The Experience Of Diagnosis And Treatment Of 4 Cases Of Carbamazepine-induced Drug Eruptions And Detections Of Their HLA-B*1502 Gene And A Review Of The Literature

Background and Objective:Carbamazepine(CBZ)is widely used in clinical,mainly for the treatment of nervous system diseases such as epileptic seizures and trigeminal neuralgia.Adverse drug reactions induced by Carbamazepine have many manifestations,such as fixed drug eruption form?dermatitis/eczema form?urticaria form?scarlatina form and so on.Patients' skin and mucous membrane can be involved in varying degrees in different types.From all manifestations,TEN(Toxic epidermal necrolysis)can be the most serious one which belongs to the severe drug eruption.It's not only do damage to the skin and mucous membrane of the whole body,and often cause life-threatening or even death due to secondary infection?liver and kidney dysfunction?water and electrolyte disorders.According to studies at home and abroad,the drug eruption caused by Carbamazepine has no relationship with the patient's sex?age?drug dosage and medication time and is unpredictable?However,some experts confirmed that the initial dose and incubation period can be a great risk factor for the drug eruptions caused by CBZ.Scholars conferred that the severe cutaneous adverse drug reactions may be closely associated with the human leukocyte antigen(HLA)gene.The HLA-B75 family is mostly studied which includeing HLA-B*1502?HLA-B*1508?HLA-B*1511?HLA-B*1515?HLA-B*1521 and so on.From all HLA family,HLA-B*1502 is almost only exists in Asian races.It is estimated that 10%to 15%or even more people in these areas can carry HLA-B*1502 alleles.They mainly distributed in East and South East Asia countries.About 1?8%population in our country carry this gene while the number in Southeast Asia is 2?12%.While Japanese and Koreans are less likely to carry the gene which less than 1.0%.Chung found that there is a strong correlation between HLA-B*1502 and SJS/TEN for the first time in 2004.And many subsequent studies prove this point of view.Each of us thas our own specific drug genes that determine drug metabolism and tolerated doses.Their selective expression affects the sensitivity of the individual to the response to the drug.Thus,The U.S.Food and Drug Administration(FDA)issued a notice in December 12,2007 that recommend Asians should dectect HLA-B*1502 genes before begining to use aromatics antiepileptic drugs such as CBZ.Once is positive,other drugs should be used to reduce the probability of side effect.How to prevent from happening and treat this kind of patients effectively is what we concerned most.Therefore we collect the clinical data of these 4 patients in our department and analysis their clinical manifestations and treatment.And we test their HLA-B*1502 gene.We want to provide some references for clinical prevention and treatment through this study.Methods??Clinical part:4 cases of drug eruption caused by CBZ in Department of Dermatology of Shandong Provincial hospital for 2017-2018 years were selected.We collecting basic information of the 4 patients,including age?gender?medication time?examination and treatment.??Laboratory part:4ml peripheral blood sample was drawn from each patients after signing the consent form(divided into two tubes).We use the PCR-SSP method to detect the genotype of HLA-B*1502 allele.Results1?The average incubation period of the 4 Carbamazepine-induced drug eruptions patients is 20 days..2?Drug eruptions caused by Carbamazepine have different symptoms and various manifestations.3?Carbamazepine-induced drug eruptions can be accompanied with bacterial and/or viral infections4?The effect of systematic hormone therapy on Carbamazepine-induced drug eruptions is obvious.The combination of IVIG is5?Measures must be taken to avoid the side effects of Glucocorticoid in advance during the treatment.6?None of the 4 patients presents this allele.Conclusion1?Glucocorticoid is the first choice for the treatment of severe drug eruptions.2?Glucocorticoid combined with IVIG in the treatment of SJS/TEN can improve the curative effect and shorten the course of disease.3?Patients with infection should use sensitive antimicrobial agents earlier according to the drug sensitivity test.4?We need to pay more attention to skin and mucous membrane nursing and psychotherapy of the patients,avoid other adverse consequences.5?Patients with negative gene of HLA-B*1502 should still be alert to the occurrence of drug eruption in a gene negative patient.