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V o l u m e
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SkinCareGuide
N u m b e r
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M a r c h
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Indexed by the US National Library of Medicine and MEDLINE
EDITOR-IN-CHIEF
Cutaneous Cleansers
Stuart Maddin, MD
ASSOCIATE EDITORS
Jeffrey S. Dover, MD - Surgical Dermatology
Yale University School of Medicine, New Haven, USA
Dartmouth Medical School, Hanover, USA
Jason Rivers, MD - Medical Dermatology
University of British Columbia, Vancouver, Canada
Hugo Degreef, MD, PhD - Medical Dermatology
Catholic University, Leuven, Belgium
B. L. Kuehl, PhD1 , K. S. Fyfe, H BBA2, N. H. Shear, MD, FRCPC3
1
Scientific Insights Consulting Group, Mississauga, Ontario Canada
GlaxoSmithKline, Consumer Healthcare, Oakville, Ontario Canada
3
Departments of Medicine (Divisions of Dermatology and Clinical Pharmacology), and
Pharmacology, University of Toronto Medical School; and Division of Dermatology, Sunnybrook &
Women's College Health Sciences Centre, Toronto, Ontario, Canada
2
ASSISTANT ASSOCIATE EDITOR
Murad Alam, MD - Surgical Dermatology
Northwestern University Medical School, Chicago, USA
EDITORIAL ADVISORY BOARD
Kenneth A. Arndt, MD
Beth Israel Hospital
Harvard Medical School, Boston, USA
Wilma Fowler Bergfeld, MD
Cleveland Clinic, Cleveland, USA
Jan D. Bos, MD
University of Amsterdam, Amsterdam, Holland
Enno Christophers, MD
Universitäts-Hautklinik, Kiel, Germany
Richard L. Dobson, MD
Medical University of South Carolina, Charleston, USA
Boni E. Elewski, MD
University of Alabama, Birmingham, USA
Barbara A. Gilchrest, MD
ABSTRACT
Skin cleansers may be an important adjunct to the regimen of those who use cosmetics,
have sensitive or compromised skin, or utilize topical therapies. Cleansers emulsify dirt,
oil and microorganisms on the skin surface so that they can be easily removed. During
cleansing, there is a complex interaction between the cleanser, the moisture skin barrier,
and skin pH. Cleansing, with water, soap or a liquid cleanser, will affect the moisture skin
barrier. Soap will bring about the greatest changes to the barrier and increase skin pH.
Liquid facial cleansers are gentler, effecting less disruption of the barrier, with minimal
change to skin pH, and can provide people with a cleanser that is a combination of surfactant classes, moisturizers and acidic pH in order to minimize disruption to the skin barrier.
Key Words: cleansers, emulsiÞers, detergents, surfactants, soaps
Boston University School of Medicine, Boston, USA
W. Andrew Griffiths, MD
St. Johns Institute of Dermatology, London, UK
Aditya K. Gupta, MD, PhD
University of Toronto, Toronto, Canada
Vincent C. Y. Ho, MD
University of British Columbia, Vancouver, Canada
Mark Lebwohl, MD
Mt. Sinai Medical Center, New York, USA
James J. Leydon, MD
University of Pennsylvania, Philadelphia, USA
Harvey Lui, MD
University of British Columbia, Vancouver, Canada
Howard I. Maibach, MD
University of California Hospital, San Francisco, USA
Larry E. Millikan, MD
Skin cleansers are surface-active substances (i.e., emulsiÞers/detergents/surfactants/
soaps) that lower the surface tension on the skin and remove dirt, sebum,
microorganisms and exfoliated corneum cells in an emulsiÞed form. The ideal cleanser
should do this without irritating, damaging or disrupting the skin and the moisture skin
barrier. Water alone removes approximately 65% of oil and dirt from the skin, but is
less effective at removing oils of cosmetic import and some environmental insults.
Soaps are the oldest surfactants, and are chemically deÞned as the alkali salt of fatty
acids with a pH of 9.5-10. Synthetic detergents vary in composition and surfactant
types (i.e., anionic, amphoteric, cationic, non-ionic, and silicone) and pH. In modern
usage, the term “soap” generally refers to any cleansing agent regardless of chemistry.1
Tulane University Medical Center, New Orleans, USA
Takeji Nishikawa, MD
Keio University School of Medicine, Tokyo, Japan
Constantin E. Orfanos, MD
Freie Universitäts Berlin
Univeritätsklinikum Benjamin Franklin, Berlin, Germany
Stephen L. Sacks, MD
Viridae Clinic Sciences, Vancouver, Canada
Alan R. Shalita, MD
SUNY Health Sciences Center, Brooklyn, USA
Richard Thomas, MD
University of British Columbia, Vancouver, Canada
Stephen K. Tyring, MD, PhD
University of Texas Medical Branch, Galveston, USA
John Voorhees, MD
University of Michigan, Ann Arbor, USA
Klaus Wolff, MD
University of Vienna, Vienna, Austria
MANAGING EDITOR
Penelope Gray-Allan
Skin cleansers consist of the following:
• Water
• Surfactants (to emulsify the debris)
• Moisturizers (to hydrate the skin and maintain the skin barrier)
• Binders (to stabilize the formulation)
• Lather enhancers (found in some products)
• Fillers (generally used to harden bar soaps and cleansers)
• Preservatives (to prevent the growth of microorganisms)
• Fragrance (generally used to mask the odour of surfactants)
• Dyes or pigments (found in some products)
Skin cleansing may disrupt or disturb the moisture skin barrier, affect the skin surface
pH, and irritate the skin. The moisture skin barrier protects against transepidermal
water loss, chemical insult and xenobiotic penetration while preserving water to
moisturize and maintain the smoothness and ßexibility of
the skin. A compromised barrier has been correlated with
psoriasis, ichthyoses, and atopic dermatitis.2 Moisturizers,
both emollients and humectants, within cleansers can
maintain skin hydration as well as maintaining and restoring
barrier function.3 Emollients impair evaporation of skin
moisture by forming a Þlm on the skin surface to impede
water loss. Humectants attract and bind water, drawing it up
from the dermis into the epidermis. The acid mantle of the
skin plays an integral role in skin barrier function as well as
regulating bacterial ßora.4 Studies have shown that skin
barrier regeneration/repair proceeds more slowly at neutral
pH (7.2) than at physiological pH 5.5.5 Cleansers may also
cause irritant or allergic contact dermatitis and this effect is
enhanced if the skin barrier is compromised.
Types of Cleansers
Surfactants can be utilized quite differently in personal
hygiene products. They are selected for their functionality
and ability to act as detergents/emulsiÞers and foaming
agents. Personal hygiene products include soaps,
superfatted soaps, beauty bars, dermatological bars or
cakes, liquid cleansers including facial liquid cleansers,
antiseptic foaming solutions, antibacterial washes, and
emulsions. Table 1 outlines different types of cleansers.
Soap, the most commonly used, is a combination of fats
and oils (of animal or vegetable origin) and salt.1 Soap is
the simplest anionic surfactant, forming soap salts in water
that emulsify whatever is on the skin surface while
increasing the pH of the skin. Soap salts also provoke
stratum corneum swelling and loss of natural humectants
and water leaving the skin dry and the barrier
compromised. Enriching soaps (superfatted soaps and
beauty bars) with lanolin, sweet almond oil or glycerin
helps to alleviate the drying of the skin.6
Dermatological bars or cakes are chemically different from
soaps, and contain modiÞed detergents to enhance their use.
Weak organic acids and emollients need to be added to lower
the pH of the product and reduce drying of the skin caused
primarily by anionic surfactants. Liquid cleansers are
complex formulations that contain a combination of
surfactants including anionic, amphoteric, nonionic, and
silicone. Liquid cleansers also offer anti-bacterial activity by
maintaining the skin at physiological pH and by the activity
of the surfactants that emulsify and encapsulate (depending
on surfactant and formulation) bacteria for easy removal.
One study demonstrated that, following hand cleansing, a
liquid cleanser removed 85% of bacteria while a bar soap
was able to remove only 65%.7 Other studies have shown a
Types of Cleansers
Formulation Comments
Soap
•
•
•
•
Composed of anionic surfactants.
Drying and irritating to skin.
Causes follicular plugging
Raises pH of skin (neutral to alkaline).
Superfatted Soap and
Beauty Bars
•
•
•
•
•
Composed of anionic surfactants.
Drying and irritating to skin.
Causes follicular plugging
Raises pH of skin (neutral to alkaline).
Emollient may be added to reduce dryness.
Dermatologic Bars/Cakes
•
•
•
Composed of amphoteric, anionic, and non-ionic surfactants.
May raise pH of skin.
Emollients added to reduce dryness and irritation.
Cosmetic Liquid Cleansers
•
•
•
•
•
Composed of amphoteric, anionic, non-ionic and silicone surfactants.
Can be mild and less irritating to skin.
Generally have pH similar to skin.
Have high rinsibility factor.
Generally have emollients and humectants added.
Antiseptic and
Antibacterial Washes
•
•
•
•
•
•
Composed of amphoteric, anionic, and non-ionic surfactants.
May raise pH of skin.
Emollients added to reduce dryness and irritation.
Adjunct to acne treatment.
May help control bacteria, not believed to penetrate follicle.
Potentially less irritating and drying than topical bactericide.
Table 1: Different forms of cleansers
2
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
relationship between cutaneous surface pH, bacterial
microßora and the inßuence of skin cleanser. Use of an
acidic liquid cleanser led to a reduction in inßammatory acne
lesions and the number of Propionibacterium acnes (P.
acnes) on the skin.4,8 Generally, liquid cleansers are mild,
have an acidic pH, and have a high rinsibility factor.
Antiseptic foaming and antibacterial washes are used as an
adjunct to acne treatment, since they contain bacteriostatic
agents. When used properly, these washes may effect a
reduction in P. acnes and prevent secondary infections in
acne skin, but they are drying and irritating to most skin.
Effectiveness/Recent Research Findings
Surfactants cause the majority of adverse skin reactions and
disrupt or disturb the moisture skin barrier as surface debris
and microorganisms are removed. Anionic/sodium
containing surfactants such as sodium lauryl sulphate,
sodium tallowate and sodium stearate have been shown to
disrupt lipids in the moisture skin barrier, as well as
increase the pH of the skin by as much as 2-3 units.9,10
Disruption and depletion of barrier lipids and an increased
skin pH leads to a compromised skin barrier11 leaving the
skin in a negative physiologic state with an increased
sensitivity to potential irritants.8 Other “gentler” surfactant
types, i.e., amphoteric (cocamidopropyl betaine) and
nonionic (propylene glycol), have been shown to cause a
range of skin and sensory irritations.12,13
Preservatives are required in all cosmetic, especially
liquid, formulations to prevent the growth and infection by
microorganisms. Liquid formulations are also protected
from microorganisms by being enclosed in a container, so
that the bulk of the formulation remains protected from
contamination, which can occur with handling.
Preservatives, fragrances and dyes used in cleansers also
cause irritant or allergic contact dermatitis. Parabens and
formaldehyde donors (e.g., diazolidinyl urea, Quaternium15, DMDM hydantoin) are the major classes of
preservatives. Both classes have reported incidents of
allergic and contact sensitivity and dermatitis.14-16 Some
compounds are more allergenic than others and cause
greater numbers of reactions.
One example is
Quaternium-15, which is the sixth most common allergen
in cosmetic products.16
Liquid facial cleansers are the most effective and beneÞcial
cleansers for sensitive and compromised skin. Their
formulations are complex, utilizing a combination of
surfactants, moisturizers, binders and preservatives to form
a product that will cause the fewest problems and the
Cleanser
Surfactants
Moisturizers
Preservatives Cost*
Possible
Adverse Events
Cetaphil®
Gentle
sodium lauryl
sulfate
cetyl alcohol, propylene
glycol, stearyl alcohol
Parabens (butyl, $15.99/460ml Disrupt skin barrier,
methyl, propyl)
irritant dermatitis
Derma Jel®
5 anionic sodium
glycerin, glycol
based surfactants
distearate, laureth-10,
(including sodium
PEG-150 distearate
laureth sulfate),
amphoteric and
nonionic surfactants
DMDM
hydantoin,
Quaternium-15
$10.99/500ml Disrupt skin barrier,
irritant dermatitis
Neutrogena®
Liquid Facial
Cleanser
4 anionic sodium
based surfactants,
amphoteric
surfactants
glycerin
BHT,
Lauraimide
DEA
$10.99/200ml Disrupt skin barrier
irritant dermatitis
Spectro Jel®
dimethicone
copolyol,
polysorbate 20N
butylene glycol,
cetyl alcohol,
dimethicone copolyol,
glycerin, hydrated silica
diazolidinyl
urea
$12.99/500ml Disturb skin barrier,
irritant dermatitis
Toleraine®
capryl glycol
capryl glycol,
capryl glycol,
dipropylene glycol,
octoxyglycerin
glycerin, octyl palmitate,
octoxyglycerin
$17.00/200ml Disturb skin barrier,
irritant dermatitis
Table 2: Comparison of Cosmetic Liquid Cleansers
*Cost in Canadian dollars to consumer as determined from one supplier (Shopper’s Drug Mart, Ontario, Canada)
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
3
greatest beneÞts. A well-designed liquid facial cleanser will
use nonionic and silicone surfactants. Nonionic surfactants
(e.g., polysorbate) combine low irritancy with surfactant
class and pH compatibility. Silicone surfactants (e.g.,
dimethicone), provide both a surfactant that can penetrate
follicles and crevices thereby bringing debris to the skin
surface, and an emollient that softens the skin and creates a
film to impede transepidermal water loss.17 Silicone
surfactants also offer properties such as low irritation, and
are noncomedogenic and hypoallergenic. Liquid facial
cleansers should also contain a mixture of emollients and
humectants to help restore the moisture skin barrier and
limit the disruption caused by the surfactant. Tolerance is
an issue for people with skin conditions such as rosacea,
atopic dermatitis, acne vulgaris and sensitive skin. A
compromised skin barrier results in their being more
susceptible to the effects of topical treatments including
cleansing. A liquid facial cleanser with an acidic pH,
nonionic/silicone surfactants, moisturizers, and minimal
skin residue (high rinsibility) offers the greatest beneÞts
and synergy with topical or systemic therapy. Although
liquid facial cleansers are formulated to be less irritating to
the skin, some of its components may disrupt the skin
barrier or cause contact sensitivities.
Conclusion
Table 2 outlines five cosmetic liquid cleansers that
represent a combination of those recommended by
dermatologists and those most popular with consumers in
Canada. Some of these products are not available outside
Canada, and one (Derma Jel®) is the in-store brand for
Shopper’s Drug Mart, a nationwide drugstore chain. Most
retailers in Canada have a store brand cleanser that is
positioned to compete with Spectro Jel®. However, from
an ingredients comparison the products are quite different.
Limitations/Adverse Effects
Liquid cleansers are the best choice for whole body
cleansing, but cost can be prohibitive. Liquid facial
cleansers are more expensive than soap ($2.20 to
$7.50/100mL versus $1.00/bar respectively), but prices also
vary widely even within the category. The greatest
differences between soaps and liquid cleansers are the
degree of disruption to the moisture skin barrier and the
change to the skin pH. It is difficult, when reading a product
label, to determine the function of each ingredient. Many
ingredients have more than one function, and the packaging
can also be confusing, i.e., phrases such as no preservatives,
no surfactants, and fragrance free can be misleading. For
example, propylene glycol is a moisturizer but also provides
anti-bacterial and emulsiÞer activity. The term fragrance
free can be used in a product if a natural ingredient (not a
synthetic ingredient) is used to alter the scent of the product.
4
The choice of facial cleanser is important for people with
normal skin, as well as for those people with sensitive skin
and skin diseases such as atopic dermatitis, acne vulgaris.
Liquid facial cleansers are the best choice for facial cleansing
as they have an acidic pH, moisturizers and high rinsibility.
Within the liquid cleanser category, the least irritating cleanser
will contain non-ionic/silicone-based surfactants combined
with moisturizers, as they will cause the least disruption to the
moisture skin barrier and the normal skin ßora.
References
1.
Friedman M, Wolf R. Chemistry of soaps and detergents: various types of
commercial products and their ingredients. Clin Dermatol 14(1):7-13 (1996
Jan-Feb).
2.
Marstein S, Jellum E, Eldjarn L. The concentration of pyroglutamic acid (2pyrrolidone-5-carboxylic acid) in normal and psoriatic epidermis,
determined on a microgram scale by gas chromatography. Clin Chim Acta
49(3):389-95 (1973 Dec).
3.
Elias PM. Lipids and the epidermal permeability barrier. Arch Dermatol Res
270(1):95-117 (1981).
4.
Korting HC, Hubner K, Greiner K, Hamm G. Chanages in skin pH and
resident ßora by washing with synthetic detergent preparations at pH 5.5 and
8.5. J Soc Cosmet Chem 42:147-58 (1991).
5.
Schreiner V, Maerker H, Hoppe U. Dependence of barrier repair in human skin
on intra- and extracellular pH (abstract). J Invest Dermatol 106:917 (1996).
6.
Solomon BA, Shalita AR. Effects of detergents on acne. Clin Dermatol
14(1):95-9 (1996 Jan-Feb).
7.
Osborne RC, Grube J. Hand disinfection in dental practice. J Clin Prev Dent
4(6):11-5 (1982 Nov-Dec).
8.
Korting HC, Braun-Falco O. The effect of detergents on skin pH and its
consequences. Clin Dermatol 14(1):23-7 (1996 Jan-Feb).
9.
Lee CH, Maibach HI. The sodium lauryl sulfate model: an overview.
Contact Dermatitis 33(1):1-7 (1995 Jul).
10. Rippke F, Schreiner V, Schwanitz HJ. The acidic milieu of the horny layer:
new Þndings on the physiology and pathophysiology of skin pH. Am J Clin
Dermatol 3(4):261-72 (2002).
11. Imokawa G, Akasaki S, Minematsu Y, Kawai M. Importance of intercellular
lipids in water-retention properties of the stratum corneum: induction and
recovery study of surfactant dry skin. Arch Dermatol Res 281(1):45-51 (1989).
12. Pigatto PD, Bigardi AS, Cusano F. Contact dermatitis to
cocamidopropylbetaine is caused by residual amines: relavance, clinical
characterisics and review of the literature. Am J Contact Dermatitis 6:13-6
(1995).
13. Funk JO, Maibach HI. Propylene glycol dermatitis: re-evaluation of an old
problem. Contact Dermatitis 31(4):236-41 (1994 Oct).
14. Soni MG, Burdock GA, Taylor SL, Greenberg NA. Safety assessment of
propyl paraben: a review of the published literature. Food Chem Toxicol
39(6):513-32 (2001 Jun).
15. Fransway AF, Schmitz NA. A problem of preservation in the 1990s: (II).
Formaldehyde and formaldehyde-releasing biocides: incidences of crossreactivity and the signiÞcance of the positive response to formaldehyde. Am
J Contact Dermatitis 2:78-88 (1991).
16. Marks JG, Belsito DV, DeLeo VA, et al. North American Contact Dermatitis
Group patch test results for the detection of delayed-type hypersensitivity to
topical allergens. J Am Acad Dermatol 38(6 Pt 1):911-8 (1998 Jun).
17. Gordon ML. The role of clobetasol propionate emollient 0.05% in the
treatment of patients with dry, scaly, corticosteroid-responsive dermatoses.
Clin Ther 20(1):26-39 (1998 Jan-Feb).
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
Adverse Reactions to Herbal Therapy in Dermatology
R.B. Vender, MD, FRCPC
Dermatrials Research and Faculty of Medicine, McMaster University, Hamilton, Ontario, Canada
ABSTRACT
There are many herbal therapies available for dermatological diseases that patients have already begun to discover. Dermatologists
must be educated not only in the beneÞts of these therapies, but must also be aware of some of the risks and adverse effects. They
need information about the effects of herbal remedies in order to better serve their patients who may be using herbs to treat their
dermatological conditions. This brief review summarizes some of the more common herbal therapies used by many dermatology
patients for their skin diseases, and the adverse reactions and drug interactions that may occur.
Key Words: herbal remedies, adverse effects, dermatology, anti-inßammatory
The use of herbal therapy by dermatology patients is on the
rise. Because of their convenient availability, many patients
with chronic dermatological diseases have attempted to
take more control over their health by using herbal
remedies along with or instead of conventional treatments.
Some patients have lost hope; standard treatments have
failed to be effective for them. As a result, they seek newer
therapies in an attempt to Þnd a “cure” for their problems.
Government Regulations
The exact frequency of herbal use is not known because of
its non-regulatory status. However, some regulations do
exist at the federal level in Canada with the Natural Health
Products Directorate (est. 03-99). Most of these regulations
are still under review. However, regulations do exist with
regard to deÞnitions, product licensing, adverse reaction
reporting, site licensing, good manufacturing practices,
clinical trials, and labeling/packaging. These are pursuant
to the subsection of the Food and Drugs Act entitled
Natural Health Products Regulations. Some of these are
expected to be phased in over the next two years. At the
provincial level, British Columbia established the College
of Traditional Chinese Medicine (TCM) Practitioners and
Acupuncturists of B.C., becoming the Þrst province in
Canada to regulate the practice of TCM.1 No other
province thus far has a similar regulatory body.
There are many herbal remedies that have scientiÞc merit;
they may be of clinical beneÞt and provide safe, effective
and reliable alternatives to conventional medicine.
However, herbal products cannot be patented.2 They are
intended for the self-treatment of a self-diagnosed, selflimiting condition. Although there are numerous herbal
therapies that are relevant to the specialty of dermatology,
many of these have not been studied in proper randomized,
double-blind, placebo controlled trials. Most herbal
treatments have evidence that is based on sparse anecdotal
reports and word of mouth.
Drug Interactions and Side-Effects
Many of these therapies are considered “natural” and
therefore harmless. However, because of the poor
regulations that exist in monitoring these drugs, adverse
reactions do occur.3 Herbal therapy, therefore, should be
avoided in pregnancy, infants and children because of the
uncertainty of adverse reactions that could occur. There is
little incentive for pharmaceutical companies to investigate
or standardize these preparations because it is unlikely
patents would be applicable.
Because of the assumed safety of natural products, many
patients believe these products have “fewer” side-effects.
Herbal therapies should be regarded as drugs. Since drugs
have side-effects, such events can be seen with herbals.
Drug interactions although infrequent, can also occur with
herbal therapies and conventional medications.4,8 This may
be due to altered absorption, distribution, biotransformation
and/or excretion.6 These interactions are often patientinitiated because of the lack of consultation with a
physician. These effects can increase or decrease the
activity of the corresponding drugs and lead to untoward or
unexpected adverse events or changes in drug efficacy.5
Some herbals may be contaminated with toxic substances or
the herbal can be toxic alone. Others may have traces of
potent topical steroids.7 This makes it even more important
for physicians to take a proper and complete drug history,
including herbal medications.
The most common dermatologic reaction from herbal
therapies is allergic contact dermatitis.8 Herbs that are
known for causing this condition include: aloe, arnica,
bromelain, calendula, chamomile, goldenseal, tea tree oil
and yarrow.6,4,9 However, more serious events have
occurred including erythroderma and Stevens-Johnson
syndrome from combination herbal preparations.8 Serious
systemic adverse events have been reported with herbal
therapies for the treatment of dermatological diseases as
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
5
Drug
Function
Uses
Evidence Based
Medicine
Zemaphyte®
(Chinese Herbal Therapy)6,10-14
Anti-inßammatory, antihistaminic, immunosuppressive
Atopic Dermatitis
Yes
Evening Primrose Oil
(EPO)(Efamol®)4,6,8
Anti-inßammatory
Acne, atopic dermatitis, psoriasis
Yes
Borage Oil115
Anti-pruritic, anti-inßammatory
Atopic Dermatitis
No
Aloe Vera
Anti-inßammatory, antimicrobial,
vulnerary (promotes wound healing)
Abrasions, acne, aphthous ulcers,
AD, bites, burns, dermabrasions,
frostbite, leg ulcers, poison ivy,
psoriasis, sunburn
Yes
Calendula
(Calendula officionalis)4,8,9,16
Anti-inßammatory, anti-septic,
vulnerary
Boils, burns, eczema, herpes simplex Yes (re:wound
or zoster, mouth irritations, ulcers,
healing)
wounds
Capsaicin (Zostrix®)8,9,16
Deplete neuronal stores of
substance P
Pityriasis Rubra Pilaris, post herpetic Yes (re: PHN,
neuralgia (PHN), prurigo nodularis, Psoriasis)
pruritus associated with psoriasis
(Ps) and PUVA
Goldenseal
(Hydratis canadensi)4
Anti-inßammatory, antimicrobial,
antiseptic, astringent, vulnerary
Boils, hemorrhoids, tinea
No
Licorice (Glycyrrhiza
glabralensis or ura)4,6,8,16
Anti-inßammatory, antiviral,
demulcent (mucous membrane
soother)
Eczema, melasma, “sore mouth”
No
Purple Cone Flower
(Echinacea angustifolia or
pupurea)4
Anti-inßammatory, antimicrobial,
antiseptic, immunomodu-lator
external-Boils, burns, herpes
simplex, ulcers internalPrevention of yeast infections
No
Slippery Elm Bark (Ulmas fulva)4
Antiviral, demulcent, emollient
external-Abscesses, boils, herpes
simplex, skin irritations, ulcers
No
St. Johns Wort
(Hypericum perforatum)4,6
Anti-inßammatory, astringent,
antimicrobial, immunomodu-lator
external- Burns, neuralgia,wounds
No
Thyme
(Thymus vulgaris)4
Antimicrobial, astringent, antiseptic
Combined with herbs for
alopecia, halitosis, stomatitis
No
Ginkgo (Ginkgo biloba)
Garlic, Ginger, Ginseng
(Panax ginseng)4,8,17
Various
Various
No
Tea Tree Oil
(Melaleuca alternifolia)6,8,9
Antimicrobial, antiseptic
Acne, impetigo, mouth ulcers,
psoriasis, tinea infections
Yes
Bromelain-Pineapple
(Ananas comosus)16
Anti-inßammatory
Wound healing, ↓postsurgical pain
No
Yarrow (Achillea millefolium)16
Anti-inßammatory
Compress for weeping lesions, pruritus No
Fenugreek (Trigonella
foenum-graecum)16
Anti-inßammatory
Compress for weeping lesions
No
Chamomile (Matricaria
recuita L)4,6,9,16.18
Anti-bacterial, anti-inßammatory,
fungicidal
AD, Candida albicans, grampositive infections,
Yes
Arnica (A Montana)8,9
Anti-inßammatory
Acne, boils, bruises, gingivitis,
hemorrhoids, insect bites
No
Horse Chestnut seed extract
(Aesculus hippocastanum)6,8
Anti-inßammatory
Chronic venous insufficiency
(↓swelling, pruritus, tenderness)
Yes
4,6,8,9,16
Table 1: A review of some herbal remedies.
6
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
Drug
Side-Effects
Drug Interactions
Zemaphyte®
(Chinese Herbal Therapy)10-14
Diarrhea, increased liver function tests, reversible
dilated cardiomyopathy, reversible acute hepatic illness,
fatal hepatic necrosis, symptomatic nephropathy &
bladder carcinoma, worsening of atopic dermatitis,
acute urticaria
Methotrexate
Evening Primrose Oil (EPO)
(Efamol®)4,6,8
GI upset, headaches
phenothiazines, ↓seizure threshold of
phenobarbital, phenytoin
Borage Oil115
Potential for hepatotoxicity orally, no toxicity data for
topical use
None Known (NK)
Aloe Vera4,6,8
Contact dermatitis
↑ corticosteroids, ↓ Potassium
Calendula
(Calendula officionalis)4,9,16
Allergic reactions, ACD
NK
Capsaicin (Zostrix®)9,16
Severe burning, intolerability, allergy: can cross react
with latex, bananas, kiwi, chestnut, avocado
NK
Goldenseal
(Hydratis canadensi)4
Allergic Contact Dermatitis
NK
Licorice (Glycyrrhiza
glabralensis or ura)4,6,16
Contraindicated in hypertension, diabetes mellitus,
hypokalemia, liver/kidney disorders
Cyclosporin A (CyA) , ↑digoxin,
prednisone, ↑thiazides
Purple Cone Flower (Echinacea
angustifolia or pupurea)4,6,8
Recurrent erythema nodosum
CAUTION!: in HIV, CTD, TB, MS, ragweed,
sunßower allergies
Immunomodulators and CyA,
Methotrexate, coticosteroids
Slippery Elm Bark (Ulmas fulva)4
Dermatitis
CAUTION! Oral form induces miscarriage
NK
St. Johns Wort
(Hypericum perforatum)4,6,17
Oral form can cause photosensitivity, erectile dysfunction ↓amitriptyline ↓CyA , ↓digoxin,
↓paroxetine, ↓HIV protease inhibitors,
↓oral contraceptives, ↓retrovirals
Thyme (Thymus vulgaris)4
Essential oils can be a mucous membrane irritant
NK
Ginkgo (Ginkgo biloba)
Garlic, Ginger, Ginseng
(Panax ginseng)4,6,8,17
Can cause spontaneous bleeding
Can potentiate aspirin, NSAIDs,
warfarin, heparin
Coma with Ginkgo and Trazadone
Tea Tree Oil
(Melaleuca alternifolia)6,8,9
ext- ACD, burning, dryness, itching, 5 irritation,
systemic allergic reactions, can cross react with
colophony. int- TOXIC
NK
Bromelain-Pineapple
(Ananas comosus)16
ACD, GI upset, diarrhea
Ethyl acrylate
Yarrow (Achillea millefolium)16
ACD
NK
Fenugreek (Trigonella
foenum-graecum)6,16
ext-Skin irritation int-Hypoglycemia
Hypoglycemics
Chamomile (Matricaria
recuita L)4,6,9,25,26
ACD, anaphylaxis
Hypersensitivity cross-reactions to
ragweed, Chrysanthemums
(Compositae family)
Arnica (A Montana)8,9
ext-ACD int-TOXIC
NK
Horse Chestnut seed extract
(Aesculus hippocastanum)6,8
ext-ACD int-Dizziness, drug induced lupus, GI upset,
headache, pruritus
NK
Table 1: Side-effects and drug interactions of some herbal remedies
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
7
9.
Norman R, Nelson D. Do Alternative & Complementary Therapies work for
common Dermatologic Conditions? Skin & Aging 8:28-33 (2000 Feb).
well.7 Most are hepatotoxic effects and some have been
fatal although this is rare.8 Herbals that are recommended
for topical use should not be ingested and vice-versa. Drug
interactions that most commonly occur are due to
immunomodulatory reactions, however effects on
anticonvulsants and anticoagulants can occur.5
11. Vender RB. Alternative treatments for Atopic Dermatitis: A Selected
Review. Skin Therapy Lett 7(2):1-5 (2002 Feb).
Conclusion
12. Rustin MH, Poulter L. Chinese Herbal Therapy in atopic dermatitis.
Dermatol Ther 1:83-93 (1996).
A brief search of the literature reveals many therapies used
for dermatological disease however there are fewer reports
of their side effects in dermatologic or medical literature.
Only those therapies relevant to the specialty of dermatology
that also have had reports of side-effects are discussed.
Those therapies without known side-effects are excluded
from this manuscript. It is important for dermatologists to
become aware of these adverse events and interactions in
order to better educate their patients and possibly prevent
potential and unexpected adverse reactions.8
References
1.
Wong HGC. Chinese Patent Medicines of Herbal and Unknown Used for
Allergic and other Condidtions. Can J Allergy Clin Immunol 6(4):77-9
(2001).
10. Ferguson JE, Chalmers RLG, Rowlans DJ. Reversible dilated
cardiomyopathy following treatment of atopic eczema with Chinese herbal
medicine. Br J Dermatol 136(4):592-3 (1997 Apr).
13. Perharic-Walton L, Murray V. Toxicity of Chinese herbal remedies. Lancet
340(8820):674 (1992 Sep).
14. Luciuk G. Chinese Herbal Medicines. Allergy & Asthma 13(4):1-2 (2000
Aug/Sep).
15. Levin Cl, Maibach H. Exploration of "Alternative" and "Natural" Drugs in
Dermatology. Arch Dermatol 138(2):207-11 (2002).
16. Graf J. Herbal anti-inßammatory agents for skin disease. Skin Therapy Lett
5(4):3-5 (2000).
17. Generali, JA. Keeping Up Alternative Medicines: Year in Review Druglink.
pp12-14 (2001 Feb).
18. Patzelt-Wenczler R. Proof of efficacy of Kamillosan(R) cream in atopic
eczema. Eur J Med Res 5(4): 171-5 (2000 Apr).
19. Wong HCG. Allergic Reactions Associated with Chinese Herbal Medicine.
Allergy & Asthma 13(4):13-8 (2000 Aug/Sep).
20. Wong HGC. Acute Urticaria associated with Chinese Herbal Medicine Used
for Atopic Dermatitis. Can J Allergy & Clin Immunol 6(2):162-5 (2001).
2.
Neldner KH. Complementary and Alternative Medicine. Dermatol Clin
18(1):189-93 (2000 Jan).
3.
Gold JL, Laxer DA, Rochon, PA. Herbal Remedies: A Critical Perspective.
Ann RCPSC 33(8):497-8 (2000 Dec).
4.
Gardiner P, Kemper KJ. Herbs in pediatric and adolescent medicine. Pediatr
Rev 21(2):44-57 (2000 Feb).
5.
Sitar DS. Important Drug Interactions. Can J CME pp:77-87 (2002 Feb).
6.
Dinehart SM, Hordinsky MK, Jaworsky C. Alternative Medicine and the
Skin. Presented at: the American Academy of Dermatology Annual General
meeting, Washington DC, March 2001.
24. Kane JA, Kane SP, Jain S. Hepatitis induced by traditional Chinese herbs;
possible toxic components. Gut 36(1):146-7 (1995 Jan).
7.
Keane FM, du Vivier AW, et al. Analysis of Chinese herbal creams
prescribed for dermatological conditions. BMJ 318(7183):563-4 (1999 Feb).
25. Giordano-Labadie F, Schwarze HP, Buzex J. Allergic contact dermatitis from
camomile used in phytotherapy. Contact Dermatitis 42(4):247 (2000 Apr).
8.
Bedi MK, Shenefelt PD. Herbal Therapy in Dermatology. Arch Dermatol
138(2):232-42 (2002 Feb).
26. Gordon LA. Compositae dermatitis. Australas J Dermatol 40(3):123-8;quiz
129-30 (1999 Aug).
21. Wong HGC. Acute Generalized Maculopapular Eruption, Abnormal Liver
Function, and elevated Blood Mercury Level Associated with Chinese Herbal
Medicine. Can J Allergy & Clin Immunol 7(5/6):92-6 (2002 July-Aug).
22. Tanaka A, Nishida R, Sawai K, et al. [Traditional remedy-induced Chinese
herbs nephropathy showing rapid deterioration of renal function] Nippon
Jinzo Gakkai Shi 39(8):794-7 (1997 Dec).
23. Graham-Brown R. Toxicity of Chinese Herbal remedies. Lancet
340(8820):673-4 (1992 Sep).
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Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
Reviewers for 2002
During 2002, the reviewers noted below gave generously of their time and talents and completed manuscript reviews for the
Skin Therapy Letter. On behalf of the Editorial Board and our readership, we thank them for their efforts.
Stuart Maddin, MD, FRCPC
Editor-In-Chief
Abdulmajeed Alajlar
Murad Alam
Lorne Albrecht
Hugo Degreef
Jeffrey S. Dover
Jan Dutz
Boni E. Elewski
Lyn Guenther
Vincent Ho
Ian Landells
Harvey Lui
Eugene Monroe
Barbara Reed
Jason K. Rivers
D. Richard Thomas
Guy Webster
Catherine Zip
WE ’RE ON THE NET! www.skincareguide.com
————— INDUSTRY NEWS —————
Important Safety Information About DIANE-35
and the Risk of Venous Thromboembolism
In April 2003, Berlex Canada sent out a Dear Health Care Professional letter outlining recent published information
on the risk of venous thromboembolism (VTE) with DIANE®-35 (cyproterone acetate and ethinyl estradiol).
DIANE®-35, like all estrogen/progesterone combinations, is associated with an increased risk of VTE.
DIANE®-35 is indicated for the treatment of women with severe acne and its associated symptoms of androgenization,
including seborrhea and mild hirsutism, that has been unresponsive to oral antibiotics and other available treatments.
Based on an independent analysis that was commissioned by Berlex, cases of non-fatal VTE ranging in incidence from
1.2 to 9.9 events per 10,000 women-years have been observed in users of DIANE®-35. As context, the incidence of
VTE in non-users of any oral contraceptive is estimated to be 0.5 to 1 event per 10,000 women-years, and increases
to 4 events per 10,000 women-years in long-term users of low estrogen content (<50_g ethinyl estradiol) combination
oral contraceptives. These event rates are rare, but still justify caution in the use of DIANE®-35.
Since its market introduction in 1998, Health Canada has received 11 reports of VTE equivalent to a reporting rate
of 0.33 events per 10,000 women-years. One of these cases involved a death. It should be noted that reporting rates
determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to
underestimate the risks associated with drug treatments.
Women with androgen-related conditions, e.g., severe acne or hirsutism, may have an inherently increased
cardiovascular risk. The excess risk of VTE is highest during the Þrst year a woman ever uses a combination oral
contraceptive.
Berlex summarized by saying that:
• DIANE®-35, as with all estrogen/progestogen combinations, is contraindicated in women with thrombophlebitis,
thromboembolic disorders, or a history of these conditions.
• DIANE®-35 users appear to have an elevated risk of venous thromboembolic events compared to users of
combination oral contraceptives in some published studies.
• DIANE®-35 should not be prescribed for the purpose of contraception alone.
• During treatment with DIANE®-35, other oral contraceptives should not be used.
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
9
Update on Drugs
Class
Name/Company
Approval Dates and Comments
Atopic
Dermatitis
Agents
Pimecrolimus
Elidel® Cream 1%
Novartis
TPP Canada approved this non-steroid cream in March 2003, for shortterm and intermittent long-term therapy of mild-to-moderate atopic
dermatitis in non-immunocompromised patients ≥ 2 years of age.
Monoclonal
Antibody
Adalimumab
Humira®
Abbott Pharmaceuticals
The US FDA approved this product in February 2003, as the Þrst
human monoclonal antibody for reducing signs and symptoms, and
inhibiting the progression of structural damage to adults with
moderately-to-severely active rheumatoid arthritis who have had an
insufficient response to >1 traditional disease modifying
antirheumatic drug. Presently undergoing clinical trials for use in
moderate-to-severe psoriasis.
Antihelmenthic Lindane Lotion &
Shampoo
Agent
Generic
Several suppliers
The US FDA added a boxed warning in March 2003, highlighting
important issues with the use of this lotion and shampoo for lice
treatment. The warning covers four issues:
• They should be used only as second-line treatment of lice
infestation or in patients who cannot tolerate treatment with safer
medications.
• Lindane exposure poses a greater risk for serious neurotoxicity in
infants, children, the elderly, patients with skin conditions other
than lice infestation, and persons weighing less than 110 pounds.
• Use is contraindicated in premature infants and patients with a
known uncontrolled seizure disorder.
• Patients must be instructed on how to use this product properly.
It was determined that most serious adverse events are caused by
misuse or overuse of this product, consequently the US FDA has
sent a 2-ounce limit on the size of the Lindane containers.
Drug News
Wound Care
In a case series study, researchers from Ohio State University found that brief exposures to pure
oxygen help chronic and other hard-to-heal wounds to heal faster and more completely. Surgical
scientists used topical oxygen therapy to treat 30 patients with a total of 56 wounds. The therapy
required placing a bag containing pure oxygen over the wound for 90 minutes/day. Ultimately, more
than two-thirds of the wounds healed with the oxygen treatment alone.
Source: Pathophysiology 9(2):81-87 (2003 Jan)
Vaccines
According to a poster presentation at the 21st Annual Meeting of the European Society for Paediatric
Infectious Diseases in April 2003, the introduction of a varicella vaccine in the US in 1995 was
followed by a reduction in the rate of hospitalizations for the serious complications of the infection.
Data was collected from three states, California, Connecticut and Washington where by the year 2000,
hospitalization rates dropped by 21.3%, 19.7% and 11.7%, respectively. For children under the age of
2 years, the vaccine coverage was 74% for California, 72% for Connecticut and 48% for Washington.
Skin Therapy Letter(ISSN 1201–5989) Copyright 2003 by SkinCareGuide.com. The Skin Therapy Letter© is published 10 times annually by SkinCareGuide.com Ltd, 1107 – 750 West Pender, Vancouver, British Columbia,
Canada, V6C 2T8. Managing Editor: Penelope Gray-Allan, Tel: 604-926-4320, Fax: 604-926-5455, email: [email protected]. All rights reserved. Reproduction in whole or in part by any process is strictly forbidden
without prior consent of the publisher in writing. While every effort is made to see that no inaccurate or misleading data, opinion or statement appears in the Skin Therapy Letter©, the Publishers and Editorial Board wish to make
it clear that the data and opinions appearing in the articles herein are the responsibility of the contributor. Accordingly, the Publishers, the Editorial Committee and their respective employees, officers and agents accept no liability
whatsoever for the consequences of any such inaccurate or misleading data, opinion or statement. While every effort is made to ensure that drug doses and other quantities are presented accurately, readers are advised that new
methods and techniques involving drug usage, and described herein should only be followed in conjunction with the drug manufacturer’s own published literature. Printed on acid free paper effective with Volume 1, Issue 1, 1995.
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Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 8 No. 3 • March 2003
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