Key Words: Phytoskin[R] Cream, psoriasis, atopic dermatitis, juglans regia (walnut), symphytum officinale (comfrey)
A new cream containing low molecular extracts from juglans regia and symphytum officinale was evaluated in 43 patients with psoriasis or atopic dermatitis in an observational study. The majority of the patients judged the properties like content of fat, effect on skin moisture, grooming properties and tolerability as well as the effects on symptoms of their disease like scaling, reddening, itching and burning, as excellent. They observed a reduction in the severity of their disease in 70% (95%-confidence interval 58%-83%) and a remission of acute flares in psoriasis in 61% of the cases. The improvement in severity of disease with 83% in psoriasis was significantly higher than in atopic dermatitis (55%). The hypothesis on the efficacy of Phytoskin[R] will be tested in an appropriate study.
Phytoskin[R] cream (development code TS 9912) was developed by Thymuskin Cosmetic GmbH, Germany, as an agent for skin grooming in psoriasis and atopic dermatitis. It is well known that proteins are not able to penetrate into the skin to a notable extent. Small peptides, though, reach lower skin regions to a higher extent, be it through existing channels of dermal organelles (glands and hair follicles) or via micro-fissures of affected skin. To enhance the grooming and curative actions of plants well known in herbal medicine by cleavage of their proteins into peptides was the rationale for this development. The walnut (juglans regia) as one herb was selected because its extracts were successfully applied topically in these diseases by an osteopath, and comfrey (symphytum officinale) as the second, because of its favourable effects well known in herbal medicine and applied over a long time.
Phytoskin[R] cream contains the low molecular extracts from walnut and comfrey root in 2 vol.%, and 0.8 vol.% respectively, in a lipophilic cream for application to psoriatic lesions as Phytoskin[R] lipophil and in a hydrophilic cream as Phytoskin[R] hydrophil for use in neurodermatitis or atopic dermatitis, respectively. In the observational study to be reported here only the lipophilic cream was used. The hydrophilic formulation was developed after the analysis of this study as a result of the evaluation of its grooming properties by the patients. This new formulation will be submitted to a re-evaluation.
Data Collection on the Application of TS 9912
Initially several patients with psoriasis and atopic dermatitis were treated tentatively with Phytoskin[R] cream. The results of this free application were to be documented retrospectively in a questionnaire, which was developed with support by the Dermatology Clinic, Darmstadt, Germany, which was done in 4 patients. On this questionnaire also were the results of further 39 patients, who were treated prospectively at two trial-centres (Dr. med. W. Stein, Mannheim, and J. G. Schilling, Maintal-Hochstadt, Germany), and documented. The questionnaire comprised data with regard to demography, medical history, presence and therapy of the underlying disease, psoriasis or atopic dermatitis, and of concomitant illness. The grooming properties of the test preparation and its influence on important symptoms of the disease had to be evaluated. Comparisons in the presence of acute flares and the degree of severity at the commencement of application of the test preparation and at its termination had to be made. Finally, adverse reactions and reasons for a premature termination had to be documented. The biometric evaluation was performed by the Institute of Medical Informatics, Biometry and Epidemiology of the Medical School in Essen, Germany.
In a total of 43 patients with psoriasis or atopic dermatitis the cosmetic properties and effects of Phytoskin[R] were documented and evaluated biometrically. The diagnosis was psoriasis in 23 and atopic dermatitis in 20 patients. The female gender prevailed slightly with 57% in the study population. The mean age of the patients with psoriasis was 56 years and 40 years in the atopic dermatitis group. According to the difference in age the number of concomitant diseases was higher in the psoriasis patients. Otherwise the groups were comparable. Of the patients with atopic dermatitis 1 patient each suffered from allergic asthma and allergic rhinitis, respectively, which led to a therapy with corticoids in one case. The further concomitant diseases and therapies should not have an effect on the skin diseases from a medical point of view. The duration of therapy ranged from 28 to 200 days, was exactly 28 days in 12 patients and ranged from 29 to 100 days in 19 patients. The prevailing majority of patients applied the cream regularly to the affected areas of the body, besides the extremities in both groups, the body in the psoriatic patients and the head in the patients with atopic dermatitis prevailed.
Pre-Medication: The previous medication including topicals, which are medicines but not cosmetics, were documented. Ten patients used a pre-medication consisting of externals containing vitamin B6 or corticoids or those which served only for skin grooming. Nine of these did not apply their previous medication at the end of the treatment period with the trial preparation, which apparently points to their satisfaction with the Phytoskin[R] cream.
Judgement on Skin Care Properties: At the termination of the application period of Phytoskin[R], its fat content, its effect on skin moisture, the grooming properties and the tolerability were rated in a scale ranking with "very good," "good," "satisfactory" and "bad." The results are summarized together with the 95%-confidence interval in table 1 and figure 1. The marks "very good" and "good" together were given for the fat content by 77%, for the action on the skin moisture by 72%, for the grooming properties by 81% and the tolerability by 80% of the study participants. While the majority of psoriatic patients ranked all properties as "very good," those with atopic dermatitis distributed their ranking with 1/3 to each of the marks of "very good," "good" and "satisfactory" (figure 2). Both groups, though, were especially satisfied with the tolerability. The patients with atopic dermatitis considered the fat content as a bit too high, while those with psoriasis were highly satisfied with all properties of the cream.
Expression of Symptoms at Start and End of Application: The degree of expression of 4 symptoms as reddening, scaling, itching and burning as well as the overall condition at the beginning of application had to be rated as "strong," "weak" or "scarcely." Furthermore a comparison of these parameters at the end of the application period versus the condition at the beginning was to be made. Independent of the disease the majority of patients rated the reddening (77%) and itching as strong (figure 3). A greater number of patients with atopic dermatitis (86%) listed reddening in the first place, while in psoriasis, burning (30%) had a low rank, and the other 3 symptoms were mentioned with about the same frequency of 57-65% in both groups.
Changes after Application vs Before: Comparing the overall condition of symptoms at termination of application of TS 9912 in comparison to the state before, was rated as better by 80% of the study population. With regard to diagnosis (figure 4) and single symptoms, improvement was stated by patients with psoriasis for reddening (86%), scaling (82%) and itching (82%) with about equal frequency while in atopic dermatitis, reddening (85%) and itching (82%) was reduced with similar frequency, but scaling with only 60%--remarkably less, a finding which is explained by the lower presence of scaling in atopic dermatitis. For the same reasons probably, itching was also affected in both groups to a lesser extent of 46 and 65%, respectively.
Frequency of Acute Flares: At the commencement of the application of TS 9912, 26 patients were in the state of an acute flare (table 2). In 14 of these (54%) no acute flare was recorded at the termination, while in 12 patients (46%) it was still present. All 17 patients, who were free of activity at the beginning, were still free at the termination of the application of TS 9912. Independent of incidence and development of flares the majority of the study population reported an improvement of their symptoms. The presentation of the data in table 2, separated for diagnoses, shows different frequencies and remission rates for the two diseases. An acute flare at the beginning was present in 78% of patients with psoriasis and in 40% of those suffering from atopic dermatitis; it had subsided at the end of the application period in 61% of the psoriasis patients in contrast to 38% in the atopic dermatitis group (figure 5). Because of the small sample size, a probability test was not performed. Patients whose acute flare subsided after termination of treatment gave higher ratings to the properties of TS 9912 regarding fat content, effect on skin moisture, cosmetic qualities and tolerability, than the other patients.
Severity of disease: The patients had to rate the severity of their disease at initiation of the application of TS 9912 and at its termination according to the ranks "severe," "moderate" or "weak." The change in severity is depicted in table 3. An improvement of the severity (figure 6) occurred in 30 patients over the application period; 25 times by 1 and 5 times by 2 ranks from severe to weak. In 11 patients the condition remained unchanged and in 2 cases deteriorations from moderate to severe took place. For the improvement rate in 70% of patients, a 95% confidence interval of 54%-83% was calculated. In table 3 the data are given additionally for the diagnoses in brackets and in the legend the calculated respective percentages are mentioned. The difference between the improvement rate of 83% in psoriasis versus the improvement rate in atopic dermatitis of 53% is statistically significant.
Premature Termination: A total of 4 participants terminated the application prematurely. In 2 cases failure of improvement was stated as the reason and in 1 case, an independent illness. One patient suffered in the second week of application from intolerance in the form of a skin reaction with reddening and burning. The application of TS 9912 was discontinued and the reaction subsided spontaneously without other measures.
Summary and Discussion of the Results
The study population was rather homogeneous regarding the distribution of gender and disease. The severity of the diseases was relatively marked. The patients with psoriasis had a higher mean age than those with atopic dermatitis, which is also reflected in a higher number of concomitant illnesses and therapies.
The grooming properties of TS 9912 (table 1) were rated predominantly as positive underlining the good tolerability. The 95% confidence intervals show that the good evaluation is not by chance but is based on solid ground. In general the patients with psoriasis value the properties of the cream higher than those with atopic dermatitis, who would prefer a slightly lower content of fat. This desire was immediately taken into account with the development of a more hydrophilic formulation, namely with Phytoskin[R] hydrophil which will be submitted for re-evaluation.
The evaluation of the question regarding an acute flare (table 2) results in an unexpectedly high remission rate of 54%. The higher incidence of an acute flare at the beginning of application in psoriasis of 78% in comparison to 40% in atopic dermatitis indicates that the patients with psoriasis had a higher activity of disease. At the end of the treatment period the remission rates were 61% in psoriasis and 38% in atopic dermatitis. If this difference in remission indicates a better efficacy in psoriasis or is influenced by the higher initial activity of psoriasis remains to be seen. Because of the relatively small number of patients with flare, a probability calculation on this item was not performed. Nevertheless, the high rate of remission, exceeding the fluctuations generally encountered in the course of the disease, point to an efficacy of TS 9912 especially in active psoriasis, surpassing general grooming properties.
The severity of the disease (table 3) at the commencement of the application of TS 9912 was rated by 91% of the participants as severe and medium, thus giving sufficient room for improvement. In 70% of the patients an improvement of the individual severity by at least one degree took place. The calculated 95% confidence interval of 54%-83% means that repeating the application of TS 9912 to comparable patients under similar conditions would yield the high probability of 95%--a positive result ranging between 54% and 83%. This finding represents a statistically significant result. Nevertheless, in a strict scientific sense efficacy of the study can only be proven in a controlled clinical trial, in order to be able to exclude placebo or other unknown effects. Looking at the improvement rates according to diagnoses, a statistical significant difference between psoriasis with 82% versus 55% in atopic dermatitis becomes apparent. Thus the higher efficacy of TS 9912 in psoriasis over atopic dermatitis is sufficiently clear. But since 55% of the patients with atopic dermatitis also reported a reduction in severity at the termination of the application, the efficacy of TS 9912 should be proven in a comparative trial. This comparison was not planned prospectively but performed subsequently. It is not a comparison of two different therapies, like TS 9912 and placebo.
As a synopsis, it can be stated that Phytoskin[R] cream has obtained a high acceptance for its grooming properties by patients with psoriasis or atopic dermatitis. In addition, several parameters like symptoms, acute flares and degree of severity have developed very favourably, indicating a good efficacy in atopic dermatitis but especially in psoriasis. This is supported by the experience at the trial centres in that patients having participated in this study insist on a continuation of their therapy with TS 9912. A prospective controlled study, which is in a late planning stage, will give the final answer regarding efficacy.
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