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PROSPECTIVE, RANDOMIZED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY ON THE EFFICACY AND SAFETY OF A SERIES OF HERBAL SKINCARE PRODUCTS FOR STABLE CHRONIC PLAQUE PSORIASIS

Authors:
  • Independent Researcher
PROSPECTIVE, RANDOMIZED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY
ON THE EFFICACY AND SAFETY OF A SERIES OF HERBAL SKIN-CARE
PRODUCTS FOR STABLE CHRONIC PLAQUE PSORIASIS
Harald Maier, Peter Donath, Michael Tirant, Dragana Relic, Shahla Farokhnia, Herbert
Hönigsmann, Adrian Tanew
Division of Special and Environmental Dermatology, Department of Dermatology, University
of Vienna Medical School
INTRODUCTION
At present, topical cortisone is still the mainstay of therapy for stable chronic plaque psoriasis
as long as the affected skin area is not too extensive. However, there is growing concern
among patients about possible side effects of steroid therapy. A recent study showed that
overall, 42 % patients were unsatisfied with the current management of their skin disease.
This is the reason why , like in other medical specialities
1 ,
patients with psoriasis more and
more, turn to complementary treatment options such as magnetic field resonance therapy,
traditional Chinese medicine (TCM) and herbal medicine.
2
It is the young, the well-educated,
patients with higher income, women and patients with chronic disease who are most open-
minded to complementary methods.
2
Actually, a flourishing market for complementary
health products has developed.
3
Unfortunately, most providers refuse to have their products
tested according to international scientific standards.
4, 5
Advertising is merely based on
anecdotal reports and the single opinions of (mostly prominent) persons.
3
At the very best,
uncontrolled clinical observations are presented.
STUDY OBJECTIVE
We assessed the efficacy and safety of an Australian series of herbal skin-care products (Dr.
Michaels
®
skin-care products for psoriasis) for the management of stable chronic plaque
psoriasis. The producer claims that the skin disease improves significantly within a 6 to 8
weeks treatment course.
MATERIALS AND METHODS
We chose a prospective, randomized, placebo-controlled, double-blind design. After obtaining
written consent, 34 (15 female/ 19 male) patients with mild to moderate stable chronic plaque
psoriasis were randomly assigned to either verum or control group. Exclusion criteria were:
severe psoriasis, arthropathic psoriasis, intertriginous psoriasis, palmoplantar psoriasis, use of
any antipsoriatic treatment modality, any medication which may influence or interfere with
the course of the disease. Both verum and control series consisted of a cleansing gel, an
ointment and an oil blend (skin conditioner). The products were packed in neutral bottles.
The products had to be used twice daily and in the same manner. All skin lesions except the
scalp were treated. The cleansing gel was distributed generously on the lesions and washed
off after three to five minutes with warm water. Afterwards the lesion was covered with the
ointment. After the ointment had dried up the plaques were covered with a thin layer of oil.
Except for a small amount of coal tar (0.8 %) in the cleansing gel only, the verum products
contained only herbal oils and waxes plus the normal emulsifiers, stabilisers and preservatives.
6
As control products we used compositions of well-known neutral ointments and a medicinal
bathing oil. The study period was eight weeks. Assessment, using the Psoriasis Activity
Severity Index (PASI) scores, was done before treatment, after 2, 4, 6 and 8 weeks by a blind
observer (dermatologist). The values of scalp involvement were not included. For each patient,
photographs of typical lesions were taken at the beginning, 4 weeks and 8 weeks follow-up.
Patient improvement was determined by the percentage reduction of the PASI scores.
Statistical analysis was carried out using the Mann-Whitney-U Test with SPSS for Windows.
7
Dermal toxicology and safety tests were also undertaken on 20 patients including children
to evaluate any hypersensitivity that may result from the application of the product family.
RESULTS
The data presented here are the results of a group of 24 patients ( 14 verum / 10 control) with
a mean age of 48.2 years who had completed the 8 weeks treatment course. Two patients (1
verum / 1 control) could only be followed for 6 weeks. The data of these patients were not
included in the statistical analysis. Another six patients (2 verum / 4 controlo) dropped out.
Another two verum patients had to be excluded because of non-compliance. For two of the
drop-outs assigned to the placebo group it was too obvious that they had been given the
control products and therefore refused further participation. The other two control patients
stopped the treatment because of side effects.
Before therapy, the mean PASI score of the verum group was 6.8 ± 2.4 SD, and 5.5 ± 2.0 SD
in the control group, respectively. After the 8 weeks treatment course, the mean PASI score in
the verum group was 1.02 ± 1.01 SD, which is equivalent to a PASI score reduction of
89%.±14.9% . The respective values in the control group at the 8 weeks follow-up were 4.1 ±
1.7 SD for the PASI and 22 ±28.7 % for the PASI score reduction. Figure 1 shows the mean
values of the PASI score for the different follow-up dates which are given in Table 1 in detail.
The difference of the PASI score reduction at 8 weeks follow-up between the two groups was
statistically significant (p < 0.001). Figure 2 a shows the indicator plaque of a patient with
complete remission after 6 weeks treatment with Dr. Michaels
®
skin-care products for
psoriasis and Figure 2 b a patient with partial remission after 8 weeks treatment.
The verum patient who could be followed-up only for 6 weeks showed a PASI score reduction
of 70 % . The respective data of the control patient with the shorter follow-up period was 4.8
%. Three patients in the verum and three patients in the control group reported mild side
effects (verum group: 1 irritation, 2 folliculitis / control group: 3 irritation). In the dermal
toxicology and safety test group, one (1) patient showed a minor irritation to the cleansing
gel. The remainder of the test cases results fell well within the acceptable parameter range
provided by EADV and EU.
DISCUSSION
This study shows that the herbal skin-care products tested improves mild to moderate stable
chronic plaque psoriasis significantly. One strength of this study is the clear study design
which is regarded as the gold standard of clinical tests. The left and right sides comparison
was not undertaken to avoid any potential mistakes of mixing up the sides or the use of the
more effective product only on both sides. In addition to the personal instructions given on
how to use the products, a very simple structured leaflet was also handed out. The patients
were informed not to give the blind observer (Assessor) any information on the products used.
Furthermore, they did not apply the products on the days of the follow-ups in order to prevent
the observer from identifying the verum products by their characteristic odour. The blind
observer is a consultant of dermatology and is very experienced in clinical scoring. As is well
known, the PASI is a standardized internationally accepted evaluation score which in the
hands of an experienced clinician is a reliable assessment tool. Additionally, photographs
were taken with standardized focussing. Images, however, lack the third dimension which
represents the infiltration of a psoriatic plaque and contributes to the clinical picture of a
lesion essentially.
It was so obvious in the study course that the verum products were superior to the placebo
preparations. Except for coal tar which is present in only the cleansing gel, none of the listed
herbal ingredients is a known antipsoriatic remedy. Therefore, an analysis for undeclared
drugs (cortisone, calcipotriol, macrolides) was undertaken
8
although the producer (who is one
of the authors, M.T.) gave a statement of innocuousness and provided the complete list of
constituents and the respective material safety data sheets. Two samples of different batches
of each product were analysed. None of the products contained any of the compounds
mentioned above.
Some aspects of this study have to be adressed in detail. Dr. Michaels
®
skin-care products are
a complex mixture of botanical ingredients.There is a lack of information on the active
pharmacologic principle(s) which is (are) responsible for the effectiveness. Coal tar is the
only (known) antipsoriatic ingredient. However, the surprising improvement is inconsistent
with our clinical experience with standard compositions containing coal tar. It is speculated
here that the products contain other antiproliferative and anti-inflammatory compound (s)
which is (are) not known at present. Therefore , it was not possible to compose a “true”
placebo (formulation of the verum minus active ingredient). The management of the patients
of the placebo group was challenging. Several patients had been treated with different topical
antipsoriatics and skin-care products previously. They could therefore compare the effect of
the present treatment with previous responses. The follow-up visits at two weeks interval
were close enough to give them the “love and tender care” and to encourage them to continue.
Actually, only two “very experienced” patients with a long history of psoriasis and a lot of
different treatment modalities dropped out. All compliant placebo patients showed an
improvement of the condition which could be expected by the use of greasy skin-care
products only.
To make sure that a herbal product does not contain intended or unintended adulterants and /
or contaminants, is part of the quality control.
4, 5
Dr. Michaels
®
skin-care products are
manufactured according to Good Manufacturing Practice (GMP) certified by the Therapeutic
Goods Administration of the Australian Health and Family Services. In contrast to synthetic
drugs, herbal remedies may show a considerable variation in the composition (e.g., genetic
variability of the plants, variable growing conditions, differences in harvesting procedures and
processing of extacts).
4,
5
Chromatographic analysis and marker compounds do not ensure
consistency and stability.
5
These methods can only define a range within which product
quality is acceptable.
The third requirement is dermal toxicology and safety.
4, 5
Before to the start of the clinical
trial, a dermal toxicology and tolerability test
9
was done on a group of 20 healthy volunteers
with good results. Among the population of the study presented one patient developed a mild
irritative dermatitits. That patient stopped using the cleaning gel as the irritation was
attributed to the tar in the cleansing gel. The improvement of the disease in that patient was in
agreement with the general course of the verum group. We are aware that the excellent (short-
term) tolerability of Dr. Michaels
®
skin-care products does not necessarily exclude long-term
side effects.
4
Coal tar and solar radiation may be a problem. However, serious side effects are
unlikely due to the toxicologic profile of the constituents.
6
In order to assess all the allergic
potency, the products should undergo a field test.
CONCLUSIONS
The products tested already fulfill a lot of aspects adressed by the European Parliament in
the proposal for a directive on traditional herbal medicinal products.
10
As long as the
products are composed of a mixture of various plant extracts a range of variation should be
defined. The next step, however, should be the attempt to identify the active pharmacologic
principle.
Our investigation demonstrates that complementary methods may play a role in dermatologic
therapy as far as they undergo standardised clinical trials and fulfill the basic requirements
such as product safety and quality assurance. Dr Michaels skin-care products can be used
successfully in the treatment of stable chronic plaque psoriasis.
ACKNOWLEDGEMENT
We gratefully acknowledge Dr. Michals RICA GmbH, Traiskirchen, Austria, for providing
the study products, Eva Hofbauer, Pharmacovigilance Unit, Federal Ministery of Health and
Women, for initiating undeclared constituents testing and Andreas Mayrhofer PhD,
Bundesinstitut für Arzneimittel (BifA), Vienna, for conducting the analysis for undeclared
constituents.
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Heichlinger Druckerei GmbH, 1998.
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Untersuchung corticoidverdächtiger Proben mittels HPLC-UV und HPLC-PB-MS. Sci
Pharm 1996; 64: 225-44.
9. Frosch P J & Kligman A M. The soap chamber test: a new method for assessing the
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of the European Communities. C126 E/May 28, 2002; pp 263-7.
... A number of studies have illustrated that certain corticosteroids, such as clobetasol propionate, have a low absorption rate when applied and as a result are associated with approach may be an attractive option for patients who demonstrate contraindications to traditional therapies or have growing concerns regarding sideeffects of long-term steroid and systemic therapies. report are supported by those of the Austrian clinical trial study performed by Maier and colleagues, in which they compared the efficacy of Dr Michaels ® (Soratinex ® and Nailinex ® ) product family to a placebo group in plaque psoriasis (23), albeit independent of nail involvement. However, this study highlights a potential anti-inflammatory, antimicrobial and antifungal role for the Dr Michaels ® (Soratinex ® and Nailinex ® ) product family, which may be applicable to nail psoriasis. ...
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The chamber test for assessing the irritancy of soaps entails five weekday exposures to 8% solutions with readings of scaling, redness, and fissuring on the following Monday. Eighteen well-known toilet soaps were evaluated. Great differences were noted. Most had an appreciable irritancy potential. These results contrast with a number of studies which failed to show differences among soaps or which concluded that soaps were innocuous.
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This article has no abstract; the first 100 words appear below. We are in the midst of a public health experiment that much of academic medicine has failed to acknowledge until recently. In spite of the greatest health and longevity in history in the United States and Europe, millions are turning back to traditional herbal medicines in order to prevent or treat a host of illnesses. Thus, the review by De Smet (pages 2046–2056) and the accompanying Sounding Board article by Marcus and Grollman (pages 2073–2076) in this issue of the Journal are very timely. Both articles identify serious problems with the overall quality, safety, and efficacy of herbal products. In . . . Stephen E. Straus, M.D. National Center for Complementary and Alternative Medicine, Bethesda, MD 20892
Drug therapy : Herbal remedies
  • De A G Smet
De Smet P A G M. Drug therapy : Herbal remedies. N Engl J Med 2002 ; 347 :
Entwicklung eines Screening-Systems für die Untersuchung corticoidverdächtiger Proben mittels HPLC-UV und HPLC-PB-MS
  • A Mayrhofer
  • M Wieser
  • Wollein
Mayrhofer A, Wieser M, Wollein G. Entwicklung eines Screening-Systems für die Untersuchung corticoidverdächtiger Proben mittels HPLC-UV und HPLC-PB-MS. Sci Pharm 1996; 64: 225-44.
Proposal for a directive of the European parliament and the council amending the directiveEC as regards traditional herbal medicinal products
Proposal for a directive of the European parliament and the council amending the directive 2001/83/EC as regards traditional herbal medicinal products. Official Journal of the European Communities. C126 E/May 28, 2002; pp 263-7.
Nutzen und Risiken sanfter Heilmethoden. Stiftung Warentest-Berlin, Verein für Konsumenteninformetion-Wien
  • K Federspiel
  • V Herbst
  • Die Andere Medizin
Federspiel K & Herbst V. Die Andere Medizin. Nutzen und Risiken sanfter Heilmethoden. Stiftung Warentest-Berlin, Verein für Konsumenteninformetion-Wien, eds. Stuttgart, Germany: Zenit-Pressevertrieb, 1996.