Eczema is a skin inflammatory disease caused by a variety of internal and external factors, including immune factors, genetic factors, endocrine changes, environmental factors, and infectious factors [
Longdan Xiegan decoction (LDXGD) is originated from Wang Ang’s Prescriptions and composed of 10 herbs, including Longdancao (
This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [
Seven electronic databases, including PubMed (https://
Type of participants: research involved patients with any type of eczema. Type of study: only RCTs that assessed the efficacy of LDXGD for the treatment of eczema were eligible. Type of intervention: LDXGD must be included in the herbal formula used in the experimental group. There were no restrictions on the drug dosage, frequency, or treatment time. The control group was treated with WM, including cetirizine, loratadine, ebastine, and azelastine. Type of results: the efficacy of LDXGD on the treatment of eczema was evaluated through the cure rate and the total effective rate. Secondary outcomes included the recurrence rate and the levels of IL-6, IL-8, and TNF-
If the above-described conditions were not met, the literature is to be excluded. Besides, the following conditions should also be excluded: Duplicate publications. Animal experiments, mechanisms, studies, reviews, experience, and case reports. Not available full text of the literature. Whenever in the experimental group, LDXGD was used as adjuvant therapy or contained other traditional Chinese medicine formulation. Whenever the control group contained LDXGD.
Two reviewers (Fan Zhang and Shuai Kang) separately searched the aforementioned databases and listed the titles of all articles. According to the inclusion criteria, by looking through the title and abstract, they excluded papers that were not eligible. Next, they screened the contents of the unclear articles further. If there were some overlaps or repetitions in the article, only the latest information was included. Through discussions with the corresponding authors of the study, the dispute about the selection of documents was resolved.
According to the inclusion and exclusion criteria, two reviewers (Fan Zhang and Shuai Kang) independently screened the literature, extracted the data, and carried out cross-checking. When differences arose, a third party (Weiling Yuan) was involved in discussion or consultation, to assist in judgment. The extracted data included the first author, publication time, basic data of the study subjects, the sample size of the experimental group and control group, specific details of the intervention measures, outcome indicators, and data [
Two reviewers (Lidong Gao and Chengxian Li) independently evaluated the methodological quality of these trials according to Cochran’s Systematic Review Handbook risk assessment tool. The risk of bias includes 7 items: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other bias. Differences among the reviewers were resolved by a discussion [
RevMan 5.3 statistical software was used for statistical analysis. Relative risk (RR) and 95% confidence interval (CI) were used for the binomial variables. The mean difference (MD) and 95% CI were used when the continuous variables were the same unit of measurement, and the standard mean difference (SMD) and 95% CI were used when different units of measurement were used. Heterogeneity was judged on the basis of the results of
A total of 487 studies were retrieved from the seven electronic databases (PubMed (
Inclusion process and results of the relevant articles.
A total of 14 RCTs involving 1080 patients were included, published from 2009 to 2019. All studies were published in China. Sample sizes ranged from 50 to 125, with significant differences in the course of disease and age. The intervention of the experimental group included LDXGD alone or combined with WM, while the control group was based on WM monotherapy, including cetirizine, loratadine, ebastine, and azelastine. The course of treatment ranged from 10 to 21 days. Five studies [
The general characteristics of the 14 trials.
Study | Sample size (T/C) | Course of the disease (mean or range) (T/C) | Age (mean or range) (T/C) | Intervention | Duration of use | Outcome | |
---|---|---|---|---|---|---|---|
T | C | ||||||
Jin Deng, 2017 [ | 65/60 | NR | 44.2 ± 5.3/42.8 ± 4.6 | LDXGD + ebastine | Ebastine | 10d | 1, 2, 4 |
Xiangbo Dong, 2013 [ | 36/36 | NR | NR | LDXGD + ebastine | Ebastine | 14d | 1, 2 |
Hui Hui, 2016 [ | 50/50 | NR | NR | LDXGD + compound econazole nitrate cream | Compound econazole nitrate cream | 15d | 1, 2, 3 |
Dashan Qian, 2019 [ | 26/26 | (3.25 ± 1.13/4.23 ± 1.11) m | 35.31 ± 10.24/36.25 ± 10.16 | LDXGD + azelastine | Azelastine | 10d | 1, 2, 4, 5, 6, 7 |
Dahua Wu, 2019 [ | 39/39 | NR | NR | LDXGD + cetirizine | Cetirizine | 21d | 1, 2, 4, 5, 6, 7 |
Zhulan Zhou, 2010 [ | 44/41 | NR | 38.95 ± 15.36/39.31 ± 15.71 | LDXGD + qumixin cream | Qumixin cream | 21d | 1, 2, 3 |
Xianggong Zhu, 2016 [ | 40/40 | (5.5 ± 2.3/5.3 ± 2.1) m | 44.1 ± 4.8/43.5 ± 4.7 | LDXGD + cetirizine | Cetirizine | 10d | 1, 2, 4, 5, 6, 7 |
Zushu Duan, 2011 [ | 30/30 | (5.15 ± 3.76/6.74 ± 4.47) d | 37.54 ± 9.36/35.13 ± 12.91 | LDXGD | Cetirizine | 14d | 1, 2 |
Qifang Gao, 2016 [ | 25/25 | (9.03 ± 0.96/8.64 ± 0.81) d | 41.09 ± 8.03/40.63 ± 7.65 | LDXGD | Loratadine | NR | 1, 2 |
Jianming Li, 2019 [ | 25/25 | (2.1 ± 0.60/2.10 ± 0.57) y | 36.6 ± 2.17/36.78 ± 2.25 | LDXGD | Cetirizine | 21d | 1, 2, 3 |
Chengcheng Liao, 2017 [ | 34/34 | (1.53 ± 0.53/1.32 ± 0.64) d | 34.67 ± 12.75/35.21 ± 13.25 | LDXGD | Loratadine | 14d | 1, 2 |
Yanshun Lu, 2011 [ | 42/41 | (5.39 ± 1.22/5.27 ± 2.13) d | 36.25 ± 4.38/35.94 ± 6.03 | LDXGD | Levocetirizine | 21d | 1, 2 |
Jihong Luo, 2013 [ | 40/40 | (2.6 ± 1.1/2.8 ± 1.3) y | 64.2 ± 5.4/65.3 ± 4.8 | LDXGD | Cetirizine | 21d | 1, 2 |
Wenwei Ye, 2009 [ | 52/45 | 112/113 d | 36.6/36.9 | LDXGD | Ebastine | 20d | 1, 2, 4 |
T: experimental group; C: control group; NR: no record; d: day; m: month; y: year; 1: cure rate; 2: total effective rate; 3: recurrence rate; 4: adverse reaction rate; 5: IL-6; 6: IL-8; and 7: TNF-
Although randomization was announced in all of the included trials, 6 studies [
Risk of bias graph of the 14 articles.
Risk of bias summary graph of the 14 articles.
The curative-effect standard of eczema referred to “Guiding Principles of Clinical Research of Traditional Chinese Medicine.” Standard of cure: all skin lesions and itching symptoms disappeared. The treatment efficiency reached 100%. Standard of significantly effective: most of the skin lesions disappeared, and pruritus symptoms were significantly reduced. The treatment efficiency was more than 70%. Standard of effective: skin lesions partially disappear, and pruritus symptoms were improved. The treatment efficiency was more than 30%. Standard of invalidity: skin lesions had not subsided significantly, and pruritus had not improved or worsened. Or the treatment efficiency had not reached the effective standard. The total effective rate was the sum of the cure rate, significant effective rate, and effective rate.
A total of 14 [
Forest plot and meta-analysis of the cure rate.
A total of 14 [
Forest plot and meta-analysis of the total effective rate.
A total of 3 [
Forest plot and meta-analysis of the recurrence rate.
A total of 3 [
Analysis of IL-6, IL-8, and TNF-
Outcomes | Number of included studies | Heterogeneity | Effect model | SMD (95%CI) | ||
---|---|---|---|---|---|---|
IL-6 | 3 | 0.49 | 0 | Fixed-effects model | −1.61 [−1.91, −1.30] | <0.00001 |
IL-8 | 3 | 0.31 | 13 | Fixed-effects model | −1.68 [−1.99, −1.38] | <0.00001 |
TNF- | 3 | 0.59 | 0 | Fixed-effects model | −1.68 [−1.98, −1.37] | <0.00001 |
The main adverse reactions included abdominal pain, diarrhea, nausea, dry mouth, fatigue, dizziness, and lethargy. A total of 5 [
Forest plot and meta-analysis of the adverse reaction rate.
Sensitivity analysis showed that all single studies could not change the final outcomes, which meant that this meta-analysis had good stability.
Publication bias was analyzed by funnel plots of the total effective rate and the cure rate. The funnel plots showed incomplete symmetry between right and left, which may be caused by factors such as a small number of selected studies, low quality, unpublished negative results, or small sample effect (see Figures
Funnel plot of the cure rate.
Funnel plot of the total effective rate.
The risk of bias, inconsistency, indirectness, imprecision, and publication bias of each outcome indicator were analyzed and summarized. GRADE evaluation was conducted for each outcome indicator, among which the cure rate and the total effective rate were moderate-quality evidence, and the recurrence rates and posttreatment levels of IL-6, IL-8, and TNF-
Evidence grading of the outcomes.
Interventions for [condition] in [population] | |||||||
---|---|---|---|---|---|---|---|
Outcomes | Intervention and comparison intervention | Illustrative comparative risks | Relative effect (95% CI) | Number of participants (studies) | Quality of the evidence (GRADE) | Comments | |
Assumed risk | Corresponding risk | ||||||
Cure rate | 1080 | ⊕ ⊕ ⊕ ⊝ | |||||
Total effective rate | 1080 | ⊕ ⊕ ⊕ ⊝ | |||||
Recurrence rate | 235 | ⊕ ⊕ ⊝⊝ | |||||
IL-6 | The mean LDXGD combined with WM in the intervention groups was | 226 | ⊕ ⊕ ⊝⊝ | SMD −1.61 | |||
IL-8 | The mean LDXGD combined with WM in the intervention groups was | 226 | ⊕ ⊕ ⊝⊝ | SMD −1.68 | |||
TNF- | The mean LDXGD combined with WM in the intervention groups was | 226 | ⊕ ⊕ ⊝⊝ | SMD −1.68 |
In summary, compared with WM used alone, LDXGD used alone or combined with WM had a higher cure rate (RR = 1.56, 95% CI (1.35, 1.81),
There are several limitations in our primary studies as well. Firstly, the methodological quality of the 14 RCTs included in this study was not high. Some RCTs did not elaborate on the specific randomization method, and all RCTs did not elaborate on allocation concealment or whether the blind method was used, which may affect the conclusions of this study. Secondly, the RCTs included in this study were all published studies, and due to the limitation of retrieval resources, part of the gray literature was not available, so potential publication bias could not be excluded. Finally, ITT analysis was not performed on the final data in all RCTs, which was likely to cause a loss of follow-up bias. Thus, the conclusions of this meta-analysis need to be provided with more reliable evidence-based medical evidence by future multicenter, large-sample, and high-quality randomized controlled clinical trials.
LDXGD is composed of 10 herbs and can improve the CD4+T cell proportion in the body while reducing the CD8+T cell proportion [
Longdancao contains numerous kinds of chemical components, mainly including iridoid glycosides, alkaloids, and flavonoids [
So far, over 40 compounds have been isolated and identified from Huangqin, including flavonoids, terpenoids, volatile oils, and polysaccharides [
Zhizi contains iridoid glycosides, organic acid esters, saffron glycosides, and flavonoids [
Dual regulation of Chaihu to adenylate cyclase can enhance the immunity of mice [
Modern research indicates that phthalides, organic acids and their esters, and polysaccharides are the main chemical components related to the bioactivities and pharmacological properties of Danggui [
Shengdihuang contains iridoid glycosides, glycosides, amino acids, and other active ingredients [
Modern pharmacological research shows that Gancao contains total flavonoids, glycyrrhizic acid, glycyrrhetinic acid, triterpenoids, glycyrrhizin, and other ingredients [
The chemical components of Zexie include triterpenes, sesquiterpenes, and diterpenes [
The main components of Mutong are triterpenes and their saponins [
The chemical components of Cheqianzi mainly include polysaccharides, phenethyl alcohol glycosides, iridoids, flavonoids, alkaloids, triterpenes, and sterols [
The results indicated that the clinical efficacy of LDXGD used alone or combined with WM was superior to that of WM alone in treating eczema, but it was not possible to draw a definite conclusion as for the safety of LDXGD. The curative effect of LDXGD on eczema is certain according to the moderate-quality evidence assessed through GRADE, while other outcomes were uncertain based on current studies. Thus, further research is needed to find more convincing proof.
The data supporting this systematic review and mate-analysis are from previously reported studies and datasets, which have been cited. The processed data are available in the supplementary files.
The author declares that there are no conflicts of interest in this article.
Ziteng Hu did most of the work; Lidong Gao and Chengxian Li’s workload was the second most. Additionally, Alberto Cucco contributed to translation and article polishing. Weiling Yuan helped to give suggestions for revision and was the author of the communication. Shang Wang was involved in searching the pharmacological-related literature. Fan Zhang and Shuai Kang were responsible for screening documents and Min Wang was responsible for the fluency of the text.
This work was supported by the National Natural Science Foundation of China (NSFC no. 81273613), Special Research Project of Chinese Medicine Industry (no. 201107006), and Tianjin University of Traditional Chinese Medicine Preventive Treatment Project (no. XJ201801).
Table S1: search Strategy. Table S2: PRISMA Checklist.