The Management of Persistent Pain in Older Persons AGS Panel on Persistent Pain in Older Persons scribed are those who are most frail, with health and dis- Background and Significance ability problems typically encountered in the older popula-tion. By age 75 many persons exhibit some frailty and Pain is an unpleasant sensory and emotional experi-
Topical treatment of psoriasisTopical treatment of psoriasis Philip M Laws & Helen S Young†The University of Manchester, Salford Royal Hospital (Hope), Manchester Academic Health SciencesCentre, Department of Dermatology, Stott Lane, Salford, Manchester M6 8HD, UK Importance of the field: The majority of patients with psoriasis can be safelyand effectively treated with topical therapy alone, either under the supervision of a family physician or dermatologist. For those requiring systemic agents, top- ical therapies can provide additional benefit. Optimal use of topical therapy requires an awareness of the range and efficacy of all products.
Areas covered in this review: The review covers the efficacy and role of topi-cal therapies including emollients, corticosteroids, vitamin D analogs, calci-neurin inhibitors, dithranol, coal tar, retinoids, keratolyics and combinationtherapy. The report was prepared following a PubMed and Embase literaturesearch up to April 2010.
What the reader will gain: The paper provides a broad review of the relevanttopical therapeutic options available in routine clinical practice for themanagement of psoriasis and a recommendation for selection of treatment.
Take home message: Topical therapies used appropriately provide a safe andeffective option for the management of psoriasis. An awareness of theavailable products and their efficacy is key to treatment selection andpatient satisfaction.
Keywords: psoriasis, severity, topical therapy, treatment Expert Opin. Pharmacother. (2010) 11(12):1999-2009 For personal use only.
Psoriasis is a chronic, immune-mediated, inflammatory disease of the skin whichaffects between 1.5 and 3% of the population in Northern Europe and Scandina-via . Psoriasis may present at any age, although a clear subgroup develop diseasebefore the age of 40 years (type 1 or early-onset psoriasis), accounting for > 75%of patients .
Approximately 80% of patients who suffer from psoriasis have mild disease .
Whilst physical disability may be slight, the psychological impact of their psoriasismay be significant, particularly when the hands, face or genital area are affected.
Psoriasis is associated with a greater incidence of depression and suicidal idea-tion [4,5], and the burden of psoriasis is reported to be comparable to other chronic Expert Opin. Pharmacother. Downloaded from informahealthcare.com by University of Szeged on 01/03/11 diseases such as diabetes and heart disease .
Topical therapy remains a key component of the management of all patients with psoriasis. Mild disease is typically managed with topical therapy alone and accountsof the majority of patients. Moderate to severe psoriasis is usually treated with pho-totherapy, systemic therapies or biological agents. However, use of topical therapyin moderate to severe disease may be helpful and can potentially reduce the amountof phototherapy or systemic agent required to achieve satisfactory disease control.
The aim of therapy is to minimize the extent and severity of psoriasis to the point at which it is no longer detrimental to a patient's quality of life. Treatment choiceshould be guided by the expectations and needs of each individual patient. Whenemployed under these circumstances a topical treatment regimen is more likely toproduce a satisfactory clinical outcome than one whereby patients have beenexcluded from the decision-making process.
10.1517/14656566.2010.492778 2010 Informa UK Ltd ISSN 1465-6566 All rights reserved: reproduction in whole or in part not permitted Topical treatment of psoriasis The importance of the psychological impact of psoriasis is Article highlights.
increasingly recognized and several assessment tools have . Topical therapies remain an important part of the been devised to provide an integrated measure of disease therapeutic armamentarium even in patients receiving burden. This includes the Salford Psoriasis Index, which pro- systemic agents.
vides a three-figure assessment of past severity based on treat- . Topical therapy used effectively can control disease in ment history, current clinical severity and psychosocial patients with psoriasis.
. Choice of therapeutic option is dependent on numerous factors, including disease severity and extent but alsopatient expectation and motivation.
. Choice of formulation should be considered and agreed with the patient.
Despite the above limitations in quantifying disease, it is . Patient education and compliance is essential.
generally accepted that psoriasis affecting < 5% body surfacearea (BSA) is amenable to topical therapy . However, this This box summarizes key points contained in the article.
can only be seen as a guide and should be interpreted on acase-by-case basis in light of the patient's disease burden and the patient's expectations. A highly motivated individual This review has been developed following literature searches may wish to use exclusively topical therapy despite widespread via PubMed and Embase. This includes a Cochrane review, disease. This contrasts with others, who may wish to explore which provides a comprehensive review of topical therapies the use of systemic therapy for significantly less extensive for psoriasis and has been updated where required . All cutaneous involvement in which the psychological burden studies discussed in the text refer to adult patients with is significant.
chronic plaque psoriasis unless otherwise stated.
Topical therapy is safe and effective when used appropri- ately and has the benefit of limited systemic effects. When 1.2 Assessment tools prescribing a topical therapy one must consider several Several assessment tools have been used to evaluate the sever- factors, including patient motivation and understanding, ity and response to treatment. Perhaps the most commonly vehicle of medicament, volume of treatment required and used in clinical trials, involving topical therapy, is the physi- need for dressings.
cian's global assessment (PGA). The PGA is a seven-pointscore ranging from 0 (clear) to 6 (very severe). Whilst For personal use only.
relatively easy to use, there are few validated studies as the Ensuring that patients understand how to apply their treat- lack of clear definitions for each point score limits ment is central to optimizing compliance with topical therapy. Patients must be willing to use the chosen therapy The Investigators Global Assessment (IGA) tool is a similar and have relatively localized disease. It is interesting to note construct to PGA, albeit with a scoring range of 0 (clear) to that, in a single study, 39% of patients admitted to nonadher- 4 (very severe) .
ence with topical therapy . In order to optimize compli- The Psoriasis Area and Severity Index (PASI) was designed ance, simple regimens with once-daily applications are in 1978 to assess objectively the response of patients with pso- preferred [15,16]. Where the patient is particularly motiva- riasis to treatment with an oral retinoid and is based on an ted, a more complex treatment regimen could be adopted.
assessment of erythema, induration and scale of the psoriasis Where facilities exist, nurse-led educational sessions should plaques with weighting for body surface area . The score be encouraged.
ranges from 0 to 72. Since inception it has become accepted Expert Opin. Pharmacother. Downloaded from informahealthcare.com by University of Szeged on 01/03/11 A PASI ‡ 10 is generally accepted as indicating severe The choice of medicament vehicle is important in patient disease [11,12].
compliance and treatment success. There is an array of Whilst the PASI score provides an objective assessment of options available including creams, ointments, foams, oils, disease severity, it does not quantify the burden of psoriasis.
gels and sprays. The use of creams may be more appropriate The psychological impact of psoriasis may be high despite where greasy preparations limit functional ability (e.g., very limited disease. The Dermatology Life Quality Index increase the risk of falls when feet are affected) or are cosmet- was designed to provide a measure of the impact of skin dis- ically unacceptable (e.g., on the facial skin). Foams, gels or ease on various aspects of an individual's life, including sprays may be preferable when there is scalp involvement.
work, relationships and social life. A Likert scale is used tograde each answer from 0 to 3, where 0 is ‘no impact' and 3 is ‘very much'. In patients with psoriasis, a score of 10 or Volume of a given prescription is frequently overlooked more indicates that the disease is causing a significant and yet it is key to delivering an effective dose. An average patient will require about 400 g/week of topical therapy for Expert Opin. Pharmacother. (2010) 11(12) a twice-daily regimen involving application of product to more than 2 weeks and that the patient should be under close the trunk and limbs . The fingertip unit is widely used to medical observation .
provide guidance on volume of topical agent required .
Clinical trials of topical corticosteroids for the treatment of Dressings are frequently used to enhance drug delivery. This psoriasis have reported efficacy rates of between 41 and 92% is particularly true of corticosteroids . The choice of . It is important to note that most of these studies were individual dressings will be dictated by local availability and done over a short time period and consequently do not pro- patient preference.
vide information on long-term therapeutic gain. Concernover rapid relapse on cessation of therapy remains an unresolved issue.
Emollients provide a safe and useful adjunct in the treatmentof psoriasis. Optimizing skin hydration is universally recog- 2.6.4 Tachyphylaxis nized to improve signs and symptoms of psoriasis . Clinical The persistence and recurrence of psoriasis in an individual trials involving topical corticosteroids demonstrated a placebo who has previously found therapeutic benefit from a topical response of 15 - 47%, indicating that the emollient effect of corticosteroid was first described by du Vivier and Stoughton the vehicle provides a significant therapeutic benefit .
in 1975 . Additional studies have failed to determine if this The choice of emollient will be guided by the severity of is truly a clinical entity or whether this simply reflects patient xerosis and the preferences of both the clinician and patient.
nonadherence . This latter study highlights the importance The emollient is generally applied 1 - 3 times a day. There of engaging the patient in a given regimen - topical therapy is are no known contraindications to emollient therapy, and time consuming and can be difficult to apply. Close supervi- emollients are regarded as safe in children, pregnancy and sion in the initial stages of treatment to provide support and address patient concerns is recommended.
2.6 Corticosteroids 2.6.5 Side effects Corticosteroids are universally used in the management of all Topical corticosteroids are a useful intermittent therapy for grades of psoriasis, both as monotherapy and as a complement controlling stable disease affecting relatively small areas of to systemic therapy. They are available in a wide range of the body. The potency of topical corticosteroid should be preparations including gel, cream, ointment, foam, spray, moderated for flexural and/or facial skin. Therapy should be For personal use only.
lotion and oil. Choice of agent will depend on patient choice, monitored by a competent healthcare professional to limit distribution of disease and local availability.
the risk of cutaneous or systemic side effects. The side effectsof topical corticosteroids can be broadly categorized as local 2.6.1 Pharmacology or systemic.
Corticosteroids have a wide range of effects upon cellular meta- Local side effects include skin atrophy, telangiectasia, striae bolism. Therapeutic response is mediated via vasoconstrictive, distensae, folliculitis, acne and purpura. Other conditions anti-inflammatory and immunosuppressive effects.
such as rosacea, perioral dermatitis and fungal infections Corticosteroids are lipophilic and readily migrate through may be exacerbated by overuse of topical corticosteroids.
the cell membrane to bind the corticosteroid receptor within The risk of skin atrophy is reduced by good medical super- the cell . The receptor- corticosteroid complexes form vision of treatment, treatment holidays and use of the cortico- dimmers, which then migrate to the cell nucleus where they steroid with the lowest potency to maintain effect. In general, bind to corticosteroid response elements. Binding of the cor- class I topical corticosteroids should be used for no more than Expert Opin. Pharmacother. Downloaded from informahealthcare.com by University of Szeged on 01/03/11 ticosteroid response elements induces the therapeutic effect 2 weeks [12,23]. The development of contact allergy to topical via regulation of gene expression .
corticosteroids is well recognized and should be investigatedwhere efficacy is lost or when the patient feels that application of treatment exacerbates their condition.
A classification of corticosteroid potency was suggested in Systemic side effects of corticosteroids include hyperten- 1985 by Stoughton and Cornell to reflect the vasoconstrictive sion, osteoporosis, Cushing's syndrome, cataracts, glaucoma, properties of each drug . In the UK, there are four potency diabetes and avascular necrosis of the femoral head or humeral groups: mild, moderately potent, potent and very potent.
head. In clinical practice evidence of these complications Selection of potency for a given corticosteroid is guided by following topical therapy are relatively uncommon.
several factors, including area affected, previous treatment, Hypothalamic pituitary adrenal (HPA) suppression is disease severity and patient preference. In general, less potent rarely symptomatic but well recognized. In a single trial of corticosteroids are preferred for facial or intertriginous/ 40 patients treated with clobetasol ointment (class I), eight genital skin and for use in children. It is generally accepted (20%) had evidence of HPA suppression on laboratory that high-potency corticosteroids should not be used for analysis . Children are at a greater risk of such effects Expert Opin. Pharmacother. (2010) 11(12) Topical treatment of psoriasis compared with adult patients, owing to their greater body 2.6.8 Class III corticosteroids (moderately potent) surface area to weight ratio.
Class III corticosteroids have been shown to be effective in The effects of topical corticosteroid during pregnancy four clinical trials.
have been extensively reviewed recently . This review Franz et al. performed a double-blind, placebo-controlled included seven studies: one study found a link between top- study of 172 patients treated with betametasone valerate ical corticosteroid use in the first trimester and orofacial 0.12% foam over 4 weeks, achieving an improvement in clefting, another study found a link between very potent PGA in 72% of patients compared with 47% of the control topical corticosteroid and low birth weight. Whilst the rela- tive risk of topical corticosteroid in pregnancy seems low, Two randomized controlled trials of 383 patients treated the decision to treat should be made on an individual with fluticasone propionate 0.005% ointment demonstrated basis with full involvement of the patient. Their safety in good, excellent or clear skin in 68 - 69% of patients at breast-feeding is also unknown.
4 weeks. This compared with 29 - 30% in the controlarm .
2.6.6 Class I corticosteroids (superpotent) A placebo-controlled trial involving 40 patients treated Five controlled trials for class I corticosteroids are reported in with betamethasone valerate 0.12% foam for 12 weeks the literature.
demonstrated a > 50% improvement in psoriasis in 70% of Bernhard et al. demonstrated a 92% improvement in PGA subjects compared with 24% in the placebo arm .
in a 2-week, double-blind, placebo-controlled trial of204 patients treated with halobetasol propionate 0.05% oint- 2.6.9 Class IV corticosteroids (mild) ment to non-scalp disease. This compared with 39% in the Class IV corticosteroids have been shown to be effective in placebo arm .
two clinical trials.
Olsen et al. demonstrated that 81% of patients treated with A study of 190 patients with mild to moderate psoriasis clobetasol priopionate 0.05% scalp application achieved a treated with hydrocortisone 17-butyrate 21-propionate 0.1% 50% or greater improvement in their scalp psoriasis after cream for 3 weeks demonstrated excellent or good improve- 2 weeks of treatment in a study involving 378 patients. This ment in 41% of patients compared with 18% of patients compared with 22% in the control arm .
who received placebo .
A 2-week, double-blind, placebo-controlled study of clobe- A randomized, double-blind, controlled trial of 89 patients tasol propionate 0.05% foam, involving 279 patients, demon- examining the efficacy of fluocinolone acetonide 0.01% oil strated a 68% clear or almost clear attainment at 2 weeks for 3 weeks demonstrated 83% of patients had good or better For personal use only.
compared with 21% in the placebo arm in non-scalp sites .
improvement from baseline compared with 36% in the A double-blind, placebo-controlled trial of clobetasol pro- placebo arm .
pionate 0.05% foam for non-scalp psoriasis used for 2 weeks Trial data for topical corticosteroids discussed above are achieved a moderate or better improvement in 58% of treated summarized in Table 1.
patients compared with 15% of the placebo arm in a studyinvolving 81 patients .
2.7 Vitamin D analogs A randomized, double-blind, placebo-controlled trial of Vitamin D analogs provide a useful adjunct in the treatment amcinonide 0.1% lotion, involving 157 patients with scalp of chronic plaque psoriasis. Their discovery was prompted psoriasis, treated for 3 weeks, demonstrated clearance in by the realization that oral vitamin D had a therapeutic effect 26% of the treatment arm compared with 1% in the placebo on psoriatic plaques .
arm . A > 50% improvement was observed in 78 and 27%for the treatment arm and placebo arm, respectively .
2.7.1 Pharmacology Expert Opin. Pharmacother. Downloaded from informahealthcare.com by University of Szeged on 01/03/11 Vitamin D analogs bind to the intracellular vitamin D recep- 2.6.7 Class II corticosteroids (potent) tor and then dimerize. These units migrate to the nucleus, Two clinical trials have demonstrated efficacy of potent where they bind the vitamin D response element, which topical steroids.
directly regulates genes involved in epidermal proliferation, A double-blind, vehicle-controlled study of halcinonide inflammation and keratinization.
0.1% solution to treat scalp psoriasis in 27 patients demon- There are three vitamin D analog preparations available to strated that 74% of patients achieved an excellent or good treat psoriasis: calcitriol, tacalcitol and calcipotriol.
response to treatment after 2 weeks compared with 45% ofpatients who were treated with vehicle alone .
2.7.2 Side effects Desoximetasone 0.25% cream used for 3 weeks to treat The most common adverse effects of treatment are skin irrita- non-scalp disease achieved an improved mean overall evalua- tion (burning, itching or stinging), dryness, peeling, erythema tion score in 68% of patients compared with 23% in the and edema which may occur in up to 35% of patients [41,42]. It placebo arm in a double-blind clinical trial involving would seem that adverse effects diminish with prolonged use.
35 patients .
Concerns over calcium homeostasis appear to be minimal if Expert Opin. Pharmacother. (2010) 11(12) Table 1. Efficacy of topical corticosteroid preparations in clinical trials.
Clobetasol propionate 0.05% ointment Clobetasol propionate 0.05% > 50% improvement in scalp application  Clobetasol propionate 0.05% Moderate or better improvement in PGA Clobetasol propionate 0.05% PGA clear or almost clear foam Amcinonide 0.1% lotion  > 50% improvement Halcinonide 0.1% solution  Excellent or good Desoximetasone 0.25% Improved mean overall Betamethasone valerate 0.12% foam Fluticasone propionate 0.005% ointment Betamethasone valerate 0.12% Improved composite Physicians evaluation of 21-propionate 0.1% cream  Fluocinolone acetonide 0.01% improvement of PGAfrom baseline the maximum dose is not exceeded: 210 g calcitriol 3 µg/g, available as an ointment or lotion. A study of 304 patients For personal use only.
70 g tacalcitol 4 µg/g, 100 g calcipotriol 50 µg/g.
treated with once-daily tacalcitol 4 µg/g for up to 18 monthsdemonstrated a median reduction in PASI from 9.5 to 4.6 at 3 months with a further reduction to 3.25 at 18 months .
Calcitriol (1,25-dihydroxycholecalciferol) is the active form of At the conclusion of the study, 197 patients remained on vitamin D and is available as an ointment only. A randomized treatment with 5.9% dropping out because of skin irritation.
trial of 258 patients treated with either betamethosone dipro- No alteration of calcium homeostasis was detected. This pionate 0.05% ointment or calcitriol 3 µg/g ointment showed has been supported by other studies demonstrating superior improvement in 82 and 79%, respectively, at 6 weeks. Whilst efficacy to placebo [47,48]. Tacalcitol is safe and effective in the extent of response was greater in the corticosteroid arm, managing mild to moderate psoriasis (up to 20% BSA) over the duration of remission was greater in the calcitriol arm; an 18-month period on an intermittent basis.
25 and 48%, respectively, remained in remission at8 weeks .
2.7.5 Calcipotriol Expert Opin. Pharmacother. Downloaded from informahealthcare.com by University of Szeged on 01/03/11 A significant concern over treatment with vitamin D Calcipotriol (Calcipotriene) is a vitamin D analog designed to analogs is the potential influence on calcium homeostasis.
retain therapeutic efficacy whilst reducing potential effects on A trial of 59 patients treated with calcitriol 3 µg/g for 12 weeks calcium metabolism. It is available as a cream, ointment or and followed up for a further 8 weeks demonstrated no signif- scalp solution. A randomized, double-blind, within-patient icant change in calcium metabolism . Higher dosing of trial of 50 patients treated with 25, 50 and 100 µg/g calcipo- calcitriol demonstrated no greater efficacy but was associated triol ointment for 8 weeks showed a marked improvement of with increased hypercalciuria . A study of twice-daily calci- 40, 63 and 80%, respectively . The safety of calcipotriol triol for up to 78 weeks demonstrated long-term efficacy and has only been established up to 1 year of follow up.
safety in a cohort of 253 patients. Slight hypercalcemia wasnoted in five (2%) patients .
2.8 Calcineurin inhibitors (pimecrolimusand tacrolimus) Calcineurin inhibitors have an established role in the manage- Tacalcitol is a synthetic vitamin D analog differing from ment of eczema. Treatment of facial or intertriginous psoriasis calcitriol by hydroxylation in the 1- and 24- positions. It is is less well established and is an off-license therapy. There are Expert Opin. Pharmacother. (2010) 11(12) Topical treatment of psoriasis two topical preparations of calcineurin inhibitors: tacrolimus 2.9.1 Pharmacology ointment (0.03 and 0.1%) and pimecrolimus cream (1.0%).
The mechanism of action of dithranol remains obscure,although it is clear that anthracyclines inhibit mitochondria 2.8.1 Pharmacology by disrupting structure and function resulting in apoptosis .
Calcineurin is a protein phosphatase essential in the prolifera- This results in antiproliferative effects that produce an tion of lymphocytes via induction of nuclear factor of acti- observable reduction in psoriatic plaques.
vated T cells, a transcription factor that upregulatesexpression of interleukin (IL)-2. In addition, inhibition of transcription of IL-3, IL-4, IL-5, GM-CSF, TNF-a and The principle limitation of dithranol is mess and skin irrita- IFN-g is observed . Inhibition of calcineurin is immuno- tion. Dithranol may stain clothes and furniture. An extensive suppressive and oral preparations have utility in maintaining review of topical therapy revealed adverse events occurring in organ transplants.
72% of patients treated with dithranol . There are twostandard application methods of dithranol: i) short-contact dithranol cream applied to affected lesions as a day case or Initial trials indicated treatment efficacy in patients with pso- outpatient; ii) application of dithranol paste or ointment for riasis when used under occlusion. This observation led to the 24 h typically as an inpatient. The short-contact regimen belief that the penetration of treatment into thick plaques of offers a more realistic treatment option in the outpatient psoriasis was limited. Consequently, tacrolimus and pimecro- setting but is less effective than applications of dithranol limus have been used in areas of skin where their penetration ointment or paste for 24 h . In isolation, dithranol is less is naturally enhanced, such as in flexural or facial skin.
effective than topical corticosteroids or vitamin D analogs .
A double-blind, randomized, controlled trial of 57 patients Incremental concentrations of dithranol paste or ointment with flexural disease treated with 1% pimecrolimus cream are often used in conjunction with ultraviolet (UV)B demonstrated that 54% of patients in the treatment arm phototherapy - the Ingram regimen .
were clear or almost clear at 2 weeks compared with 21% in A double-blind, controlled trial of 27 patients treated with the vehicle arm. This improved up until the end of the study 2% dithranol for 1 min on one half of the body and with (8 weeks), when 71% of patients had an IGA score of 0 or placebo on the other half reported a statistically significant 1 (clear or almost clear) . A double-blind, randomized, con- difference in erythema, infiltration and scaling on the trolled trial involving 167 patients demonstrated that 65.2% dithranol-treated areas after 8 weeks . A second trial using of patients treated with 0.1% tacrolimus ointment were clear dithranol gel demonstrated a reduction in combined severity For personal use only.
or almost clear, based on the static severity score, at 8 weeks score after 4 weeks of treatment from 6.3 at the start of the compared with 31.5% clear or almost clear in the control trial to 1.1 and 4.1 for the treatment and placebo arms respec- tively. An additional, comparative study of calcipotriol versus A comparative study of 80 patients treated with 1% pime- dithranol gel demonstrated similar efficacy over 8 weeks but crolimus, 0.005% calcipotriol or 0.1% betamethasone valer- with a greater number of side effects in the dithranol-treated ate demonstrated pimecrolimus was less effective than either calcipotriol or betamethasone, but more effective than vehiclealone. Maintenance treatment using pimecrolimus withintermittent rescue therapy with topical corticosteroids has been suggested as a mechanism to reduce the long-term Coal tar has been an established treatment option for psoriasis complications of prolonged corticosteroid use for more than a hundred years. There are a number of tar-based preparations including crude coal tar, wood tar Expert Opin. Pharmacother. Downloaded from informahealthcare.com by University of Szeged on 01/03/11 2.8.3 Side effects (e.g., pine and juniper) and shale tar . Whilst effective, Adverse reactions with the calcineurin inhibitors include local the main limitations of tar are poor cosmetic acceptability reactions such as burning and stinging, which tend to dimin- and staining of clothes, skin and furniture. It is frequently ish with ongoing use. Clinical studies have not confirmed ini- used as part of an inpatient or daily dressing regimen. Its tial concerns over an association with malignancy use in conjunction with UVB - effect in pregnancy remains unknown. Traces of the calci- regimen - is well recognized . In an attempt to limit neurin inhibitor have been found in breast milk, and these mess, refined preparations are available and have proven products should not be used in mothers who are breast useful in the outpatient setting.
2.10.1 Pharmacology The mode of action of coal tar is not precisely known, Dithranol is an anthracycline that is well established in although it clearly has antiproliferative actions. This is proba- the treatment of psoriasis. Its use has declined as more bly through suppression of DNA synthesis, thereby reducing cosmetically acceptable treatments have become available.
the hyperproliferative state of keratinocytes.
Expert Opin. Pharmacother. (2010) 11(12) low concentration and alternate-day application may help Few controlled trials are reported in the literature. A random- alleviate such symptoms . Concomitant use of topical ized, double-blind, controlled study of 18 patients treated corticosteroid may also minimize symptoms. Retinoids may with 5% liquor carbonis detergens demonstrated a 48.7% reduce UV tolerance and concomitant UVB and tazarotene mean improvement compared with 35.3% of patients treated has proven more efficacious than UVB alone . Given with vehicle only . A randomized control trial of the established risk of fetal harm with systemic retinoids, 324 patients, comparing 1% coal tar lotion with 5% crude tazarotene is contraindicated in pregnancy.
coal tar, demonstrated a significantly greater improvementin mean PASI of 2.4 and 1.5, respectively .
2.12 KeratolyticsKeratolytics provide a useful adjunct to treatment where 2.10.3 Side effects hyperkeratosis is symptomatic or limits the efficacy of other Coal tar is often difficult to use, and adverse effects include topical treatments. Options for therapy include salicylic folliculitis, skin irritation, and contact dermatitis. Occupa- acid, urea, propylene glycol and glycolic acids.
tional coal tar exposure is a recognized carcinogen. However,there is no evidence to support an association with carcino- 2.12.1 Salicylic acid genesis in patients with psoriasis who have had treatment Salicyclic acid is a topical keratolytic used in the treatment of with preparations containing coal tar [64-66]. Treatment with a variety of papulosquamous lesions.
psoralen (P)UVA and coal tar is not recommended and has The action of salicylic acid in inducing keratolysis is been estimated to produce a 2.4-fold increased risk of skin unclear, although disruption of keratinocyte- keratinocyte cancer . Coal tar may be used during pregnancy .
binding in addition to reducing the pH within the stratumcorneum is thought to be important .
Salicylic acid preparations are often used in conjunction The development of topical preparations of retinoids in the with other treatments with the intention to increase absorp- late 1990s promised an additional option in the therapeutic tion and efficacy of the second drug. They should be avoided armamentarium for psoriasis. Tazarotene is available as a gel when an oral salicylate is being used and should not be used to or cream and at concentrations of 0.1 or 0.05%.
treat patients with > 20% BSA involvement when systemicabsorption is likely to be significant. Salicylic acid reduces 2.11.1 Pharmacology the efficacy of UVB therapy owing to its filtering effect. It A retinoid derivative, tazarotene binds the retinoic acid should not be applied immediately before treatment. Salicylic For personal use only.
receptor (RAR) in a class-specific manner, preferentially acid preparations are generally avoided during pregnancy, binding RAR-g and RAR-b over RAR-a . It does not although there is limited evidence for harm.
bind retinoid X receptor (RXR) . The regulation oftranscription induced by tazarotene binding the receptor results in reduced epidermal hyperproliferation, normalizing Urea reduces transepidermal water loss and induces keratino- keratinocyte differentiation and decreasing inflammation .
cyte differentiation in psoriasis . It may prove a usefuladjunct where xerosis and hyperkeratosis is particularly marked or problematic.
Two placebo-controlled trials comparing 0.1 and 0.05%tazarotene cream over a 12-week study have been performed.
2.13 Combination therapy A total of 1303 patients were recruited, of which 892 patients The use of multiple therapies is routine in dermatological completed the trial. Treatment success, as defined by at least a practice and may provide significant benefit in certain situa- Expert Opin. Pharmacother. Downloaded from informahealthcare.com by University of Szeged on 01/03/11 moderate global response or better and assessed by plaque tions. Consideration of patient burden both in terms of thickness, erythema and scale, was achieved in 49 - 59% of mess and time are important and can dramatically impact patients treated with 0.1% tazarotene, 42 - 48% of patients on compliance with treatment. This emphasizes the need for treated with 0.05% tazarotene and 30 - 37% treated with involvement of the patient in treatment decisions.
vehicle only .
A trial involving 348 patients, comparing tazarotene 0.1% 2.13.1 Vitamin D analog and corticosteroid gel, tazarotene 0.05% gel and fluocinonide 0.05% cream The combination of a vitamin D analog and a corticosteroid showed comparable efficacy in all three arms of the study has proven more effective than either agent alone and is rou- with significantly greater remission rates at 12 weeks tinely used in the treatment of psoriasis. It is available as an post-treatment amongst the tazarotene cohort .
ointment or scalp gel. Combined 50 µg/g calcipotriol andbetamethasone dipropionate 0.5 mg/g has been studied in 2.11.3 Side effects several trials [77-80]. A double-blind, randomized, vehicle- Tazarotene may cause skin irritation, including burning, controlled trial of 1603 patients treated with combination stinging and itch in up to 30% of users . The use of cream, therapy (as ointment), betamethasone alone, calcipotriene Expert Opin. Pharmacother. (2010) 11(12) Topical treatment of psoriasis Table 2. Suggested topical therapy for management of controlled trial involving 568 patients treated for 8 weeks with combination therapy, betamethasone, calcipotriene orvehicle achieved ‘absent' or ‘very mild' in 68.4, 61.0 and 43.3% of patients, respectively .
Potent corticosteroid Salicylic acid preparations Calcipotriol and betamethasone The wide range of options available to manage mild to Potent corticosteroid and moderate psoriasis presents a significant challenge to deliver- ing good-quality patient care. Our suggested options are Tar based shampoo summarized in Table 2.
As per mild plusCalcipotriol and betamethasonePotent corticosteroid 4. Expert opinion As per moderate plusSalicylic acid/tar based Topical therapy is used predominantly for individuals with mild disease and may also provide additional benefit for Potent corticosteroid partially controlled psoriasis managed with systemic agents.
Refined tar preparations It is important when using topical therapy to remember: Calcipotriol and betamethasoneDithranol . That the goal of treatment is to control or reduce the extent of psoriasis so that it no longer impacts on a Mild potency corticosteroid patient's quality of life.
Calcineurin inhibitor . That patient education is essential.
Moderate potency corticosteroid . That discussion of treatment options is important so plus antimicrobial preparations that patients know what to expect from treatment in Mild potency corticosteroid terms of overall results, time scale of improvement and Mild potency corticosteroid plusantimicrobial preparations the personal effort involved.
Mild potency corticosteroid plus . To consider the psychological wellbeing of the patient.
refined tar preparations . To allow enough time for a treatment to demonstrate Moderate potency corticosteroid For personal use only.
efficacy before considering an alternative.
. To prescribe appropriate quantities of treatment.
. To follow up verbal advice with information leaflets.
. To review patients regularly.
alone or vehicle alone demonstrated a 71.3, 57.2, 46.1 and22.7% reduction in PASI respectively at 4 weeks .
Other treatments available at present for the management Long-term safety of combination therapy with calcipotriol of psoriasis are: phototherapy for moderate disease; and sys- and betamethasone remains a significant concern. A double- temic agents including photochemotherapy, oral agents and blind, placebo-controlled, trial of 634 patients treated with biological agents for the management of severe psoriasis. It one of i) combination therapy (as ointment), ii) 4-weekly is appropriate to consider use of these therapeutic strategies under the following circumstances: iii) 4 weeks combination followed by 48 weeks calcipotriol Expert Opin. Pharmacother. Downloaded from informahealthcare.com by University of Szeged on 01/03/11 reported that after 52 weeks adverse drug reactions associated . > 20% BSA involvement with long-term topical corticosteroid therapy occurred in 4.8, . Psoriasis that is unresponsive to topical therapy 2.8 and 2.9%, respectively . This was not statistically sig- . Psoriasis that is unstable or frequently flaring nificant. Atrophy developed in 4 patients (1.9%) in the con- . Psoriasis associated with a high psychological burden tinuous combined therapy arm. The authors concluded that . Generalized pustular psoriasis combination therapy provides a safe, long-term option . Erythrodermic psoriasis.
More recently, the introduction of combined calicoptriene Declaration of interest 50 µg/g and betamethasone dipropionate 0.5 mg/g gel(combination therapy) has added another option to the HS Young has received sponsorship from Leo Pharma and management of scalp psoriasis. A randomized, double-blind, Expert Opin. Pharmacother. (2010) 11(12) Griffiths CE, Barker JN. Pathogenesis and on topical therapies. J Eur Acad the less they work? Clin Dermatol clinical features of psoriasis. Lancet Dermatol Venereol 2008;22:859-70 2006;24:229-30; discussion 30 Kirby B, Fortune DG, Bhushan M, et al.
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Oral Diseases (2005) 11, 374–378. doi:10.1111/j.1601-0825.2005.01133.x Ó 2005 Blackwell Munksgaard All rights reserved Norwegian LongoVitalÒ and recurrent aphthousulceration: a randomized, double-blind, placebo-controlledstudy I Kolseth1, BB Herlofson1, A Pedersen2 1Department of Oral Surgery and Oral Medicine, University of Oslo, Norway; 2The Oral Medicine Clinic, Jyllinge, Denmark