Chinese medicine for herpes zoster

Herpes zoster (HZ) is a neurocutaneous disease caused by reactivation of the varicella zoster virus. The characteristic clinical manifestations of HZ include grouped blistering vesicles erupting on a red base of skin, and burning or stabbing pain with a unilateral dermatome distribution. The pain of HZ is associated with significant reduction on patients’ health related quality of life (HRQoL). Conventional treatments include antiviral therapies and pain management. These therapeutic approaches have not been able to provide effective relief of these symptoms for all patients.<br>Hence other therapies such as Chinese medicine (CM) have been used to treat symptoms of HZ, either alone or as add-on therapy to conventional approaches. Over the long history of Chinese medicine development, valuable information on clinical manifestations, diagnosis, and treatment for HZ have been described and explained in-depth in the classical literature, which continues to be included in the contemporary guidelines and textbooks for CM practice. Currently the classical literature evidence for HZ has not been systematically evaluated.<br>Chinese herbal medicine (CHM) and acupuncture are the two main CM therapies for HZ included in contemporary CM textbooks and guidelines. The clinical evidence based on several systematic reviews (SRs) of CM indicated that they are beneficial for pain control and cutaneous outcomes. However, the quality of current evidence is limited by the databases searched, study inclusion criteria, and statistical analyses. To address this gap, SRs based on a more comprehensive search of databases and strict inclusion criteria are needed.<br><br>Objectives<br>Guided by the “Whole Evidence” approach, this thesis aims to:<br>1. Examine the evidence of Chinese medicine classical literature for HZ.<br>2. Evaluate the current clinical trial evidence of CHM and acupuncture for HZ.<br>3. Review the current experimental evidence of CHM treatment for HZ.<br>4. Design a rigorous trial protocol on a CHM formula for HZ.<br><br>Methods<br>Classical literature evidence research<br>The comprehensive classical literature search was conducted using the Zhong Hua Yi Dian 中华医典 (ZHYD). Citations identified by search terms were extracted for further analysis. Descriptive statistical analyses were performed to identify the frequency of each search term, signs and symptoms and treatment. Cluster analyses were performed to discover the potential relationships of the HZ symptoms in the data set which were judged to be most likely HZ citations.<br>Modern literature evidence research<br>Nine English and Chinese databases were searched for evidence from randomised controlled trials (RCTs). Overviews of CHM and acupuncture therapies were conducted to summarise and discuss the characteristics of included studies. Two specific interventions were selected as the foci for the SRs: a CHM formula Long dan xie gan tang 龙胆泻肝汤 (LDXGT), and acupuncture combined with moxibustion. The general methods for the SRs followed the<br>methods of Cochrane Handbook for Systematic Reviews and Interventions. Data were extracted and risk of bias was assessed. All statistical analyses were carried out in RevMan 5.3.<br>A literature search for experimental evidence of the most frequently used herbs in the included CHM studies was conduct in PubMed. In vivo and in vitro studies which described mechanisms relevant to HZ were included for a general review.<br><br>Trial protocol design<br>According to the classical and modern literature evidence in this research, LDXGT formula was the most commonly cited CHM intervention. Clinical evidence showed LDXGT was a well-tolerated and effective treatment. However the evidence was limited by the methodological limitations. A rigorous trial protocol using LDXGT integrated with antiviral therapy was developed to generate new clinical evidence data.<br><br>Results<br>Classical literature evidence<br>Ninety-six (96) classical citations were included. Chan yao 缠腰 and huo dan 火丹 were the most common terms in included citations. The symptoms and CHM treatments described in classical literature are consistent with contemporary conventional medicine and CM textbooks. The most frequently reported formula was LDXGT. A hypothetical symptom structure for HZ has been proposed based on cluster analysis, with a key symptoms classification of heat disease in CM theory highlighted in further inferential analysis.<br><br>Clinical trial evidence<br>Ninety-four (94) RCTs were included for the overview of CHM for HZ. A variety of CHM formulae, single herbs and chemical compounds were evaluated. Findings show that LDXGT was the most commonly used formula. Twenty-six (26) studies were included for the SR of LDXGT for HZ. Modified LDXGT formula was found to shorten the time to alleviate pain and reduce postherpetic neuralgia (PHN) incidence compared with pharmacotherapies. Mild adverse events such as gastrointestinal discomfort were reported from one study.<br>Experimental evidence of the most commonly used herbs in the included CHM clinical trials found that many of the constituents isolated from these herbs have shown anti-inflammatory actions. Inhibition of inflammatory cytokines and pro-inflammatory enzymes have been reported, which may contribute to relieving the acute inflammatory response of HZ.<br>Twenty- seven (27) RCTs were included for the overview of acupuncture therapies for HZ. Acupuncture approaches and acupuncture points selection were consistent with the contemporary acupuncture guideline. Nine studies were included for the SR of acupuncture plus moxibustion for HZ. Key findings showed promising benefit from acupuncture and moxibustion in reducing pain, improving rash healing, and reducing the incidence of PHN, with few mild adverse events such as haematoma and bleeding reported.<br><br>Trial protocol design<br>Guided by the findings from the reviews, a randomised, double-blinded, placebo controlled trial protocol using LDXGT integrated with antiviral therapy in the management of HZ was developed. The participants are expected to be immunocompetent patients aged ≥50 years with acute stage HZ; and CM syndrome of Stagnant heat in the Liver meridian. Both the<br><br>intervention and control group will receive antiviral therapy. Participants in the intervention group will also receive LDXGT granules and those in the control group will receive placebo granules. The primary outcome will be evaluation of pain, and secondary outcomes will be HRQoL assessment and adverse events.<br><br>Conclusion<br>This research applied a systematic approach to summarise the whole evidence of CM therapies in the management of HZ. Data mining results from the classical literature demonstrated that the inflammation symptoms cluster was one of the components of the HZ symptoms structure. Modern literature research showed CM therapies of both CHM and acupuncture plus moxibustion were well tolerated with promising benefit in hastening pain relief, improving cutaneous outcomes, and decreasing the incidence of PHN. The anti-inflammatory effects of the most commonly used herbs from the experimental studies help to elucidate the potential mechanism of actions of these herbs for HZ. To further determine the benefit of LDXGT formula as an add-on therapy to antiviral drugs, a rigorous RCT has been proposed to be undertaken.