Download Evidence-Based Review of Topical Treatments for Psoriasis

DERMATOLOGY
Evidence-Based Review of
Topical Treatments for Psoriasis
Maryann Mikhail and Noah Scheinfeld, MD
A
BSTRACT
PURPOSE: To understand the appearance, clinical variation, epidemiology, and pathophysiology of psoriasis and the indications and options for its topical treatment.
EPIDEMIOLOGY: Psoriasis occurs in 1% to 3% of the US population. In 20% to 25% of
these individuals, the disease will be more than limited. Plaque psoriasis is more common
in individuals with haplotypes HLA-B13, -B17, and -Cw6. It worsens with HIV infection,
stress, other infection, and exposure to ultraviolet light.
REVIEW SUMMARY: Limited plaque psoriasis can be treated effectively with topical therapies. The mainstay of treatment is topical corticosteroids, which come in a variety of
strengths. Adjustments regarding their sites of application and their durations of use allow
prescribers to maximize the therapeutic effects of topical corticosteroids and minimize
their side effects for patients. The new sequential administration of calcipotriene and topical corticosteroids is an effective treatment; however, older agents such as anthralin,
emollients, and keratolytics are useful, as well. Tazarotene, a vitamin A derivative, also is
an effective topical agent.
TYPE OF AVAILABLE EVIDENCE: Double-blinded randomized trials.
GRADE OF AVAILABLE EVIDENCE: Good.
CONCLUSION: Mild psoriasis can be treated effectively with topical medication. When
the disease is present on more than 20% of the body surface area or has not responded
to topical therapy, systemic treatment should be discussed with patient. Research should
be directed toward developing more potent medications with fewer side effects that also
possess the ability to induce a remission of the disease.
(Adv Stud Med. 2004;4(8):420-429)
P
soriasis is an eruption that can be
systemic, chronic, and inflammatory, and that can involve the skin,
nail, mucous membranes, gastrointestinal tract, and joints. It also may
manifest with arthritis. Of the various cutaneous
manifestations, plaque psoriasis is the most common. In these genetically predisposed individuals, environmental factors contribute to the
development of sharply demarcated, erythematous, scaling plaques that may be pruritic,
painful, and disfiguring.1-3 This evidenced-based
review focuses on the fundamental features of
psoriasis and its topical care.
EPIDEMIOLOGY
Psoriasis occurs in 1% to 3% of the US population. Although it occurs at all ages, the initial
Ms Mikhail is a medical student at New York University School of Medicine, New York, NY.
Dr Scheinfeld is Assistant Clinical Professor of Dermatology, Columbia University; Director, Consultation Dermatology Service, St
Luke Roosevelt Hospital Center, and Director of Consultation Dermatology Service, Beth Israel Medical Center, New York, NY.
Conflict of Interest: Ms Mikhail and Dr Scheinfeld report no financial or advisory relationship with corporate organizations related to this activity.
Off-Label Product Discussion: The authors do not include discussion of off-label use of products.
Correspondence to: Noah Scheinfeld, MD, St Luke Roosevelt Hospital, Department of Dermatology, 1090 Amsterdam
Ave, Suite 11B, New York, NY 10025.
420
Vol. 4, No. 8
■
September 2004
PSORIASIS
onset of psoriasis peaks in young adults between the
ages of 16 and 22 years and in older persons 57 to 60
years of age.2,3 More than 50% of patients have positive
family histories, and concordance rates among
monozygotic twins range from 65% to 72%. Psoriasis
affects male and female patients equally, although
female and genetically predisposed individuals tend to
have earlier ages of initial onset.4 Psoriasis can affect all
races; however, epidemiological studies have shown a
higher prevalence in northern European and
Scandinavian populations. It is less common in
Japanese and African populations. It almost never
occurs in North American and South American Indian
populations.
GENETICS
Plaque psoriasis is more common in individuals
with haplotypes HLA-B13, -B17, and -Cw6.
Polygenetic mechanisms and etiologies are probably
involved, as well. HIV infection, stress, alcoholism,
smoking, and ultraviolet light exposure all can affect
the course, duration, and clinical picture of plaque
psoriasis. Many kindred exhibit autosomal dominant
patterns of inheritance with decreased penetrance.
Studies of twin siblings have shown concordant disease in 73% of monozygotic twins, compared with
20% in dizygotic twins. Whereas this relationship
suggests a genetic etiology for psoriasis, the absence
of 100% concordance among monozygotes seems to
indicate that environmental factors are related to the
pathophysiology of psoriasis.2 Investigations have
defined 4 key genes (named pSOR1-4) that are related to the etiology of psoriasis. Of particular interest
are the genes located in regions on specific chromosomes that are linked to HLA and tumor necrosis
factor, an immune component strongly associated
with psoriasis.5
the appearance of minute blood droplets (Auspitz
sign).1 The eruption of psoriasis is frequently bilateral
and often symmetrical, usually sparing exposed areas
and favoring the elbows, knees, sacrum, and scalp.
Involvement may be universal, affecting the entire
skin, or it may be localized to one area or region.1 Nail
findings, which may be a clue to the presence of psoriatic arthritis, include pitting, onycholysis, subungual
hyperkeratosis, or the oil-drop sign.2 Other variations
Table 1. Defining Characteristics of the Various
Types of Psoriasis
Type
Characteristics
Plaque psoriasis
Dry, scaling patches
Guttate psoriasis
Drop-like, discrete papules and small
plaques after streptococcal infection
Erythrodermic psoriasis
Exfoliation of fine scales, widespread, often accompanied by
severe itching and pain
Pustular psoriasis
Pus-like blisters, noninfectious, fluid
contains WBCs
Nail psoriasis
Pitting, subungual hyperkeratosis,
onycholysis, yellow/brown spots
under nail plate
WBC = white blood cell.
Figure 1. Plaque Psoriasis on the Sacrum
PATHOPHYSIOLOGY OF PSORIASIS
Psoriasis is fundamentally a disease of human T
cells. The abnormal T cells in psoriasis lead to abnormal epidermal differentiation and hyperproliferation. Whereas in normal skin the turnover of the
epidermis takes 21 to 28 days, in psoriatic plaques it
takes 3 to 4 days.
CLINICAL PRESENTATION AND NATURAL HISTORY
Psoriasis has a wide range of expressions and may
involve the nails, scalp, and joints in addition to the
skin (Table 1). The most frequent type is psoriasis vulgaris, which is characterized clinically by variably pruritic, erythematous, sharply demarcated, salmon-pink
papules and rounded plaques covered by silvery, micaceous scales (Figure 1). Scales are lamellar, mica-like,
and readily removed when scratched, which results in
Advanced Studies in Medicine
421
DERMATOLOGY
Figure 2. Guttate Psoriasis on the Back
Figure 3. Nail Psoriasis
Figure 4. The Koebner Phenomenon and Plaque
Psoriasis
422
of psoriasis that exist include guttate psoriasis, in which
lesions are tear-shaped (Figure 2), and nail psoriasis
(Figure 3). New psoriatic lesions can occur at sites of
injury or trauma to the skin, the so-called Koebner
phenomenon (Figure 4).
STANDARD OF CARE
Psoriasis is, at present, a chronic disease without
a definitive cure. The aim of treatment is substantial
improvement in and continued suppression of the
disease to a level at which it no longer interferes with
the patient’s personal, social, or occupational wellbeing.2,3 The 3 basic treatment modalities for the
management of psoriasis are topical agents, phototherapy, and systemic agents. All of these may be
used alone, in combination, or in rotation with one
another.6 Because psoriasis is a chronic skin condition that affects each patient differently, treatment
regimens should be individualized based on the disease’s impact on quality of life, body surfaces
involved, lifestyle, comorbid health problems, and
patient expectations.7
Treatment of mild to moderate chronic plaque psoriasis often starts with emollients and keratolytics, topical corticosteroids, vitamin D analogs, coal tar, topical
retinoids, and, less frequently, anthralin. A trial of topical therapy is indicated in patients with less than 5%
body surface area involvement, unless they have previously failed topical therapy or are debilitated because of
their symptoms or sites of involvement.7 For more
severe disease, options include therapy with ultraviolet
B light, psoralen plus ultraviolet A light, oral retinoids,
methotrexate (particularly for arthritis), cyclosporine,
and biologics.2,7
EMOLLIENTS AND KERATOLYTICS
Emollients are an inexpensive, safe, active, but
weak treatment for psoriasis that work by hydrating
and softening the scaly hyperkeratotic surfaces of the
plaques. Application of emollients is effective in reducing itching, soreness, redness, scaling, and lesional
extension in about 35% of patients.3 The only adverse
effects seen are contact dermatitis and folliculitis.8 Oilbased preparations such as petrolatum or aquaphor
cream are more effective but less well tolerated because
they are sticky and make the skin appear shiny.3 While
some patients find emollients alone to be sufficient,
most require additional treatment.9
Emollients that contain keratolytic agents such as
salicylic acid can be useful for converting scaly,
rough, or fissured plaques into smoother, pink
plaques.8 Ointments containing 2% to 10% salicylic
acid often are used in conjunction with topical corticosteroids or agents such as anthralin or coal tar,
which improve penetration.10
Vol. 4, No. 8
■
September 2004
PSORIASIS
A controlled, randomized, double-blind, parallelgroup, multicenter comparison in 408 psoriasis
patients demonstrated that twice-daily use of a combination ointment that consisted of mometasone
furoate 0.1% plus salicylic acid 5% was more effective than mometasone furoate 0.1% alone after 21
days of treatment.11
Such combinations are most appropriate for use on
thick, scaly, or recalcitrant plaques; however, caution
should be exercised in the treatment of widespread
psoriasis (>20% involvement) as overapplication may
cause systemic side effects related both to the corticosteroid and the salicylate.12 Signs of salicylate toxicity
include tinnitus, dizziness, gastrointestinal distress,
and psychic disturbances.6
Though the release of combination products in
the United States has been hampered by regulatory
issues, corticosteroid–salicylic combinations such as
0.05% betamethasone dipropionate ointment plus
3% salicylic acid (Diprosalic® ointment) are available
in other countries.13
CORTICOSTEROIDS
Topical corticosteroids are the most widely used
treatment for psoriasis in the United States because
they are fast acting, cosmetically acceptable to
patients, and relatively low in cost. In a survey of US
dermatologists, 85% of responders indicated topical
steroids as their first choice for the treatment of mild
to moderate psoriasis.14
The mechanism of action of corticosteroids is complex. They have anti-inflammatory, antiproliferative,
immunosuppressive, and vasoconstrictive properties.15
Clinical efficacy is directly related to potency, can be
measured by vasoconstrictive ability, and varies
depending on vehicle of delivery16 (Table 2) and concomitant use of occlusive agents.15
As monotherapy, topical corticosteroids are most
appropriate for the treatment of limited disease.10,17
Low-potency preparations (Table 3) are generally used
in maintenance therapy as well as for treatment of thin
plaques and plaques on thin skin surfaces, such as
those of the face, groin, and genital region.10 Stronger
corticosteroid preparations are more suitable for acute
flares, thick plaques, and resistant lesions as well as
plaques on thickened skin surfaces, such as those of the
palms and soles.10 Treatment with both of the potent
corticosteroids, betamethasone dipropionate optimized vehicle (OV) ointment and clobetasol 17-propionate, has been shown to improve moderate to severe
psoriasis vulgaris by at least 75% in 75% of patients.
SIDE EFFECTS OF CORTICOSTEROID THERAPY
An uncommon but clinically important side effect
of the use of high-potency corticosteroids is adrenal
Advanced Studies in Medicine
suppression. One out of 5 (20%) of those treated had
temporary reversible suppression of the hypothalamic–pituitary-adrenal axis, as evidenced by subnormal
laboratory corticoid levels during the first weeks of
management (Table 4).18
In patients with sufficient adrenal reserve, such
transient laboratory corticosteroid aberrations lack
clinical significance. On the other hand, protracted use
of potent agents in patients with poor adrenal reserve
capacity or with impaired barrier function can lead to
clinically significant, iatrogenic, topical corticosteroid–induced adrenal insufficiency.15
Other potential side effects include thinning of
the skin, striae, masking of local infections, and
hypopigmentation.15 Repeated, long-term application of potent topical agents also can eventuate in
loss of efficacy (tachyphlaxis), and the use of systemic or potent topical agents over large areas can
result in rebound exacerbations immediately following withdrawal.15,19 In order to prevent such side
effects, superpotent corticosteroid use should be limited to less than 50 g per week for no longer than 2
to 4 weeks. Furthermore, all but the weakest of corticosteroids should not be used on the face or intertriginous areas and should be minimized in children
whenever possible.7
One maintenance regimen that is intended to lessen
the side effects of potent corticosteroids is known as
“weekend therapy” or “intermittent pulse dosing.” In this
regimen clearing is achieved by treating patients with a
potent corticosteroid twice daily for 2 to 3 weeks; remission is maintained with continued application of the
steroid in 3 consecutive doses at 12-hour intervals once a
week. In one clinical trial, administration of betamethasone OV in this fashion successfully kept 74% of patients
in remission for 12 weeks.20 A subsequent study that used
augmented betamethasone dipropionate showed that
this regimen could effectively extend remission to 6
months in 60% of patients.21 No serious local or systemic
treatment-related adverse events were reported in either
trial (Table 4).20,21
Table 2. Recommended Sites for Various Vehicles of
Corticosteroid Delivery
Vehicle
Preferred Site
Cream
Gel
Impregnated tape
Lotion
Ointment
Glabrous, intertriginous, hair bearing
Hair bearing
Glabrous
Intertriginous, hair bearing
Glabrous, hair bearing
423
DERMATOLOGY
RECENT NEW CORTICOSTEROID PREPARATIONS
There have been several advances in topical corticosteroid therapy. Citing the association of psychosocial factors and anxiety with the onset and exacerbation of
psoriasis, a group of investigators demonstrated significant differences in disease improvement and measures of
psychologic status with the use of diflucortolone valerate
ointment with moclobemide, an antidepressant, as
opposed to the use of placebo.22 Recently, the Food and
Drug Administration (FDA) approved foam formulations designed by the pharmaceutical company
Connetics (Palo Alto, Calif ) for the delivery of
betamethasone valerate (Luxíq®, 0.12%) and clobetasol
propionate (Olux®, 0.05%).13 Originally, these foam
Table 3. Steroid Potency Chart
Brand Name
Generic Name
Brand Name
CLASS 1 - Superpotent
Clobex Lotion, 0.05%
Cormax Cream/Solution, 0.05%
Diprolene Gel/Ointment, 0.05%
Olux Foam, 0.05%
Psorcon Ointment, 0.05%
Temovate Cream/Ointment/
Solution, 0.05%
Ultravate Cream/Ointment, 0.05%
Clobetasol propionate
Clobetasol propionate
Betamethasone dipropinate
Clobetasol propionate
Diflorasone diacetate
Clobetasol propionate
Halobetasol propionate
CLASS 2 - Potent
Cyclocort Ointment, 0.1%
Diprolene Cream AF, 0.05%
Diprosone Ointment, 0.05%
Elocon Ointment, 0.1%
Florone Ointment, 0.05%
Halog Ointment/Cream, 0.1%
Lidex Cream/Gel/Ointment, 0.05%
Maxiflor Ointment, 0.05%
Maxivate Ointment, 0.05%
Psorcon Cream 0.05%
Topicort Cream/Ointment, 0.25%
Topicort Gel, 0.05%
CLASS 3 - Upper Mid-Strength
Aristocort A Ointment, 0.1%
Cutivate Ointment, 0.005%
Cyclocort Cream/Lotion, 0.1%
Diprosone Cream, 0.05%
Florone Cream, 0.05%
Lidex-E Cream, 0.05%
Luxiq Foam, 0.12%
Maxiflor Cream, 0.05%
Maxivate Cream/Lotion, 0.05%
Topicort Cream, 0.05%
Valisone Ointment, 0.1%
Triamcinolone acetonide
Fluticasone propionate
Amcinonide
Betamethasone dipropinate
Diflorasone diacetate
Fluocinonide
Betamethasone valerate
Diflorasone diacetate
Betamethasone dipropionate
Desoximetasone
Betamethasone valerate
Flurandrenolide
Fluticasone propionate
Prednicarbate
Desonide
Betamethasone dipropionate
Triamcinolone acetonide
Hydrocortisone
Hydrocortisone
Fluocinolone acetonide
Betamethasone benzoate
Betamethasone valerate
Hydrocortisone valerate
Amcinonide
Betamethasone dipropionate
Betamethasone dipropionate
Mometasone furoate
Diflorasone diacetate
Halcinonide
Fluocinonide
Diflorasone diacetate
Betamethasone dipropionate
Diflorasone diacetate
Desoximetasone
Desoximetasone
CLASS 4 - Mid-Strength
Aristocort Cream, 0.1%
Cordran Ointment, 0.05%
Elocon Cream, 0.1%
Kenalog Cream/Ointment/
Spray, 0.1%
Synalar Ointment, 0.025%
Uticort Gel, 0.025%
Westcort Ointment, 0.2%
CLASS 5 - Lower Mid-Strength
Cordran Cream/Lotion/
Tape, 0.05%
Cutivate Cream, 0.05%
DermAtop Cream, 0.1%
DesOwen Ointment, 0.05%
Diprosone Lotion, 0.05%
Kenalog Lotion, 0.1%
Locoid Cream, 0.1%
Pandel Cream 0.1%
Synalar Cream, 0.025%
Uticort Cream/Lotion, 0.025%
Valisone Cream/Ointment, 0.1%
Westcort Cream, 0.2%
Generic Name
Triamcinolone acetonide
Flurandrenolide
Mometasone furoate
Triamcinolone acetonide
Fluocinolone acetonide
Betamethasone benzoate
Hydrocortisone valerate
CLASS 6 - Mild
Aclovate Cream/Ointment, 0.05%
Derma-Smoothe/FS Oil, 0.01%
DesOwen Cream, 0.05%
Synalar Cream/Solution, 0.01%
Tridesilon Cream, 0.05%
Valisone Lotion, 0.1%
Alclometasone dipropionate
Fluocinolone acetonide
Desonide
Fluocinolone acetonide
Desonide
Betamethasone valerate
CLASS 7 - Least Potent
Topicals with hydrocortisone, dexamethasone,
methylprednisolone and prednisolone
Reprinted with permission from Steroids [booklet]. Portland, OR: National Psoriasis Foundation; 2004:14-16.
424
Vol. 4, No. 8
■
September 2004
PSORIASIS
preparations were indicated for the treatment of scalp
psoriasis; however, Connetics received approval to
expand label claims for Olux to include the short-term
topical treatment of mild to moderate plaque-type psoriasis of nonscalp regions, excluding the face and intertriginous areas.23 The hope is that continued development
will lead to increases in the benefit/risk ratio and provide
safer treatment options for patients who require continuous therapy as well as for those with involvement of
steroid-sensitive areas.13
COAL TAR (DHS TAR®, DOCTAR®, THERAPLEX T®)
Coal tar is inexpensive, relatively free of side effects,
and safe for use on large body surfaces. It is an antipruritic and antibacterial that inhibits deregulated epidermal proliferation and dermal infiltration without
causing injury to normal skin when applied widely.
Coal tar (5% liquor carbonis detergens solution)
has been shown to be more effective than vehicle
emollient following 4 weeks of treatment by its generation of a 48% improvement in disease severity
compared with a 35% improvement with emollient
alone.24 A comparative study against calcipotriol,
however, suggests that coal tar (15% solution in
aqueous cream) is less effective than calcipotriol after
6 weeks of treatment (Table 5).25
Exorex® (1% prepared coal tar) is a relatively new
coal tar–based, FDA-approved psoriasis medication
deemed safe for use on sensitive skin. It contains 1%
coal tar and a synthetic esterified essential fatty acid
that resembles a component of banana skin, which
purportedly has therapeutic benefit in the treatment
of inflammatory skin diseases.28 Although 2 singleblinded studies—a small pilot study and a subsequent trial in a slightly larger cohort—found Exorex
to be similar in efficacy to calcipotriene,28,29 a doubleblind analysis revealed that it was no more effective
than traditional coal tar, which suggests that the
added component is functionally inert (Table 5).30
In the United States, coal tar has fallen out of
favor because it is messy, has an unpleasant odor, and
stains clothing and other fabrics.10 Also, it can cause
skin irritation that may lead to acneiform eruptions
and folliculitis and has been, in rare cases, implicated in the development of skin cancer.31 In current
therapeutic regimens, tar preparations are most often
used in shampoos for treatment of scalp psoriasis or
as a sensitizing agent prior to phototherapy in the
Goeckerman treatment.2,32
CALCIPOTRIENE (DOVONEX®)
Calcipotriene, known as calcipotriol or Dovonex,
is a synthetic vitamin D analog that is an effective
first- or second-line treatment for mild to moderate
chronic plaque psoriasis. Like calcitriol, the biologiAdvanced Studies in Medicine
cally active form of vitamin D, calcipotriene is a
potent regulator of cell differentiation and an
inhibitor of proliferation in keratinocytes. The
advantage of calcipotriene over calcitriol is that the
adverse effects on calcium metabolism of the former
are 100 to 200 times lesser than those of the latter.33
Several double-blind studies have demonstrated the
superiority of vitamin D analogs over placebo in the
treatment of plaque psoriasis33-35 (Table 6). The vitamin’s efficacy is comparable or slightly better than
mid- to high-potency corticosteroids.3,13 In one trial’s
evaluations, patient’s treated with calcipotriol 50 µg/g
had a 68% reduction in disease, while those treated
Table 4. Corticosteroids in the Treatment of Psoriasis:
Review of Clinical Studies
Study
Published Source Popul. (N)
Kanof and Blau.
Cutis. 1976.
Study Description
60
Double-blind comparison showed that halcinonide 0.1% was effective in 80% of patients
vs active corticosteroid control, which was
effective in 65%.26
Lynfield and Watsky. 59
Cutis. 1976.
Double-blind comparison showed that halcinonide cream was significantly more
effective than fluocinonide cream after 1 and
2 weeks of treatment with twice-daily
application.27
Katz et al. J Am
40
Acad Dermatol. 1987.
Randomized, double-blind comparison
showed that both betamethasone dipropionate OV and clobetasol 17-propionate
resulted in at least 75% improvement in 75%
of patients.18
Katz et al. Arch
Dermatol. 1987.
Single-center pilot study: after 12 weeks, 74%
of patients who received intermittent pulse
dosing with betamethasone OV (3 consecutive doses at 12-hour intervals once weekly)
maintained remission compared to 21% of
patients who received placebo.20
38
Katz et al.
90
Dermatologica. 1991.
Multicenter, double-blind, placebo-controlled
trial: after 6 months, remission was maintained
in 60% of patients who received intermittent
pulse dosing with augmented betamethasone
dipropionate 0.05% vs 20% of patients
who received placebo.21
Alpsoy et al. J Am
E=60
Acad Dermatol. 1998. A=42
Randomized, placebo-controlled, double-blind
study: after 6 weeks, patients who received
moclobemide 450 mg/day + diflucortolone
valerate had a 79% improvement in psoriasis
vs 64% improvement in those who
received placebo + diflucortolone valerate
(P<0.025).22
E = enrolled; A = assessed.
425
DERMATOLOGY
with 0.1% betamethasone valerate (applied sufficiently to cover the lesions) had a 61% reduction.3,36
Another study showed calcipotriene (ointment
0.005% twice a day) was significantly better than fluocinonide (ointment 0.05% twice a day).37
In general, class I corticosteroids appear to be more
efficacious in the short term than calcipotriene alone
and one double-blind study has shown that a combination regimen of both calcipotriene ointment in the
morning and halobetasol ointment in the evening was
Table 5. Coal Tar in the Treatment of Psoriasis: Review of
Clinical Studies
Study
Published Source Popul. (N)
Kanzler and
Gorsulowsky. Br J
Dermatol. 1993.
18
Tham et al. Br
J Dermatol. 1994.
E=30
A=27
Veronikis et al.
E=20
Arch Dermatol. 1999. A=15
Smith et al. Clin
E=20
Exp Dermatol. 2000. A=19
Tzaneva et al. Br J
Dermatol. 2003.
E=40
A=38
E = enrolled; A = assessed.
426
Study Description
Randomized, bilaterally controlled, doubleblind trial: after 4 weeks, plaques treated with
5% liquor carbonis detergens in an emollient
base had a mean improvement of 48.7% versus 35.3% with the emollient base alone, a
difference that was statistically significant.24
Prospective, right/left randomized, investigator-blinded controlled study: calcipotriol ointment 50 µg/g bid was applied to one half of the
body and, to the other half, white soft paraffin
was applied in the morning, and coal tar solution
BP (benzo[a]pyrene) 15% solution in aqueous
cream in the evening. After 6 weeks, the clinical
improvement of psoriasis was statistically significant in favor of calcipotriol.25
Single-blind, intrapatient comparison pilot
study: 2 similar psoriatic lesions in each patient
were treated with either 0.1 g of calcipotriene
or 0.1 g Exorex bid for 2 months. No difference was observed in improvement of scaling,
erythema, or plaque elevation.28
Double-blind, randomized, controlled trial: 4
similar target plaques were treated with
Exorex or coal tar control (identical in composition to Exorex but without the esterified
essential fatty acid) bid for 8 weeks. No difference was observed in cumulative score
(based on erythema, induration, and desquamation), Psoriasis Area Severity Index score,
and cosmetic acceptability of treatment.30
Randomized, observer-blind, intrapatient comparison trial: in each patient 2 comparable target plaques were treated twice daily with 1%
coal tar preparation or calcipotriol cream. There
was no difference in mean reduction or psoriasis (P=0.77), time to resolution (P=0.76), or
duration of remission (P=0.32); however, cosmetic acceptability was in favor of calcipotriol.29
significantly superior to twice-daily use of either agent
exclusively.38 A subsequent study showed that longterm maintenance with halobetasol ointment twice
daily on weekends and calcipotriene twice daily on
weekdays was superior to weekend therapy with halobetasol and placebo during the week (Table 6).39
Calcipotriene ointment is colorless and, unlike coal
tar, does not stain clothing.3 The most common side
effect is the development of an irritant contact dermatitis at the site of application.33,37,39 The face and
intertriginous areas are most susceptible to this effect,
with up to 20% of patients developing local irritation
after treatment of those sites.13 Development of hypercalcemia has been reported after application of excessive amounts of calcipotriene40; however, studies of
numerous parameters of calcium metabolism have
revealed that there are no clinically significant changes
in patients who apply less than the maximum dose of
100 g per week.41 Because vitamin D analogs are
almost comparable to corticosteroids in efficacy without the associated side effects, they may be useful as
adjuncts or alternatives in the design of long-term
treatment regimens.3,13
TAZORAC® (TOPICAL TAZAROTENE)
Tazarotene is a topical retinoid approved by the
FDA in 1997. It effects normalization of abnormal
keratinocyte differentiation, a reduction in keratinocyte proliferation, and a reduction in inflammation. Because it selectively binds retinoid receptor
subtypes beta and gamma, it is associated with fewer
side effects than are other retinoids.8 It is available as a
cream or a gel.
In a randomized double-blind trial, tazarotene
0.1% and 0.05% gels were more effective than placebo
when applied once daily for 12 weeks to the plaques of
psoriasis. Furthermore, its therapeutic effects were sustained for an additional 12 weeks after the cessation of
treatment.42 In another trial, tazarotene gel applied
once daily was as effective as the corticosteroid fluocinonide 0.05% cream applied twice daily.43
The major side effect of tazarotene is local skin
irritation, including pruritis, burning, and erythema,
which occurs in a dose-related manner in up to 25%
of patients.44 Though the 0.1% formulation is more
effective than the 0.05%, it is also associated with a
greater incidence and severity of irritation.8 For the
purpose of preventing retinoid dermatitis, regimens
that combine tazarotene with topical corticosteroids
have been studied.13 Concomitant use of mometasone
furoate 0.1% cream (class IV) or fluocinonide 0.05%
cream (class II) with tazarotene 0.1% gel applied
once daily enhanced improvement and diminished
local cutaneous irritation compared to topical
tazarotene used alone.45
Vol. 4, No. 8
■
September 2004
PSORIASIS
In a study that focused on long-term therapy, a
regimen of tazarotene gel 0.1% applied Mondays,
Wednesdays, and Fridays and clobetasol ointment
applied Tuesdays and Thursdays maintained remission in approximately 75% of patients for at least 5
months.46 In addition, tazarotene has been shown to
counteract the atrophogenic tendencies of corticosteroids. Compared with corticosteroid alone, concomitant application of tazarotene resulted in a
statistically and clinically significant reduction in
epidermal thinning. 47 Such adjunctive use of
tazarotene not only facilitates the long-term control
of psoriasis but helps to minimize cumulative corticosteroid exposure and associated adverse effects.48
The nonsteroidal combination of calcipotriene and
tazarotene, while chemically compatible, offers no
statistically significant benefit over monotherapy
with the corticosteroid clobetasol.49
ANTHRALIN
Anthralin, or dithranol, slows cellular proliferation,
decreases inflammation, and increases cellular differentiation in psoriasis.8 Since the introduction of vitamin D
analogs, use of anthralin has declined, mainly because of
its propensity to cause perilesional irritation and stain
skin and clothing.10 Historically, anthralin has been used
according to the Ingram regimen, which consists of a
daily coal tar bath, ultraviolet B phototherapy, and the
24-hour application of an anthralin paste that contains
salicylic acid to prevent oxidation of anthralin to inactive
compounds.3,50
Current usage patterns of anthralin include short
contact regimens and novel, more acceptable formulations. Short contact regimens, in which higher
concentrations of anthralin are applied for a shorter
period, are more efficacious, cause less staining, and
are more convenient for patients than longer applications of lower concentrations.53 In a modern version of this regimen, anthralin (1% or greater) is
applied for 5 minutes on the first day and then
increased by 5 minutes every other day until minimal irritation develops. Thereafter, the period of
application is maintained until clearing. Staining of
the skin can be minimized by application of triethanolamine before removal of the anthralin.7,13
Micanol® is a 1% anthralin formulation in a temperature-sensitive vehicle so that active medication is
only released at skin surface temperature. While
staining of skin can still occur, it is more acceptable
to patients because staining of household fabrics and
furniture is minimized. In a 6-week, randomized,
open, parallel-group study of 49 patients with psoriasis, Micanol was shown to be effective in both long
and short contact regimens, reducing Psoriasis Area
Severity Index scores by 78% in the long contact
Advanced Studies in Medicine
group and by 73% in the short.54 It has also been
particularly useful for refractory scalp psoriasis.13
CONCLUSION
Despite the wide range of treatment options,
there is currently no cure for psoriasis. Topical therapies possess the fewest side effects and are successful in treating most patients with limited disease.
Nevertheless, for those who have widespread
involvement, disabling disease, or who do not
respond to the existing topical agents, more aggressive treatment is required.
Table 6.Vitamin D Analogs in the Treatment of Psoriasis
Study
Published Source Popul. (N)
Kragballe et al.
15
Acta Derm Venereol.
1991.
Kragballe et al.
345
Lancet. 1991.
Dubertret et al.
566
J Am Acad
Dermatol. 1992.
Bruce et al. J Am
99
Acad Dermatol. 1994.
Highton and Quell. E=227
J Am Acad Dermatol. A=247
1995.
Perez et al. Br J
Dermatol. 1996.
84
Lebwohl et al.
J Am Acad
Dermatol. 1996.
44
Lebwohl et al.
J Am Acad
Dermatol. 1998.
E=44
A=40
Study Description
Open study: after 6 months of calcipotriol ointment 50 µg/g qd, 80% of patients showed
moderate improvement.51
Multicenter, prospective, randomized, doubleblind, right/left trial: mean reduction in psoriasis
was 68% with calcipotriol (50 µg/g) vs 61%
with 0.1% betamethasone valerate ointment.52
Double-blind, right/left comparison: after 4 weeks,
patients treated with calcipotriol (50 µg/g bid)
had 50% greater improvement of psoriasis.33
Randomized, multicenter, double-blind, parallelgroup, active-controlled trial: calcipotriene (ointment 0.005% bid) was significantly better than
fluocinonide (ointment 0.05% bid).37
Double-blind, multicenter, placebo-controlled
trial: after 8 weeks patients treated with calcipotriene showed ≥75% improvement in
plaque elevation, erythema, scaling, and overall
disease severity compared with 19% of vehicletreated patients.35
Double-blind, placebo-controlled, right/left comparison: after 2.4 months, 96.5% responded to
topical calcitriol therapy (1.5 µg qd) compared
with 15.5% with petroleum jelly alone.34
Double-blind, multicenter trial: after 2 weeks, a
regimen of calcipotriene ointment applied in the
morning and halobetasol ointment applied in
the evening was superior to monotherapy with
either halobetasol or calcipotriene bid.38
Double-blind, placebo-controlled, parallel group
study: remission (at least 75% improvement) at
6 months was maintained in 76% of patients
given calcipotriene 0.005% bid on weekdays
and halobetasol 0.05% bid on weekends compared to 40% in the placebo-halobetasol group
(P=0.045).39
E = enrolled; A = assessed.
427
DERMATOLOGY
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
428
Fitzpatrick TB, Johnson R, Wolff K, et al. Color Atlas and
Synopsis of Clinical Dermatology. 4th ed. Boston: McGrawHill; 2000.
Lui H, Mamelak A. Psoriasis, plaque. Emedicine Web site.
Psoriasis, plaque. 2003. Available at: www.emedicine.
com/derm/ topic365.htm. Accessed July 25, 2004.
Greaves MW, Weinstein GD. Treatment of psoriasis.
N Engl J Med. 1995;332:581-588.
Swerlick R, Lawley T. Eczema, psoriasis, cutaneous infections, acne, and other common skin disorders. In: Braunwald
E, Fauci AS, Kasper DL, et al, eds. Harrison's Principles of
Internal Medicine. 15th ed. New York: McGraw-Hill.
2001:311-312.
Bowcock AM, Barker JN. Genetics of psoriasis: the potential
impact on new therapies. J Am Acad Dermatol.
2003;49(suppl 2):S51-S56.
Shelley WB, Shelley ED. Psoriasis. In: Advanced
Dermatologic Therapy II. 2nd ed. Toledo, OH: WB
Saunders; 2001:924-972.
Lebwohl M. Psoriasis. In: Lebwohl MG, Heymann W, BerthJones J, et al, eds. Treatment of Skin Disease:
Comprehensive Therapeutic Strategies. New York: Mosby
International; 2002:533-543.
Peters BP, Weissmann FG, Gill MA. Pathophysiology and treatment of psoriasis. Am J Health Syst Pharm. 2000; 57:645-661.
Stern RS. Psoriasis. Lancet. 1997;350:349-353.
Linden KG, Weinstein GD. Psoriasis: current perspectives with
an emphasis on treatment. Am J Med. 1999;107:595-605.
Koo J, Cuffie CA, Tanner DJ, et al. Mometasone furoate
0.1%-salicylic acid 5% ointment versus mometasone furoate
0.1% ointment in the treatment of moderate-to-severe psoriasis: a multicenter study. Clin Ther. 1999;20:283-291.
Lebwohl M. The role of salicylic acid in the treatment of psoriasis. Int J Dermatol. 1999;38:16-24.
Lebwohl M, Ali M. Treatment of psoriasis. Part 1. Topical
therapy and phototherapy. J Am Acad Dermatol.
2001;45:487-498.
Liem WH, McCullough JL, Weinstein GD. Effectiveness of
topical therapy for psoriasis: results of a national survey.
Cutis. 1995;55:306-310.
Katz HI. Topical corticosteroids. Dermatol Clin. 1995;
13:805-815.
Cornell RC, Stoughton RB. Correlation of the vasoconstriction
assay and clinical activity in psoriasis. Arch Dermatol.
1985;121:63-67.
Lebwohl M, Abel E, Zanolli M, et al. Topical therapy for
psoriasis. Int J Dermatol. 1995;34:673-684.
Katz HI, Hien NT, Prawer SE, et al. Superpotent topical
steroid treatment of psoriasis vulgaris: clinical efficacy and
adrenal function. J Am Acad Dermatol. 1987;16:804-811.
du Vivier A, Stoughton RB. Tachyphylaxis to the action of topically applied corticosteroids. Arch Dermatol. 1975;
111:581-583.
Katz HI, Hien NT, Prawer SE, et al. Betamethasone dipropionate in optimized vehicle. Intermittent pulse dosing for
extended maintenance treatment of psoriasis. Arch Dermatol.
1987;123:1308-1311.
Katz HI, Prawer SE, Medansky RS, et al. Intermittent corticosteroid treatment of psoriasis: a double-blind multicenter trial
of augmented betamethasone dipropionate ointment in a
pulse dose treatment regimen. Dermatologica.
1991;183:269-274.
Alpsoy E, Ozcan E, Cetin L, et al. Is the efficacy of topical corticosteroid therapy for psoriasis vulgaris enhanced by concurrent
moclobemide therapy? A double-blind, placebo-controlled study.
J Am Acad Dermatol. 1998;38(2, pt 1):197-200.
23. Connetics Corporation. Products and Pipeline: Olux. Available
at: http://www.connetics.com. Accessed June 1, 2004.
24. Kanzler MH, Gorsulowsky DC. Efficacy of topical 5% liquor
carbonis detergens vs. its emollient base in the treatment of
psoriasis. Br J Dermatol. 1993;129:310-314.
25. Tham SN, Lun KC, Cheong WK. A comparative study of
calcipotriol ointment and tar in chronic plaque psoriasis.
Br J Dermatol. 1994;131:673-637.
26. Kanof NB, Blau S. Psoriasis: treatment with a new topical
corticosteroid. Cutis. 1976;17:796-798.
27. Lynfield Y, Watsky M. Psoriasis: topical corticosteroid therapy. Cutis. 1976;18:133, 136-137.
28. Veronikis IE, Malabanan AO, Holick MF. Comparison of calcipotriene (Dovonex) with a coal tar emulsion (Exorex) in
treating psoriasis in adults: a pilot study. Arch Dermatol.
1999;135:474-475.
29. Tzaneva S, Honigsmann H, Tanew A. Observer blind, randomized, intrapatient comparison of a novel 1% coal tar preparation (Exorex) and calcipotriol cream in the treatment of plaque
type psoriasis. Br J Dermatol. 2003;149:350-353.
30. Smith CH, Jackson K, Chinn S, et al. A double blind, randomized, controlled clinical trial to assess the efficacy of
a new coal tar preparation (Exorex) in the treatment of
chronic, plaque type psoriasis. Clin Exp Dermatol. 2000;
25:580-583.
31. Pittelkow MR, Perry HO, Muller SA, et al. Skin cancer in
patients with psoriasis treated with coal tar. A 25-year follow-up study. Arch Dermatol. 1981;117:465-468.
32. Perry HO, Soderstrom CW, Schulze RW. The Goeckerman
treatment of psoriasis. Arch Dermatol. 1968;98:178-182.
33. Dubertret L, Wallach D, Souteyrand P, et al. Efficacy and safety
of calcipotriol (MC 903) ointment in psoriasis vulgaris. A randomized, double-blind, right/left comparative, vehicle-controlled
study. J Am Acad Dermatol. 1992;27(6, pt 1):983-938.
34. Perez A, Chen TC, Turner A, et al. Efficacy and safety of
topical calcitriol (1,25-dihydroxy vitamin D3) for the treatment of psoriasis. Br J Dermatol. 1996;134:238-246.
35. Highton A, Quell J. Calcipotriene ointment 0.005% for psoriasis: a safety and efficacy study. Calcipotriene Study Group.
J Am Acad Dermatol. 1995;32:67-72.
36. Kragballe K, Fogh K, Soggard H. Long-term efficacy and tolerability of topical calcipotriol in psoriasis. Results of an
open study. Acta Derm Venereol. 1991;71:475-478.
37. Bruce S, Epinette WW, Funicella T, et al. Comparative study
of calcipotriene (MC 903) ointment and fluocinonide ointment in the treatment of psoriasis. J Am Acad Dermatol.
1994;31(5, pt 1):755-759.
38. Lebwohl M, Siskin SB, Epinette W, et al. A multicenter trial
of calcipotriene ointment and halobetasol ointment compared with either agent alone for the treatment of psoriasis.
J Am Acad Dermatol. 1996;35(2, pt 1):268-269.
39. Lebwohl M, Yoles A, Lombardi K, et al. Calcipotriene ointment and halobetasol ointment in the long-term treatment of
psoriasis: effects on the duration of improvement. J Am Acad
Dermatol. 1998;39:447-450.
40. Georgiou S, Tsambaos D. Hypercalcaemia and hypercalciuria after topical treatment of psoriasis with excessive
amounts of calcipotriol. Acta Derm Venereol. 1999;79:86.
41. Mortensen L, Kragballe K, Wegmann E, et al. Treatment of
psoriasis vulgaris with topical calcipotriol has no short-term
effect on calcium or bone metabolism: a randomized, double-blind, placebo-controlled study. Acta Derm Venereol.
1993;73:300-304.
42. Weinstein GD, Krueger GG, Lowe NJ, et al. Tazarotene gel,
a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic
effect. J Am Acad Dermatol. 1997;37:85-92.
43. Lebwohl M, Ast E, Callen JP, et al. Once-daily tazarotene
gel versus twice-daily fluocinide cream in the treatment of
Vol. 4, No. 8
■
September 2004
PSORIASIS
44.
45.
46.
47.
48.
plaque psoriasis. J Am Acad Dermatol. 1998;38
(5, pt 1):705-711.
Marks R. Clinical safety of tazarotene in the treatment of
plaque psoriasis. J Am Acad Dermatol. 1997;37(2, pt
3):S25-S32.
Lebwohl MG, Breneman DL, Goffe BS, et al. Tazarotene
0.1% gel plus corticosteroid cream in the treatment of plaque
psoriasis. J Am Acad Dermatol. 1998;39(4, pt 1):590-596.
Lebwohl M, Lombardi K, Tan MH. Duration of improvement
in psoriasis after treatment with tazarotene 0.1% gel plus clobetasol propionate 0.05% ointment: comparison of maintenance treatments. Int J Dermatol. 2001;40:64-66.
Kaidbey K, Kopper SC, Sefton J, et al. A pilot study to determine the effect of tazarotene gel 0.1% on steroid-induced
epidermal atrophy. Int J Dermatol. 2001;40:468-471.
Lebwohl M. Strategies to optimize efficacy, duration of remission, and safety in the treatment of plaque psoriasis by
using tazarotene in combination with a corticosteroid. J Am
Acad Dermatol. 2000;43(2, pt 3):S43-S46.
Advanced Studies in Medicine
49. Bowman PH, Maloney JE, Koo JY. Combination of calcipotriene (Dovonex) ointment and tazarotene (Tazorac) gel
versus clobetasol ointment in the treatment of plaque psoriasis: a pilot study. J Am Acad Dermatol. 2002;46:907-913.
50. Ingram JT. The approach to psoriasis. Br Med J. 1953;
4836:591-594.
51. Kragballe K, Fogh K, Sogaard H. Long-term efficacy and tolerability of topical calcipotriol in psoriasis. Results of an
open study. Acta Derm Venereol. 1991;71:475-478.
52. Kragballe K, Gjertsen BT, De Hoop D, et al. Double-blind,
right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris [correction published in
Lancet. 1991;337:988]. Lancet. 1991;337:193-196.
53. Runne U, Kunze J. Short duration ('minutes') therapy with
dithranol for psoriasis: a new out-patient regimen. Br J
Dermatol. 1982;106:135-139.
54. Thune P, Brolund L. Short- and long-contact therapy using a
new dithranol formulation in individually adjusted dosages
in the management of psoriasis. Acta Derm Venereol Suppl
(Stockh). 1992;172:28-29.
429