龙牡汤治疗特应性皮炎的临床疗效观察
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摘要
1目的
1.1观察龙牡汤治疗血虚风燥型特应性皮炎的近期临床疗效；
1.2对龙牡汤和西医治疗方案进行用药成本-效果分析；
1.3观察龙牡汤治疗特应性皮炎的远期疗效——复发情况的影响；
1.4评价龙牡汤的临床用药安全性；
通过以上的观察研究,为特应性皮炎的临床治疗提供一种安全、有效、价廉的治疗方案。
2方法
2.1研究设计方法
采用平行随机对照方法。用密闭信封法,参照随机数字表按照1：1产生试验组和对照组的随机安排。将对应的治疗分配信笺密封入信封,形成随机信件。按纳入病例的先后顺序将患者随机分配到试验组或对照组。
2.2病例选择
2.2.1诊断标准：
西医诊断标准：参照Hanifin与Rajka诊断标准：
主要特征包括瘙痒、典型的皮损形态和分布等4条特征；次要特征包括干皮症、鱼鳞病／掌纹症／毛囊角化症、即刻型皮试反应、血清IgE增高等23条特征,凡符合上述主要特征3项或3项以上,加次要特征3项或3项以上即可诊断为特应性皮炎。
中医辨证标准
参照《中药新药临床研究指导原则》制定的四弯风辨证分型标准中的血虚风燥证：
主症包括皮肤干燥、皮损色暗或色素沉着,或肥厚、苔藓样变、瘙痒抓痕血痂、病程久,反复发作。次症包括口干不欲饮、纳差,腹胀、舌质淡,苔白、脉弦细。当患者符合以上证型主症中3项或3项以上,同时具备次症中任何2项或2项以上,即可诊断为该证型。
2.2.2纳入标准：
(1)符合西医特应性皮炎(Atopic Dermatitis, AD)诊断标准；(2)符合中医血虚风燥证的诊断；(3)年龄2-40岁的患者；(4)签署知情同意书、依从性好的患者；(5)治疗前血常规、尿常规,肝功能(谷丙转氨酶)、肾功能(肌酐、尿素氮)检查均在正常范围。
2.2.3排除标准：
(1)已知对试验组和对照组的药物中的成分过敏者；(2)妊娠期或哺乳期的妇女；(3)入组前2周内曾系统应用影响AD治疗的糖皮质激素或其他免疫调节剂的患者；(4)患有恶性肿瘤、皮肌炎、硬皮病、红斑狼疮等免疫相关疾病的患者；(5)从事危险作业者,如驾驶员、飞行员、高空作业者等等。
2.2.4剔除标准：
(1)治疗过程中出现严重不良反应等现象,不宜继续接受试验者；(2)研究过程中依从性差或自行退出试验,影响评价者；(3)非规定范围内联合用药,特别是合用对本病疗效影响较大的药物者。
2.3治疗方法
2.3.1试验组治疗方法
采用龙牡汤内服加外敷。
药物组成：生龙骨30g,煅牡蛎30g,骨碎补10g,生地10g,地肽子10g。
用法用量：前两煎兑汁分两次温服。第三次加水煎沸放置室温,以备湿敷用。内服药：龙牡汤200ml/次,2次／日(成人及12岁以上儿童按原剂量；7-12岁儿童为原剂量的1/2；2-6岁儿章为原剂量的1/3)；外用药：使用无菌纱布折叠成4-6层,同皮损大小,将纱布置于药液中浸湿后拿出,轻拧至纱布不滴水为度,外敷于皮损处。每日2次,每次10-20分钟,每天湿敷2-3次。皮损面积过大者和幼儿湿敷时间不宜太长,并且应采取分段湿敷。
2.3.2对照组治疗方法
对照组采用氯雷他定片口服加丁酸氢化可的松乳膏外用。
用法用量：氯雷他定片口服：成人及12岁以上儿童10mg/片,1片／次,1次／F1；7-12岁儿童,5mg/日；2-6岁儿童3mg/日。睡前服或瘙痒显著发作的提前半小时服用。
外用：丁酸氢化可的松乳膏外抹于皮损处,2次／日。
两组均治疗8周。
2.4观察指标
2.4.1主要疗效评价指标——SCORAD (scoring atopic dermatitis, SCORAD)评分
采用欧洲特应性皮炎研究组(European Task Force on Atopic Dennatitis, ETFAD)提出的评分标准(SCORAD评分),包括客观体征皮肽病变范围(A)、皮损严重程度(B)和主观症状瘙痒和影响睡眠程度(C)评分进行疗效判定。
总分计算公式为A/5+7B/2+C
试验组和对照组在治疗前、第2刷、第4周、第8周各访视点记录皮肤病变面积、皮损严重程度、瘙痒和影响睡眠程度的评分及SCORAD评分。
2.4.2临床疗效评价标准
疗效判定标准按四级疗效标准评定,计算公式(尼莫地平法)：治疗率=(治疗前SCORAD分值一治疗后SCORAD分值)／治疗前SCORAD分值×100%。
2.4.3生活质量评分
采用目前最常用的皮肤病学生活质量指数量表,分DLQI (dermatology life quality index, DLQI)量表(成人及12岁以上儿童填写)、CDLQI(the Children's dermatology life quality index, CDLQI)量表(7岁<儿童≤12岁的家长填写)、IDLQI (the infants' dermatology life quality index, IDLQI)量表(2岁<儿章≤7岁的家长填写)。试验组和对照组在治疗前、第2周、第4周、第8周各访视点记录生活质量评分。
2.4.4用药成本-效果分析
本试验仅计算直接医疗成本中患者的用药成本,1个疗程(8周)后,进行用药成本-效果分析。
2.4.5复发情况的生存曲线分析
对试验组和对照组于治疗结束后的第3个月、第6个月进行随访,记录SCORAD评分。若随访时点的SCORAD分值>疗程结束后(8周)的SCORAD分值,视为复发。对复发情况进行生存曲线分析。
2.4.6安全性评价方法
试验组患者于试验前、后分别检查血常规、尿常规,肝功能(谷丙转氨酶)、肾功能(肌酐、尿素氮)。试验期间记录两组的不良事件,包括不良事件的发生时间、严重程度、持续时间、采取的措施和转归。
2.5统计原则及方法
本研究的定量资料(积分值)采用的是成组资料的t检验(如果方差不齐,则采用秩和检验)。对定性资料(疗效)则采用X2检验。对复发情况采用COX比例风险回归模型,Wald检验。统计软件为SAS9.2。
3结果
全部病例来自2008年11月至2010年10月中国中医科学院西苑医院皮肤科门诊。共纳入符合条件的AD患者64例,试验组32例,对照组32例。对照组2例病例入组后即失访,此2例剔除。试验组和对照组各1例,于治疗2周复诊后无法复诊,对此2例数据做末次访视数据结转(Last Observation Carried Forward, LOCF),试验结束后对该62例患者按意向性分析(intention to treat, ITT)
3.1基线比较试验组32例,男13例,女19例；对照组30例,男16例,女14例,两组性别比较P>0.05,无显著差异,说明两组性别具有可比性；试验组年龄2-33岁,平均年龄10.50+5.97岁；对照组年龄2-36岁,平均年龄10.52±5.76岁,两组年龄比较P>0.05,无显著差异,说明两组年龄具有可比性；试验组和对照组治疗前皮损面积、皮损严重程度、瘙痒和影响睡眠程度的评分比较,P>0.05,无显著性差异；两组治疗前SCORAD评分比较,P>0.05,无显著性差异,说明两组的病情严重程度方面具有可比性；试验组和对照组治疗前生活质量评分比较,P>0.05,无显著性差异,说明两组的生活质量评分具有可比性。
3.2试验组治疗2、4、8周后皮损面积评分,与治疗前比较无显著性差异(第2周：t=0.23,P=0.82>0.05；第4周：t=0.89,P=0.38>0.05；第8周：t=1.59,P=0.12>0.05)；对照组治疗2、4、8周后皮损面积评分,亦与治疗前比较无显著性差异(第2周：t=0.55,P=0.58>0.05；第4周：t=1.43,P=0.16>0.05；第8周：t=1.80,P=0.08>0.05)。说明两组在对皮损面积改善方面疗效不明显,或者疗程不够,皮损的色沉等尚未消退。
3.3试验组治疗4、8周后皮损严重程度评分,与治疗前比较有显著性差异(第4周：t=3.37,P=0.001<0.05；第8周：t=4.49,P=0.0001<0.05)；对照组治疗4、8周后皮损严重程度评分,与治疗前比较有显著性差异(第4周：t=2.22,P=0.03<0.05；第8周：t=4.47,P=0.0001<0.05)。说明两组在对皮损严重程度改善方面疗效明显。
3.4试验组治疗4、8周后瘙痒和影响睡眠程度评分,与治疗前比较有显著性差异(第4周：t=2.45,P=0.02<0.05；第8周：t=4.69,P=0.0000<0.05)；对照组治疗4、8周后瘙痒和影响睡眠程度评分,与治疗前比较有显著性差异(第4周：t=2.40,P=0.02<0.05；第8周：t=3.52,P=0.0009<0.05)。说明两组在对瘙痒和影响睡眠程度的改善方面疗效明显。
3.5试验组治疗4、8周后SCORAD评分,与治疗前比较有显著性差异(第4周：t=3.31,P=0.002<0.05；第8周：t=5.17,P=0.0001<0.05)；对照组治疗2、4、8周后SCORAD评分,与治疗前比较有显著性差异(第2周：t=2.20,P=O.03<0.05；第4周：t=2.43,P=0.02<0.05；第8周：t=4.19,P=0.0001<0.05)。说明两组对特应性皮炎都有显著的疗效。试验组和对照组两组之间各访视点(2周、4周、8周)SCORAD评分比较,P>0.05,无显著性差异。试验组和对照组两组之间治疗8周后比较,治疗后皮肤病变面积、皮损严重程度、瘙痒和影响睡眠程度的评分及SCORAD评分比较,P>0.05,均无显著性差异,说明两组之间比较,疗效相当。
3.6疗程结束后(8周),试验组总有效率81.25%,对照组总有效率83.33%,两组比较无显著性差异(X2=2.17,P=0.14>0.05),说明两组治疗特应性皮炎的近期(8周)疗效相当。
3.7两组皮肤病生活质量量表评分治疗前后有显著性差异(试验组t=4.43,P=0.0001<0.05；对照组t=3.77,P=0.0004<0.05),说明两组在改善生活质量方面都有疗效。两组之间治疗后比较,无显著性差异(t=-0.75,P=0.45>0.05),说明两组对生活质量的改善无显著性差异。
3.8用药成本-效果分析,试验组用药成本-效果比约为3.45；对照组用药成本-效果比约5.39。
3.9复发情况比较：试验组第3个月复发1例,对照组复发11例；试验组第6个月复发7例,对照组复发7例。疗程结束后第6个月,对照组的复发风险是试验组的3.14倍,两组比较有显著性差异(P<0.05)。
3.10试验组治疗前后实验室检查无异常,试验组和对照组的安全性比较,无显著性差异(P>0.05)。
4结论
4.1龙牡汤治疗特应性皮炎的临床疗效肯定。
4.2龙牡汤能明显改善特应性皮炎患者的生活质量。
4.3龙牡汤的经济花费较少。
4.4龙牡汤在维持病情长期稳定、延缓复发方面,有一定的优势。
4.5龙牡汤无明显毒副作用,临床用药安全。
基于以上结果,本研究初步证实了龙牡汤内服加外敷治疗特应性皮炎,疗效肯定,其特点是能延缓复发、安全、价廉,值得临床推广应用。
l.Objective:To observe the efficacy, safety, cost-effectiveness analysis (CEA) and recurrence of Longmu decoction in the treatment of Atopic dermatitis(AD).
2.Method:
2.1The method of random parallel control was used in this clinical trial.
2.2Patients selection:
2.2.1Diagnostic Criteria
Western Medicine Diagnostic Criteria:Hanifin and Rajka AD Diagnostic Criteria.
Traditional Chinese Medicine Diagnostic Criteria:Syndrome of blood deficiency and wind-dryness in Si Wan Feng according to Guiding Principles of Cinical Researches on New Drugs of Traditional Chinese Medicine.
2.2.2Inclusion Criteria
(1)In accordence with Western Medicine Diagnostic Criteria (2) In accordence with Traditional Chinese Medicine Diagnostic Criteria (3)age from2to40.(4)The patients who were informed and signed consent to participate.(5) The patients whose routine blood examination, routine urine examination, ALT, Cr and BUN were nomal. Exclusion Criterion:
(1)The patients who are allergic to the medicine.(2)Pregnancy or breast-feeding women.(3)The patients who used steroids and anti-allergy in the past2weeks.(4)Immunosuppressed patients (such as lymphoma) or in patients with a history of malignant disease.(5)The patients whose occupations are dangeroussuch as pilot and so on.
2.3Treatment Methods
2.3.1Treatment group
The patients of treatment group take Longmu decoction orally twice a day for2months. At the same time, the affected area applied with Longmu decoction externally. Component of Longmu decoction:Os Draconis(Longgu)30g, Concha Ostreae(Muli)30g, Rhizoma Drynariae (Gusuibu)10g, Radix Rehmanniae Recens(Shengdihuang)10g, Fructus Koch/ae(Difuzi)10g.
2.3.2Contol group
The patients of control group take Loratadine tablets orally once at night and Hydrocortisone Butyrate cream twice a day for external use for2months.
Visits are scheduled on preliminary diagnosis (before treatment),2,4,8,12,24weeks after treatment.
2.4Observation items
2.4.1evaluation index
The severity of skin was evaluated by the index of scoring atopic dermatitis (SCORAD) which was proposed by European Task Force on Atopic Dermatitis (ETFAD). The SCORAD index includes the change of symptoms and the physical signs, lesion area of skin, disease severity, pruritus degree,etc.
2.4.2Measurement formula
The treatment rate=(pre-treatment SCORAD score—post-treatment SCORAD score)/pre-treatment SCORAD score×100%
2.4.3Evaluation of quality of life
The effects of atopic dermatitis on the quality of life of patients was evaluated by dermatology life quality index (DLQI)(age over12), the Children's dermatology life quality index (CDLQI)(age from7to12), the infants'dermatology life quality index (IDLQI)(age from2to7)
2.4.4. Cost-effectiveness analysis
The Cost-effectiveness analysis (CEA) of the experimental group and the control group was evaluated after2months treatment.
2.4.5Analysis of recurrence
After3,6months follow-up, the recurrence were recorded by using the SCORAD index.
2.4.6. Safety evaluation
The patients'routine blood examination, routine urine examination, ALT, Cr and BUN were measured before and after treatment. The adverse events during the treatment were recorded.
2.5Statistical Analysis
Statistical analyses were performed by SAS9.2. Test oft andX2statistical methods were used to evaluate the difference between the two groups. COX regression and Wald test were used to evaluate the recurrence.The signicicance was determined as P<0.05.
Result
There were64cases included in this trial. All the cases came from the dermatologists of Xiyuan Hospital of China Academy of Chinese Medical Sciences. The number of patients of treatment group and control group was both32, but2cases of control group were lost after the first treatment. There was separately1case lost in both group after the2weeks of treatment and we used LOCF(Last Observation Carried Forward, LOCF)to evaluate the date. We made the ITT (intention to treat, ITT) Analysis after the experiment.
There were13men and19women in the treatment group and16men and14women in the control group. There is no significant difference of sex between experimental group and control group.
The treatment group aged2to33years old, average age10.50±5.97. The control group aged2to36years old, average age10.52±5.76. There is no significant difference of age between the two groups.
There is no significant difference between treatment group and control group of the total scores of symptoms and signs before the test (P>0.05).
There is no significant difference between two groups of DLQI/CDLQI/IDLQI scores (P>0.05).
Both treatment group and control group experience significant improvement respectively in the total scores of symptoms and signs including scores of lesion area of skin, scores of disease severity, scores of pruritus degree and SCORAD score (P<0.05).There is no significant difference between treatment group and control group of the total scores of symptoms and signs(P>0.05).
Both treatment group and control group experience significant improvement respectively in symptoms and feelings, daily activities, leisure and total DLQI scores, but there is no significant difference between two groups (P>0.05).
The efficacy rates are81.25%and83.33%for treatment group and control group respectively,with non-significance difference between them (P>0.05).
Among patients of treatment group there are1cases and7cases of recurrence at the third and sixth months follow-up respectively. Among patients of control group there are11cases and7cases of recurrence after3,6months follow-up respectively. The recurrence risk of control group is3.14times to the treatment group.
There is no significant difference of safty between the two groups, and Longmu decoction cost lower.
Conclusion:Longmu decoction in the treatment of Atopic dermatitis is effective and safe. At the same time, Longmu decoction can significantly lower relapse rate, prolonge time to relapse and cost lower.
1.1观察龙牡汤治疗血虚风燥型特应性皮炎的近期临床疗效；
1.2对龙牡汤和西医治疗方案进行用药成本-效果分析；
1.3观察龙牡汤治疗特应性皮炎的远期疗效——复发情况的影响；
1.4评价龙牡汤的临床用药安全性；
通过以上的观察研究,为特应性皮炎的临床治疗提供一种安全、有效、价廉的治疗方案。
2方法
2.1研究设计方法
采用平行随机对照方法。用密闭信封法,参照随机数字表按照1：1产生试验组和对照组的随机安排。将对应的治疗分配信笺密封入信封,形成随机信件。按纳入病例的先后顺序将患者随机分配到试验组或对照组。
2.2病例选择
2.2.1诊断标准：
西医诊断标准：参照Hanifin与Rajka诊断标准：
主要特征包括瘙痒、典型的皮损形态和分布等4条特征；次要特征包括干皮症、鱼鳞病／掌纹症／毛囊角化症、即刻型皮试反应、血清IgE增高等23条特征,凡符合上述主要特征3项或3项以上,加次要特征3项或3项以上即可诊断为特应性皮炎。
中医辨证标准
参照《中药新药临床研究指导原则》制定的四弯风辨证分型标准中的血虚风燥证：
主症包括皮肤干燥、皮损色暗或色素沉着,或肥厚、苔藓样变、瘙痒抓痕血痂、病程久,反复发作。次症包括口干不欲饮、纳差,腹胀、舌质淡,苔白、脉弦细。当患者符合以上证型主症中3项或3项以上,同时具备次症中任何2项或2项以上,即可诊断为该证型。
2.2.2纳入标准：
(1)符合西医特应性皮炎(Atopic Dermatitis, AD)诊断标准；(2)符合中医血虚风燥证的诊断；(3)年龄2-40岁的患者；(4)签署知情同意书、依从性好的患者；(5)治疗前血常规、尿常规,肝功能(谷丙转氨酶)、肾功能(肌酐、尿素氮)检查均在正常范围。
2.2.3排除标准：
(1)已知对试验组和对照组的药物中的成分过敏者；(2)妊娠期或哺乳期的妇女；(3)入组前2周内曾系统应用影响AD治疗的糖皮质激素或其他免疫调节剂的患者；(4)患有恶性肿瘤、皮肌炎、硬皮病、红斑狼疮等免疫相关疾病的患者；(5)从事危险作业者,如驾驶员、飞行员、高空作业者等等。
2.2.4剔除标准：
(1)治疗过程中出现严重不良反应等现象,不宜继续接受试验者；(2)研究过程中依从性差或自行退出试验,影响评价者；(3)非规定范围内联合用药,特别是合用对本病疗效影响较大的药物者。
2.3治疗方法
2.3.1试验组治疗方法
采用龙牡汤内服加外敷。
药物组成：生龙骨30g,煅牡蛎30g,骨碎补10g,生地10g,地肽子10g。
用法用量：前两煎兑汁分两次温服。第三次加水煎沸放置室温,以备湿敷用。内服药：龙牡汤200ml/次,2次／日(成人及12岁以上儿童按原剂量；7-12岁儿童为原剂量的1/2；2-6岁儿章为原剂量的1/3)；外用药：使用无菌纱布折叠成4-6层,同皮损大小,将纱布置于药液中浸湿后拿出,轻拧至纱布不滴水为度,外敷于皮损处。每日2次,每次10-20分钟,每天湿敷2-3次。皮损面积过大者和幼儿湿敷时间不宜太长,并且应采取分段湿敷。
2.3.2对照组治疗方法
对照组采用氯雷他定片口服加丁酸氢化可的松乳膏外用。
用法用量：氯雷他定片口服：成人及12岁以上儿童10mg/片,1片／次,1次／F1；7-12岁儿童,5mg/日；2-6岁儿童3mg/日。睡前服或瘙痒显著发作的提前半小时服用。
外用：丁酸氢化可的松乳膏外抹于皮损处,2次／日。
两组均治疗8周。
2.4观察指标
2.4.1主要疗效评价指标——SCORAD (scoring atopic dermatitis, SCORAD)评分
采用欧洲特应性皮炎研究组(European Task Force on Atopic Dennatitis, ETFAD)提出的评分标准(SCORAD评分),包括客观体征皮肽病变范围(A)、皮损严重程度(B)和主观症状瘙痒和影响睡眠程度(C)评分进行疗效判定。
总分计算公式为A/5+7B/2+C
试验组和对照组在治疗前、第2刷、第4周、第8周各访视点记录皮肤病变面积、皮损严重程度、瘙痒和影响睡眠程度的评分及SCORAD评分。
2.4.2临床疗效评价标准
疗效判定标准按四级疗效标准评定,计算公式(尼莫地平法)：治疗率=(治疗前SCORAD分值一治疗后SCORAD分值)／治疗前SCORAD分值×100%。
2.4.3生活质量评分
采用目前最常用的皮肤病学生活质量指数量表,分DLQI (dermatology life quality index, DLQI)量表(成人及12岁以上儿童填写)、CDLQI(the Children's dermatology life quality index, CDLQI)量表(7岁<儿童≤12岁的家长填写)、IDLQI (the infants' dermatology life quality index, IDLQI)量表(2岁<儿章≤7岁的家长填写)。试验组和对照组在治疗前、第2周、第4周、第8周各访视点记录生活质量评分。
2.4.4用药成本-效果分析
本试验仅计算直接医疗成本中患者的用药成本,1个疗程(8周)后,进行用药成本-效果分析。
2.4.5复发情况的生存曲线分析
对试验组和对照组于治疗结束后的第3个月、第6个月进行随访,记录SCORAD评分。若随访时点的SCORAD分值>疗程结束后(8周)的SCORAD分值,视为复发。对复发情况进行生存曲线分析。
2.4.6安全性评价方法
试验组患者于试验前、后分别检查血常规、尿常规,肝功能(谷丙转氨酶)、肾功能(肌酐、尿素氮)。试验期间记录两组的不良事件,包括不良事件的发生时间、严重程度、持续时间、采取的措施和转归。
2.5统计原则及方法
本研究的定量资料(积分值)采用的是成组资料的t检验(如果方差不齐,则采用秩和检验)。对定性资料(疗效)则采用X2检验。对复发情况采用COX比例风险回归模型,Wald检验。统计软件为SAS9.2。
3结果
全部病例来自2008年11月至2010年10月中国中医科学院西苑医院皮肤科门诊。共纳入符合条件的AD患者64例,试验组32例,对照组32例。对照组2例病例入组后即失访,此2例剔除。试验组和对照组各1例,于治疗2周复诊后无法复诊,对此2例数据做末次访视数据结转(Last Observation Carried Forward, LOCF),试验结束后对该62例患者按意向性分析(intention to treat, ITT)
3.1基线比较试验组32例,男13例,女19例；对照组30例,男16例,女14例,两组性别比较P>0.05,无显著差异,说明两组性别具有可比性；试验组年龄2-33岁,平均年龄10.50+5.97岁；对照组年龄2-36岁,平均年龄10.52±5.76岁,两组年龄比较P>0.05,无显著差异,说明两组年龄具有可比性；试验组和对照组治疗前皮损面积、皮损严重程度、瘙痒和影响睡眠程度的评分比较,P>0.05,无显著性差异；两组治疗前SCORAD评分比较,P>0.05,无显著性差异,说明两组的病情严重程度方面具有可比性；试验组和对照组治疗前生活质量评分比较,P>0.05,无显著性差异,说明两组的生活质量评分具有可比性。
3.2试验组治疗2、4、8周后皮损面积评分,与治疗前比较无显著性差异(第2周：t=0.23,P=0.82>0.05；第4周：t=0.89,P=0.38>0.05；第8周：t=1.59,P=0.12>0.05)；对照组治疗2、4、8周后皮损面积评分,亦与治疗前比较无显著性差异(第2周：t=0.55,P=0.58>0.05；第4周：t=1.43,P=0.16>0.05；第8周：t=1.80,P=0.08>0.05)。说明两组在对皮损面积改善方面疗效不明显,或者疗程不够,皮损的色沉等尚未消退。
3.3试验组治疗4、8周后皮损严重程度评分,与治疗前比较有显著性差异(第4周：t=3.37,P=0.001<0.05；第8周：t=4.49,P=0.0001<0.05)；对照组治疗4、8周后皮损严重程度评分,与治疗前比较有显著性差异(第4周：t=2.22,P=0.03<0.05；第8周：t=4.47,P=0.0001<0.05)。说明两组在对皮损严重程度改善方面疗效明显。
3.4试验组治疗4、8周后瘙痒和影响睡眠程度评分,与治疗前比较有显著性差异(第4周：t=2.45,P=0.02<0.05；第8周：t=4.69,P=0.0000<0.05)；对照组治疗4、8周后瘙痒和影响睡眠程度评分,与治疗前比较有显著性差异(第4周：t=2.40,P=0.02<0.05；第8周：t=3.52,P=0.0009<0.05)。说明两组在对瘙痒和影响睡眠程度的改善方面疗效明显。
3.5试验组治疗4、8周后SCORAD评分,与治疗前比较有显著性差异(第4周：t=3.31,P=0.002<0.05；第8周：t=5.17,P=0.0001<0.05)；对照组治疗2、4、8周后SCORAD评分,与治疗前比较有显著性差异(第2周：t=2.20,P=O.03<0.05；第4周：t=2.43,P=0.02<0.05；第8周：t=4.19,P=0.0001<0.05)。说明两组对特应性皮炎都有显著的疗效。试验组和对照组两组之间各访视点(2周、4周、8周)SCORAD评分比较,P>0.05,无显著性差异。试验组和对照组两组之间治疗8周后比较,治疗后皮肤病变面积、皮损严重程度、瘙痒和影响睡眠程度的评分及SCORAD评分比较,P>0.05,均无显著性差异,说明两组之间比较,疗效相当。
3.6疗程结束后(8周),试验组总有效率81.25%,对照组总有效率83.33%,两组比较无显著性差异(X2=2.17,P=0.14>0.05),说明两组治疗特应性皮炎的近期(8周)疗效相当。
3.7两组皮肤病生活质量量表评分治疗前后有显著性差异(试验组t=4.43,P=0.0001<0.05；对照组t=3.77,P=0.0004<0.05),说明两组在改善生活质量方面都有疗效。两组之间治疗后比较,无显著性差异(t=-0.75,P=0.45>0.05),说明两组对生活质量的改善无显著性差异。
3.8用药成本-效果分析,试验组用药成本-效果比约为3.45；对照组用药成本-效果比约5.39。
3.9复发情况比较：试验组第3个月复发1例,对照组复发11例；试验组第6个月复发7例,对照组复发7例。疗程结束后第6个月,对照组的复发风险是试验组的3.14倍,两组比较有显著性差异(P<0.05)。
3.10试验组治疗前后实验室检查无异常,试验组和对照组的安全性比较,无显著性差异(P>0.05)。
4结论
4.1龙牡汤治疗特应性皮炎的临床疗效肯定。
4.2龙牡汤能明显改善特应性皮炎患者的生活质量。
4.3龙牡汤的经济花费较少。
4.4龙牡汤在维持病情长期稳定、延缓复发方面,有一定的优势。
4.5龙牡汤无明显毒副作用,临床用药安全。
基于以上结果,本研究初步证实了龙牡汤内服加外敷治疗特应性皮炎,疗效肯定,其特点是能延缓复发、安全、价廉,值得临床推广应用。
l.Objective:To observe the efficacy, safety, cost-effectiveness analysis (CEA) and recurrence of Longmu decoction in the treatment of Atopic dermatitis(AD).
2.Method:
2.1The method of random parallel control was used in this clinical trial.
2.2Patients selection:
2.2.1Diagnostic Criteria
Western Medicine Diagnostic Criteria:Hanifin and Rajka AD Diagnostic Criteria.
Traditional Chinese Medicine Diagnostic Criteria:Syndrome of blood deficiency and wind-dryness in Si Wan Feng according to Guiding Principles of Cinical Researches on New Drugs of Traditional Chinese Medicine.
2.2.2Inclusion Criteria
(1)In accordence with Western Medicine Diagnostic Criteria (2) In accordence with Traditional Chinese Medicine Diagnostic Criteria (3)age from2to40.(4)The patients who were informed and signed consent to participate.(5) The patients whose routine blood examination, routine urine examination, ALT, Cr and BUN were nomal. Exclusion Criterion:
(1)The patients who are allergic to the medicine.(2)Pregnancy or breast-feeding women.(3)The patients who used steroids and anti-allergy in the past2weeks.(4)Immunosuppressed patients (such as lymphoma) or in patients with a history of malignant disease.(5)The patients whose occupations are dangeroussuch as pilot and so on.
2.3Treatment Methods
2.3.1Treatment group
The patients of treatment group take Longmu decoction orally twice a day for2months. At the same time, the affected area applied with Longmu decoction externally. Component of Longmu decoction:Os Draconis(Longgu)30g, Concha Ostreae(Muli)30g, Rhizoma Drynariae (Gusuibu)10g, Radix Rehmanniae Recens(Shengdihuang)10g, Fructus Koch/ae(Difuzi)10g.
2.3.2Contol group
The patients of control group take Loratadine tablets orally once at night and Hydrocortisone Butyrate cream twice a day for external use for2months.
Visits are scheduled on preliminary diagnosis (before treatment),2,4,8,12,24weeks after treatment.
2.4Observation items
2.4.1evaluation index
The severity of skin was evaluated by the index of scoring atopic dermatitis (SCORAD) which was proposed by European Task Force on Atopic Dermatitis (ETFAD). The SCORAD index includes the change of symptoms and the physical signs, lesion area of skin, disease severity, pruritus degree,etc.
2.4.2Measurement formula
The treatment rate=(pre-treatment SCORAD score—post-treatment SCORAD score)/pre-treatment SCORAD score×100%
2.4.3Evaluation of quality of life
The effects of atopic dermatitis on the quality of life of patients was evaluated by dermatology life quality index (DLQI)(age over12), the Children's dermatology life quality index (CDLQI)(age from7to12), the infants'dermatology life quality index (IDLQI)(age from2to7)
2.4.4. Cost-effectiveness analysis
The Cost-effectiveness analysis (CEA) of the experimental group and the control group was evaluated after2months treatment.
2.4.5Analysis of recurrence
After3,6months follow-up, the recurrence were recorded by using the SCORAD index.
2.4.6. Safety evaluation
The patients'routine blood examination, routine urine examination, ALT, Cr and BUN were measured before and after treatment. The adverse events during the treatment were recorded.
2.5Statistical Analysis
Statistical analyses were performed by SAS9.2. Test oft andX2statistical methods were used to evaluate the difference between the two groups. COX regression and Wald test were used to evaluate the recurrence.The signicicance was determined as P<0.05.
Result
There were64cases included in this trial. All the cases came from the dermatologists of Xiyuan Hospital of China Academy of Chinese Medical Sciences. The number of patients of treatment group and control group was both32, but2cases of control group were lost after the first treatment. There was separately1case lost in both group after the2weeks of treatment and we used LOCF(Last Observation Carried Forward, LOCF)to evaluate the date. We made the ITT (intention to treat, ITT) Analysis after the experiment.
There were13men and19women in the treatment group and16men and14women in the control group. There is no significant difference of sex between experimental group and control group.
The treatment group aged2to33years old, average age10.50±5.97. The control group aged2to36years old, average age10.52±5.76. There is no significant difference of age between the two groups.
There is no significant difference between treatment group and control group of the total scores of symptoms and signs before the test (P>0.05).
There is no significant difference between two groups of DLQI/CDLQI/IDLQI scores (P>0.05).
Both treatment group and control group experience significant improvement respectively in the total scores of symptoms and signs including scores of lesion area of skin, scores of disease severity, scores of pruritus degree and SCORAD score (P<0.05).There is no significant difference between treatment group and control group of the total scores of symptoms and signs(P>0.05).
Both treatment group and control group experience significant improvement respectively in symptoms and feelings, daily activities, leisure and total DLQI scores, but there is no significant difference between two groups (P>0.05).
The efficacy rates are81.25%and83.33%for treatment group and control group respectively,with non-significance difference between them (P>0.05).
Among patients of treatment group there are1cases and7cases of recurrence at the third and sixth months follow-up respectively. Among patients of control group there are11cases and7cases of recurrence after3,6months follow-up respectively. The recurrence risk of control group is3.14times to the treatment group.
There is no significant difference of safty between the two groups, and Longmu decoction cost lower.
Conclusion:Longmu decoction in the treatment of Atopic dermatitis is effective and safe. At the same time, Longmu decoction can significantly lower relapse rate, prolonge time to relapse and cost lower.
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