Pediatric Dennatology Vol. 9 No. 4 373-375
Treatment of Atopic Eczema with Traditional Chinese Medicinal Plants David J. Atherton, FRCP, Mary P. Sheehan, MRCP, Malcolm H. A. Rustin, MRCP,* Brian Whittle, Ph.D,,t and Geoffrey Guy, M.B.t Department of Dermatology, The Hospital for Sick Children, London, * Department of Dermatology, The Royal Free Hospital, London, and fPhytopharm Ltd, Brough, North Humberside, United Kingdom Although atopic eczema is often a mild disease that may respond satisfactorily to simple treatments, in an important minority of children and adults it is severe and disabling. In such patients, the disease may be unresponsive to treatment unless therapy with substantial associated toxicity is used, such as oral psoralen-photochemotherapy or oral cyclospodne. All dermatologists acknowledge the pressing need for more effective and safer treatments for this group of patients. During a period of several hundred years, the Chinese developed an extensive range of treatments based largely on native plants. The use of these evolved very gradually, and considerable knowledge of the benefits and hazards of the various parts of all these plants has now been accumulated. The effectiveness of such treatment was first suggested to us about six years ago, when a child with severe atopic eczema under the care of one of us (DJA) was taken by his parents to see a Chinese doctor. Dr. Luo. The boy was treated with a daily decoction prepared from a mixture of dried medicinal plant materials. It was impressively effective and had no obvious adverse effects. Subsequently, we followed the progress of some 30 other children treated by this doctor and observed sustained and substantial improvement in approximately 75%. In most cases, the eczema had been severe and inadequately controlled by any of the treatments that had previously been used, despite good compliance. It became clear to us that decoctions of traditional Chinese medicinal plants might be generally more effective than the conventional treatments used for atopic eczema in Europe and North America. Furthermore, careful observation of patients receiving this therapy failed to reveal evidence of any obvious toxicity.
In traditional Chinese medicine (TCM), the components of each patient's prescription are selected according to their various perceived effects on body function. The aim of treatment for any disease is to restore harmony to the functions of the body, which generally requires the simultaneous use of several plant materials. Although a limited number of formulations of these agents are available in pill, tablet, or liquid form, generally they are in the form of dried plant materials. The medication is prepared by boiling these materijils with water for a specified period, straining off the liquid (known technically as a decoction) and drinking this after cooling. The taste of the decoctions is almost invariably extremely disagreeable. Doctors and scientists in the West "generally find the theoretical basis of TCM unconvincing. However, scepticism of such treatments should not blind us to the possibility that they may be beneficial in at least some instances. Our observation of the effectiveness of TCM in atopic eczema led us to approach Dr. Luo, who offered us her expertise without hesitation. The plant formulations she uses for atopic eczema have been modified for use in English patients over a period of years. Although the practice of TCM normally requires that patients receive individujJly determined prescriptions. Dr. Luo agreed to devise a limited number of standardized formulas for patients whose eczema and general condition fulfilled certain fairly precise criteria. She wrote four formulas for mixtures of medicinal plant materials and defined the type of patient for whom each would be most appropriately prescribed. Chinese formularies provide a Latin name for each component and the appropriate dosages for patients of different ages. With the assistance of experts here and in China, we have been
373
374 Pediatric Dennatology Vol. 9 No. 4 December 1992 able to check these identifications and now have the species of origin for most of the relevant plant materials. We prescribed these standardized formulations for suitable patients whose eczema had not responded adequately to conventioned therapy, and evaluated their effects on an open basis. These pilot studies suggested that the medications would be helpful in as many as 60% of selected patients. Furthermore, blood tests on these patients demonstrated no evidence of impaired renal, hepatic, or bone marrow function after six months' continuous therapy. By this stage, we had gained the confidence to progress to a full-scale clinica! trial of a fonnula designed for patients with extensive, diffuse disease, with prominent erythema but without exudation. On ethical considerations, we decided to limit participation to children with eczema of substantial severity of the appropriate clinical type that had failed to respond adequately to previous therapy. The need for the trial to be both placebocontrolled and double-blind provided a major challenge. The active treatment contained 10 different plant materials, all in common use as medicines in China. Quality controls were run on them to verify their identity, and to minimize the possibility of contamination, particularly with respect to heavy metals. The materials were then milled to a fine powder, mixed, and sealed in porous paper sachets. Two types of sachets were prepared, larger ones containing the majority of the constituents, and smaller ones containing those that incorporated volatile components that would otherwise be lost during prolonged boiling. The placebo was a mixture of inert plant materials (bran, hops, barley, small amounts of culinary herbs) having a similar appearance, taste, and smell, but with no known benefit in atopic eczema. We used a cross-over design, with randomization of treatment order. Each treatment was given for eight successive weeks, with an intervening fourweek wash-out period. Forty-seven children of both sexes (age range 1.5-18.1 yrs) participated, after verification of a nonnal complete blood count and routine clinical chemistry. Eczema activity was assessed using a simple scoring system. The children attended the clinic every four weeks throughout the five-month trial. Further blood tests and 24-hour urine collection were made at the end of each of the two treatment periods. Parents were instructed to prepare the medication once daily, the number of sachets depending on
the child's age. The large sachets were placed in 500 ml water, which was brought to the boil and simmered for 90 minutes. The small sachets were then added and the liquid simmered for a final three minutes. Parents learned to boil the liquid at a rate that would reliably reduce its volume to about 100 ml, which was taken while still warm. Of the 47 children who started the trial, 37 completed it. Five were unable to take the treatment as instructed on account of its unpalatability, and five others were excluded from the study because they were receiving systemic corticosteroids for asthma or systemic antibiotics for skin infections. Analysis demonstrated a targe and statistically significant superiority of active treatment over placebo (1). Two-thirds of the treated children enjoyed greater than 60% reductions in eczema activity scores. Most of the improvement was apparent by the end of the fourth week of treatment. The reductions in eczema activity scores were mirrored by symptomatic improvements reported by parents. No effect on asthma was observed. No child developed any abnormality of bone marrow, kidney, or liver function during treatment. The results of the trial confirmed the effectiveness of Chinese medicinal plants as a treatment for atopic eczema in children. These results were gratifying for two reasons. First, this may be the most effective new treatment for the disorder to emerge since the introduction of topical corticosteroids some 40 years ago (apart from a small number of powerful drugs whose use is limited by serious toxicity). Second, the benefit was observed in patients in whom orthodox treatment failed to provide adequate disease control. We recently obtained similar results in a controlled trial in adults with the same type of eczema (2). Although entry to both studies was restricted to subjects with a particular subtype of atopic eczema, there is no reason to believe that this treatment would not be equally effective in other, more common types of the disorder. Indeed, observation of patients treated by Chinese colleagues in the United Kingdom and in China suggests that it would be. This issue will be addressed in future studies. Palatability is currently a great problem with this treatment. However, progress is being made in developing a more or less tasteless extract of the same plant materials used in this study. We hope to proceed to a multicenter, controlled trial of such a preparation within a few months.
The pharmacology and mechanism of action of
Atherton et al: Treating Atopic Eczema with Medicinal Plants
this treatment are unknown. However, we know that the plants employed contain large numbers of pharmacologically active molecules, and that these are certain to possess a wide spectrum of biologic effects. However, we were particularly anxious to eliminate corticosteroid-like activity as a basis for its effectiveness, and have been able to do so by demonstrating that treatment does not alter the pattem of endogenous steroid excretion (3). Although we found no evidence of short-term toxicity, either clinically or in the hmited tests undertaken in these studies, the possibility of longerterm toxicity cannot be ignored. For this reason, we are currently performing a similar range of tests at six-month intervals in a large cohort of patients receiving TCM therapy for atopic eczema. The possibility of idiosyncratic short-term adverse reactions in individual patients has been highlighted (4), and careful studies clearly will be required in many patients before the safety of this approach is established. We advise that, for the present, no patient should receive this therapy without prior checks of hematologic, renal, and hepatic function, and regular checks are required when treatment is continued over many months. Although a great deal of careful study is still required, it has been an exciting experience for us to work with this remarkable method of treatment. It is probable that other diseases, both dermatologic and nondermatologic, will in the future find effec-
375
tive therapies through further research on plant medicines already in use in China and other countries. However, plants used within the context of TCM should perhaps be the focus of special interest, because of the long period of their careful study and use within a highly cultivated medical framework, the achievements of which remain largely neglected in the West. ACKNOWLEDGMENTS
This work was conducted with the support of grants from the National Eczema Society, the Roger Waters Trust, and the Steel Trust, and with the invaluable advice of Dr. Luo Ding-Hui. REFERENCES 1. Sheehan M, Atherton DJ. A controlled trial of traditional Chinese medicinal plants in widespread nonexudative atopic eczema. Br J Dermato! 1992,126: 179-184. 2. Sheehan MP, Rustin MHA, Atherton DJ, Buckley C, Harris DJ, Ostlere L. Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis: results of a double-blind placebo-controlled study. Lancet in press. 3. Taylor N, Sheehan MP, Atherton DJ. Traditional Chinese plant decoctions for atopic eczema: effects on steroid metabolism. J Steroid Biochem (subnmtted). 4. Davis EG, Pollock 1, Steel HM. Chinese herbs for eczema. Lancet I99O;336:177.
Treatment of Atopic Eczema with Traditional Chinese Medicinal Plants David J. Atherton, FRCP, Mary P. Sheehan, MRCP, Malcolm H. A. Rustin, MRCP,* Brian Whittle, Ph.D,,t and Geoffrey Guy, M.B.t Department of Dermatology, The Hospital for Sick Children, London, * Department of Dermatology, The Royal Free Hospital, London, and fPhytopharm Ltd, Brough, North Humberside, United Kingdom Although atopic eczema is often a mild disease that may respond satisfactorily to simple treatments, in an important minority of children and adults it is severe and disabling. In such patients, the disease may be unresponsive to treatment unless therapy with substantial associated toxicity is used, such as oral psoralen-photochemotherapy or oral cyclospodne. All dermatologists acknowledge the pressing need for more effective and safer treatments for this group of patients. During a period of several hundred years, the Chinese developed an extensive range of treatments based largely on native plants. The use of these evolved very gradually, and considerable knowledge of the benefits and hazards of the various parts of all these plants has now been accumulated. The effectiveness of such treatment was first suggested to us about six years ago, when a child with severe atopic eczema under the care of one of us (DJA) was taken by his parents to see a Chinese doctor. Dr. Luo. The boy was treated with a daily decoction prepared from a mixture of dried medicinal plant materials. It was impressively effective and had no obvious adverse effects. Subsequently, we followed the progress of some 30 other children treated by this doctor and observed sustained and substantial improvement in approximately 75%. In most cases, the eczema had been severe and inadequately controlled by any of the treatments that had previously been used, despite good compliance. It became clear to us that decoctions of traditional Chinese medicinal plants might be generally more effective than the conventional treatments used for atopic eczema in Europe and North America. Furthermore, careful observation of patients receiving this therapy failed to reveal evidence of any obvious toxicity.
In traditional Chinese medicine (TCM), the components of each patient's prescription are selected according to their various perceived effects on body function. The aim of treatment for any disease is to restore harmony to the functions of the body, which generally requires the simultaneous use of several plant materials. Although a limited number of formulations of these agents are available in pill, tablet, or liquid form, generally they are in the form of dried plant materials. The medication is prepared by boiling these materijils with water for a specified period, straining off the liquid (known technically as a decoction) and drinking this after cooling. The taste of the decoctions is almost invariably extremely disagreeable. Doctors and scientists in the West "generally find the theoretical basis of TCM unconvincing. However, scepticism of such treatments should not blind us to the possibility that they may be beneficial in at least some instances. Our observation of the effectiveness of TCM in atopic eczema led us to approach Dr. Luo, who offered us her expertise without hesitation. The plant formulations she uses for atopic eczema have been modified for use in English patients over a period of years. Although the practice of TCM normally requires that patients receive individujJly determined prescriptions. Dr. Luo agreed to devise a limited number of standardized formulas for patients whose eczema and general condition fulfilled certain fairly precise criteria. She wrote four formulas for mixtures of medicinal plant materials and defined the type of patient for whom each would be most appropriately prescribed. Chinese formularies provide a Latin name for each component and the appropriate dosages for patients of different ages. With the assistance of experts here and in China, we have been
373
374 Pediatric Dennatology Vol. 9 No. 4 December 1992 able to check these identifications and now have the species of origin for most of the relevant plant materials. We prescribed these standardized formulations for suitable patients whose eczema had not responded adequately to conventioned therapy, and evaluated their effects on an open basis. These pilot studies suggested that the medications would be helpful in as many as 60% of selected patients. Furthermore, blood tests on these patients demonstrated no evidence of impaired renal, hepatic, or bone marrow function after six months' continuous therapy. By this stage, we had gained the confidence to progress to a full-scale clinica! trial of a fonnula designed for patients with extensive, diffuse disease, with prominent erythema but without exudation. On ethical considerations, we decided to limit participation to children with eczema of substantial severity of the appropriate clinical type that had failed to respond adequately to previous therapy. The need for the trial to be both placebocontrolled and double-blind provided a major challenge. The active treatment contained 10 different plant materials, all in common use as medicines in China. Quality controls were run on them to verify their identity, and to minimize the possibility of contamination, particularly with respect to heavy metals. The materials were then milled to a fine powder, mixed, and sealed in porous paper sachets. Two types of sachets were prepared, larger ones containing the majority of the constituents, and smaller ones containing those that incorporated volatile components that would otherwise be lost during prolonged boiling. The placebo was a mixture of inert plant materials (bran, hops, barley, small amounts of culinary herbs) having a similar appearance, taste, and smell, but with no known benefit in atopic eczema. We used a cross-over design, with randomization of treatment order. Each treatment was given for eight successive weeks, with an intervening fourweek wash-out period. Forty-seven children of both sexes (age range 1.5-18.1 yrs) participated, after verification of a nonnal complete blood count and routine clinical chemistry. Eczema activity was assessed using a simple scoring system. The children attended the clinic every four weeks throughout the five-month trial. Further blood tests and 24-hour urine collection were made at the end of each of the two treatment periods. Parents were instructed to prepare the medication once daily, the number of sachets depending on
the child's age. The large sachets were placed in 500 ml water, which was brought to the boil and simmered for 90 minutes. The small sachets were then added and the liquid simmered for a final three minutes. Parents learned to boil the liquid at a rate that would reliably reduce its volume to about 100 ml, which was taken while still warm. Of the 47 children who started the trial, 37 completed it. Five were unable to take the treatment as instructed on account of its unpalatability, and five others were excluded from the study because they were receiving systemic corticosteroids for asthma or systemic antibiotics for skin infections. Analysis demonstrated a targe and statistically significant superiority of active treatment over placebo (1). Two-thirds of the treated children enjoyed greater than 60% reductions in eczema activity scores. Most of the improvement was apparent by the end of the fourth week of treatment. The reductions in eczema activity scores were mirrored by symptomatic improvements reported by parents. No effect on asthma was observed. No child developed any abnormality of bone marrow, kidney, or liver function during treatment. The results of the trial confirmed the effectiveness of Chinese medicinal plants as a treatment for atopic eczema in children. These results were gratifying for two reasons. First, this may be the most effective new treatment for the disorder to emerge since the introduction of topical corticosteroids some 40 years ago (apart from a small number of powerful drugs whose use is limited by serious toxicity). Second, the benefit was observed in patients in whom orthodox treatment failed to provide adequate disease control. We recently obtained similar results in a controlled trial in adults with the same type of eczema (2). Although entry to both studies was restricted to subjects with a particular subtype of atopic eczema, there is no reason to believe that this treatment would not be equally effective in other, more common types of the disorder. Indeed, observation of patients treated by Chinese colleagues in the United Kingdom and in China suggests that it would be. This issue will be addressed in future studies. Palatability is currently a great problem with this treatment. However, progress is being made in developing a more or less tasteless extract of the same plant materials used in this study. We hope to proceed to a multicenter, controlled trial of such a preparation within a few months.
The pharmacology and mechanism of action of
Atherton et al: Treating Atopic Eczema with Medicinal Plants
this treatment are unknown. However, we know that the plants employed contain large numbers of pharmacologically active molecules, and that these are certain to possess a wide spectrum of biologic effects. However, we were particularly anxious to eliminate corticosteroid-like activity as a basis for its effectiveness, and have been able to do so by demonstrating that treatment does not alter the pattem of endogenous steroid excretion (3). Although we found no evidence of short-term toxicity, either clinically or in the hmited tests undertaken in these studies, the possibility of longerterm toxicity cannot be ignored. For this reason, we are currently performing a similar range of tests at six-month intervals in a large cohort of patients receiving TCM therapy for atopic eczema. The possibility of idiosyncratic short-term adverse reactions in individual patients has been highlighted (4), and careful studies clearly will be required in many patients before the safety of this approach is established. We advise that, for the present, no patient should receive this therapy without prior checks of hematologic, renal, and hepatic function, and regular checks are required when treatment is continued over many months. Although a great deal of careful study is still required, it has been an exciting experience for us to work with this remarkable method of treatment. It is probable that other diseases, both dermatologic and nondermatologic, will in the future find effec-
375
tive therapies through further research on plant medicines already in use in China and other countries. However, plants used within the context of TCM should perhaps be the focus of special interest, because of the long period of their careful study and use within a highly cultivated medical framework, the achievements of which remain largely neglected in the West. ACKNOWLEDGMENTS
This work was conducted with the support of grants from the National Eczema Society, the Roger Waters Trust, and the Steel Trust, and with the invaluable advice of Dr. Luo Ding-Hui. REFERENCES 1. Sheehan M, Atherton DJ. A controlled trial of traditional Chinese medicinal plants in widespread nonexudative atopic eczema. Br J Dermato! 1992,126: 179-184. 2. Sheehan MP, Rustin MHA, Atherton DJ, Buckley C, Harris DJ, Ostlere L. Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis: results of a double-blind placebo-controlled study. Lancet in press. 3. Taylor N, Sheehan MP, Atherton DJ. Traditional Chinese plant decoctions for atopic eczema: effects on steroid metabolism. J Steroid Biochem (subnmtted). 4. Davis EG, Pollock 1, Steel HM. Chinese herbs for eczema. Lancet I99O;336:177.
