Abstract
Background Psoriasis is
a common chronic inflammatory skin disease characterized
by erythematous and scaling plaques. The ongoing
understanding of its pathogenesis has led to new
therapeutic options and new areas of research which
aimed at reducing keratinocyte proliferation and
suppressing T-cell activation.
Objectives To
evaluate the efficacy and safety of topical use
of a combined formulation of zinc pyrithione 0.25%
(DermaZinc Spray/Drops) and betamethasone dipropionate
micronized 0.05% in a base of isopropyl myristate
used in mild to moderate plaque psoriasis.
Methods
A total of 32 patients were enrolled into a prospective
open clinical trial. Patients were first treated
with the combined formulation of DermaZinc Spray/Drops
and betamethasone dipropionate, which was topically
administered twice daily for two weeks. After the
2nd week of therapy, DermaZinc Spray/Drops alone
was applied twice daily for two weeks and twice
daily two to three times a week for the following
two weeks. Efficacy and safety were assessed.
Results
Our results showed that the combination of DermaZinc
Spray/Drops and betamethasone dipropionate micronized
0.05% in a base of isopropyl myristate rapidly reduced
erythema, thickness and scaling. Clinical improvement
and Psoriasis Area and Severity Index (PASI) reduction
occurred in less than two weeks of therapy. The
maintenance product, DermaZinc Spray/Drops alone,
was able to complete the clinical remission, reduce
the frequency of recurrences and avoid a long term
use of topical corticosteroids.
Adverse reactions, such as lesional/perilesional
dryness and mild itching, occurred in 12.5% of all
patients (4/32), but improved throughout therapy
by applying an emollient once daily when needed.
Conclusions Our
findings suggest that a combined formulation of
DermaZinc Spray/Drops and betamethasone dipropionate
micronized 0.05% in a base of isopropyl myristate
is an effective and well tolerated topical treatment
worthy of consideration for patients with mild to
moderate plaque psoriasis.
Keywords: Psoriasis
vulgaris – Zinc pyrithione – Betamethasone
dipropionate
Introduction
Psoriasis is a chronic cell-mediated
inflammatory skin disease. It is one of the most
common chronic dermatoses in the world with a prevalence
that varies widely among different populations,
up to a 5% in some areas of the world.1,2 Its histopathology
is characterized by abnormal keratinocyte differentiation
and proliferation, a high number of type 1 T cytotoxic
CD-8-positive T lymphocytes (TC1) is present in
the epidermis, whereas activated type 1 helper CD-4-positive
T lymphocytes (TH1) predominate in the dermis. TH1
and TC1 lymphocytes release the inflammatory cytokines
interferon-? (IFN- ?), interleukin-2 (IL-2), tumor
necrosis factor-a (TNF-a) upon activation, and both
these cell types are considered to be effector cell
populations (rather than regulatory T cells, which
are chiefly type 2 cells). Also neutrophils are
found in increased amounts in psoriatic skin; they
leave the dermal vasculature and are directed to
the site of inflammation by chemokines, such as
leukotriene-B4 (LTB-4) and interleukin-8 (IL-8).3,4,5
In recent years, a variety of topical and systemic
treatments for psoriasis are available including
retinoids, photochemotherapy with psoralens and
ultraviolet A (PUVA), phototherapy with ultraviolet
B (UVB), methotrexate and cyclosporine A, however
these therapies may cause side effects in the long
term and/or do not always give acceptable responses.6
In general, the therapeutic approach to treating
this life altering disease will be dependant on
its clinical type and severity, which is linked
to how it alters the quality of life in terms of
percentage of body surface area (BSA) involved,
location of the plaques, symptoms, patient’s
attitude about the disease, impact on daily physical
and social activities.8
Topical corticosteroids are the most frequently
used medications for treating mild to moderate plaque
psoriasis. Betamethasone dipropionate is a synthetic
fluorinated corticosteroid classified as a potent
WHO Group III steroid. This drug is available on
prescription for a once or twice daily topical use
to treat plaque psoriasis on a short-term basis.
Zinc pyrithione has bacteriostatic and fungistatic
properties and is used at 1-2% in the control of
seborrhoeic dermatitis, in which epidermal cells
proliferate, dandruff, eczema, erythema and psoriasis.
Several short-term studies have shown the effectiveness
of 0.25%-0.5%-1% zinc pyrithione in the treatment
of dandruff and seborrhoeic dermatitis. The ultimate
goal of the use of zinc pyrithione in shampoo formulation
(applied twice a week for 4 weeks) was to remove
scales and reduce multiplication of the resident
lipophilic yeast Malassezia furfur (formerly known
to be Pityrosporum ovale), which is increased in
the scaly epidermis of both conditions. Zinc pyrithione
reduced the severity and area affected of the scaling.7
We report our experience with zinc pyrithione 0.25%
and betamethasone dipropionate micronized 0.05%,
topically administered, in 32 patients affected
by mild to moderate plaque psoriasis.
Materials and Methods
32 patients (20 males and 12 females,
aged 7-77 years, median age 46.3) affected by mild
to moderate plaque psoriasis were enrolled in this
study. Patients were affected by this disease for
a minimum time frame of 2 month up to 34 years.
10/32 patients had a 1st degree familiarity with
plaque psoriasis. Most of patients tried other conventional
therapies, such as tacalcitol, calcipotriol, ditranol,
tazarotene, PUVA among others, but achieved only
temporary and unacceptable responses.
All patients gave signed consent to participate
in the trial after review and approval of the present
study by all ethics committees and health authorities.
Furthermore, patients had no topical or systemic
treatments for 2 weeks prior to the topical use
of zinc pyrithione.
Patients had a Psoriasis Area and Severity Index
(PASI) score of 4 to 12, 10% to 30% of body surface
area (BSA) coverage involving at least 10% of one
or more body regions (face, arms, legs and trunk).
All patients were treated with DermaZinc Spray/Drops
and betamethasone dipropionate micronized 0.05%,
topically administered twice daily for the first
two weeks of treatment. After the 2nd week of therapy
patients began to use DermaZinc Spray/Drops OTC
(maintenance) alone twice daily for another two
weeks and when affected areas were clinically improved
or clear, patients were recommended to continue
the application of DermaZinc Spray/Drops OTC (maintenance)
twice a day two-three times a week.
To maintain clear skin, DermaZinc Spray/Drops OTC
was applied, as a maintenance program, once a day
three times a week on the affected areas providing
substantial relief.
Clinical and photographic documentation and PASI
assessment were performed before treatment, and
then at week 2 and 6 of therapy. Extension, severity
of psoriasis (thickness, redness and scaliness)
and side effects were recorded at each visit (week
0, 2 and 6).
Results
At the end of our study we evaluated
32 patients (20 men and 12 women) affected by mild
to moderate plaque psoriasis.
Among 32 patients, 18 (56.3%) achieved a significant
improvement of the thickness, redness and scaling
already after 2 weeks of treatment with DermaZinc
Spray/Drops compounded with the mild steroid. 13
patients (40.6%) showed a complete clinical remission.
1 (3.1%) patient interrupted therapy after only
two applications due to incoercible itching and
erythema. The percentage change in PASI score from
baseline to visit 2 (end of 2nd week) was significant
(48.4%).
After 4 weeks of treatment with DermaZinc Spray/Drops
alone (from week 3 to week 6), 22/31 (64.5%) patients
achieved complete clinical remission, 8/31 (32.3%)
showed a partial response and 1/31 (3.2%) had mild
flair-ups.
After another 4 weeks (from week 7 to week 10) of
the maintenance program, DermaZinc Spray/Drops alone
once a day two-three times a week, only 2 patients
showed recurrences.
Adverse events, lesional/perilesional dryness and
mild itching occurred in 4 patients (12.5%). These
side effects improved throughout therapy by applying
an emollient once daily. In this study no case of
skin atrophy was reported.
Discussion
The present study wanted to evaluate
the efficacy and safety of a combined formulation
of DermaZinc Spray/Drops with betamethasone dipropionate
micronized 0.05% in a base of isopropyl myristate
in the treatment of mild to moderate plaque psoriasis.
Psoriasis is a chronic life-altering disease, which
often requires long-term topical therapy. Although
patients treated were affected by plaque psoriasis,
which may be considered a mild-moderate type of
this disease, with a low PASI score at the baseline
and more than 10% of body surface area involved;
they had a strong will to achieve a better quality
of life. There are multiple factors that encompass
a clinical definition of severity issue that may
not be based only on BSA. 8
Topical DermaZinc Spray/Drops OTC treatment is an
effective anti-itching, anti-flaking, anti-fungal
and bacteriostatic agent for chronic skin conditions,
such as seborrheic dermatitis and dandruff, eczema,
erythema and mild to moderate plaque psoriasis.7,9
Histopathology of psoriasis treated with DermaZinc
Spray/Drops was described by Rowlands C.G. and other
authors whose purpose was to examine the histological
changes induced by this drug, applied twice daily,
in a well developed psoriatic plaque. After 2 weeks
of treatment, histological features of psoriasis
resolved completely. The mechanism of this normalization
was unknown. However, hypotheses include blockage
of cytokine and growth factor effect, disappearance
of neutrophils and induction of apoptosis.10,11
In our study, 32 patients were treated with DermaZinc
Spray/Drops combined with a mild steroid such as
betamethasone dipropionate micronized 0.05%. This
topical treatment was well tolerated in 31/32 patients
and showed a high number of complete clinical remission,
40.6% and 64.5% respectively at visit 2 (2nd week)
and at visit 3 (6th week). Only 4 cases of lesional/perilesional
dryness.
The combination of DermaZinc Spray/Drops with betamethasone
dipropionate micronized 0.05% in a base of isopropyl
myristate is a new formula and first of its kind
that exhibits a synergistic action with anti-inflammatory,
bacteriostatic and anti-fungal properties which
allows a shorter time of application for the patient
with maximum absorption. It is thought that the
zinc may be able to reduce epidermal proliferation.
Although the exact mechanism of action of the “activated”
DermaZinc Spray/Drops preparation is unknown it
may be speculated that the possible anti-proliferative
mechanism of action involves the regulation of DNA
transcription factors containing “zinc fingers”
binding domains. It is also recognized that many
enzymes require the binding of metal ions for activation,
perhaps one of these ”zinc requiring”
enzymes or transcription factors plays a key role
in the cell proliferation. It is also well known
that a deficiency of zinc produces a disease state,
acrodermatitis enteropathica, that includes psoriasiform
lesions.
The particular use of a micronized form of this
mild steroid is fundamental to insure positive results
thus reducing the amount of topical corticosteroid.
Therefore, the combined formulation used twice daily
shows remarkable responces in less then 14 days
of therapy and accomplishes it avoiding the negative
effects associated with long term corticosteroid
usage. Also the maintenance formula of DermaZinc
Spray/Drops OTC without the steroid showed a better
absorption rate and quicker response time than other
competitive products available on the market with
a higher concentration (up to 2%) and indicated
to treat dandruff and mild cases of seborrhoea.
This capacity may be related to the specific isopropyl
myristate vehicle utilized that permits a physiologic
level of zinc to be reached at the target cells,
either epidermal and/or lymphocytic.
The tolerability of a drug and its safety are fundamental
for the success of a therapy. We report a great
acceptance of treatment and an increase of patient’s
compliance due to ease of administration, quick
drying capability, odor and stain free characteristics.
Moreover, for maintenance DermaZinc OTC products
without the steroid had an important psychological
effect on stress reduction, peace of mind and attitude
towards such chronic disease.
Our findings suggest that DermaZinc Spray/Drops
with betamethasone dipropionate micronized 0.05%
in a base of isopropyl myristate is a new well tolerated
topical treatment worthy of consideration for patients
with mild to moderate plaque psoriasis.
BETAMETHASONE
STUDIES
