diseases at autopsy in children in tertiary care institute

Background To study the etiology of hepatic diseases in children at autopsy in North India. Material and methods One hundred and eighty-one pediatric autopsy cases, (age range 0-14 years) who presented with signs and symptoms of hepatic diseases were analyzed. Results Of these 66.9% were males. Metabolic disorders (38.7%) were the most common followed by hepatitis (viral, autoimmune and others) (19.9%), infiltration by leukaemia/lymphoma (11.0%), infections (6.1%), histiocytic disorders (5.5%), vascular disorders (2.2%), extra hepatic biliary atresia (EHBA, 2.2%), congenital hepatic fibrosis (1.1%), progressive familial intrahepatic cholestasis (0.6%), benign recurrent intrahepatic cholestasis (0.6%), tumors (0.6%), and other causes (12.2%). Conclusion Liver diseases are common in children with a male dominance. Amongst the metabolic disorders, cystic fibrosis (CF), Reye syndrome, Indian childhood cirrhosis (ICC), galactosemia and Wilson disease were the most common. In CF, cholestasis was seen in 6 and invasive fungal infection in 5 cases. Both classical and atypical types of ICC were noted. Predominant macrovesicular steatosis was present in 2 cases of Reye syndrome. In galactosemia, steatosis was absent in 3 cases wherein frank micronodular cirrhosis was present. Acute hepatitis was more common than chronic. It being an autopsy study, incidence of EHBA was low.

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye's syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively. We obtained primary information from clinicians who identified causes of these sADRs and reviewed factors contributing to delayed identification of these toxicities. Overall, 3,500 aspirin-associated RS cases in the United States, 1,605 gadolinium-associated NSF cases, and 181 epoetin-associated PRCA cases were reported. Delays in FDA regulation of over-the- counter medications and administration of aspirin to children contributed to development of RS. For NSF, in 1996, the Danish Medicine Agency approved high-dose gadodiamide administration to chronic kidney disease (CKD) patients undergoing MR scans. Overall, 88 % of Danish NSF cases were from two hospitals and 97 % of United States' NSF cases were from 60 hospitals. These hospitals frequently administered high-doses of gadodiamide to CKD patients. Another factor was the decision to administer linear chelated contrast agents versus lower risk macrocyclic chelated agents. For PRCA, increased use of subcutaneous epoetin formulations to CKD patients, in part due to convenience and cost-savings considerations, and a European regulatory requirement requiring removal of albumin as a stabilizer, led to toxicity. Overall, 81, 13, and 17 years elapsed between drug introduction into practice and identification of a causal relationship for aspirin, erythropoietin, and gadodiamide, respectively. A substantial decline in new cases of these sADRs occurred within two years of identification of the offending drug. Clinicians should be vigilant for sADRs, even for frequently-prescribed pharmaceuticals, particularly in settings where formulation or regulatory changes have occurred, or when over-the-counter, off-label, or pediatric use is common.

Reye's and Reye's‐like syndromes

The review reports various questions about Reye's syndrome and Reye's-like syndromes. Although there is a significant decrease in the classic Reye's syndrome cases, because of the reduced employment of salicylates in children (salicylate seems to be the most important inducing factor of the syndrome in paediatric subjects affected by viral infection), the problem is still of interest considering the presence of different Reye's-like forms. All these pathological situations are associated with various aetiologic or predisposing causes that are examined in the text. Particular attention is placed on metabolic disorders, especially of fatty acid metabolism, and also of one amino acid. In fact, a latent form can also be the basis of possible biochemical disturbances induced by various exogenous factors such as viral infections, particularly of the respiratory tract (more rarely of bacterial aetiology), or produced by microbial toxins, or by chemical substances, including some therapeutic drugs. A full discussion of biochemical mechanisms of salicylate-induced Reye's syndrome is reported. Finally a possible diagnostic differentiation from classic Reye's syndrome and Reye's-like syndromes plus therapeutic prospects are briefly examined.

Reye Syndrome – A Case Report with Review of Literature .

Here we describe a case of Reye syndrome diagnosed at postmortem liver biopsy of a three-year old girl who presented with vomiting, low grade fever for three days and loss of consciousness for 18 hours. Clinically, the differential diagnoses were meningitis, encephalitis and septicemia. No history of past illness or any drug ingestion including aspirin were present. Laboratory investigations indicated a diagnosis of Reye syndrome. The child was given supportive treatment but died after two days of admission and postmortem needle-biopsy of the liver showed microvesicular steatosis consistent with Reye syndrome.

A case of Reye syndrome with rotavirus infection accompanied with high cytokines

We report on a 23-month-old boy with a rare complication of rotavirus gastroenteritis. He was diagnosed as acute encephalopathy with DIC accompanied with high levels of cytokines. The liver pathology also revealed mild infiltration and fatty changes. He was suspected to be suffering from a cytokine storm followed by Reye syndrome.

Incidence of Reye's syndrome in France: A hospital-based survey

At the time of the study no information was available in France about the incidence of Reye's Syndrome (RS) and no warnings about RS and aspirin. The objective was to evaluate the incidence of RS in France by a hospital-based study. For a period of 1 year from November 1995 to November 1996, all French paediatric departments were required to report any child under 15 years with unexplained noninflammatory encephalopathy (i.e., CDC consciousness level stage I or deeper with normal CSF) and a threefold (or greater) increase in serum aminotransferase and/or ammonia. All suspected cases were classified by a panel of experts as probable RS or excluded RS. In 10% of randomly selected paediatric departments we checked that every suspected case had been reported. Forty-six suspected cases were reported during the year of the survey, of which 14 were classified as RS. Five of these 14 cases had a metabolic disorder. Nine children were definitively diagnosed as having RS (i.e., an estimated incidence of RS of 0.79/1,000,000 children, i.e., below 15/year). Eight children had been exposed to aspirin, four to aspirin alone and four to aspirin and acetaminophen. On the basis of these results the incidence of RS in France in 1996–1997 was not substantially different from that of countries where warning labels were already in use, but it was higher than in the US after 1994. This was probably due to the reduction in aspirin prescription in France because of warnings in Europe and the US and also because many cases of RS are now identified as metabolic disease. On the basis of these results and because the relationship between aspirin and RS has already been proved, public and professional warnings concerning RS on aspirin-containing products in cases of varicella and viral febrile illness have been adopted by the French Drugs Agency.

A Fatal Case of Reye Syndrome after Varicella and Ingestion of Aspirin

A Fatal Case of Reye Syndrome after Varicella and Ingestion of Aspirin

Reye syndrome revisited: a descriptive term covering a group of heterogeneous disorders.

Reye syndrome, characterised by the combination of liver disease and noninflammatory encephalopathy, is a non-specific clinicopathological entity and a descriptive term covering a group of heterogeneous disorders. Nowadays, some of these patients are diagnosed more correctly as having infectious, metabolic, toxic or other disease. The non-specific case definition implies that the epidemiological studies suggesting a link with acetylsalicylic acid have been performed on a heterogeneous group of children, whereby the value of these studies and their ensuing hypothesis is weakened. Moreover, a detailed analysis of the epidemiological surveys of the Centers for Disease Control, the Yale study and of the British risk factor study provides evidence that not only the use of acetylsalicylic acid but also that of phenothiazines and other anti-emetics is significantly greater in Reye syndrome cases than in controls. As to the decline of Reye syndrome, recent literature data reveal that this is related to more accurate modern diagnosis of infectious, metabolic or toxic disease, reducing the percentage of idiopathic or true cases of Reye syndrome. Reye syndrome is a non-specific descriptive term covering a group of heterogeneous disorders. Moreover, not only the use of acetylsalicylic acid but also of antiemetics is statistically significant in Reye syndrome cases. Both facts weaken the validity of the epidemiological surveys suggesting a link with acetylsalicylic acid.

１９９８年〜１９９９年の冬期に大流行したインフルエンザに伴うＲｅｙｅ症候群の２例

１９９８年〜１９９９年の冬期に大流行したインフルエンザに伴うＲｅｙｅ症候群の２例

Hereditary Isolated Glucocorticoid Deficiency Associated with Reye's Syndrome• 506

The hallmarks of Reye's Syndrome which include hyperammonemia, elevated liver enzymes and progressive encephalopathy, have been associated with certain inherited metabolic disorders, thus, current recommendations are to screen atypical Reye's Syndrome cases for defects in amino acid, organic acid and carbohydrate metabolism. Hereditary isolated glucocorticoid deficiency(HIGD) is characterized by undetectable cortisol levels, normal mineralocorticoids and elevated ACTH levels while molecular analysis has demonstrated a point mutation in the MC2R gene of the ACTH receptor in some cases. The presenting symptoms of HIGD in early childhood have been hypoglycemia and/or hyperpigmentation. A 3 5/12 year male with expressive language delay and at least one previous unexplained episode of ataxia had a metabolic evaluation which yielded normal levels of plasma carnitine and non diagnostic urine for amino and organic acids. At 3 10/12 years he presented with 24 hours of vomiting followed by diarrhea and seizures. No aspirin had been given. He was lethargic and stimulation produced asymmetric decorticate posturing. Initial glucose was 28 mg/dl, maximal AST 163 U/L (<58), and NH4 126 μmol/L (10-47). Stool for Rotavirus was positive. The urine contained 30H butyric acid, adipic and suberic acids. Neurologic findings were not immediately reversed by normalization of blood glucose nor administration of dexamethasone. The EEG was reported to be consistent with diffuse cerebral dysfunction of a moderate degree compatible with State I to II Reye's Syndrome. Recovery occurred over 24-48 hours. At 4 2/12 years, after a seizure with ketotic hypoglycemia, cortisol was undetectable with ACTH of 2655 pg/ml(normal adult 9-52) while electrolytes and plasma renin activity were normal. There was no cortisol response to exogenous ACTH stimulation. Genomic DNA was extracted from peripheral blood lymphocytes and amplified by PCR with primers flanking the entire MC2R coding region. Single stranded DNA was generated by PCR and sequenced which revealed a homozygous Ser-74-Ile mutation of the MC2R gene. Two cases have been previously described with a postmortem diagnosis of HIGD following a Reye-like episode. This is the first case of Reye's Syndrome associated with HIGD due to an MC2R gene mutation. Determination of a cortisol level is recommended as part of the evaluation for metabolic disorders associated with Reye's Syndrome.

A study of urinary metabolites in patients with dicarboxylic aciduria for differential diagnosis

Dicarboxylic aciduria (DCA-uria) is a relatively common finding in the screening of organic acidemias by gas chromatography/mass spectrometry (GC/MS). A considerable number of patients with DCA-uria are involved in disturbances of mitochondrial and peroxisomal fatty acid beta-oxidation. The differential diagnosis of DCA-uria was investigated using a combination of organic acid analysis by GC/MS, carnitine determination, acylcarnitines by fast atom bombardment/mass spectrometry (FAB/MS) and acylglycines by stable-isotope dilution analysis. The relative distribution of urinary metabolites was examined in 46 patients with DCA-uria of different origins, including physiological ketosis of childhood, disorders of propionic acid metabolism, glutaric aciduria type II, Zellweger syndrome and patients who were clinically diagnosed as having Reye syndrome. Zellweger syndrome seemed to be distinguishable from other disorders by the high sebacic acid/adipic acid ratio of DCA-uria and increased excretion of 4-hydroxyphenyllactic acid and 2-hydroxysebacic acid. The mild form of glutaric aciduria type II was often missed by current organic acid analysis alone, but was readily diagnosed by acylcarnitine and acylglycine determination. The ratio of free/total carnitine was low in most of the DCA-uria patients except for two of five cases of Zellweger syndrome and one of three cases of Reye syndrome. The acylcarnitine analysis by FAB/MS showed adipyl-, suberyl-, sebacyl- or dodecanedioylcarnitine as major peaks in most of these patients, although these were not specific. Disease-specific peaks were detectable only in congenital organic acidemias such as glutaric aciduria type II, methylmalonic acidemia and propionic acidemia.

Adult Reye's syndrome

A 42-year-old woman developed a flu-like illness and died 8 days later with Reye's syndrome (RS). There are 26 other cases of adult-onset RS reported. Biochemical, immunologic, and molecular studies of liver, brain, and skeletal muscle revealed a non-uniform decrease in several mitochondrial residual enzyme activities in liver and brain. Pyruvate carboxylase activity was negligible. Cross-reacting material was present in normal abundance in isolated liver mitochondria for several enzymes that had reduced catalytic activity including pyruvate carboxylase. Subunit II (encoded by mitochondrial DNA) and subunit IV (encoded by nuclear DNA) of cytochrome c oxidase also were present in normal abundance with normal electrophoretic mobility. These observations, combined with pertinent findings of other investigators, allow us to speculate that the intramitochondrial matrix chemical environment is disturbed by preceding pathophysiologic events resulting in a lowered ATP/ADP ratio. The lowered intramitochondrial energetic state interferes with the refolding and assembly of imported mitochondrial proteins, causing a loss of the catalytic efficiency of these enzymes. This explains the selective vulnerability of mitochondria in RS and the non-uniform, disproportionate loss of enzyme activity.

Reye Syndrome Surveillance—United States, 1986

Reye syndrome (RS) is an acute illness that occurs almost exclusively in children; it is characterized clinically by profuse vomiting and neurologic dysfunction, sometimes progressing to delirium, coma, and death. Continuous national surveillance for RS was established in December 1976. This report summarizes RS cases for the 1989 surveillance year (December 1, 1988-November 20, 1989).

Reye Syndrome and Aspirin

Twenty-six cases of Reye syndrome occurring between 1973 and 1982 have been reviewed in relation to aspirin ingestion at the Children’s Hospital, Camperdown, Australia (formerly the Royal Alexandra Hospital for Children in Sydney), where Reye first described his syndrome of encephalopathy and fatty degeneration of the viscera in 1963.

Public Health Service Study of Reye's Syndrome and Medications

Between January 1985 and May 1986, following completion of a pilot study, a main study concerning the possible association between Reye's syndrome and salicylates was conducted. Twenty-seven patients with stage II or deeper Reye's syndrome whose diagnoses were confirmed by an expert panel and who had appropriate antecedent illnesses (chickenpox, respiratory illness, or gastrointestinal illness) prior to the onset of Reye's syndrome were compared with 140 controls matched for age, race (black or not black), and type and timing of onset of antecedent illness. Controls were selected from the same hospital, emergency room, or school as case-patients or were identified by random-digit telephone dialing. As in the pilot study, a strong statistical association with ingestion of salicylates during the antecedent illness and prior to the onset of Reye's syndrome was observed (odds ratio, 40; lower 95% confidence limit, 5.8). Analysis of the independent risk of aspirin and nonaspirin salicylates revealed a significant association with aspirin (odds ratio, 26; lower 95% confidence limit, 6.4); the independent risk of nonaspirin salicylates could not be assessed because only two cases were not exposed to aspirin. Assessment of epidemiologic issues of concern, including case-control differences in the severity of the antecedent illness, did not explain the high odds ratios that were observed. The high percentage of patients with Reye's syndrome exposed to salicylates (greater than or equal to 90%) in this and prior studies suggests that, though the reported incidence of Reye's syndrome has declined in recent years, concomitant with a decline in salicylate use among children, a majority of Reye's syndrome cases may be attributable to salicylate use.

UPDATE ON REYE'S SYNDROME.

According to the Centers for Disease Control, 101 cases of Reye's syndrome were reported between December 1985 and November 1986. Eighty-eight percent of the reported cases occurred in white persons, and 38 percent of the patients were under four years …

Reye's syndrome in Denmark. A retrospective study.

We tried to determine the incidence of Reye's syndrome (RS) in Denmark in a retrospective study. As RS is often preceded by influenza B, we chose the year 1979, where an epidemic of influenza B was registered in Denmark. All children aged 1 month to 18 years, who died, were identified, excluding children who died from accidents or malignant diseases. Two hundred and forty-two children died in hospital. Review of the records revealed one case of RS. One hundred and five died outside hospital. Reviewing death certificates and autopsy reports, none of these fulfilled the criteria for RS. All paediatric departments were asked if they had made a diagnosis of RS. None had. In 1979 approximately 1.1 mill. children aged 1 month to 14 years lived in Denmark. This gives an incidence of 0.09 per 100 000 for 1979. Although this is a minimum figure, the incidence of RS in Denmark, for unknown reasons, seems very low.

Cerebral Tubuloreticular Inclusions In Reye's Syndrome

IntroductionTubuloreticular inclusions (TRI) were first reported in patients with herpesvirus encephalitis or systemic lupus erythematosus (SLE). TRI are abnormal subcellular structures which consist of fine irregularly branched, anastomosing tubules within cisternae of endoplasmic reticulum. TRI have also been reported in blood lymphoreticular cells, vascular endothelial cells, mesenchymal cells, and epithelial cells in a variety of clinical conditions which include SLE and other autoimmune diseases, congenital immunodeficiency, lymphoproliferative disorders, neoplasms, neurodegenerative disorders, T-cell leukemia, and acquired immune deficiency syndrome (AIDS). We have recently reported an association of TRI with Reye's syndrome (RS). The inclusions were found in peripheral leukocytes of two unrelated patients with RS following a prodromal influenza respiratory infection. Subsequent to those studies we have retrospectively examined biopsy material from earlier cases of RS, and have identified TRI in the capillary endothelial cells from brain biopsies of three RS patients. The purpose of this report is to present these observations and to discuss the association of TRI with RS.

Jamshedpur Fever and Reye's Syndrome

To the Editor.— The additional details of Jamshedpur fever provided by Dr Khan 1 are of interest. Contrary to Dr Khan's impression, however, the identity of Jamshedpur fever with Reye's syndrome has previously been discussed. When we first reported the epidemic occurrence of Reye's syndrome in northeastern Thailand, we listed Jamshedpur fever as one of other syndromes of encephalopathy and fatty degeneration of the viscera. 2 The source of our information was from personal correspondence with T. Jacob John of the Christian Medical College in Vellore (September 1969) and the report of John et al 3 from that institution of three cases of Reye's syndrome. Dr John and his colleagues noted the similarity of their cases and those of Jamshedpur fever and cited Dr Khan's article as well as Chari and Swamy's 4 publication on the subject. Subsequent investigations in Thailand convinced us that aflatoxin was the etiologic agent of the