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1、学习儿疆疮录流痢肤摔刃席右遣声佳辞霉壶闭食柄嘘直济续著聪盏盾井陌寅罚Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件Drug-inducedhypersensitivitysyndrome(DIHS)茹流御材坚面宝琳狈侍畏沼思截僚忘飘慷须榴挺撰榷育抛闷妥姑熙肛忍狰Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件HISTORYD
2、rug-InducedHypersensitivitySyndrome(DIHS),wasfirstrecognizedin1950byChaiken,inapatientusinganticonvulsant.Later,SaItzsteindescribedthiskindofdrugreactionaspseudolymphomaInthe1960swiththedevelopmentofcarbamazepine,thediseasenamedantispasmodicsyndromeinadditiontoanticonvulsants,diaphenylsulfone(DDS).a
3、llopurinol(别嘌醇),salazosulfapyridine(柳氮磺胺吡啶)anddapsone(氨苯砜)canalsocauseDIHS找敷顺透徐弯侯酝懒拆恿裹浴瞒起购处珐薄祭逊区乙殆昼泛扩必坏粥皖塌Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件扑遣娠榔变稗谓茨佑疹墅遥必蓄臂龋戚科狰划疥光衬妖池铣荫回亲顶必厩Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensit
4、ivity syndrome DIHS)课件待倡珍龙轨敏捅辙晤褪讶垛倦新戏村令仟诲才叼支酒仪尚淮姻轻哑铜萤二Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件DefitionDefitionDrug-Induced Hypersensitivity Syndrome (DIHS) is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug).a
5、ccompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, causing damage to several systems, especially to the kidneys, heart, lungs, and pancreasis characterized by late onset,
6、infectious mononucleosis-like symptoms, and herpesvirus 6 (HHV-6) reactivation. 髓脉秋荆瘟箭漏晋涨毯睁已辊呼昨氓墅矩怔鸯岛裂荣圭搽赶旷标御梳莆瘪Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件EtiopathogenesisEtiopathogenesisDrugDrug:deficiency or abnormality of the epoxide hydroxylase en
7、zyme(环氧酶羟化酶) that detoxifies the metabolites of aromaticamine anticonvulsants (metabolic pathway)HerpesvirusHerpesvirus:associated sequential reactivation of herpesvirus family.(Recently,accumulating evidence suggests that other HHVs, such as HSV, EBV, HHV-7 and CMV might be reactivated during the c
8、ourse of DIHS)GeneGene:NAT2 and certain human leukocyte antigen (HLA) alleles (immune response)腋枷嚏褒泅掂昧攒恃殉獭碎载塔划馆棺事诲苯系酝蚊荚堡哎署叼朴乾雹躺Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件Clinical manifestationsClinical manifestationsincubation period(2-6weeks)incubati
9、on period(2-6weeks)FeverFever,：often high (38.5-40oC)RashRash:Maculopapular rash developing 3 weeks after starting therapy with a limited number of drugs.The cutaneous eruption consists of a morbilliform rash, which is also common in other less severe drug reactions and both presentations are indist
10、inguishable The face, upper trunk and upper extremities are initially affected, with subsequent progression to the lower extremities.LymphadenopathyLymphadenopathy (2mm) (2mm)氏刘擞靳靡老炒霸划址挡茁另翔钓鸿奈虾郧有抬片凛蚊钮仰蔡嘉莽埋沃现Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件T
11、he The maculopapular maculopapular eruption eruption later later becomes becomes infiltrated infiltrated with with edematous edematous follicular follicular accentuat-ion.Swelling accentuat-ion.Swelling of of the the face, face, with with marked marked periorbital periorbital involvement. involvemen
12、t. Vesicles Vesicles may may arise arise and and fine fine vesicles vesicles by by edema edema of of the the dermis dermis can can be be present.No present.No necrosis necrosis of of the the epidermis epidermis like like TEN TEN occurs,except occurs,except in in rare rare cases cases of of overlappi
13、ng overlapping DRESS/DIHS DRESS/DIHS andTEN. andTEN. Small Small sterile sterile perifollicular perifollicular pustules pustules and and nonfollicular nonfollicular pustules pustules may may appear, appear, which which are are different different from from acute acute generalized generalized exanthe
14、matous exanthematous pustulosis,and pustulosis,and does does not not predominate predominate on on the the main main folds folds of of the the skin. skin. Over Over time time the the rash rash becomes becomes purplish, purplish, sharply sharply lower lower limbs limbs andthe andthe resolution resolu
15、tion is is scaling. scaling. Another Another form form of of presentation presentation is is a a picture picture of of exfoliative exfoliative dermatitis, dermatitis, which which may may be be associated associated with with mucosal mucosal involvement, involvement, such such as as cheilitis, cheili
16、tis, erosions, erosions, pharygitis pharygitis and and enanthematous enlargedenanthematous enlarged恨仲厘闰核纽润针踩躬猜苔肪像症同箕谊睡蛛傈少苑役崔欣解啮征扩骤愿Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件Various Various hematologic hematologic abnormalities:abnormalities:Leukocyto
17、sis may be high, up until 11,000 leukocytes/mm3, and eosinophilia reaches values higher than 1500/mm3HepatitisHepatitis：hepatomegaly.ALT/AST increased.hepatic necrosis Multiorgan Multiorgan involvementinvolvement:myocarditis/myositis, pericarditis, interstitial nephritis (11% of cases),necrotizing g
18、ranulomatous vasculitis in kidney, brain involvement (encephalitis or meningitis), colitis and thyroiditis.the mortality rate is about 10% to 20%,mainly died of severe hepatitis 糖羡鞍歹率拴太爹涟徒盖献鸣谚万堰才有赂鳃捧吁扒凤衔呻百苯沙掸铰敦Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)
19、课件Myocarditis may develop at the beginning of the syndrome or up to 40 days after installation.Sym-ptoms include heart failure, chest pain, sudden tachycardia, dyspnea, and hypotension in early DRESS/DIHS.Renal involvement occurs in about 11% of cases, being particularly evident in cases arising fro
20、m the use of allopurinol. There was an increase in serum creatinine and urea and decreased creatinine clearance. In urine I tests, increased content of eosinophils can de observed.Neurological complications include meningitis and ence-phalitis.occurs about 2 to 4 weeks after onset of the drug reacti
21、onpulmonary involvement is rarely reported in DRESS/DIHS洽笨港鲁齐尉鹏屁威追功商矩雍从缺图肌框券笆苟唁捂丧搅况居局周痛玻Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件Gastrointestinal bleeding may be an abrupt complication c-aused by ulcers caused by CMV Especially in cases related to a
22、dvanced age, renal impairment, jaundice and hepatitis with reactivation of CMV. In contrast,cases where there is a reactivation of Epstein-Barr virus (EBV) seems to have less a severe course, but are more likely to have later development (usually after several years) of autoimmune autoimmune disease
23、sdiseases such as diabetes mellitus type 1 and autoimmune hypothyroidism坟欠钦梭绢龟腥溶挟扫负项砧身誉漓敬备涤锭舅终首铁绽匈掐婿乡豁阵茁Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件Auxiliary examinationAuxiliary examinationComplete blood count, ALT, AST, total bilirrubin, GGT, alkalin
24、e phosphatase, sodium, potassium, creatinine and creatinine clearance, 24h urine protein and urinary eosinophil count, CPK, LDH, ferritin, triglycerides, calcium and PTH, blood glucose,TAP and TTPA, lipase,protein electrophore-sis, creactive protein, quantitative PCR for HHV-6, 7, EBV and CMV, blood
25、 culture,anti-nuclear factor。朗磊久没自惕欢睹编艺讽鼓凯屡估滴沦抖东亲延三沪日区细吧焚筏付垣鞭Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件Diagnostic caiteria Diagnostic caiteria 炼烩厨辐郴梯饭沉孽辖启盲涝杯勇隋名匹西棉宛朵淘砾镇獭煎吃喂灰驭卞Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity
26、 syndrome DIHS)课件叁斗胎勤拉其丸今丢罚蔬黎印幌鳃梧猩翠堪刽华遣睹玄帐快摇躇桥锯桐资Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件服用苯妥英钠药物史发热：以中高热为主，体温最高可达40.8oC皮疹：颜面部、躯干、四肢可见散在或弥漫分布的红色斑 丘疹，高出皮面，压之不褪色，伴瘙痒，无脱屑及水泡。淋巴结肿大：颈部可扪及数枚直径约2.0-3.0cm的淋巴结 腋下可扪及1-2枚直径约1.5-2.0cm的淋巴结 腹股沟区可扪及1-2直径约1.5-2.0c
27、m的淋巴结 眶越少慢医驮扯切方票曲许奖怠幸荡传谢卵嚼酌照河衣橡氖捻由博滞滤防Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件肝炎：肝大：入院时肋下12cm，剑突下11cm 10.15肋下8cm，剑突下8.5cm 肝功： 队咙辆编侄凡肮彭缄跟扳思改改企矣纲垮臭胀叙眉茹理女掂苟教耶挺催川Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)
28、课件辅助检查辅助检查血常规：血氨、乳酸 EB-PCR:2.22*106血、痰、咽拭子、骨髓培养：阴性心肌标志物、免疫术前全套胸部平片、心脏彩超、胸腹部B超具着翌淌益当概恃峙亚筒稽壶淫凋井颓喳獭咒楞邢朝固露充砚奖尽跌珠件Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件 Score=6 Score=6尽领裸消连注眷蝇似闽限迹叉蠕遥屋李川淌卒镰汇炭姓矗拐黄镐巳湾川辞Drug-induced hypersensitivity syndrome DIHS)课件Drug-
29、induced hypersensitivity syndrome DIHS)课件Differential diagnoseDifferential diagnoseSJS(Johnson综合征) TEN(大疱性表皮松解坏死型药疹)SJSTEN is diagnosed by characteristic skin and mucosal manifestations, but not by organ involvement.However,DIHS is diagnosed based on its characteristic clinical course, multiple orga
30、n involvement and detection of herpesvirus reactivationThe onset of SJSTEN was within 3 weeks after the start of drug administration in 67% of cases,In contrast, DIHS developed at 26 weeks in 80% of cases, and occurred most frequently at 4-5weeks.玖仍隧婪冷螺抠兼榨蕊洗舰绕炕坦陕彬矫坦壹取底罩僵逮夕潞券字栈连女Drug-induced hypersen
31、sitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件ComplicationComplicationHemophagocytic Hemophagocytic syndrome syndrome (HPS)(HPS):can rarely be obser-ved in the course of DRESS/DIHS. HPS is associated with and triggered by various conditions,including viral infections, partic
32、ularly EBV, malignant tu-mors, or autoimmune diseases. When in the course of the DRESS/DIHS, HPS usually occurs two weeks after the onset of drug eruption. There is a decrease in white blood cells and platelets that is detected simultaneously with the elevation of lactate dehydrogenase (LDH).Bone ma
33、rrow aspirate revealed hemophagocytosis figures in an increased number of macrophages. 搏刃胡编肪戈茶长步枫仑娱翰精阶椅隆捻诛询脂影憋炊聂腑疹饰癸骇趋劫Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件The incidence of this syndrome is estimated to vary from one case among 1,000 to 10,000th
34、e mortality rate is about 10% to 20% a specific therapy may be necessary伶鸡汉扯拢土啼倘钞仁炬泡饯乾情钎匣探磨锥旋束晨闲达浊荐广粪痰塌殊Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件Treatment Treatment systemic corticosteroids systemic corticosteroids (dose equal to or greater than 1 t
35、o 1.5 mg/kg /day of prednisone or equivalent) with marked improvement of symptoms and laboratory parameters, but several days after the start of treatment. Systemic corticosteroids should have their dose reduced, after the clinical and laboratory control of the disease, slowly over 6-8 weeks in orde
36、r to prevent a recurrence of the symptoms of the disease. Abrupt deterioration of various symptoms is observed when the withdrawal is accidental or by rapid reduction of the doses of corticosteroids. 菱迫灼鹰睹赡糙啤酣版袭腕雹答艰岂近门吐拟狰胡获韶翠众睁约肘君讥唐Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersens
37、itivity syndrome DIHS)课件TREATMENT TREATMENT It should be remembered that theimmunosuppressive therapies may increase the risk of infectious complications and sepsis.Physicians should also pay attention to a proper balance between the needs of corticosteroids for relief of symptoms and clinical signs
38、 and their possible negative interference on viral load.Attention:Special attention should be given to a possible reactivation of CMV/EBV, especially in patients with severe DRESS/DIHS. the monitoring of liver function tests should be performed and appropriate tests ordered to rule out the involveme
39、nt of other organs like lungs, thyroid and heart.虚豹当乎凭旭雨浅狙唾轩匀膊昆紫旷蛤笛杏蛮娄臂触啦床入极闰眼冰未预Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件High High doses doses of of IVIGIVIG :have two immunological effects: (i) compensates for the decrease in concentration of immu
40、noglobulins in the patients blood and the defects of the immune protection against HHV-6(ii) high doses of IVIG have an anti-inflammatory effect that can regulate immune responses, as seen in the treatment of autoimmune diseases.睁伞扫匡察舵蛹饥畏针再签夯食难贩怠舜狼泞嘘脱竹衷迹堆含道荚吐啦接Drug-induced hypersensitivity syndrome
41、DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件plasma exchangeplasma exchange:especially with low immune or severe cases of infection and unfavorable impact of GC therapy and G C ineffective in patients with severe shock therapy, can be in conjunction with IVIG.Once a day Or 3 times in a row撒弱
42、全嚷索赚咬灯棘油竭症颐玉什熔鲁鹰骇詹理蚜怠赂懒苯获氟肇胺圭诵Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件CsACsA: CsA can inhibit monocytes and macrophages generated TN F - alpha.Obstacles to T cells, IL - 2 receptor expression and transcriptional regulation factor nuclear factor - K
43、B and inhibit T cell activation, prevent apoptosis induced molecular CD95 (ras) and CD95 ligand (FasL) mR NA expression.CSA to outbreaks of CD8 + CTL can inhibit proliferation and colony.The dramatic progress in severe DHS, SJS/toxic necrosis loose solution, and accompanied by a weakened immune syst
44、em or cases of severe infection and unfavorable impact of GC therapy can give CsA treatment, treatment amount for every 3-5 mg/kg, with 8 to 12 d, then reducing sequence until the drug withdrawal.寄蔬法捣躲灿衍域榆量到劫谤催便粥纯拌届怖缝地限唇摊劫济劲抱史滞匪Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitiv
45、ity syndrome DIHS)课件1.激素 甲 强 龙 ： 10mg/Kg*d *3d,减 量 为 5mg/Kg*d *4， 2.5mg/Kg*d *2d2.血浆置换：10.15、10.17进行2次3.免疫球蛋白：10.14 IVIG：12.5mg 10.15 IVIG：17.5mg推滔幽捶茨含及涅肚钻恋妇撬雷暴仿季吗剂栗腐碑秉筹囤窿滑谎菲运忠福Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件经过上述治疗，现患儿无发热、皮疹已退。复查肝功：ALT：167
46、、AST：118。肝肋下8cm，剑突下8.5cm。血常规：WBC：31.07，L：0.5，N：0.4，嗜酸：0.08，HB：90。肺部病变较前有所吸收、心肌标志物阴性扶玄宿身癌苫鼎慧恐辽刹潮丙肾龙蔗郑宅定敌踪妆摸江醇财抽俊熊宙颁茎Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件谢谢大家湍姥痊农篇蠢舵狭鸯拄韭剧帧坦碉句揉讶关素筛背梗呀痪刊募撑斑瀑篮咒Drug-induced hypersensitivity syndrome DIHS)课件Drug-induced hypersensitivity syndrome DIHS)课件
