Plain language summary
Chinese herbal medicine taken by mouth or applied to the skin for atopic eczema in children and adults
Atopic eczema (eczema in short) is a common skin condition, where skin changes occur and cause redness, scaling, swelling, and skin thickening due to chronic scratching. It is associated with loss of sleep, self-esteem, and quality of life. The frequency of eczema has increased over the past 10 years.
A former Cochrane review published in 2004 found some evidence of a possible benefit of using oral Chinese herbal medicine (CHM) for eczema; however, the results from only 4 included studies were inconclusive and need to be updated (those four studies have not been included in this update as they investigated a product that has been withdrawn from the market since 2004). As well as updating that review, we have also widened the scope of the review to assess the effects of topical CHM for eczema. We wrote a new protocol to expand the scope of this review.
This review included 28 randomised controlled trials (RCTs), with 2306 children and adults, of which 4 compared CHM to placebo, 22 to conventional medications, and 2 to CHM taken by mouth.
Most of the included studies reported a higher number of participants who had recovered and significantly improved, with less itching in the CHM groups than the control groups. Where CHM was compared to conventional drugs, although the total effectiveness rate outcome was superior with CHM, it was based on very low quality evidence. One study reported that the quality of life (QoL) score in the CHM group was better than in the placebo group after using a CHM formula taken by mouth for 12 weeks. We assessed most of the studies as at high 'risk of bias' and therefore not of good quality, and there was substantial inconsistency between the studies, so any positive effect in CHM must be treated with caution.
One study reported one severe adverse event. Minor adverse events were observed in 24 studies, including temporary elevation of enzymes in 3 cases, which was reversed soon after stopping CHM.
Eight included studies received government funding.
We could not find conclusive evidence that CHM taken by mouth or applied to the skin was of benefit to children or adults with eczema.
Well-designed, adequately powered RCTs are needed to evaluate the efficacy and safety of CHM for eczema.
Les plantes médicinales chinoises prises par voie orale ou appliquées sur la peau pour l'eczéma atopique chez les enfants et les adultes
L'eczéma atopique (eczéma )) est une affection cutanée courante qui s'accompagne de modifications cutanées et entraîne rougeur, desquamation, gonflement et épaississement de la peau en raison du grattage chronique. Elle est associée à une diminution du sommeil, de l'estime de soi et de la qualité de vie. La fréquence de l'eczéma a augmenté au cours des 10 dernières années.
Une précédente revue Cochrane publiée en 2004 a trouvé certaines preuves d'un possible bénéfice de l'administration orale de plantes médicinales chinoises (PMC) pour l'eczéma; cependant, les résultats des seulement 4 études incluses n'étaient pas concluants et doivent être mis à jour (ces quatre études n'ont pas été incluses dans cette mise à jour, car elles examinaient un produit qui a été retiré du marché depuis 2004). Avec la mise à jour de cette revue, nous avons élargi la portée de cette revue pour évaluer aussi les effets des PMC topiques contre l'eczéma. Nous avons écrit un nouveau protocole pour élargir la portée de cette revue.
Cette revue a inclus 28 essais contrôlés randomisés (ECR), avec 2306 enfants et adultes, dont 4 ont comparé les PMC à un placebo, 22 à un traitement conventionnel et 2 aux PMC prises par voie orale.
La plupart des études incluses ont rapporté un plus grand nombre de participants qui avaient récupéré ou avaient eu une amélioration significative, avec moins de démangeaisons dans les groupes PMC que dans les groupes témoins. Lorsque les PMC étaient comparées aux médicaments conventionnels, alors que le résultat concernant le taux d'efficacité globale était supérieur avec les PMC, il était basé sur des éléments de preuve de très faible qualité. Une étude avait rapporté que le score de qualité de vie (QdV) dans le groupe PMC était meilleur que dans le groupe sous placebo après l'utilisation d'une formule de PMC prise par voie orale pendant 12 semaines. Nous avons évalué la plupart des études comme étant à haut risque de biais et donc pas de bonne qualité et il y avait des incohérences importantes entre les études, de sorte qu'un quelconque effet positif des PMC doit être considéré avec prudence.
Une étude a rapporté un événement indésirable grave. Des événements indésirables mineurs ont été observés dans 24 études, notamment une élévation temporaire d'enzymes dans 3 cas, rapidement réversible après l'arrêt des PMC.
Huit études incluses avaient reçu un financement gouvernemental.
Nous n'avons pas trouvé de preuve concluante que les PMC administrées par voie orale ou appliquées sur la peau procuraient un bénéfice pour des enfants ou des adultes atteints d'eczéma.
Des ECR bien conçus et présentant une puissance statistique adéquate sont nécessaires pour évaluer l'efficacité et l'innocuité des PMC pour l'eczéma.
Notes de traduction
Traduit par: French Cochrane Centre 15th December, 2013
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Sant� du Canada, Minist�re de la Sant� et des Services Sociaux du Qu�bec, Fonds de recherche du Qu�bec-Sant� et Institut National d'Excellence en Sant� et en Services Sociaux; pour la France : Minist�re en charge de la Sant�
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版（英語版）の内容をご確認ください。
Kineski biljni lijekovi za liječenje atopijskog dermatitisa u djece i odraslih
Atopijski dermatitis (ekcem) je čest poremećaj kože kod kojeg, zbog kroničnog svrbeža i češćanja kože, nastaju kožne promjene: crvenilo, ljuskanje, otekline i zadebljanje. Povezan je s nedostatkom sna, samopouzdanja i smanjenom kvalitetom života. Učestalost atopijskog dermatitisa povećala se zadnjih deset godina.
U prethodnom Cochrane pregledu objavljenom 2004. godine pronađeni su određeni dokazi o potencijalnoj koristi upotrebe kineskih biljnih lijekova koji se uzimaju na usta za dermatitis; no međutim, bile su uključene samo četiri studije čiji su rezultati bili neuvjerljivi te je dokaze potrebno ažurirati (navedene četiri studije nisu uključene u ovaj pregled jer je ispitivani proizvod povučen s tržišta 2004. godine). U ovome Cochrane sustavnom pregledu je, uz ažuriranje prethodnog, proširena tema tako da su uključene i procjene učinaka lokalnih pripravaka na bazi kineskih biljnih lijekova za liječenje atopijskog dermatitisa. Napisan je novi protokol u svrhu proširenja opsega ovog pregleda.
Ovaj pregled uključuje 28 randomiziranih kontroliranih ispitivanja, s 2306 djece i odraslih osoba, od kojih se u 4 studije uspoređuju kineski biljni lijekovi u odnosu na placebo, u 22 studije se kineski biljni lijekovi uspoređuju s konvencionalnim lijekovima, te 2 studije u kojima se ispituju kineski biljni lijekovi koji se uzimaju na usta.
U većini ispitivanja zabilježen je veći broj ispitanika kod kojih je došlo do oporavka i značajnog poboljšanja sa smanjenjem svrbeža u skupini liječenoj kineskim biljnim lijekovima u odnosu na kontrolnu skupinu. Iako su kineski biljni lijekovi pokazali veću učinkovitost u studijama u kojima su uspoređivani sa standardnim lijekovima, ti se rezultati temelje dokazima vrlo niske kvalitete. U jednom je ispitivanju zabilježen veći porast kvalitete života u skupini koja je uzimala kineski biljni lijek na usta u odnosu na placebo skupinu nakon 12 tjedana terapija. Većina studija procijenjena je kao "studije visokog rizika pristranosti" i stoga nisu dobre kvalitete, te je također među studijama uočen značajna nedosljednost, stoga bilo kakav pozitivan učinak kineskih biljnih lijekova treba uzeti s oprezom.
U jednoj je studiji opisan jedan ozbiljan štetni događaj. Manje ozbiljne nuspojave zabilježene su u 24 studije, uključujući i privremeni porast enzima u 3 slučaja, koji se vratio u normalu ubrzo nakon prestanka terapije kineskim biljnim lijekovima.
Osam uključenih studija financirano je iz vladinih izvora.
Nisu nađeni uvjerljivi dokazi da oralni ili lokalni kineski biljni lijekovi koriste djeci ili odraslim osobama s atopijskim dermatitisom.
Potrebno je provesti nova dobro osmišljena, nepristrana randomizirana klinička ispitivanja za procjenu učinkovitosti i sigurnosti kineskih biljnih lijekova kao potencijalne terapije dermatitis.
Prevela: Maja Kišan
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: firstname.lastname@example.org
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Ubat-ubatan herba Cina yang diambil melalui mulut atau disapu pada kulit untuk ekzema atopik dalam kalangan kanak-kanak dan orang dewasa
Ekzema atopik (ekzema secara ringkasnya) adalah keadaan kulit yang lazim, di mana perubahan kulit berlaku dan menyebabkan kemerahan, mengelupas, bengkak, dan penebalan kulit akibat menggaru kronik. Ia dikaitkan dengan kehilangan tidur, harga diri, dan kualiti hidup. Kekerapan ekzema telah meningkat sejak 10 tahun yang lalu.
Ulasan Cochrane terdahulu yang diterbitkan pada 2004 mendapati beberapa bukti tentang kemungkinan manfaat penggunaan ubat herba Cina oral (CHM) untuk ekzema; namun, hasil daripada hanya 4 kajian tidak muktamad dan perlu dikemas kini (empat kajian itu tidak dimasukkan dalam kemas kini ini kerana mereka menyiasat produk yang telah ditarik balik dari pasaran sejak 2004). Selain mengemas kini ulasan itu, kami juga meluaskan skop ulasan untuk menilai kesan CHM topikal untuk ekzema. Kami telah menulis satu protokol baru untuk mengembangkan skop ulasan ini.
Ulasan ini melibatkan 28 kajian rawak terkawal (RCT), dengan 2306 kanak-kanak dan orang dewasa, di mana 4 membandingkan CHM dengan plasebo, 22 dengan ubat-ubatan konvensional, dan 2 dengan CHM yang diambil melalui mulut.
Kebanyakan kajian yang terlibat melaporkan lebih ramai bilangan peserta yang telah pulih dan bertambah baik dengan ketara, dengan pengurangan kegatalan dalam kumpulan CHM berbanding dengan kumpulan kawalan. Di mana CHM dibandingkan dengan ubat-ubatan konvensional, walaupun jumlah hasil kadar keberkesanan lebih tinggi daripada CHM, ia adalah berdasarkan bukti kualiti yang sangat rendah. Satu kajian melaporkan skor kualiti hidup (QoL) dalam kumpulan CHM adalah lebih baik daripada kumpulan plasebo selepas menggunakan formula CHM yang diambil melalui mulut selama 12 minggu. Kami menilaikan kebanyakan kajian tersebut berisko bias tinggi dan oleh itu, tidak berkualiti tinggi, tidak konsisten yang ketara di antara kajian-kajian, oleh itu sebarang kesan positif dalam CHM mesti dinilai dengan berhati-hati.
Satu kajian melaporkan satu peristiwa buruk yang teruk. Peristiwa buruk yang ringan dilihat dalam 24 kajian, termasuk peningkatan enzim sementara dalam 3 kes, yang dibalikkan tidak lama selepas CHM dihentikan.
Lapan kajian yang dimasukkan menerima pembiayaan kerajaan.
Kami tidak menemui bukti muktamad bahawa CHM yang diambil melalui mulut atau diaplikasi pada kulit adalah bermanfaat kepada kanak-kanak atau orang dewasa dengan ekzema.
RCT yang direka dengan baik dan cukup berkuasa diperlukan untuk menilai keberkesanan dan keselamatan CHM untuk ekzema.
Diterjemahkan oleh Ng Chia Shyn (International Medical University). Disunting oleh Noorliza Mastura Ismail (Kolej Perubatan Melaka-Manipal). Untuk sebarang pertanyaan berkaitan terjemahan ini sila hubungi Ng.ChiaShyn@student.imu.edu.my
Description of the condition
Atopic eczema is a common skin condition, which affects around one in five children in developed countries. In 2009, the International Study of Asthma and Allergies in Childhood (ISAAC) published data on symptoms of eczema (Odhiambo 2009). In this study, the authors found in 6 to 7 year-old children from 143 centres in 60 countries, disease prevalence ranged from 0.9% in India to 22.5% in Ecuador. Amongst 13 to 14 year-olds from 230 centres in 96 countries, disease prevalence was found to range from 0.2% in China to 24.6% in Colombia. Industrialised countries have previously been reported to have higher disease prevalence (Kerdel 2003; Schultz-Larsen 2002), although data from this most recent ISAAC study (Odhiambo 2009) suggest that eczema is a disease in developing countries as well, especially in Latin America and some countries in Africa. The prevalence of atopic eczema has increased over the last 10 years in both developed and developing countries, especially in those aged 6 to 7 years (Williams 2008), for reasons that are unclear. The causes of atopic eczema are still not fully understood, but probably involve an interaction between genetic factors that determine the integrity of the skin barrier and immune responses, and environmental factors, such as early-life gut bacteria; humidity; irritation from soaps; microbes, such as Staphylococcus aureus; and allergens, such as house dust mites. Most children with atopic eczema improve with time, but around 40% persist with the condition into adulthood (Williams 2000).
There was no such terminology as 'atopic eczema' in the classical literature of ancient Chinese medicine. The definition of 'Si Wan Feng' (wind of the four fossae) in Chinese medicine however correlates to atopic eczema in conventional medicine based on the comparison of Chinese medical literature records and the descriptions of clinical features in conventional medicine. 'Si Wan Feng' in Chinese medicine was officially defined as atopic eczema in the Criteria of Diagnosis and Therapeutic Effect of Disease and Syndromes in Traditional Chinese Medicine published by the State Administration of Traditional Chinese Medicine, China (SATCM 1994). Although the term 'atopic' eczema is frequently used, not all people with typical atopic eczema are truly atopic; that is, they do not demonstrate specific immunoglobulin E (IgE) antibodies to common environmental allergens, such as house dust mite, pollens, grass, and foods (Flohr 2008). In accordance with the World Allergy Organisation recommendations on nomenclature (Johansson 2004), we used the term 'eczema' throughout this review.
Eczema is characterised by poorly demarcated redness of the skin and associated surface changes, such as scaling, swelling (oedema), accentuation of the hair follicles, and skin thickening (lichenification) as a result of chronic scratching. Eczema is an itchy skin condition, which can result in sleep loss for the child and family members. The stigma of a visible skin disease can affect a person's self-esteem, and severe disease is associated with a poor quality of life (QoL) (Schmid-Ott 2003).
Description of the intervention
Current treatment for eczema has limitations. Topical administration of corticosteroids, as one of the standard first-line therapies for the management of inflammatory episodes of eczema, can be associated with certain adverse events, such as skin thinning, if used for too long or in a too-strong concentration for sensitive sites, such as the face where the skin is naturally thinner. Long-term application of steroids has been a great concern to those using them and to healthcare professionals (Hanifin 2004). A study showed up to 72.5% of people who were using steroids (or their guardians) were concerned about the application of corticosteroids for the treatment of eczema (Charman 2000). New drugs for the treatment of eczema, such as tacrolimus and pimecrolimus (these two drugs are categorised as topical immunomodulators (TIMs) or calcineurin inhibitors), have been developed as second-line therapies. However, issues regarding the long-term safety of these new drugs, particularly the potential link between TIMs and cancer, have been raised (CDER 2005). Therefore, many eczema sufferers have chosen to use complementary and alternative medicine, including Chinese herbal medicine (CHM), for the management of eczema (Hon 2005).
How the intervention might work
In Chinese medicine, those with eczema are recognised as having a specific constitution that leads to internal dampness-heat accumulated because of the reduced function of the spleen. Exposure to wind, dampness, and heat pathogens can trigger symptoms (Zhao 1983). Clinically, eczema is classified into the following patterns from a Chinese medicine viewpoint: accumulation of internal dampness, excess of dampness with spleen deficiency, or Yin deficiency with dryness of blood (Chen 1991). Chinese herbal medicine is one of the important components in Chinese medicine for prevention and treatment of diseases. Botanical resources, such as barks, seeds, flowers, roots, or animal or mineral substances, are prescribed and administered in the form of decoctions (liquids from extraction of herbs by boiling), pills, washing lotions, or ointments for conditions diagnosed by practitioners qualified to practice Chinese medicine or Oriental medicine. Chinese herbal medicines may be neither Chinese nor herbal; the term CHM in this review is used loosely to refer to any medicinal substances used within the paradigm of Chinese medicine practice. Chinese herbal medicines have been employed for the treatment of eczema for many years. They may be administered orally or topically or by a combination of oral ingestion and topical application (Chen 2001). Oral ingestion of CHM is under the guidance of the Chinese medicine pattern differentiation method, known as 'individualised treatment', whilst topical administrations have been devised with little or no consideration of pattern differentiation (Guo 2007; Zhou 2008).
Why it is important to do this review
The Cochrane systematic review on oral ingestion of CHM for eczema was published in 2004 (Zhang 2004). It is timely to update this review to take into account new evidence that has emerged in relation to oral ingestion of herbal interventions. Furthermore, there has been no systematic evaluation of the effectiveness and safety of the topical application of CHM for eczema.
We decided it would be best to review both oral ingestion and topical CHM since people with eczema are likely to be interested in both types of treatment. We therefore wrote a new protocol to plan for the expanded scope of this review.
Summary of main results
This review is an updated version with a new team of authors and a newly published protocol. We did not include the four studies that were included in the previous version of this review as they all investigated a Chinese herbal medicine (CHM) product, Zemaphyte, which the manufacturer withdrew from the market in 2004 (Zhang 2004). And we think it would skew the significance of systematically produced evidence-based medicine if we incorporated data that is not linked to current clinical practice or research.
This review included 28 studies, with a total of 2306 participants. Chinese herbal medicines and comparators were taken orally or applied topically by children and adults with eczema. Four studies compared CHM to placebo. Two studies compared a combination of oral and topical CHM to the same oral CHM formula alone, and 22 studies and 1 arm of the Chao 2003 study compared CHM to Western medications.
We found evidence from one 12-week study of moderate to severe eczema, comparing an oral CHM to placebo, of a statistically significant difference between the 2 groups with respect to QoL score (MD -2.50, 95% CI -4.77 to -0.23; see Analysis 1.5) (Hon 2007). The mean QoL score in the CHM groups was 2.5 lower than that in the placebo groups, which indicated that oral ingestion of CHM could improve QoL. Although the overall effect in the outcomes of 'total effectiveness rate', 'severity of itching score', and 'overall severity score' showed a statistically significant difference between the groups in favour of CHM, these findings were inconclusive because of the high risk of bias with regard to blinding of participants and research personnel, incomplete outcomes, or other unclear risk of bias that existed across these four studies (see Summary of findings for the main comparison). Unexplained high heterogeneity (I² statistic = 87%; see Figure 4) among the 4 studies in the outcome measured by 'overall severity score' further weakened the strength of the positive estimates.
The majority of the included studies (22 studies and 1 arm of the Chao 2003 study) used conventional medicines (Western medications) as comparators, which included oral ingestion of antihistamine tablets; topical use of corticosteroid cream; and other agents, such as antifungals, antiseptics, or emollients. Twenty-one studies expressed their primary outcome as 'total effectiveness rate', and all reported that effectiveness of CHM interventions was superior to the comparators except the Chao 2003 and Chen 2011 studies, which used corticosteroid cream as the control intervention. In addition to these two studies, our meta-analyses showed no statistically significant difference between the CHM and conventional medicine groups observed in the studies of Gong 2010; Huang 2010; Lang 2007; Tian 2005; Wang 2008; Xiao 2011; and Zhang 2009, although the overall effects of the 21 included studies favoured the CHM groups (RR 1.43, 95% CI 1.27 to 1.61; see Analysis 2.1).
The claim of positive effects with CHM intervention needs to be interpreted with caution because of substantial heterogeneity (I² statistic = 65%; see Figure 5) across the studies. The result from a posthoc subgroup analysis (subgroup differences I² statistic = 74.4%) also confirmed there was unexplained heterogeneity. We also found there was high risk of bias in the domains for blinding of participants and research personnel and blinding of outcome assessment, as well as other potential sources of bias (absence of usage of published and validated scoring systems for outcome measures) in this group of studies (see Summary of findings 2). All included studies in this group were associated with several major methodological weaknesses. For example, although all studies used randomisation for grouping of participants, none of them provided information of the procedure for allocation concealment (see Figure 3). Inadequate randomisation could give rise to an investigator's bias for grouping of participants, which consequently affects the outcomes (Liu 2006).
Two studies reported a statistically significant difference in outcomes of 'total effectiveness rate' or 'severity of itching score measured by VAS', respectively, and overall effects in the combination of oral and topical CHM groups were always superior to the oral CHM control groups (Lin 2010; Rao 2010). We did not pool data from the two studies as the Lin 2010 study was a within-patient study. The Lin 2010 study had a high risk of performance bias and attrition bias. The Rao 2010 study had a high risk of bias in the domain of blinding of the participants and research personnel, and both studies had small sample sizes (a total of 42 participants in 2 studies evaluated). Their claims that overall effects in CHM groups were superior to the control groups were in doubt (see Summary of findings 3).
It is worth pointing out that nearly half of the included studies did not use published and validated scoring systems for measuring the severity of the condition. Some studies used the scoring system but did not provide continuous data for the scores. The absence of these data made quantifiable data analysis impossible and downgraded the credibility of the results (Eichenfield 2003). We were unable to further estimate if CHM has potential for short-term or long-term improvement of eczema because of limited data provided by the included studies.
Chinese herbal medicines' possible association with hepatotoxicity (liver toxicity) was discussed when 11 cases of liver damage following oral ingestion of some raw Chinese herbal mixtures for skin conditions were reported in the UK between 1991 to 1993 (Perharic 1995). The reporters indicated that the mechanism of toxicity was not clear. The adverse effects of those CHM mixtures seemed to not be dose-related and were probably idiosyncratic. The safety issue of oral ingestion of CHM has been a concern of healthcare professionals and the public (Chitturi 2000). In this review, we evaluated both beneficial effects and adverse effects of interventions from the included studies. We found only a quarter (7/28) of the included studies had monitored the liver and renal function of the participants during the period of the trial (Cheng 2010; Hon 2007; Luo 2010; Rao 2010; Xiao 2008; Xiao 2011; Zou 2011).
With regard to adverse events including liver or kidney dysfunction, there was one withdrawal due to aggravation of the condition (a severe adverse event) after using CHM (Lin 2010), no severe adverse events were reported in 23 studies, and the remaining 4 studies did not report adverse events (Jin 2007; Xue 2011; Zhang 2009; Zhang 2011). Twenty-four studies reported minor adverse events; 2 studies observed transient elevation of aspartate aminotransferase or alanine transaminase in the trial participants (Cheng 2010; Rao 2010). Apart from the Hon 2007 study, which recorded a statistically significant difference in minor adverse events with a higher incidence in the CHM group, pooled data from other included studies demonstrated significantly less minor adverse events with CHM interventions than their comparators. Nevertheless, the quality of evidence was low.
There were eight included studies (Cheng 2010; Gong 2010; Hon 2007; Ma 2010; Sun 2009; Xue 2011; Yang 2007; Yu 1999) that were funded by governments. In addition, 75% of the included studies, all conducted in mainland China, reported identical numbers of participants randomised and analysed. These studies reported no incomplete outcome data. We were not able to find out the underlying reasons for such unusually high compliance in RCTs.
Overall completeness and applicability of evidence
We included studies with CHM interventions administered orally or applied topically, or a combination of both, for children or adults diagnosed with eczema. All 28 included studies specifically focused on management of eczema with CHM. Based on a Chinese medicine description, the selected Chinese herbs in the included studies were under categories of "exterior-releasing", "heat-clearing", "purgative", "wind-damp-dispelling", "damp-resolving", "damp-draining", "interior-warming", "Qi-regulating", "digestant", "haemostatic", "blood-activating and stasis-resolving", "liver-pacifying wind-extinguishing", "resuscitative", "tonifying", "astringent", and "externally applied and miscellaneous" (Li 2008). The top seven most commonly used herbs were Gancao (Radix glycyrrhizae) (16 studies), Cangzhu (Rhizoma atractylodis) (13 studies), Danggui (Radix angelicae sinensis) (11 studies), Baizhu (Rhizoma atractylodis macrocephalae) (9 studies), Baixianpi (Cortex dictamni) (9 studies), Fuling (Poria) (9 studies), and Shengdihuang (Radix rehmanniae) (9 studies). We also included studies in which the CHM formulae were modified based on Chinese medicine syndrome differentiation, as well as the studies that only recruited people with eczema who had a prespecified Chinese medicine syndrome. Many of the included studies were conducted in Chinese medicine teaching hospitals or general medical teaching hospitals, which are expected to have standardised facilities and qualified personnel and represent the standard of clinical practice of the profession (MEPRC 1992). The results have reflected the up-to-date management of eczema with CHM. The findings of this review could provide a crucial reference for current evidence-based Chinese medical practice and research.
Quality of the evidence
We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, recommended by the Cochrane Handbook for Systematic Reviews of Interventions, to assess the level of evidence on outcome measures reported by the included studies (Schünemann 2011). Overall, the quality of the included studies was poor except the Hon 2007 study where the level of quality of the evidence was 'moderate' in the outcome measured by QoL. The majority of the included studies showed unclear risk of bias for allocation concealment and high risk of bias due to lack of blinding; thus, we had to downgrade the strength of evidence of those studies into 'low level' because of serious limitations in their design and implementation (absence of allocation concealment and blinding). The 2306 participants within the 28 included studies were diverse, with their ages ranging from newborn babies to 65 years, and most of the studies had mixed children with adults. There were heterogeneous Chinese herbs or formulae with regard to the ingredients, dosage, and administration in the included studies. This contributed to a high level of inconsistency of the outcomes across the studies although such underlying sources of heterogeneity have not been confirmed by statistical analyses because of insufficiency of data.
Potential biases in the review process
The randomised controlled trial is a gold standard to test efficacy of an intervention for a defined condition within a population (Kane 2004). It is debatable however whether results from RCTs can really reflect the intrinsic effect obtained from an individualised treatment, which is one of the essential features of Chinese medicine practice. For this reason, we scrupulously aimed to include studies using individualised treatments or studies only recruiting people with eczema who had a specific type of Chinese medicine syndrome as far as there was an appropriate control group, i.e. with balanced numbers of randomised participants, in the study. We further performed subgroup analysis in those included studies with individualised treatment. We tried our best to search for any studies that matched the inclusion criteria, but it could still be possible that we overlooked some papers, in particular those published in Chinese. This is because we had limited access to the printed Chinese medical journals that were not covered by the Chinese databases we had searched. We were unable to rule out the possibility of potential language bias in this review as Chinese medicine is also popularly used in other Asian countries, such as Japan, Vietnam, and Korea. We were not able to search databases developed by these countries.
The funnel plot in Figure 6 and Egger test did not show statistically asymmetrical distributions among those 15 studies that compared the effects of CHM and Western medications. However, we could not exclude reporting bias including publication bias in those 15 studies because of the relatively low power of the Egger test (Sterne 2011).
Agreements and disagreements with other studies or reviews
The first Cochrane systematic review of CHM for eczema was published in 2004 (Zhang 2004); it included only 4 studies with oral ingestion of a CHM product, which is no longer available on the market. We did not include these studies in this updated review. Poor trial quality and "small study effect" were found across the included studies in both the version published in 2004 and this review.
We would like to express our sincere thanks for those who provided help:
Dr Finola M Delamere, Managing Editor, Cochrane Skin Group, for co-ordination of the project;
Ms Liz Doney, Trials Search Co-ordinator, Cochrane Skin Group, for searching the databases and inputting the search results;
Miss Laura Prescott, Editorial Assistant, Cochrane Skin Group, for providing assistance;
Ms Miranda Cumpston, Systematic Review Trainer, Australasian Cochrane Centre, for providing author training and advice;
Dr Tony Zhang, Head, Discipline of Chinese Medicine, School of Health Sciences, Royal Melbourne Institute of Technology (RMIT) University, Australia, for providing advice on interpretation of statistical data;
Professor Chuanjian Lu, Deputy Director, Guangdong Provincial Academy of Chinese Medical Sciences, China, for providing expert advice;
Dr Chijing Liu, Director, Chi Herbal Australia P/L, for providing conference proceedings; and
Mr Kun Zou, PhD student, Division of Academic Rheumatology, School of Clinical Sciences, University of Nottingham, UK, for testing publication bias.
Our sincere thanks are also extended to those authors who made their contribution to the previous version of the review. They were Tina Leonard, Fiona Bath-Hextall, Colette Chambers, Caroline Lee, and Rosemary Humphreys.
The Cochrane Skin Group editorial base wishes to thank Robert Dellavalle who was the Key Editor for this review; Jo Leonardi-Bee and Ching-Chi Chi who were the Statistical and Methods Editors, respectively; the clinical referees, Jerry Tan and Kam-Lun Ellis Hon; and the consumer referee, the late Shirley Manknell.
Appendix 1. CENTRAL (Cochrane Library) search strategy
#1 MeSH descriptor Eczema explode all trees
#2 MeSH descriptor Dermatitis, Atopic explode all trees
#3 MeSH descriptor Dermatitis explode all trees
#4 eczema or dermatitis or "besnier* prurigo"
#5 (#1 OR #2 OR #3 OR #4)
#6 MeSH descriptor Medicine, Chinese Traditional explode all trees
#7 MeSH descriptor Drugs, Chinese Herbal explode all trees
#8 MeSH descriptor Plants, Medicinal explode all trees
#9 MeSH descriptor Medicine, Traditional explode all trees
#10 MeSH descriptor Plant Extracts explode all trees
#11 MeSH descriptor Phytotherapy explode all trees
#14 (traditional or herbal) and (therap* or medicine*)
#15 "aconite root" or camelia or cayenne or "chinese cucumber" or "chrysanthemum flower*" or "cocklebur fruit" or "cow dipper" or "croton seed" or ginger or ginkgo or ginseng or "goji berry" or "horny goat weed" or rhubarb or "thunder vine" or "strychnine tree" or "sweet wormwood" or "willow bark"
#16 (#6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15)
#17 (#5 AND #16)
Appendix 2. MEDLINE (OVID) search strategy
1. exp Eczema/ or eczema.mp.
2. atopic dermatitis.mp. or exp Dermatitis, Atopic/
3. exp Dermatitis/ or dermatitis.mp.
4. Besnier$ prurigo.mp.
6. exp drugs, chinese herbal/ or exp medicine, chinese traditional/
7. exp Plants, Medicinal/
8. exp Medicine, Traditional/
9. exp Plant Extracts/
10. exp Phytotherapy/
13. traditional medicine$.mp.
14. traditional therap$.mp.
15. herbal medicine$.mp.
16. herbal therap$.mp.
17. aconite root.mp.
20. chinese cucumber.mp.
21. chrysanthemum flower$.mp.
22. cocklebur fruit.mp.
23. cow dipper.mp.
24. croton seed.mp. or exp Croton/
25. ginger.mp. or exp Ginger/
26. ginkgo.mp. or exp Ginkgo biloba/
27. ginseng.mp. or exp Panax/
28. goji berry.mp.
29. horny goat weed.mp.
30. rhubarb.mp. or exp Rheum/
31. thunder vine.mp.
32. strychnine tree.mp.
33. sweet wormwood.mp.
34. willow bark.mp.
35. randomized controlled trial.pt.
36. controlled clinical trial.pt.
39. clinical trials as topic.sh.
42. 35 or 36 or 37 or 38 or 39 or 40 or 41
43. (animals not (human and animals)).sh.
44. 42 not 43
45. 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34
46. 5 and 44 and 45
Appendix 3. EMBASE (OVID) search strategy
1. eczema.ti,ab. or *eczema/
2. exp *DERMATITIS/ or dermatitis.ti,ab.
3. atopic dermatitis.ti,ab. or *atopic dermatitis/
4. Besnier$ prurigo.ti,ab.
6. exp oriental medicine/ or exp medicinal plant/ or exp Chinese medicine/ or exp traditional medicine/ or exp Chinese drug/
7. exp herb/ or exp Chinese herb/
8. exp herbal medicine/
9. (herb or herbs).mp. or herbal.ti,ab.
10. exp plant medicinal product/ or exp plant extract/
11. exp phytotherapy/
13. traditional medicine$.ti,ab.
14. traditional therap$.ti,ab.
15. herbal medicine$.ti,ab.
16. herbal therap$.ti,ab.
17. aconite root.ti,ab.
20. chinese cucumber.ti,ab.
21. chrysanthemum flower$.ti,ab.
22. cocklebur fruit.ti,ab.
23. cow dipper.ti,ab.
24. croton seed.ti,ab.
28. goji berry.ti,ab.
29. horny goat weed.ti,ab.
31. thunder vine.ti,ab.
32. strychnine tree.ti,ab.
33. sweet wormwood.ti,ab.
34. willow bark.ti,ab.
37. (crossover$ or cross-over$).mp.
38. placebo$.mp. or PLACEBO/
39. (doubl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]
40. (singl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]
41. (assign$ or allocat$).mp.
42. volunteer$.mp. or VOLUNTEER/
43. Crossover Procedure/
44. Double Blind Procedure/
45. Randomized Controlled Trial/
46. Single Blind Procedure/
47. 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46
49. 5 and 47 and 48
Appendix 4. AMED (OVID) search strategy
1. exp Eczema/ or eczema.mp.
3. Dermatitis/ or exp Dermatitis atopic/
4. besnier$ prurigo.mp.
6. exp Drugs chinese herbal/ or exp Traditional medicine chinese/
7. exp Plant extracts/ or exp Herbs/ or exp Herbal drugs/ or exp Plants medicinal/
8. exp Traditional medicine/
9. exp Herbalism/
10. exp Phytotherapy/
12. traditional medicine$.mp.
13. traditional therap$.mp.
14. herbal medicine$.mp.
15. herbal therap$.mp.
16. aconite root.mp.
19. chinese cucumber.mp.
20. chrysanthemum flower$.mp.
21. cocklebur fruit.mp.
22. cow dipper.mp.
23. croton seed.mp.
25. ginkgo.mp. or exp Ginkgo biloba/
26. ginseng.mp. or exp Panax ginseng/
27. goji berry.mp.
28. horny goat weed.mp.
30. thunder vine.mp.
31. strychnine tree.mp.
32. sweet wormwood.mp.
33. willow bark.mp.
34. (plant$1 or herb$).mp. [mp=abstract, heading words, title]
35. randomized controlled trial$/
36. random allocation/
37. double blind method/
38. single blind method.mp.
39. exp Clinical trials/
40. (clin$ adj25 trial$).mp. [mp=abstract, heading words, title]
41. ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$ or dummy)).mp. [mp=abstract, heading words, title]
42. (placebo$ or random$).mp. [mp=abstract, heading words, title]
43. research design/ or clinical trials/ or comparative study/ or double blind method/ or random allocation/
44. prospective studies.mp.
45. cross over studies.mp.
46. Follow up studies/
48. (multicent$ or multi-cent$).mp. [mp=abstract, heading words, title]
49. ((stud or design$) adj25 (factorial or prospective or intervention or crossver or cross-over or quasi-experiment$)).mp. [mp=abstract, heading words, title]
50. 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49
52. 5 and 50 and 51
Appendix 5. LILACS search strategy
((Pt RANDOMIZED CONTROLLED TRIAL OR Pt CONTROLLED CLINICAL TRIAL OR Mh RANDOMIZED CONTROLLED TRIALS OR Mh RANDOM ALLOCATION OR Mh DOUBLE-BLIND METHOD OR Mh SINGLE-BLIND METHOD OR Pt MULTICENTER STUDY) OR ((tw ensaio or tw ensayo or tw trial) and (tw azar or tw acaso or tw placebo or tw control$ or tw aleat$ or tw random$ or (tw duplo and tw cego) or (tw doble and tw ciego) or (tw double and tw blind)) and tw clinic$)) AND NOT ((CT ANIMALS OR MH ANIMALS OR CT RABBITS OR CT MICE OR MH RATS OR MH PRIMATES OR MH DOGS OR MH RABBITS OR MH SWINE) AND NOT (CT HUMAN AND CT ANIMALS)) [Words] and chinese or herb$ or traditional [Words] and eczema or dermatitis [Words]
Appendix 6. CINAHL (EBSCO) search strategy
S1 (MM "Eczema") OR (MM "Dermatitis, Atopic")
S2 (MH "Medicine, Chinese Traditional") OR (MH "Drugs, Chinese Herbal")
S3 TI (Chinese and (herb* or medicin* or traditional or plant*))
S4 AB (Chinese and (herb* or medicin* or traditional or plant*))
S5 S2 or S3 or S4
S6 TI eczema or dermatitis
S7 S1 or S6
S8 S5 and S7
S9 (MH "Clinical Trials+")
S10 PT clinical trial
S11 TX (clinic* n1 trial*)
S12 (MH "Random Assignment")
S13 TX random* allocat*
S14 TX placebo*
S15 (MH "Placebos")
S16 (MH "Quantitative Studies")
S17 TX allocat* random*
S18 "randomi#ed control* trial*"
S19 TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) )
S20 S9 or S10 or S11 or S12 or S13 or S14 or S15 or S16 or S17 or S18 or S19
S21 S8 and S20
Appendix 7. Chinese database CQVIP search strategy
Appendix 8. Chinese database CNKI search strategy
(发表时间 between (1979,2011)) 并且 (( (题名=中英文扩展(异位性皮炎) 或者 题名=中英文扩展(异位性湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
(发表时间 between (2011, 2012)) 并且 (( (题名=中英文扩展(异位性皮炎) 或者 题名=中英文扩展(异位性湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
(发表时间 between (2012-09-14, 2013-06-12)) 并且 (( (题名=中英文扩展(异位性皮炎) 或者 题名=中英文扩展(异位性湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
(发表时间 between (1979,2011)) 并且 (( (题名=中英文扩展(特应性皮炎) 或者 题名=中英文扩展(特异性湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
(发表时间 between (2011, 2012)) 并且 (( (题名=中英文扩展(特应性皮炎) 或者 题名=中英文扩展(特异性湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
(发表时间 between (2012-09-14, 2013-06-12)) 并且 (( (题名=中英文扩展(特应性皮炎) 或者 题名=中英文扩展(特异性湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
(发表时间 between (1979,2011)) 并且 (( (题名=中英文扩展(婴幼儿湿疹) 或者 题名=中英文扩展(儿童湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
(发表时间 between (2011, 2012)) 并且 (( (题名=中英文扩展(婴幼儿湿疹) 或者 题名=中英文扩展(儿童湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
(发表时间 between (2012-09-14, 2013-06-12)) 并且 (( (题名=中英文扩展(婴幼儿湿疹) 或者 题名=中英文扩展(儿童湿疹))) 并且 全文=中英文扩展(中医药)) (精确匹配)
Appendix 9. Chinese database Wanfang data search strategy
title:异位性皮炎 keyword:中医药 date:1982-2013
title:异位性湿疹 keyword:中医药 date:1982-2013
title:特应性皮炎 keyword:中医药 date:1982-2013
title:特应性湿疹 keyword:中医药 date:1982-2013
title:婴幼儿湿疹 keyword:中医药 date:1982-2013
title:儿童湿疹 keyword:中医药 date:1982-2013
Appendix 10. List of contacted Chinese medicine dermatologists or experts
Professor Rudi Ai, Professor Dacan Chen, Dr Chi Jing Liu, Professor Chuanjian Lu, Dr Xiumei Mo.
Contributions of authors
SG was the contact person with the editorial base.
SG co-ordinated contributions from the co-authors and wrote the final draft of the review.
SG and AWY screened papers against eligibility criteria.
SG and AWY obtained data on ongoing and unpublished studies.
HCW, WZ, CCX, and CGL appraised the quality of papers.
SG and AWY extracted data for the review and sought additional information about papers.
SG and AWY entered data into RevMan.
SG, AWY, HCW, WZ, CCX, and CGL analysed and interpreted data.
SG, AWY, HCW, WZ, CCX, and CGL worked on the methods sections.
SG, AWY, HCW, and WZ drafted the clinical sections of the background and responded to the clinical comments of the referees.
SG, AWY, HCW, and WZ responded to the methodology and statistics comments of the referees.
CP was the consumer co-author and checked the review for readability and clarity, as well as ensuring outcomes are relevant to consumers.
SG is the guarantor of the update.
The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health, UK.
Declarations of interest
Kam-Lun Ellis Hon, who peer-reviewed this review as a clinical referee, was also the Principal Investigator in the following included study:
Hon KL, Leung TF, Ng PC, Lam MCA, Kam WYC, Wong KY, et al. Efficacy and tolerability of a Chinese herbal medicine concoction for treatment of atopic dermatitis: a randomized, double-blind, placebo-controlled study. British Journal of Dermatology 2007;157(2):357-63. [MEDLINE: 17501956]
Differences between protocol and review
We added "in children and adults" under the heading of 'Objectives' to define the participants in this review.
In the Methods section under 'Type of interventions', we found in the protocol that the words "or formula" were missing and CHM had been listed as one of the control interventions, which was inappropriate. We changed the wording to: "Oral ingestion and topical applications of a single Chinese medicinal herb or formula, manufactured or clinician self-designed Chinese medicinal formulae, (a clinician self-designed formula is usually composed of different types of Chinese herbs prescribed by a Chinese medicine practitioner who determines the selection of herbs based on a patient’s condition) compared to the following control interventions: placebo, no intervention, and active controls, including acupuncture or conventional medicines."
To make the meaning of the statement more precise, in the Methods section under 'Measures of treatment effect' and then the subheading 'Studies with multiple treatment groups', we rephrased the wording to: "For studies with more than two interventions, we selected the comparison group that met the inclusion criteria."
To reflect the actual process of the review, in the Methods section under 'Data collection and analysis' and then the subheading 'Data synthesis', we deleted the following sentence: "In the presence of substantial heterogeneity that cannot be explained, we would not undertake statistical pooling." We replaced it with, "We performed the meta-analyses irrespective of the level of heterogeneity for the purpose of explanation of potential inconsistency across the included studies. When substantial heterogeneity was found (I² statistic greater than 50%), then we explored the sources of such heterogeneity by rechecking the data, and by subgroup analysis based on clinical and methodological diversity factors."
We performed a posthoc subgroup analysis to further investigate heterogeneity across the included studies where Western medications were used as comparators.
A search of MEDLINE and PubMed in November 2015 found only 1 RCT study, and a search by the lead author of CNKI yielded 3 potential studies, but he does not think the inclusion of these new findings could substantially change the conclusions made in 2013. An update has not been considered necessary for two successive years. Our Trials Search Co-ordinator will run a new search in 2016 to re-assess whether an update is needed.