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.
