Сlinical and laboratory features of Reye’s syndrome in children: a clinical case

Reye’s syndrome is a very rare disease that occurs in the pediatric population with a frequency of approximately 6 cases per 100,000 children, but the mortality due to this nosology is quite high and depends on its severity and prognostic factors. This pathology should be a warning for practitioners in terms of diagnosis and timely precautions for possible progression of the disease, taking into account the high mortality rate, the rapid progression of neurological symptoms, and lack of clear predictors of Reye’s syndrome. The article presents modern views on the etiology, pathogenesis, clinical course, laboratory and morphological diagnosis of Reye’s syndrome. Recommended by the Center for Disease Control and Prevention in Atlanta criteria for the diagnosis of Reye’s syndrome are given in the article. The article describes the differential diagnosis between classical (aspirin-associated, idiopathic) and atypical Reye’s syndrome (Reye’s-like syndrome), as well as focuses on a set of diagnostic and therapeutic measures. A clinical case of the classic Reye’s syndrome in pediatric practice is presented, which occurred in the Regional Municipal Non-Profit Enterprise “Chernivtsi Regional Children’s Clinical Hospital”. The presented clinical case, unfortunately, was fatal and the body was subjected to an autopsy, the results of which, as well as morphological changes in the section material after specific staining with Sudan III, are also described in the article. The review of the case ends with a summary and conclusions, authors emphasize the need to draw the attention of practitioners to the possibility of developing rare Reye’s syndrome in children after the use of acetylsalicylic-containing drugs; for the verification of nosology, a doctor should take into account specific changes in clinical and paraclinical parameters, and due to the absence of a minimum permitted dose of acetylsalicylic acid it should be prohibited for use in pediatric practice as an antipyretic drug.

Reye's Syndrome

Reye's syndrome is a rare and potentially fatal pediatric illness defined as acute noninflammatory encephalopathy with fatty liver failure. It rarely occurs in elderly patients and is equally distributed between the sexes [1]. It has been usually associated with acute viral infections and the use of salicylate [1- 3]. There is no specific test to diagnose the disease. However, the most common lab finding is an early rise in serum ammonia levels occurring within 1 to 2 days of mental status changes [4-8]. Treatment of the Reye’s syndrome is mainly supportive and requires close monitoring best accomplished in an intensive care unit setting [9,10].

Valproic Acid Administration in Management of Status Epilepticus Causing Reye’s Syndrome

Introduction Valproic acid is commonly used to treat seizures in children. Regular use of valproic acid is known to cause hepatic dysfunction, and in extremely rare cases, it is known to have caused Reye’s syndrome. There are very few reports of Reye’s syndrome caused by valproic acid use. Methods A 2-year asymptomatic girl underwent modified Blalock–Taussig shunt surgery for correction of tetralogy of Fallot. Postoperatively the girl developed status epilepticus, which did not subside with initial use of intravenous midazolam and phenytoin sodium. She eventually responded to two doses of intravenous valproic acid administered 10 minutes apart. She developed depressed sensorium and was put on mechanical ventilation. The following day’s laboratory investigations revealed raised levels of serum ammonia, serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamic-pyruvic transaminase (SGPT) with normal serum bilirubin. Thus, a diagnosis of Reye’s syndrome was established. The patient succumbed to disease 2 days later. Discussion Reye’s syndrome is a rare and a fulminant illness seen typically in children following a viral illness and/or use of salicylates or other medications. There are rare reports of Reye’s syndrome following use of medications like valproic acid. This patient had a noninflammatory encephalopathy with hepatic dysfunction following two doses of valproic acid. Conclusion There are very few reports on Reye’s syndrome in the literature as it is a rare condition and diagnosis is difficult. Knowledge of the presentation of Reye’s syndrome is essential for treatment and management. When using drugs like valproic acid in children, liver enzymes and serum ammonia levels should be monitored.

Case Report: MIS-C Temporarily Associated With COVID-19 Complicated by Reye's Syndrome

We describe a 7-year-old child with multisystemic inflammatory syndrome that was temporarily associated with the novel coronavirus disease which evolved into serious illness, with coronary aneurysm, using human immunoglobulin and acetylsalicylic acid, in which clinical manifestations including hepatitis, convulsions, and coma were aggravated with Reye's syndrome. To date, there has been no report of the association of multisystemic inflammatory syndrome that is temporarily associated with the novel coronavirus disease and Reye's syndrome.

Regulation of the CoA Biosynthetic Complex Assembly in Mammalian Cells

Coenzyme A (CoA) is an essential cofactor present in all living cells. Under physiological conditions, CoA mainly functions to generate metabolically active CoA thioesters, which are indispensable for cellular metabolism, the regulation of gene expression, and the biosynthesis of neurotransmitters. When cells are exposed to oxidative or metabolic stress, CoA acts as an important cellular antioxidant that protects protein thiols from overoxidation, and this function is mediated by protein CoAlation. CoA and its derivatives are strictly maintained at levels controlled by nutrients, hormones, metabolites, and cellular stresses. Dysregulation of their biosynthesis and homeostasis has deleterious consequences and has been noted in a range of pathological conditions, including cancer, diabetes, Reye’s syndrome, cardiac hypertrophy, and neurodegeneration. The biochemistry of CoA biosynthesis, which involves five enzymatic steps, has been extensively studied. However, the existence of a CoA biosynthetic complex and the mode of its regulation in mammalian cells are unknown. In this study, we report the assembly of all five enzymes that drive CoA biosynthesis, in HEK293/Pank1β and A549 cells, using the in situ proximity ligation assay. Furthermore, we show that the association of CoA biosynthetic enzymes is strongly upregulated in response to serum starvation and oxidative stress, whereas insulin and growth factor signaling downregulate their assembly.

Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite

ABSTRACTCerebral malaria caused by Plasmodium falciparum is the severest form of the disease resulting in the morbidity of a huge number of people worldwide. Development of effective curatives is essential in order to overcome the fatality of cerebral malaria. Earlier studies have shown the presence of salicylic acid (SA) in malaria parasite P. falciparum, which plays a critical role in the manifestation of cerebral malaria. Further, the application of SA for the treatment of acute symptoms in cerebral malaria increases the activity of iNOS leading to severe inflammation-mediated death, also called as Reye's syndrome. Therefore, modulation of the level of SA might be a novel approach to neutralize the symptoms of cerebral malaria. The probable source of parasite SA is the shikimate pathway, which produces chorismate, a precursor to aromatic amino acids and other secondary metabolites like SA in the parasite. In this work, we performed the immunological, pathological and biochemical studies in mice infected with chorismate synthase knocked-out Plasmodium berghei ANKA, which does not produce SA. Fewer cerebral outcomes were observed as compared to the mice infected with wild-type parasite. The possible mechanism behind this protective effect might be the hindrance of SA-mediated induction of autophagy in the parasite, which helps in its survival in the stressed condition of brain microvasculature during cerebral malaria. The absence of SA leading to reduced parasite load along with the reduced pathological symptoms contributes to less fatality outcome by cerebral malaria.

Assessment of Reye’s syndrome profile with data from the US Food and Drug Administration Adverse Event Reporting System and the Japanese Adverse Drug Event Report databases using the disproportionality analysis

Objectives: Reye’s syndrome is a rare and potentially fatal illness that is defined as encephalopathy accompanied by liver failure. The aim of this study was to assess Reye’s syndrome profiles by analyzing data from the spontaneous reporting system database. Methods: We analyzed reports of Reye’s syndrome using the US Food and Drug Administration Adverse Event Reporting System and the Japanese Adverse Drug Event Report databases. The reporting odds ratio and proportional reporting rate were used to detect the pharmacovigilance signal. Results: The US Food and Drug Administration Adverse Event Reporting System contains 12,201,620 reports from January 2004 to June 2020, of which 186 are on Reye’s syndrome. The Japanese Adverse Drug Event Report contains 646,779 reports from April 2004 to September 2020, of which 30 are on Reye’s syndrome. In the US Food and Drug Administration Adverse Event Reporting System database, the reporting odds ratios (95% confidence interval, number of cases) of aspirin, diclofenac, ibuprofen, acetaminophen, and valproate sodium were 404.6 (302.6–541.0, n = 80), 15.1 (6.7–34.1, n = 6), 26.2 (16.1–42.6, n = 18), 10.7 (5.5–20.9, n = 9), and 47.1 (26.2–84.6, n = 12), respectively. In the Japanese Adverse Drug Event Report database, the reporting odds ratios (95% confidence interval, number of cases) of aspirin, diclofenac, ibuprofen, loxoprofen, acetaminophen, and valproate sodium were 14.1 (5.4–36.8, n = 5), 51.7 (22.2–120.5, n = 7), 135.0 (40.8–446.2, n = 3), 17.6 (6.7–46.0, n = 5), 24.0 (9.2–62.6, n = 5), and 13.8 (3.3–57.9, n = 2), respectively. The reported number of female patients aged 30–39 years was the highest in the Japanese Adverse Drug Event Report. Conclusion: Although the frequency of the occurrence of Reye’s syndrome is low, the possible risk of the disease occurring in adult females should be considered.

Non Salicylate-Associated Reye Syndrome: A Case Report

Reye's syndrome (RS) is a rare disease, usually associated with consumption of salicylates during viral illness. In 1965, the first case of association between RS and salicylates was described in United Kingdom (UK). The incidence of RS decreased dramatically after warnings of UK and US health agencies against using aspirin in children. Patients with RS presented with neurologic compromise, cerebral edema, acute hepatitis, and liver failure-especially in the children. In this paper, a four-month-old boy with diagnosis of RS was described, who presented with malaise, cyanosis and decreased level of consciousness, but the history of salicylates consumption was negative for him and his mother. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(5):332-334.