Potential Acupoint Prescriptions and Outcome Reporting for Acupuncture in Atopic Eczema: A Scoping Review

Background Acupuncture is considered a complementary therapy for atopic eczema. The aim of this scoping review is to identify, examine, and summarize the potential acupoint prescriptions and outcome reporting regarding the clinical trials of acupuncture for eczema. Methods We searched different databases from inception to September 30, 2020. The data were screened and extracted to identify the potential acupuncture prescription and examine the variation in outcome reporting, outcome measurement instruments (OMIs), and measurement time points in clinical trials of acupuncture. Results A total of 116 clinical studies were included. The acupoint combination of LI11 and SP10 was used frequently. The core acupoint association networks were acupoints LI11, SP10, ST36, SP6, and LI4. For clinical trials of acupuncture, a total of 6 outcome distinct domains were identified in the 32 outcome measurements. The most frequently reported outcome was the eczema area, which was reported 97 times (83.6%, 97/116). Immune system outcomes were assessed in 15 outcome measurements, which totally reported 37 times. Adverse events were reported 51 times. TCM syndrome, which could reflect the characteristics of TCM, was reported 4 times. 29 outcomes (90.6%, 29/32) were provided definitions or OMIs. Among these outcomes, the outcome measurement times ranged from 0 to 34. Conclusions This scoping review provides potential knowledge that should be considered as priority in future research of acupuncture for eczema.


Introduction
Atopic eczema (AE) is a chronic inflammatory skin disease, clinically characterized by exacerbations and remissions of eczematous skin with inflammation, pruritus and excoriations, scaling, dry skin, and susceptibility for cutaneous bacterial and mycotic infections [1]. In the past 30 years, lifetime prevalence has shown a worldwide increase, which plateaus at 10-20% in developed countries and continues to increase in China and many developing countries but lower [2]. e concurrent use of terms such as "eczema," "atopic eczema," "atopic dermatitis," "atopic eczema/dermatitis syndrome," and "neurodermatitis" has led to confusion and inconsistency in their application. In China, AE is also called as chronic eczema (CE) [3]. erefore, the nomenclature review committee of the World Allergy Organization has proposed the use of "eczema" as a unifying term, and this term is also used throughout the text of this review [4].
Acupuncture was frequently applied in cases of allergy [5]. In recent years, it has been increasingly utilized as an adjuvant therapy to conventional treatment of eczema [6]. A large number of clinical trials related to acupuncture for eczema have been published in various journals [7]. However, evidence of acupuncture for eczema keeps unclear. e treatment prescriptions are various, and outcome reporting showing heterogeneity makes it impossible to merge data or compare efficacy of different interventions in a systematic review. e aim of this scoping review is to identify potential treatment prescriptions and compare the outcome reporting for acupuncture clinical trials with the existing core outcome domains developed by the Harmonizing Outcome Measures for Eczema (HOME) consensus, which may help acupuncturists establish potential prioritized treatment prescriptions and choose appropriate outcomes in their future research.

Search Strategy.
We conducted a systematic electronic search from Medline, PubMed, Cochrane Library, CBM, CNKI, Wanfang Database, and VIP Database from their inception to September 30, 2020. e search terms included acupuncture, acupoints, electroacupuncture, needle warming therapy, autologous whole blood injection, autohemotherapy, acupoint injection, catgut implantation, filiform steel needle, fire needle, plum-blossom needle, atopic dermatitis, chronic eczema, and atopic eczema. Language was restricted to Chinese and English. e search strategy is shown in the supplementary materials (available here).

Inclusion Criteria and Exclusion Criteria.
e inclusion criteria are as follows: ① Population: patients diagnosed with either AD, AE, or CE were included as participants in this study [2,8,9]. ere were no restrictions on age, sex, race, or region. ② Intervention: the included studies examined the use of acutherapy (acupuncture therapy). e studies could use multimodal interventions, but acutherapy had to be included. ③ Comparison: comparison of the intervention group with the control group in addition to treatment methods other than acutherapy, such as drugs or other forms of traditional Chinese medicine. ④ Outcomes: no restriction. ⑤ Study types: all kinds of clinical studies including randomized clinical trials, observational studies, and case series were included in this scoping review. e exclusion criteria are as follows: Comments, animal experiments, and narrative reviews were excluded.

Literature Identification.
We imported the results from different databases into NoteExpress 3.2.0 [10] and then deleted duplicate studies. Two reviewers (Zeng Y. J. and Zhang J. L.) conducted data identification independently. ey reviewed the abstracts and full texts and extracted relevant information from the included studies. If the studies involved in comparison of therapeutic effects of different acupoint prescriptions, then the most effective acupoint prescription according to the criteria of therapeutic effect was extracted. Any discrepancies were resolved by consensus.

Data Extraction.
e following information was extracted pertaining to the reference title, first author's name, publication year, study location, study design, intervention and comparisons, duration, results, and outcome measurements. ese data were charted in a custom-made data extraction file and double checked by ZZ.

Data Analysis.
To overcome some weaknesses of previous studies and to determine whether acupuncture requires a different outcome set that will reflect particular effects of acupuncture on eczema symptom management, the outcomes reporting was analyzed by description analysis. Two researchers (ZZ and DZ) merged the overlapping outcomes according to the definition of core outcome domains recommended by HOME consensus including signs, symptoms, quality of life, and long-term control and grouped individual outcomes into the appropriate outcome domain independently. In addition, immune system outcomes and adverse events were added to outcome domains. ese outcome sets are often preferred in what to consider as evidence relative to efficacy and safety in clinical trials of acupuncture on eczema.
Treatment prescriptions were analyzed by SPSS Modeler 18.0 [11]. We first analyzed the frequency of acupoints and meridians with text mining. en, we determine common acupoint combinations, the support degree of different acupoint combinations, and the core acupoint association network of acupuncture for eczema by association rule mining. We obtain the core acupoints using hierarchical cluster analysis. We also analyzed the co-occurrence matrix of the top 18 acupoints using Heml 1.0.3.7 [12]. e results are illustrated by a heat map.

Study Identification.
A total of 1332 records were identified from the literature search, and a total of 116 eligible studies were included. e flowchart of the review is shown in Figure 1.

Characteristics of the Inclusive Studies.
e characteristics of the inclusive studies are shown in Supplementary  Table 1. e studies included were published between 1998 and 2020. Most of the studies (81%, 94/116) were published in 2010 and after. e majority of the studies were conducted in China (n � 111). e rest of the studies originated from Germany, United States, and Korea. Most of the studies used a randomized controlled trial design with two or three arms (n � 91). Nine studies used a control design with simple randomized assignment of participants to the experimental and control groups. 14 studies used a single group design such as a longitudinal prospective design. e duration of treatment sessions ranged from 7 d to 140 d throughout the studies, while two studies did not report duration. e sample sizes of all the studies range from 10 to 323, with an average of 82 participants. Intervention procedures varied among the 116 studies. Most of the studies (44%) included investigated manual acupuncture. Only two studies discussed electroacupuncture. Other studies involved the assessment of acupoint therapies such as autologous whole blood injection (n � 21), acupoint injection (n � 18), catgut implantation (n � 7), fire needle (n � 24), and plum-blossom needle (n � 7). Non-RCT studies discussed treatments such as acupuncture, autologous whole blood injection, acupoint injection, catgut implantation, fire needle, and plum-blossom needle (n � 23). All of the included studies demonstrated statistically significant (P < 0.05) improvements in at least one targeted eczema outcome.

Common Acupoint Combinations.
A total of 15 common acupoint combinations were frequently used over 17 times.
ere were four acupoint combinations with frequency ≥35: LI11 and SP10, LI11 and ST36, SP10 and ST36, and LI11, SP10, and ST36. e most frequently used acupoint combination was LI11 and SP10, with 58 times. LI11 and ST36 was used 48 times, SP10 and ST36 was used 40 times, and LI11, SP10, and ST36 was used 37 times. Detailed information can be checked in Table 1. e cooccurrence matrix of the 18 acupoints is presented in Figure 3, which were consistent with the common acupoint combinations.

Association Rules of Acupoints.
ere were 13 acupoint combinations with confidence levels ranging more than 80% and support degree more than 20%, of which SP6, SP10⟶LI11 was listed as the association rules of 96.55%, indicating that when SP6, SP10 was selected, the probability of selecting LI11 was 96.55%. Also, the highest support degree was SP10⟶LI11, which was 54.31%. e association rules for acupoints are described in Table 2.
e core acupoint association network of acupuncture for eczema is listed in Figure 4. e degree of support from strong to weak was acupoint LI11 combined with SP10, ST36 with LI11, SP6 with LI11, SP6 with SP10, and LI4 with LI11.

Outcomes Reporting in Clinical Trials of Acupuncture for
Eczema. For included clinical trials, a total of 6 outcome distinct domains were identified in the 32 outcome measurements (Table 3). Seven (21.9%, 7/32) outcomes were reported only once. e most frequently reported outcome was the eczema area, which was reported 97 times (83.6%, 97/116). Immune system outcomes were assessed in 15 outcome measurements, which totally reported 37 times. Adverse events were reported 51 times. TCM syndrome, which could reflect the characteristics of TCM, was reported 4 times.

Discussion
e meridians, acupoint combinations, and core acupoints identified from the studies included in this scoping review broadly cover the characteristics of acupuncture prescriptions that could be offered in eczema treatment providing antipruritus and anti-inflammatory effect. Acutherapy offers an area for further clinical practice and research for treating eczema.
From the previous systematic review, we found that the majority of clinical trials of acupuncture for eczema are in low methodological quality and quality of evidence [13][14][15], so it is difficult to draw a definite conclusion. In addition, the researchers and clinicians may use different acupoints, so it is impossible for some clinical trials to include in systematic review when there is heterogeneity in prescription. From the results of data mining, the core acupoints may provide potential prescription to researchers.
is scoping review suggests that specific outcome measures for future clinical trials of acupuncture are clinician-reported signs, patient-reported symptoms, health-related quality of life and long-term control, TCM syndrome, immune system outcomes, and adverse events, which are different form the HOME. In addition, researchers choose different outcome measurement instruments, so some clinical trials will be excluded from systematic reviews, which produce waste and lower the value of research. For acupuncture clinical trials, following the HOME core outcome set for eczema may help improve the consistency of outcomes and outcome measurement instruments. e theory of TCM is totally different from that of western medicine. When clinicians use acupuncture, the TCM syndromes are important factors that should be considered in the process of treatment and efficacy evaluation. erefore, in the core outcome set for eczema, TCM syndromes should be considered. In addition, the HOME is developed by stakeholders from developed countries, and the perspectives of professionals and patients from low-and middle-income countries are missed. erefore, the core outcome set for eczema should be achieved consensus in researchers, clinicians, and patients in China. e current research had several strengths. To our knowledge, this was the first study that used bioinformatics methods and searched Chinese and English databases to assess which acupoints have been used to treat eczema. First, previous research was limited in that it could only "qualitatively" interpret the characteristics of acupoint prescriptions used in eczema treatment. We overcame this limitation by extracting significant "quantitative" characteristics using the association rule mining. Second, we explored core acupoints used in eczema treatment. Moreover, we evaluated

Limitations
Our

Conclusions
e preference of core acupoints is LI11, SP10, ST36, SP6, and LI4 in acupuncture clinical studies on eczema. In the future, the researchers could focus on them to prove the efficacy of potential core acupoints. However, researchers should use the core outcome set for eczema to improve the consistency of outcomes and outcome measurement instruments so that the clinical trials will be not exclude from systematic reviews because of the heterogeneity of outcome reporting and outcome measurement instruments.

AE:
Atopic eczema AD: Atopic dermatitis Evidence-Based Complementary and Alternative Medicine