摘要 義大醫院藥劑部藥師顏靜卉 陳宛君 林梅芳 義大醫院神經內科醫師王彥棠 (Stevens-Johnson syndrome, SJS) (toxic epidermal necrolysis, TEN) (drug reaction with eosinophilia and systemic symptoms, DRESS) 6.49% SJS TEN DRESS carbamazepine SJS/TEN phenytoin DRESS 壹 前言 HLA-B*1502 2014 3 (Stevens- Johnson syndrome) (toxic epidermal necrolysis) 2011 carbamazepine phenytoin lamotrigine 1 貳 嚴重皮膚過敏反應之分類 (severe cutaneous adverse drug reactions, SCARs) (1) (toxic epidermal necrolysis, TEN) (2) (Stevens- Johnson syndrome, SJS) (3) (drug reaction 31 1 Mar. 31 2015 藥學雜誌 122 59 臨床藥物治療學抗癲癇藥與嚴重皮膚過敏反應
臨床藥Therapeutics of Clinical Drugs 物治療學THE JOURNAL OF Mar. 31 2015 繼續教育 60 TAIWAN PHARMACY Vol.31 No.1 with eosinophilia and systemic symptoms, DRESS) SJS 10% TEN 30% 3 一 毒性表皮溶解症 (toxic epidermal necrolysis, TEN) 和史帝文生 - 強生症候群 (Stevens-Johnson SJS TEN syndrome, SJS) TEN SJS TEN SJS 70% TEN SJS 2005 Letko E SJS 1-7.1 TEN 0.4-1.2 2 10% SJS 30% TEN 10%-30% SJS/TEN overlap syndrome ( ) TEN 表一 SJS, SJS/TEN overlap syndrome, TEN 之臨床表徵 SJS SJS/TEN overlap TEN (primary lesion) (distribution) (+) (++) (+++) (mucosal involvement) (systemic symptoms) (%) < 10% 10-30% 30% 2000 Bastuji-Garin 表二 SCORTEN 評分 24 (BSA, %) > 40 yrs =1 = 0 0-1 3.2% (BUN) (glucose) =1 = 0 2 12.2% (bicarbonate) BSA > 10% =1 = 0 3 35.5% (A Severity-of- Illness Score for Toxic Epidermal Necrolysis, Bicarbonate < 20 mmol/l =1 = 0 4 58.3% SCORTEN) ( ) 4 TEN Glucose > 252 mg/dl BUN > 28 mg/dl Heart rate > 120 beat/min =1 = 0 =1 = 0 =1 = 0 5 90%
身症狀 (drug reaction with eosinophilia and systemic symptoms, DRESS) DRESS 1/1,000 1/10,000 2 carbamazepine phenytoin DRESS ( ) ( ) 50% (aminotransferase) (alkaline phosphatase) (bilirubin) DRESS 1-6 10% 3 DRESS T 參 藥物基因檢測 2004 (carbamazepine) SJS/TEN HLA-B*1502 2007 Man CB HLA-B*1502 藥物疹合併嗜伊紅血症及全學二 HLA-B*1502 SJS/TEN 100% HLA-B*1502 5 FDA HLA-B*1502 carbamazepine oxcarbazepine phenytoin lamotrigine HAL-B*1502 ( ) 6 表四 HLA-B 與抗癲癇藥引發的 SCARs 之關聯性 Causative drug HLA-B Race SCARs Carbamazepine *1502 Han Chinese (Taiwan) SJS/TEN Han Chinese (Hong Kong) SJS/TEN Asians in Europe SJS/TEN Thai SJS Indians SJS Caucasians SJS/TEN Japanese SJS/TEN Han Chinese (Taiwan) DRESS Caucasians DRESS *1511 Japanese SJS/TEN Phenytoin *1502 Han Chinese (Taiwan) SJS/TEN Thai SJS/TEN Lamotrigine *1502 Han Chinese (Taiwan) SJS Oxcarbazepine Han Chinese (Taiwan) SJS SCARs, severe cutaneous adverse drug reactions; HLA, human leukocyte antigen; SJS, Stevens Johnson syndrome; TEN, toxic epidermal necrolysis, DRESS, drug reaction with eosinophilia and systemic symptoms 肆 抗癲癇藥與皮膚過敏之現況 HAL-B*1502 31 1 Mar. 31 2015
臨床藥繼續教育 Therapeutics of Clinical Drugs 物治療 學 Carbamazepine Phenytoin SJS TEN 7-21 60 DRESS 2013 Kim JY carbamazepine 7 2008 Gau SS valproate carbamazepine valproate carbamazepine 8 lamotrigine Joseph R. Calabrese lamotrigine 8 9 Lamotrigine oxcarbazepine 2011 FDA gabapentin DRESS 7 3 (incubation time) 2 10 2011 Yang CY carbamazepine 12.32 5.07 (lamotrigine, oxcarbazepine, phenobarbital, phenytoin) 27 20 SJS/TEN 62 THE JOURNAL OF TAIWAN PHARMACY Vol.31 No.1 Mar. 31 2015 DRESS 1 伍 處置 治療 (dialysis) (extracorporeal blood purification techniques) corticosteroids SJS/TEN 11 corticosteroids 12 corticosteroids Wolf Verma TEN/SJS 3 dexamethasone (1.5-2 mg/kg/ daily) 11,13 cyclophosphamide cyclosporin IVIG SJS TEN 11 DRESS 2-3 prednisolone 1-2 mg/kg
臨床藥物治療 13 HLA-B*1502 學 carbamazepine 100 陸 結論 6 carbamazepine carbamazepine HLAB*1502 phenytoin phenobarbital benzodiazepine valproate lamotrigine felbamate Antiepileptic Drugs Related Severe Cutaneous Adverse Reactions Ching-Hui Yen 1, Wang-Chun Chen 1, Yan-Tang Wang 2, Mei-Fang Lin 1 Department of Pharmacy 1, Department of Neurology, E-Da Hospital 2 Abstract Severe cutaneous adverse drug reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) are delayed-type drug hypersensitivity reactions. They occured in associated with different medications, including some commonly used antiepileptic drugs (AEDs). The mortality rate of AED-SCARs were 6.49%. In Taiwan, it seems that aromatic AEDs is the main cause for SJS and TEN, and is a secondary reason for DRESS occurred. Among those AEDs, carbamazepine is the most common drug to cause SJS/TEN, and DERSS usually caused by phenytoin. In order to provide proper medical care and avoid severe adverse drug reactions, the patients should not only know to carry out some laboratory test before taking these agents, but also need to know these ADEs related symptoms and close monitor these drugs related side effects after taking these anti-epileptic agents. 藥學雜誌 122 63 31 1 Mar. 31 2015
臨床藥繼續教育 Therapeutics of Clinical Drugs 物治療學參考資料 : 64 THE JOURNAL OF TAIWAN PHARMACY Vol.31 No.1 Mar. 31 2015 1. Yang CY, Dao RL, Lee TJ et al: Severe cutaneous adverse reactions to antiepileptic drugs in Asians. Neurology. 2011; 77(23): 2025-33. 2. Smith, JD: Drug-induced skin disorders. US Pharm. 2012; 37(4): HS11-HS18. 3. Yang MS, Kang MG, Jung JW et al: Clinical features and prognostic factors in severe cutaneous drug reactions. Int Arch Allergy Immunol. 2013; 162(4): 346-54. 4. Bastuji-Garin S, Fouchard N, Bertocchi M et al: SCORTEN: A severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000; 115: 149-53. 5. Hazin R, Ibrahimi OA, Hazin MI et al: Stevens-Johnson syndrome: pathogenesis, diagnosis, and management. Ann Med. 2008;40:129-38. 6. Aihara M. Pharmacogenetics of cutaneous adverse drug reactions. J Dermatol. 2011; 38(3):246-54. 7. Kim JY, Lee J, Ko YJ et al: Multi-indication carbamazepine and the risk of severe cutaneous adverse drug reactions in Korean elderly patients: a Korean health insurance data-based study. PLoS One. 2013; 8(12): e83849. 8. Gau SS, Chao PF, Lin YJ et al: The association between carbamazepine and valproate and adverse cutaneous drug reactions in patients with bipolar disorder: a nested matched case-control study. J Clin Psychopharmacol. 2008; 28(5): 509-17. 9. Buzan RD, Dubovsky SL. Recurrence of lamotrigineassociated rash with rechallenge (letter). J Clin Psychiatry 1998; 59: 87. 10. Roujeau JC, Stern RS. Severe adverse cutaneous reations to drugs. N Engl Med 1994; 331: 1272-85. 11. Wolf R, Davidovici B. Severe cutaneous adverse drug reactions: who should treat, where and how?: Facts and controversies. Clin Dermatol. 2010; 28(3): 344-8. 12. Lee HY, Dunant A, Sekula P et al: The role of prior corticosteroid use on the clinical course of Stevens-Johnson syndrome and toxic epidermal necrolysis: a case-control analysis of patients selected from the multinational EuroSCAR and RegiSCAR studies. Br J Dermatol. 2012; 167(3): 555-62. 13. Verma R, Vasudevan B, Pragasam V. Severe cutaneous adverse drug reactions. Med J Armed Forces India. 2013; 69(4): 375-383. 禪荷