Oxcarbazépine et syndrome DRESS : un cas pédiatrique révélé par une hépatite fulminante

doi:10.1016/j.arcped.2004.05.018

Archives de Pédiatrie

Volume 11, Issue 9, September 2004, Pages 1073-1077

https://doi.org/10.1016/j.arcped.2004.05.018 Get rights and content

Résumé

Le syndrome DRESS (Drug Rash with Eosinophilia and Systemic Symptoms), autrefois appelé réaction d'hypersensibilité, est une réaction idiosyncrasique sévère à la prise médicamenteuse, préférentiellement aux antiépileptiques. Ce syndrome se caractérise par la survenue d'une éruption cutanée avec fièvre et poly-adénopathies, associée à une atteinte d'un ou plusieurs organes pouvant mettre en jeu le pronostic vital. De nombreux cas ont été décrits chez l'adulte avec les différents anti-convulsivants aromatiques comme la phénytoïne, le phénobarbital et la carbamazépine, mais également avec d'autres médicaments. Les nouveaux antiépileptiques, comme l'oxcarbazépine (Trileptal^®), sont connus aussi pour donner des effets secondaires à type d'éruption cutanée, mais semblent moins impliqués dans ce syndrome. Les cas pédiatriques d'hypersensibilité sont rares ou sous-diagnostiqués. Nous rapportons ici le cas clinique d'une jeune fille de 11 ans ayant présenté une hépatite aiguë grave pouvant se rattacher à un tel syndrome induit par l'oxcarbazépine.

Abstract

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, also called hypersensitivity reaction, is a severe idiosyncratic reaction to drugs, especially to anti-epileptic drugs. Clinical features associate cutaneous eruption, fever, multiple peripheral ganglions, and potentially life-threatening damage of one or more organs. DRESS syndrome is well described in adults treated with aromatic anti-epileptic drugs, such as phenytoin, phenobarbital, and carbamazepine, but also with other drugs. The new anti-epileptic drugs, such as oxcarbazepine also induce various cutaneous eruptions, but with less report of DRESS syndrome. In children, DRESS syndrome is rare and probably underdiagnosed. We report on the case of a 11-year-old girl hospitalised with an acute severe hepatitis revealing an oxcarbazepine-induced DRESS syndrome.

Section snippets

Observation

Une jeune fille de 11 ans était traitée par une aminopénicilline pour une infection ORL, associant fièvre élevée (40 °C), adénopathie cervicale volumineuse et angine. Malgré la prise correcte du traitement, son état général s'est altéré rapidement en 72 heures, avec survenue d'une éruption maculeuse érythémateuse disséminée justifiant son hospitalisation. Dans ses antécédents, on note une épilepsie révélée tardivement à huit ans par un état de mal convulsif. Le bilan étiologique de cette

Discussion

La fréquence du syndrome DRESS est imprécise, estimée entre 1/1000 à 1/10 000 expositions chez l'adulte [1]. Cette imprécision s'explique par la méconnaissance de cette réaction médicamenteuse et l'existence de dénominations multiples pour cette même entité. Ce syndrome a longtemps été connu sous le nom de « réaction d'hypersensibilité aux anti-convulsivants » [1] ou de « Phenytoin Hypersensitivity Syndrome » [2]. Il s'agissait alors de réactions aux anticonvulsivants aromatiques. Des cas ont

Conclusion

Le syndrome DRESS demeure une pathologie rare en pédiatrie, mais peut-être est-il simplement sous-diagnostiqué. L'importance de sa prise en charge précoce, en termes de morbidité et de mortalité justifie l'arrêt d'un traitement dès suspicion de son implication.

La chronologie des signes cliniques, leur type et l'association à une atteinte organique doivent conduire tout clinicien à rechercher une hyperéosinophilie. L'association de ces éléments confirme le diagnostic.

Références (15)

C.C. Vittorio et al.
Anticonvulsivant hypersensitivity syndrome
Arch Intern Med
(1995)
J. Garcia-Samaniego et al.
Phenytoin hypersensitivity syndrome
An Med Interna
(1994)
N. Picart et al.
Syndrome d'hypersensibilité du à l'acide valproïque
Presse Med
(2000)
V. Conilleau et al.
Hypersensitivity syndrome due to 2 anticonvulsivant drugs
Contact Dermatitis
(1999)
V. Callot et al.
Drug-induced pseudolymphoma and hypersensitivity syndrome
Arch Dermatol
(1996)
H. Bocquet et al.
Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms : DRESS)
Semin Cutan Med Surg
(1996)
M.C. Carroll et al.
Drug-induced hypersensitivity syndrome in pediatric patients
Pediatrics
(2001)

There are more references available in the full text version of this article.

Cited by (38)

Hepatic Injury due to Drugs, Dietary and Herbal Supplements, Chemicals and Toxins
2023, MacSween's Pathology of the Liver, Eighth Edition
The liver may sustain injury from a variety of environmental, dietary and therapeutic agents. Injury from drugs and toxins may mimic patterns of injury found in other liver diseases, but different agents affect the liver in different ways. Liver biopsy of cases of suspected toxic injury may be used to exclude alternate causes of injury and assess the severity of the injury as well as to compare the injury to literature reports of toxic injury. This chapter reviews the patterns of injury observed in toxic injury as well as what is known about injury due to particular substances.
DRESS syndrome to phenobarbital: A hypersensitivity reaction to drugs known but forgotten by prescribers–A case report
2022, Therapies
Association between HLA-A*3201 allele and oxcarbazepine-induced cutaneous adverse reactions in Eastern Han Chinese population
2019, Seizure
Citation Excerpt :
In particular, cutaneous adverse drug reactions (cADRs) to AEDs are considered to be a prevalent issue in the course of medical treatment for epilepsy [8,9], with an incidence of 5-9% [10–12], which result in drug termination and initiation of new therapeutic options in nearly all cases [11]. OXC-induced cADRs show various clinical presentations ranging from mild maculopapular eruption (MPE) to the more severe cutaneous reactions, which seriously endanger the life of the patient, comprising Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) [13–17]. Although OXC is applied just as frequently as CBZ in the therapy of partial epilepsy [18–20], few studies have focused on its effects on cADRs.
To determine genetic associations between oxcarbazepine (OXC)-induced cutaneous adverse drug reactions (cADRs) and human leukocyte antigen (HLA) variants in the Eastern Han Chinese population.
A total of 120 patients were enrolled in this study, including 30 subjects with OXC-induced cADRs (case group) and 90 OXC-tolerant patients (control group). High-resolution HLA genotyping was conducted for HLA-A, HLA-B, HLA-C, and HLA-DRB1, and allele frequencies were compared.
No patient carried the HLA-B *1502 allele in the case group, the frequency of HLA-B *1502 allele in the control group was 6.1%. HLA-A*3201 allele was detected in 13.3% of 30 patients with OXC-induced cADRs (4/30) and 0% of 90 OXC-tolerant patients (0/90). The difference in HLA-A*3201 frequency between the two groups was statistically significant [P = 0.004, odds ratio (OR) = 15.877, 95% confidence interval (CI) = 1.817-138.720].
Eastern Han Chinese patients with the HLA-A*3201 allele may be more susceptible to OXC-induced cADRs, while the HLA-B*1502 allele is not correlated with it. The precise association between HLA alleles and OXC-induced cADRs warrants further study.
Drugs and Toxins
2018, MacSween's Pathology of the Liver
The liver may sustain injury from a variety of environmental, dietary and therapeutic agents. Injury from drugs and toxin may mimic patterns of injury found in other liver diseases, but different agents affect the liver in different ways. Liver biopsy of cases of suspected toxic injury may be used to exclude alternate causes of injury and assess the severity of the injury as well as to compare the injury to literature reports of toxic injury. This chapter reviews the patterns of injury observed in toxic injury as well as what is known about injury due to particular substances.
Antiepileptic Drugs and Liver Disease
2017, Pediatric Neurology
Citation Excerpt :
Most cases occurred with previous exposure to another AED or in the setting of elevated liver enzymes. There are isolated reports of anticonvulsant hypersensitivity syndrome and hepatitis.112-114 Topiramate can produce hyperammonemia when combined with valproic acid, but hepatotoxicity when used as monotherapy is very rare.
Acute, symptomatic seizures or epilepsy may complicate the course of hepatic disease. Choosing the most appropriate antiepileptic drug in this setting represents a difficult challenge, as most medications are metabolized by the liver. This article focuses on the acute and chronic treatment of seizures in patients with advanced liver disease and reviews the hepatotoxic potential of specific antiepileptic drugs. Newer antiepileptic drugs without, or with minimal, hepatic metabolism, such as levetiracetam, lacosamide, topiramate, gabapentin, and pregabalin should be used as first-line therapy. Medications undergoing extensive hepatic metabolism, such as valproic acid, phenytoin, and felbamate should be used as drugs of last resort. In special circumstances, as in patients affected by acute intermittent porphyria, exposure to most antiepileptic drugs could precipitate attacks. In this clinical scenario, bromides, levetiracetam, gabapentin, and vigabatrin constitute safe choices. For the treatment of status epilepticus, levetiracetam and lacosamide, available in intravenous preparations, are good second-line therapies after benzodiazepines fail to control seizures. Hepatotoxicity is also a rare and unexpected side effect of some antiepileptic drugs. Drugs such as valproic acid, phenytoin, and felbamate, have a well-recognized association with liver toxicity. Other antiepileptic drugs, including phenobarbital, benzodiazepines, ethosuximide, and the newer generations of antiepileptic drugs, have only rarely been linked to hepatotoxicity. Thus physicians should be mindful of the pharmacokinetic profile and the hepatotoxic potential of the different antiepileptic drugs available to treat patients affected by liver disease.
EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure
2017, Journal of Hepatology
The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction. In the context of hepatological practice, however, ALF refers to a highly specific and rare syndrome, characterised by an acute abnormality of liver blood tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately necessary when the patient presents for medical attention. These, as well as additional clinical procedures will be the subject of these clinical practice guidelines.

View all citing articles on Scopus

View full text

Fait cliniqueOxcarbazépine et syndrome DRESS : un cas pédiatrique révélé par une hépatite fulminanteOxcarbazepine and DRESS syndrome: a paediatric cause of acute liver failure

Résumé

Abstract

Section snippets

Observation

Discussion

Conclusion

Anticonvulsivant hypersensitivity syndrome

Arch Intern Med

Phenytoin hypersensitivity syndrome

An Med Interna

Syndrome d'hypersensibilité du à l'acide valproïque

Presse Med

Hypersensitivity syndrome due to 2 anticonvulsivant drugs

Contact Dermatitis

Drug-induced pseudolymphoma and hypersensitivity syndrome

Arch Dermatol

Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms : DRESS)

Semin Cutan Med Surg

Drug-induced hypersensitivity syndrome in pediatric patients

Pediatrics

Fait clinique
Oxcarbazépine et syndrome DRESS : un cas pédiatrique révélé par une hépatite fulminanteOxcarbazepine and DRESS syndrome: a paediatric cause of acute liver failure