本文選題：藥物不良反應 + 重癥藥疹　； 參考：《重慶醫(yī)科大學》2012年碩士論文

【摘要】：背景及目的藥疹又稱藥物性皮炎（drug eruption），是藥物通過各種途徑進入人體后引起的皮膚粘膜炎癥反應。其中皮損廣泛、粘膜損害明顯、可導致嚴重內(nèi)臟損害、致死率高者我們稱之為重癥藥疹。重癥藥疹（severe cutaneous adverse drug reactions SCADRs）包括重癥多形紅斑型即Steven-Johson syndrome（SJS）、大皰性表皮松解型（drug-induced bullosa epidermolysis）又稱中毒性表皮壞死松解型（toxicepidermal necrolysis TEN）、剝脫性皮炎型（exfoliative dermatitis ED）及藥物超敏反應綜合征（drug hypersensitivity syndrome DHS）。在疾病初期，其皮損表現(xiàn)多樣，特別是在兒童，尤其難與感染性疾病引起的皮膚損害相鑒別。加之藥疹的檢測和識別在臨床上無靈敏度高、特異性強的實驗室指標，其診斷主要依靠藥物接觸史及臨床表現(xiàn)。故對兒童重癥藥疹的發(fā)病規(guī)律及其特點進行分析總結對指導臨床診斷及治療具有重要的意義。本文就我院兒童重癥藥疹住院病例的臨床特點、致敏藥物及治療預后情況進行臨床回顧性研究，希望能為早期診斷及治療疾病提供相關的臨床依據(jù)。 方法對我院2007年1月-2011年12月51例重癥藥疹住院患兒進行臨床回顧性分析，其中包括好發(fā)年齡、住院情況、潛伏期、致敏藥物、臨床表現(xiàn)、治療方法及轉(zhuǎn)歸。男32例，女19例，發(fā)病年齡為3月-14.5歲，平均年齡為（6.00±3.64）歲。 結果 1.好發(fā)年齡：發(fā)病的高峰年齡為1-3歲（21.57%）及6-9歲（35.29%），青春期及嬰兒期的發(fā)病人數(shù)相對較少，分別為3.92%、7.84%。男女之比為1.69：1，男性稍高于女性。 2.本研究中，重癥藥疹病例占全院總住院患兒的比例為0.22‰。2007-2011年，每年的比例分別為0.13‰、0.22‰、0.24‰、0.18‰、0.31‰，整體呈增長趨勢。 3.藥疹類型：51例兒童重癥藥疹中常見的臨床類型比例依次為SJS(54.90%)，TEN(27.45%)，ED(9.80%)，DHS(7.85%)。 4.潛伏期：SJS、TEN、ED及DHS的平均潛伏期為（5.66±6.45）d、（6.61±9.65）d、（16.00±7.41）d、（18.00±6.97）d，ED及DHS的平均潛伏期較SJS及TEN延長，其比較有明顯的統(tǒng)計學差異（F=5.5,P0.05），而ED與DHS比較，其平均潛伏期無明顯的統(tǒng)計學差異（F=0.005,P0.05）。 5.致敏藥物：常見的致敏藥物為抗生素類(39.21%)、解熱鎮(zhèn)痛類(21.57%)及抗癲癇類藥物(17.65%)。其中SJS主要以抗生素為主（57.90%），TEN以抗生素（41.67%）及解熱鎮(zhèn)痛藥（50.00%）為主，ED以抗生素（60.00%）為主，而DHS以抗癲癇類藥物（75.00%）為主�？拱d癇藥的平均潛伏期較抗生素及解熱鎮(zhèn)痛藥明顯延長，其差異有顯著的統(tǒng)計學意義（F=19.5,P0.05）。 6.用藥原因：感染性疾病(56.85%)是兒童用藥后引起重癥藥疹最主要的原因，尤以上呼吸道感染（43.14%）最為常見。 7.臟器受累：最常見的為肝臟（39.22%），其次為腎臟（5.08%）和肺部（7.84%），心臟受累者（1.96%）少見。粘膜受累主要見于SJS(21例)及TEN（14例），而ED（1例）及DHS粘膜受累少見，DHS嗜酸性粒細胞升高（3例）明顯。 8.預后及治療：治愈32例（62.75%），好轉(zhuǎn)18例（35.29%），死亡1例（1.96%），治愈率高。有病毒感染、粘膜受累、內(nèi)臟損害的患兒其平均病程分別為（18.86±2.34）d、（15.94±4.39）d、（18.90±2.86）d，無病毒感染、粘膜受累、內(nèi)臟損害的患兒平均病程分別為（12.38±5.11）d、（8.00±1.93）d、（9.90±2.76）d，有病毒感染、粘膜受累及內(nèi)臟損害者病程延長，其比較均有統(tǒng)計學意義（P0.05）；激素用量與疾病病程關系不大（相關系數(shù)γ=0.23，P0.05）。 結論 1.近年來，兒童重癥藥疹住院病例占總住院患兒的比例呈上升趨勢，其多器官受累明顯，主要以肝臟損害最為常見，肺部、腎臟、心臟也可發(fā)生病變，危害性大，需早期診斷。 2.兒童重癥藥疹根據(jù)其既往藥物過敏史、可疑藥物接觸史、潛伏期及臨床皮損等特點，可早期診斷，及時治療，治愈率高。 3.重癥藥疹一旦確診，需立即停止可疑致敏藥物，根據(jù)病情嚴重程度及時給予適量糖皮質(zhì)激素。目前我們不提倡大劑量激素治療，建議根據(jù)病情嚴重程度，使用適量的激素，，以可控制病情為標準。糖皮質(zhì)激素聯(lián)合靜脈注射丙種球蛋白（IVIG）治療可減少激素用量，降低激素副作用的發(fā)生。同時丙種球蛋白有一定抗病毒的作用，可用于伴有病毒感染治療效果不佳者。 4.對于有病毒感染、粘膜受累及內(nèi)臟功能損害者，需積極予以相關對癥支持治療，以免延長病程。
[Abstract]:Background and objective drug rash, also known as drug dermatitis (drug eruption), is an inflammatory response to the skin and mucous membrane caused by various ways of entering the body. There are extensive skin lesions and obvious mucosal damage, which can lead to severe visceral damage. The high fatality rate is called severe drug rash. The severe drug rash (severe cutaneous adverse drug reactions SCA) DRs) including severe polymorphic erythema, Steven-Johson syndrome (SJS), bullous epidermolysis (drug-induced bullosa epidermolysis), also known as medium toxic epidermal necrosis and loosening (toxicepidermal necrolysis TEN), exfoliative dermatitis (exfoliative dermatitis) and drug hypersensitivity syndrome S). In the early stages of the disease, its skin lesions are diverse, especially in children, especially in the identification of skin damage caused by infectious diseases. In addition, the detection and identification of drug rash in the clinic is highly sensitive and specific, and its diagnosis depends mainly on the history of drug contact and clinical manifestations. The analysis and summary of its characteristics is of great significance for guiding clinical diagnosis and treatment. The clinical features, sensitized drugs and treatment prognosis of hospitalized children with severe drug rash in our hospital are reviewed in this paper, hoping to provide a clinical basis for early diagnosis and treatment of diseases.
Methods the clinical retrospective analysis of 51 cases of severe drug eruption in January 2007 -2011 years in our hospital, including good onset age, hospitalization, latent period, sensitizing drugs, clinical manifestation, treatment and prognosis, 32 men and 19 women, age -14.5 in March, the average age was (6 + 3.64) years old.
Result
1. the age of good onset: the peak age of the disease is 1-3 (21.57%) and 6-9 (35.29%). The incidence of adolescence and infancy is relatively low, which is 3.92%, the ratio of 7.84%. to men and women is 1.69:1, and the male is slightly higher than that of the female.
2. in the 2. study, the proportion of severe drug eruptions in the total hospitalized children was 0.22 per thousand.2007-2011 years, the proportion of each year was 0.13 per thousand, 0.22 per thousand, 0.24 per thousand, 0.18 per thousand, 0.31 per thousand, and the overall growth trend.
3. type of drug eruption: 51 cases of severe drug eruption in children were followed by SJS (54.90%), TEN (27.45%), ED (9.80%) and DHS (7.85%).
4. incubation period: the average latency of SJS, TEN, ED and DHS is (5.66 + 6.45) d, (6.61 + 9.65) d, (16 + 7.41) d, (18 + 6.97) d, and the average latency of ED and DHS is higher than that of SJS and TEN.
5. sensitizing drugs: the common sensitizing drugs are antibiotics (39.21%), antipyretic and analgesic (21.57%) and antiepileptic drugs (17.65%). Among them, SJS is mainly antibiotics (57.90%), TEN is mainly antibiotics (41.67%) and antipyretic analgesics (50%), ED is mainly antigenic (60%), and DHS is mainly antiepileptic drugs (75%). Antiepileptic drugs The average incubation period was significantly longer than that of antibiotics and antipyretic analgesics, and the difference was statistically significant (F=19.5, P0.05).
6. reasons for drug use: infectious diseases (56.85%) are the main causes of severe drug eruption after medication in children, especially respiratory tract infections (43.14%).
7. organs were involved: the most common were liver (39.22%), followed by kidney (5.08%) and lung (7.84%), and heart involvement (1.96%). Mucous membrane involvement was mainly seen in SJS (21 cases) and TEN (14 cases), while ED (1 cases) and DHS mucous membrane were rarely involved, DHS eosinophilic Bao Shenggao (3 cases) was obvious.
8. the prognosis and treatment: 32 cases (62.75%) cured, 18 cases (35.29%), 1 cases of death (1.96%), high cure rate. The average course of children with virus infection, mucous membrane involvement, and visceral damage was (18.86 + 2.34) d, (15.94 + 4.39) d, (18.90 + 2.86) d, no virus infection, mucous membrane involvement, and the average course of children's visceral damage was D, respectively. 00 + 1.93) d, (9.90 + 2.76) d, virus infection, mucous membrane involvement and visceral damage prolonged the course of disease, the comparison was statistically significant (P0.05), and the dose of hormone was not related to the disease course (correlation coefficient gamma =0.23, P0.05).
conclusion
1. in recent years, the proportion of children with severe drug rash in the total hospitalized children is on the rise, and the multiple organ involvement is obvious. The most common cases are liver damage, lung, kidney, and heart can also be diseased, and the early diagnosis is needed.
2. children with severe drug eruption can be diagnosed early and treated timely according to their previous drug allergy history, suspected drug exposure history, latent period and clinical skin lesions. The cure rate is high.
3. severe drug rash, once confirmed, should immediately stop suspicious sensitizing drugs and give proper amount of glucocorticoid in time according to the severity of the disease. We do not advocate large dose hormone therapy at present. We suggest that a moderate amount of hormone should be used to control the condition according to the severity of the disease. Glucocorticoid combined with intravenous immunoglobulin (IVIG) is a combination of glucocorticoid and intravenous injection. Treatment can reduce the amount of hormone and reduce the occurrence of side effects of hormone. At the same time, the gamma globulin has a certain antiviral effect, which can be used in patients with poor treatment of virus infection.
4. for patients with viral infection, mucosal involvement and visceral dysfunction, relevant symptomatic and supportive treatment should be actively taken so as not to prolong the course of disease.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R758.25

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