Mild-to-Moderate Psoriasis - part 10 potx

PHOTOTHERAPY Although the majority of patients with mild-to-moderate psoriasis aretreated successfully with topical agents, some may also require photother-apy.. Treatment of psoriasis v

and facial areas, their side effects may mitigate use in these areas Topicaltacrolimus offers the potential for an anti-inflammatory effect, while avoid-ing the atrophy and acneiform eruptions commonly associated with the use

of topical corticosteroids (48) Several studies have shown the benefits oftacrolimus for facial and intertriginous psoriasis (49,50) One study showedexcellent improvement at the end of an eight-week treatment period, with65.2% of the tacrolimus ointment group, versus 31.5% of the vehicle group,giving a clear or almost clear response (50) Adverse events were similar inthe 0.1% tacrolimus ointment and vehicle groups In a study of pimecroli-mus in 57 patients with moderate to severe inverse psoriasis, 54% of thepimecrolimus group versus 21% of the placebo group had an Investigator’sGlobal Assessment score of 0 or 1 (clear or almost clear) at week 2 (51) Byweek 8, 71% of the pimecrolimus group had an Investigator’s Global Assess-ment score of 0 or 1 Pimecrolimus was safe and well-tolerated, with adverseevents similar between groups Topical tacrolimus and pimecrolimus areineffective for standard plaque psoriasis

Coal Tar

This agent is messy, malodorous, and stains clothing and other fabrics, ing to poor patient compliance despite being inexpensive Liquor carbonisdetergens is better tolerated and may be compounded in various vehicles (57)

lead-We frequently use 10% to 20% liquor carbonis detergens with one-fourthstrength betamethasone valerate in a hydrophilic emollient base at night forthin plaque psoriasis or as an adjunct to phototherapy It is important toinstruct patient not to apply tar preparations prior to their phototherapy

to avoid ‘‘tar smarts.’’

Safety

From a safety standpoint, skin irritation, acneiform eruptions, and liculitis are common The carcinogenicity of coal tar has clearly been

demonstrated by in vitro and animal studies, and appears to be potentiated

by concomitant use of UV radiation (58) In addition, cases of skin cancerhave been linked with coal tar use, especially on the genitalia (59) Tarpreparations are frequently used by dermatologists as shampoos for thetreatment of scalp psoriasis In addition, a vast array of over-the-countertar-containing products are advertised and still used by psoriasis patients.Coal tar is safe to apply during pregnancy (pregnancy class A), and aretrospective study of 23 pregnant patients during which the dermatologicaluse of tar was clear was not associated with any adverse outcomes (60).Anthralin

Anthralin, or dithranol, has historically been used as part of the Ingramregimen (daily coal-tar bath, UVB, followed by application of an anthralin–salicylic acid paste) (3) Anthralin, like coal tar, commonly causes irritation,and also has a significant problem with the staining of skin, fabric, andbathroom tile, and therefore it has largely been abandoned outside of photo-therapy and outpatient regimens Short contact regimens (minutes to 1–2hours) and more cosmetically acceptable formulations are used in the out-patient setting as monotherapy or in combination with other agents toreduce these side effects Short contact anthralin therapy, using concentra-tions of 1% or greater, entail application of five minutes on the first dayand then increasing by five minutes every other day until minimal irritationdevelops, after which the period of application is maintained until clearing(61) Staining of the skin and irritation may be lessened by application

of triethanolamine before removal of the anthralin (62) Micanol1 is a1% anthralin formulation in a temperature-sensitive vehicle that releasesactive medication at skin surface temperature (63) It is possibly moreacceptable to patients because staining of household fabrics and furniture

is minimized Studies have demonstrated efficacy of Micanol1 in and long-term regimens, as well as utility in scalp psoriasis refractory toother treatments

short-Safety

Anthralin should be used with care because of potential for irritation andstaining Thus, it must be applied only to plaques and not to surroundingnormal skin, as irritation and staining of the skin may develop Anthralin

is pregnancy category C and no reproduction studies, human or animal, orreports of adverse fetal effects have been published (59) While studies haveshown that anthralins is a tumor promoter producing transient changes inthe growth or differentiation of the epidermis, no significant increase inpre-malignant or malignant skin tumors have been noted in over 50 years

of usage (64)

Therapeutic Options for Mild-to-Moderate Psoriasis 255

Emollients and Keratolytics

These agents are recommended as concomitant therapy for the treatment ofpsoriasis Hydration of the dysfunctional epidermal barrier helps decreaseerythema, pruritus, and scaling within lesions (65) In general, while oint-ments are the most effective, patient preference and compliance is betterwith less greasy emollient bases (66) In addition, in certain body areas(e.g., legs) and patient populations (e.g., elderly), emollients should be used

as an adjunct to topical steroid usage, especially after bathing

The only combination keratolytic creams commercially available inthe United States are lactic acid/urea based (67) Outside the United States,

a combination of 0.05% betamethasone dipropionate ointment and 3% cylic acid is available (68) Salicylate-containing preparations should not beapplied before light therapy given their photoprotective effects We usuallylimit the use of these products for hands, feet, elbows, and knees to aid inexfoliation on the penetration of concomitant topical agents

sali-Safety

While keratolytics containing salicylic acid are generally regarded as safe,their use should be limited to less than 20% BSA to avoid salicylate toxicity,classically characterized by tinnitus, dizziness, gastrointestinal distress, andpsychiatric disturbances (69) Keratolytics are pregnancy class C (safety foruse during pregnancy has not been established) and application to the face,genitalia, and eyes should be avoided (70)

PHOTOTHERAPY

Although the majority of patients with mild-to-moderate psoriasis aretreated successfully with topical agents, some may also require photother-apy Because of its efficacy and safety profile, UVB continues to havewidespread use in spite of the development of newer treatment modalitiesfor psoriasis Studies have shown that UVB in conjunction with other treat-ment modalities shows additional benefits, and results in lesion clearing withless frequent UVB radiation treatments UVB therapy with a lubricatingbase results in shorter treatment periods, which means the surrounding skinwill be exposed to smaller doses of UVB, with a diminished risk of actinicdamage (71) UVB combination with tazarotene 0.1% gel may be more ben-eficial than UVB alone (40,41) Similarly, the addition of calcipotriene toUVB results in lesion clearing with less frequent UVB radiation treatments(22,23) UVB phototherapy combined with topical corticosteroids hasshown no dose-sparing effect or therapeutic advantage, and may evenshorten remission time The use of broadband UVB has diminished in recentyears with the introduction and widespread availability of narrow-bandUVB, which has a quicker and more sustained onset of action The excimer

laser is a beam of 308 nm light and has been successfully used to treat lized plaques of psoriasis (‘‘targeted phototherapy’’), including those on thepalms and soles (72).

loca-PUVA therapy is considered more durable than UVB, with somepatients even achieving long-term remission without maintenance therapy.Methoxsalen is pregnancy category C and should be given to pregnantfemales only in cases where it is clearly needed Because PUVA is mutagenicand induces sister chromatid exchanges, it should be considered a potentialteratogen and women at risk of becoming pregnant who are treated withPUVA should consider using contraception (73)

SUMMARY

Biologic systemic therapies for psoriasis have dominated the literature, ings, and marketing efforts over the past three years However, topicaltherapy is likely to remain an essential form of therapy for the majority ofpsoriasis patients, either as monotherapy for patients with limited disease,

meet-or as an adjunctive therapy to phototherapy and systemic agents fmeet-or mmeet-oresevere psoriasis While writing a prescription for a single topical preparation,

or combination of agents, is relatively quick and easy, time must be spent ineducating each individual patient on the nuances of topical therapy in order

to optimize the positive effects of these preparations, while minimizing theirside effects As the majority of patients with psoriasis are part of the spectrum

of mild-to-moderate disease, it is hoped that the practical points outlined inthis chapter will be of value for the practicing dermatologist

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Therapeutic Options for Mild-to-Moderate Psoriasis 261

mutilans, 227psoriatic, types of, 227Asymmetric oligoarthritis, 227Axial disease, 227

Basal cell carcinoma (BCC), 131Beau’s lines, 223, 230

Betamethasone dipropionateb.i.d., 77

cream, 95ointment, 76, 256once-daily, 78, 80Betamethasone dipropionate plussalicyclic acid, 62

Betamethasone dipropionate/calcipotriene combination,84–85

with biologics, 85–86clinical trials and analyses of, 77effectiveness of, 77

formulation of, 76with other systemic agents, 86

263

beneficial effects of, 60

chemical structure of, 61

and corticosteroids combination, 2

plus narrowband UVB, 64

for psoriasis treatment, 165

side effect of, 66

skin irritation from, 66–68

and systemic agents, 65–66

and tazarotene, 64

topical, 75–76

steroids, 63

versus other topical agents, 62

Calcipotriene and halobetasol

propionate, use of, 166

Calcipotriol, 187lotion, 201ointment, 59treatment, 197Calcitriol, 59Calcium metabolism, 251Carcinogenesis, skin, 130Carcinogenic potential, 149Cellular proliferation, 235Chemotherapeutic agent, 235Chemotherapy, 235–236Class I topical steroids, 64Clear liquid emollients, 129Clinical morphology, 196Clobetasol, 157

containing topical corticosteroidproducts, 6

foam, 70Clobetasol propionate, 174foam, 46

efficacy of, 168twice-daily monotherapy with, 169lotion, 176

shampoo, 175, 199spray, 174Clobex lotion, 176Clobex shampoo See Clobetasolpropionate, shampooClobex spray See Clobetasolpropionate, sprayCoal tar

efficacy of, 116preparations of, 116psoriasis treatment with, 115–119therapeutic use of, 119

Coal tar in mild-to-moderatepsoriasis, side effects anddisadvantages, 119Coal tar lotion, efficacy of, 118Combination therapy, 127, 131, 147, 255rationale for, 147

Corticosteroid(s), 245adherence of, 46–48aspect of, 50atrophogenic effects of, 252biological activity of, 42–44and calcipotriene combination, 2

essential abilities of, 42

functional effects of changing, 43

propylene glycol present in, 45

psoriasis treated with, 41

safety profile of, 51–52

side effects from topical, 75

skin cap treatment for, 48–49

and tazarotene combination, 2

CsA See Cyclosporin A

Cutaneous immune cells, 213

Cutaneous lesions, presentation of, 207

vitro biological characteristics, 212

Cyclosporine therapy, effect of, 215

Cytokine expression, prevention of, 107

, 76Demarcated erythematousplaques, 196Dermatitis, retinoid, 252Dermatology life qualityindex (DLQI), 15Dermatophyte infection, 184Dermatoses, inflammatorytreatment of, 105Diabetic patients, acute hypoglycemia

in, 121Diprosone1

, 76, 95Disease-modifying systemic therapies, 32Distal interphalangeal (DIP) jointdisease, 227

Dithranol therapy, shortcontact, 120, 199Diversifying treatment, 147Deoxyribonucleic acid (DNA)-bindingproteins, 92

Deoxyribonucleic acid (DNA)synthesis, 155

inhibition of, 214Dovobet1

, 76, 170Dovonex1, 59, 76, 164, 233Drug reactions, 230Drug, steroid-like, 232–233Drug within vehicles, 45Duoderm1

, 176Dysfunctional epidermal barrier,hydration of, 255

Ear telangectasia, 106Efalizumab, 234Elidel1, 111Elocon1

, 95Emollientsclear liquid, 129, 186and keratolytics, 255Endothelial cells, 216Enthesopathy, 227Epidermal growth factor (EGF), 212Epidermal hyperproliferation, 212Epidermal T cell, 61

Erythema, 64

Erythrodermic psoriasis, 207

Etanercept, 32, 233

Excimer laser, 126

Fissured psoriatic lesions, 35

Fixed-dose combination therapy, 77

higher clearance of, 81

investigators and patients’

assessments of, 82

monotherapy versus, 80

psoriasis activity with, 81–82

twice-daily versus, 77

potential benefits of, 84

Flow cytometric analysis, 60

Halobetasolcream, 167ointment, 63, 70, 167propionate, 164Haplotypes, genetic, 228Hemorrhages, splinter, 223, 225Histopathology, 207

HRQOL measure, 15, 26Human immunoglobulin, 216Human leukocyte antigen (HLA)-B27genetic haplotype, 228Human–mouse monoclonal chimericantibody, 216, 233

Hydrocolloiddressings, 176patches, 177Hydrogel, 177occlusion, 177, 180patches, 176, 180use of, 180Hydrophilic emollient base, 253Hypercalcemia and hypercalciuria, 60,

67, 252Hyperkeratosisnail bed, 225subungual, 223, 227Hyponychial skin, 223Hypothalamic pituitary–adrenal (HPA)axis suppression, 211, 248

Imidazole antifungals, 199Immune cells, 207Immunogenic inflammatory disease, 107Immunomodulation, cautaneous, 126Immunomodulators, topical, 32, 253Immunopathogenesis, 216

Immunosuppression, 26agent, 236

function of, 107properties of, 132, 245

Inflammatory fungal infection, 184

Inflammatory nail changes, 229

PQOL-12 score calculation within, 26

quality-of-life measure for, 13

Lidex1

, 95Light therapy, 213Likert-type scale, 14Linear psoriasis, 230Linear verrucous epidermal nevus, 230Liquor carbonis detergens

(LCD), 116, 253Liver biopsy, 215Lupus erythematodes, 197Lymphoid malignancies, 213Lymphoma, theoretical risk of, 111Lymphoproliferative disorders, 216

Maxacalcitol, 59Maxiflor1

, 95Messenger RNA (mRNA),transcription of, 42Methotrexate, 32, 127, 155, 189, 214therapy, 66, 215

topical, 188Mid-matrix disease, 5–6, 154, 225Minimal erythema dose (MED)testing, 129, 151Minimally important difference (MID)

of PQOL-12 score, 24, 26Minimal phototoxicity dose (MPD), 135Mometasone furoate and salicylicacid ointment, combinationtherapy of, 121

Mometasone furoate monotherapy, 95Muscular skeletal pain, 177

Nailallergic contact dermatitis in, 229–230bed

hyperkeratosis, 225psoriasis, 226biopsy, 231fold plaques, 226growth center, 223inflammatory changes, 229

childhood versus adult onset, 228–229

clinical manifestations of, 224

NAPSI See Nail psoriasis severity index

Narrowband ultraviolet B (NB-UVB)

Nuclear hormone receptors, 245, 251

Nuclear retinoid receptors, 212

Nuclear transcription factor, 156

Onychomadesis, 223, 230Onychomycosis, 229Oral psoralens, 149Oral retinoid, 157, 189Oxarol1

, 59

Palmoplantar psoriasisdiagnosis of, 184phototherapy, 188–189systemic therapy, 189–190topical therapy of, 185–188treatment, 185

treatment algorithm for, 191treatment approach fortherapy of, 190–192Palmoplantar pustulosis, 185Parakeratosis pustulosa, 230Parakeratotic cells, 223, 225Paronychial skin, 184Periodic-acid–Schiff stain, 229Perioral dermatitis, 248Photoaging, 136Photocarcinogenesis, 136Photochemotherapy, 189Photodermatoses, 128Photodynamic therapy, 202Photoprotective effects, 256Photosensitivity, 152drug-induced, 128Phototheraphy, 125, 188–189,

202, 236, 256and calcipotriene, 64combinations, 148directed, 189mechanism of, 126narrowband ultraviolet B (UVB), 64psoralen and ultraviolet A (PUVA), 64targeted (localized), 137

advantages and disadvantages

of, 140adverse effects for, 141combination therapy of, 140contraindications of, 140dose and administration for, 140