The efficacy of Chinese herbal ointment in treating perianal eczema: A systematic review and meta-analysis

Background: Traditional Chinese herbal ointment has significant curative effect and few side effects in the treatment of perianal eczema (PE). Currently, there is no systematic evaluation on the treatment of PE with traditional Chinese medicine ointment. The current aim is to systematically evaluate the efficacy of traditional Chinese medicine ointment in the treatment of PE through meta-analysis. Methods: Randomized controlled trials on the treatment of PE with Chinese herbal plaster were included in the meta-analysis, which was searched in Chinese and English databases up to March 1, 2023. The search will be conducted in accordance with the object of PICOS framework. Two research will independently use EndnoteX9 to extract the data and evaluate the quality assessment of included trails. Meta-analysis was performed using Revman5.4.1 provided by Cochrane Collaboration; when the outcome indicator is a dichotomous variable, relative risk (RR) was used as the effect size; when the outcome indicator is a continuous variable, weighted mean difference (MD) was used as the effect size, each effect size should be expressed as 95% confidence interval (CI). Results: The results of meta-analysis showed that: The total effective rate of PE (RR: 1.22, 95% CI: 1.15, 1.30, P < .01; I2 = 32%, Q = 0.17). The cure rate of PE (RR: 3.37, 95% CI: 2.30, 4.94, P < .01; I2 = 21% Q = 0.26). The recurrence rate of PE (RR: 0.25, 95% CI: 0.13, 0.48, P < .01; I2 = 31%Q = 0.23). Itchy points (MD: 0.04, 95% CI: −0.19, 0.27; I2 = 26%) Skin damage area (MD: −0.37, 95% CI: −0.56, −0.19; I2 = 26%). Skin damage form (MD: −0.59, 95% CI: −0.81. −0.36; I2 = 0%). Conclusion: A total of 11 articles were included in this study for meta-analysis, and the results showed that Chinese medicine ointment is more helpful in improving the skin lesion area and skin damage form, significantly improve the response rate and cure rate, reduce the recurrence rate. Chinese herbal ointment has guiding significance for clinical practice which deserve to use ointments by further experimental and clinical investigation.


Introduction
Perianal eczema (PE) is an inflammatory skin disease with a high incidence in industrialized countries. [1] As a branch of eczema, clinical manifestations are diverse. According to incomplete statistics, eczema accounts for 2% to 10% of adults and 20% of children in the world. Eczema can be divided into atopic eczema, allergic eczema and irritant eczema. [2] It is generally believed that eczema can be divided into primary eczema and secondary eczema. The former is caused by complex causes, while the latter is mainly caused by other perianal diseases and stimulated by secretions to form PE. At present, modern medicine has not fully clarified the pathogenesis of PE which has no specific drug treatment and lack of unified treatment standard system. PE as a noninfectious skin disease, allergic skin disease which could spread to perianal skin, perineum, scrotum and other parts. [3] This disease has exudate, recurrent attacks, symmetrical skin disorders, polymorphic damage, the main form of papule, erythema, blister, and poor prognosis which is easy to develop chronic eczema in clinic. It has a serious affect in patients' quality of life, sleep quality, social interaction, etc. [4] PE has 3 types which can be divided into acute, subacute and chronic types. [5] Conventional treatment of PE mainly uses drugs, physical combination and surgery. Among them, drugs are widely used and are mainly treated with glucocorticoids, antihistamines and immune preparations. Glucocorticoids are still the main local treatment measures for PE. [6] Side effects are grievous; long-term use is easy to cause skin atrophy, and pigmentation, easy to relapse. Traditional Chinese medicine believes that PE belongs to "anal dampness," "hydrangea style," "soaking sores," and "healing prickly heat." [7] Traditional Chinese medicine treatment of PE includes oral Chinese medicine, fumigation, wet compress, external plaster, etc. In recent years, there have been many clinical studies on the treatment of PE with traditional Chinese medicine poultices, but there is no analysis of the clinical effect of traditional Chinese medicine poultices on PE. The objective of this study was to evaluate the efficacy of Chinese herbal plaster in treating PE and to provide real data for clinical application.

Materials and methods
The meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. This article is registered with PROSPERO (Registration number: CRD42023405256). These studies do not involve humans or animals for ethical or ethical review. This means that they do not involve any behavior that may cause harm to life, physical or mental health. Therefore, there is no need for patient and public participation, informed consent, or ethical approval in the design, process, and outcome of the study.

Data sources and search strategies
The search will be conducted according to the object of study, participants, interventions, comparison, outcome indicator, type of study framework.

Study selection and data extraction
Studies meeting the following criteria were included: Patients were diagnosed as PE; Randomized controlled trial; Experimental group: Chinese patent medicine ointment, mainly for local topical use. Traditional Chinese medicine ingredients should contain Phellodendron amurense, Scutellaria baicalensis, or borneol and other Qingre Huashi medicine. control group: Routine treatment of western medicine ointment. There was no limit to the duration, frequency, or dose of drug treatment; Human subjects were enrolled regardless of age, nationality, region, or race. The combined underlying disease is not limited.
Studies with the following criteria were excluded: Review and case report; Traditional Chinese medicine ingredients should contain Phellodendron amurense, Scutellaria baicalensis, or borneol and other Qingre Huashi medicine. The control group did not conform to the conventional treatment of western ointment; Duplicated studies. According to the efficacy judgment criteria in the Industry Standard of Traditional Chinese Medicine of China-The Efficacy Standard of the State Administration of Traditional Chinese Medicine, that is, the reduction of total symptom points is divided into 4 grades: effective (curative, effective, effective and invalid). Efficacy criteria: efficacy index (nimodipine method) = (pretreatment score-posttreatment score)/pretreatment score 100%; recovery: 90% efficacy index,

Quality assessment
Assessment of the methodological quality of each study was conducted by 2 authors independently. The risk of bias as to random sequence generation, allocation concealment, blinding of participants and personnel, blinding of the outcome assessment, analysis of incomplete outcome data, selective reporting, and other biases was assessed by the COCHRANE Collaboration Risk of Bias Tool. REVWAN 5.4.1 software (The Nordic COCHRANE Centre, Copenhagen, Denmark) was used for this assessment.

Meta-analysis
Two researchers used EndnoteX9 to extract data and independently assess the quality of the included trial. Metaanalysis was performed using Revman5.4 (https://training. cochrane.org/online-learning/core-software/revman) provided by COCHRANE Collaboration; when the outcome indicator is a dichotomous variable, relative risk (RR) was used as the effect size; when the outcome indicator is a continuous variable, weighted mean difference (MD) was used as the effect size, each effect size should be expressed as confidence interval (CI). I 2 and Q tests, and when I 2 was < 50% and P > .1, a fixed effect model was selected considering less heterogeneity in included studies; If I 2 was > 50% and P < .1, considering the large heterogeneity of the included studies, the random effect model was used. Conduct sensitivity analysis or subgroup analysis as necessary to explore the source of heterogeneity if necessary.  Finally, eleven studies were included in the analysis, a total of 808 patients. [8][9][10][11][12][13][14][15][16][17][18] Description of included studies are as follows. (Table 1) We summarized the screening process in our "Study selection flow diagram" (Fig. 1).

Description of included studies
The eleven randomized controlled clinical trials evaluated add-on effect of herbal ointment for PE, most were single center studies. Sample size varied from 48 to 132. The ages of participants were from 3 years to 98 years old. The durations of treatment ranged from 7 days to 3 week. In addition, the basic treatment control groups are as follows: Compound dexamethasone acrtate cream (2) Calamune Lotion and Compound dexamethasone acrtate cream (1). Desnoide cream (3),Triamcinolone acetonide and rconazole cream (3), Triamcinolone acetonide urea cream (1),Compound Beclomethasone Camphor Cream (1).experimental group: GuiJie ointment, Tibetan medicine 25 flavor tea ointment, MUSK Hemorrhoids ointments, Moist exposed burn ointment, Huazhi ointment, Longzhu ointment, baicalein oil cream, Fuzhiqing ointment, eczema ointment, MEBO moist exposed burn cream, ChuShi Zhiyang ointment.

Quality assessment of studies
There are 11 articles that reach the risk of a low degree of bias and have high-quality. In the figure, the standard is "+" and not up to the standard for "−".It is the statistical graph of each item.
Based on different drugs and different prices, blindness is less likely to do it, so they are all red. (Fig. 2,3)

The bias test
The study was tested for publication bias by drawing the funnel plot, and the funnel plot symmetry means that there is no obvious publication bias. (Fig. 10)

Discussion
With the improvement of people's living standard, the incidence of PE increases year by year. According to modern medicine, PE is an allergic disease, and its pathogenesis has not been fully elucidated.    It may be related to metamorphosis, infection, genetics, neurology, anatomy, endocrinology, perianal disease and other factors. The use of glucocorticoids, antihistamines and immunosuppressants is currently the main treatment for PE, but the side effects are more severe and prone to recurrence. Traditional Chinese medicine believes that PE is closely related to "wind, wet and heat." The Chinese medicine ointment ingredients we choose are Phellodendron amurense, Scutellaria baicalensis, or borneol, which have the common characteristics of clearing heat and dampness. The external use of Chinese ointment can make the drug directly contact with the lesion, and the lesion site can fully absorb the active ingredients of the drug. [19] Direct medicine, direct utility, high compliance, and high safety, which are easy for patients to accept, can be widely used. In recent years, traditional Chinese medicine plaster has been widely used in clinical applications. It has made great progress in promoting transdermal absorption and alleviating local skin irritation. At the same time, it also has advantages of economy, convenience and good curative effect. This study provides theoretical evidence for the advantage of traditional Chinese medicine plaster to improve the clinical effect of PE, and enriching the treatment of PE.

Conclusion
A total of 11 literatures were included in this study for meta-analysis, and the results showed that in clinical studies, traditional Chinese medicine plaster was more helpful to improve the PE skin area, skin shape and other clinical symptoms, which could significantly improve the effective rate and cure rate, and reduce the recurrence rate. In the included literature, the traditional Chinese medicine plaster containing the effect of clearing heat and drying dampness was taken as a unified whole. Based on clinical studies, the effectiveness of the whole compound was explored. As a promising therapeutic method, Chinese herbal ointment containing heat-clearing and moisture-drying effects can guide doctors to conduct clinical research. However, there are still shortcomings. The intervention measures included in this paper are uneven, and the overall quality evaluation is not high. In the following time, high-quality articles should be selected to better guide clinical practice. In the included randomized controlled studies, a potential bias was identified with regard to blinding and assignment concealment. However, due to the limited trials included trials, this study has some limitations. First of all, the intervention measures of the experimental group are different, and the ointment of the control group is different, which may affect the results of this Meta-analysis. Secondly, the inability to obtain follow-up data in some studies also affects the accuracy of the results. Therefore, more rigorously designed randomized controlled trials are needed in the future to further explore the efficacy and safety of Chinese herbal ointments in the treatment of PE. Due to the limited experimental data available at present, we are committed to further optimize the experiment in the future, indicating a comprehensive assessment of the quality of the other's jurisprudence. In order to provide effective evidence for the efficacy of Chinese herbal ointment, further rigorous Randomized controlled trials with long duration of follow-ups are still necessary.