Actinic Keratoses and Herbal Medicine Interventions
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Actinic Keratoses and Herbal Medicine Interventions A thesis submitted in fulfilment of the requirements for the degree of Master of Science Karina Anna Hilterman Dip. Med Herb. (Waikato Centre For Herbal Studies) B.H.Sc. (Nat Med) Victoria University School of Health and Biomedical Sciences College of Science, Engineering and Health RMIT University January 2020 DECLARATION BY THE CANDIDATE I, Karina Anna Hilterman, declare that: I certify that except where due acknowledgement has been made, the work is that of the author alone; the work has not been submitted previously, in whole or in part, to qualify for any other academic award; the content of the thesis is the result of work which has been carried out since the official commencement date of the approved research program; any editorial work, paid or unpaid, carried out by a third party is acknowledged; and, ethics procedures and guidelines have been followed. I acknowledge the support I have received for my research through the provision of an Australian Government Research Training Program Scholarship. Signed: Date: 31st January 2020 Karina Anna Hilterman ii ACKNOWLEDGEMENTS There have been many amazing, wise and brave individuals and groups of people who have walked the ‘herbalist path’ before me; not all were treated with the respect they deserved. Some have published books and manuscripts, others have not. They learnt from those that went before them, as I have… My gratitude to Professor Stephen Robinson, as senior supervisor; he has guided me to ensure this thesis is a positive contribution to the field of herbal medicine. To Dr Iris Wenyu Zhou, who assisted with the systematic review. Thanks to Dr Marie Pirotta, Associate Professor, School of General Practice, Melbourne University (retired), for her encouragement and guidance as my External Supervisor. For his advice and information, regarding his dermatology specialty, as an External Consultant, Dr Tony Dicker, please accept my thanks. To Julie Wilkinson-Flores, Western Herbal Medicine Practitioner, my thanks for reviewing this thesis; from your practice experience and perspective of Western Herbal Medicine. For reviewing Chapter 2.1.6. my gratitude to Dr Peter Gies, Senior Research Scientist, Ultraviolet Radiation, Radiation Health Services Branch, Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). To Nancy Patton, Sheila Jolley and Sharon Fredriksson, for your editing advice, I thank you. For editing assistance, Pam Kershaw, you are a gem and Laura Stephenson; for formatting. My heartfelt gratitude for Miss Lilly, my beautiful, furry four-legged companion, who kept me comforted with her contented purring on my lap as I typed, often late into the night. Sadly, she passed away during this thesis preparation... “To raise new questions, new possibilities, to regard old problems from a new angle, requires creative imagination and marks real advance in science” – Albert Einstein (1879-1955). iii CONTENTS PAGE Cover Page Declaration By The Candidate i Acknowledgements ii Contents iv List of Figures ix List of Tables xi Abbreviations P1 Summary Background P2 Aims P2 Methods P2 Results P3 Implications P4 Chapter 1 Introduction 1.1 Background P5 1.2 Overview of Thesis Structure P6 1.3 Rationale for Undertaking this Study P7 1.4 Objectives P9 Chapter 2 Background 2.1 What are Actinic Keratoses [AKs] P10 2.1.1 History P10 2.1.2 Pathophysiology P12 2.1.3 Differential diagnosis P17 2.1.4 Epidemiology P17 2.1.5 Development of AKs into non-melanoma skin cancer P18 2.1.6 The sun’s effect on skin P20 2.1.7 Melanocytes and vitamin D regulation and immune support P24 2.2 Topical Medical Treatments for AKs P26 2.2.1 Cryotherapy/Cryosurgery P26 2.2.2 Electrodessication P27 2.2.3 Surgical removal P27 2.2.3a Excisional biopsy P27 2.2.3b Incisional biopsy P27 2.2.3c Punch biopsy P27 2.2.3d Curettage P28 2.2.3e Shave biopsy P28 2.2.3f Moh’s micrographic surgery P28 2.2.4 Chemical peels P28 2.2.5 Dermabrasion P28 2.2.6 Retinoids P29 2.2.7 Photodynamic therapy [PDT] P29 2.2.8 Chemotherapy P29 2.2.9 Radiotherapy P30 2.2.10 Topical immune-modulating agents P30 2.2.11 Picato P30 2.2.12 Application of medical treatments P31 2.3 Prevention of Sun-Induced Skin Damage P31 Chapter 3 Herbal Medicine, Skin Disease and Herbs As Skin Treatments 3.1 Herbs for Treating Skin Disease P33 3.1.1 Background of herbs as medicine P33 3.1.2 Standardisation of herbal medicines P35 iv 3.1.3 Extraction methods and availability of herbal constituents P37 3.1.4 Safety and efficacy of herbal medicines P38 3.1.5 Herbal, complementary and alternative medicine research P39 3.1.6 Historical treatments for skin conditions P40 3.2 Herbal Medicine Approaches to Treating Skin Disease P42 3.2.1 Clinical considerations for herbal treatment of AKs P42 3.3 Herbs for Topical Treatment of AKs P45 3.4 Indicated Therapeutic Actions P46 3.5 Selected Herb Profiles P50 Chapter 4 Systematic Review: Efficacy and Safety of Herbal Treatment of AKs 4.1 Background P51 4.1.1 Considerations for undertaking a systematic review P51 4.1.2 Rationale for conducting a systematic review P51 4.1.3 Expected outcomes P52 4.2 Methodology for Systematic Review P52 4.2.1 Inclusion and exclusion criteria P52 4.2.1a Types of studies P52 4.2.1b Criteria for inclusion P52 4.2.1c Types of participants P52 4.2.1d Types of interventions P53 4.2.1e Types of outcome measures P53 4.2.2 Search methods for identification of studies P53 4.2.2a Databases searched P53 4.2.2b Searching other resources P53 4.2.2c Search terms P53 4.2.2d Selection of studies P53 4.2.3 Data extraction and management P54 4.2.4 Evaluation of bias risk of included studies P54 4.3 Results P54 4.3.1 Results of search P54 4.3.2 Summary of studies P55 4.3.3 Excluded studies P55 4.3.4 Included studies P55 4.3.5 Characteristics of included studies P56 4.3.5a Number of participants P59 4.3.5b Age range P59 4.3.5c Treatment ranges, dosages and controls P60 4.3.6 Herbal preparations used in the included studies P63 4.3.6a Colchicum autumnale P63 4.3.6b Betula species P63 4.3.6c Hypericin P64 4.3.6d Euphorbia peplus P64 4.3.6e Perillyl alcohol P65 4.3.6f Solanum incanum P65 4.3.7 Risk of bias assessment of included RCTs P65 4.3.7a Sequence generation P66 4.3.7b Allocation concealment P66 4.3.7c Blinding of participants and personnel P66 4.3.7d Blinding of outcome assessments: P66 Self-reported and subjective outcomes 4.3.7e Blinding of outcome assessments: P67 Non-self-reported and objective outcomes 4.3.7f Incomplete outcome data P67 4.3.7g Selective outcome reporting P67 4.3.7h Other potential threats to validity P67 4.3.8 Assessment of the included Non-RCTs P68 4.3.9 Instruments used for assessment and monitoring P70 4.3.10 Outcome measures P71 v 4.3.10a RCTS P71 4.3.10b Non-RCTs P72 4.3.11 Effects of the interventions P73 4.3.11a Colchicine studies P73 4.3.11b Birch Bark studies P73 4.3.11c Hypericum perforatum study P74 4.3.11d Euphorbia peplus studies P75 4.3.11e POH study P76 4.3.11f Solanum incanum study P76 4.3.12 Adverse events P79 4.3.12a Colchicine studies P80 4.3.12b Birch Bark studies P81 4.3.12c Hypericum perforatum study P81 4.3.12d Euphorbia peplus studies P81 4.3.12e POH study P82 4.3.12f Solanum incanum study P82 4.4 Discussion P83 4.4.1 Summary of main findings P83 4.4.2 Adverse events P83 4.4.3 Overall completeness and evidence applicability P84 4.4.3a Dosage rates P84 4.4.3b Differences in dropout rates P84 4.4.3c Different types of participants P85 4.4.4 Potential biases in review process P85 4.4.5 Discussion on the effect of individual substances P85 4.4.6 Search limitations P85 4.5 Conclusions P86 4.5.1 Clinical Implications P87 4.5.2 Implications for future research P87 Chapter 5 Survey of Herbalist’s Use of Herbal Medicine in AK Treatment 5.1 Survey Preparations P92 5.2 Survey Responses P93 5.3 Choices of Herbs as AK Treatments P95 5.4 Effectiveness of Treatments P98 5.5 Adverse Effects of AK Treatments P99 5.6 Awareness of AKs P100 5.7 Summary P101 Chapter 6 Discussion and Conclusions 6.1 Discussion P103 6.2 Conclusions P105 References P107 Appendices Summary P125 Appendix A A1 Elaboration of Herbs Included in Systematic Review P126 A1.1 Colchicum autumnale A1.2 Betula species A1.3 Hypericin A1.4 Euphorbia peplus A1.5 Perillyl alcohol A1.6 Solanum incanum Appendix B B1 Selected Monographs of Herbs for Consideration as AK Treatments P138 vi B1.1 Aloe vera (Aloe) B1.1.1 Constituents B1.1.2 Therapeutic actions B1.2 Arctium lappa (Burdock) B1.2.1 Constituents B1.2.2 Therapeutic actions B1.3 Avena sativa (Oats) B1.3.1 Constituents B1.3.2 Therapeutic actions B1.4 Berberis vulgaris (Barberry) B1.4.1 Constituents B1.4.2 Therapeutic actions B1.5 Calendula officinalis (Calendula/Marigold) B1.5.1 Constituents B1.5.2 Therapeutic actions B1.6 Echinacea purpurea and angustifolia (Echinacea) B1.6.1 Constituents B1.6.2 Therapeutic actions B1.7 Galium aparine (Cleavers) B1.7.1 Constituents B1.7.2 Therapeutic actions B1.8 Hypericum perforatum (St John’s Wort) B1.8.1 Constituents B1.8.2 Therapeutic actions B1.9 Matricaria chamomilla (chamomile) B1.9.1 Constituents B1.9.2 Therapeutic actions B1.10 Phytolacca americana (decandra/Poke Weed) B1.10.1 Constituents B1.10.2 Therapeutic actions B1.11 Prunella vulgaris (Self Heal) B1.11.1 Constituents B1.11.2 Therapeutic actions B1.12 Stellaria media (Chickweed) B1.12.1 Constituents B1.12.2 Therapeutic actions B1.13 Taraxacum officinale (Dandelion) B1.13.1 Constituents B1.13.