Literature review current through: Feb 2016. | This topic last updated: Mar 24, 2016.<\/p>\n
INTRODUCTIONPsoriasis is a common chronic skin disorder typically characterized by erythematous papules and plaques with a silver scale, although other presentations occur. Most cases are not severe enough to affect general health and are treated in the outpatient setting. Rare life-threatening presentations can occur that require intensive inpatient management. <\/p>\n
This topic reviews the treatment of psoriatic skin disease. The epidemiology, clinical manifestations, and diagnosis of psoriatic skin disease are discussed in detail separately, as are psoriatic arthritis and the management of psoriasis in pregnant women and special populations. (See \"Epidemiology, clinical manifestations, and diagnosis of psoriasis\" and \"Treatment of psoriatic arthritis\" and \"Pathogenesis of psoriatic arthritis\" and \"Clinical manifestations and diagnosis of psoriatic arthritis\" and \"Management of psoriasis in pregnancy\" and \"Treatment selection for moderate to severe plaque psoriasis in special populations\".) <\/p>\n
APPROACHPsoriasis is a chronic disease that can have a significant effect on quality of life. Therefore, management of psoriasis involves addressing both psychosocial and physical aspects of the disease. <\/p>\n
Numerous topical and systemic therapies are available for the treatment of the cutaneous manifestations of psoriasis. Treatment modalities are chosen on the basis of disease severity, relevant comorbidities, patient preference (including cost and convenience), efficacy, and evaluation of individual patient response [1]. Although medication safety plays an important role in treatment selection, this must be balanced by the risk of undertreatment of psoriasis, leading to inadequate clinical improvement and patient dissatisfaction [2,3]. <\/p>\n
Psychosocial aspectsPsoriasis can be a frustrating disease for the patient and the provider. The clinician needs to be empathetic and spend adequate time with the patient. It may be helpful for the clinician to touch the patient when appropriate to communicate physically that the skin disorder is neither repulsive nor contagious. <\/p>\n
Clinicians should lay out reasonable aims of treatment, making it clear to the patient that the primary goal of treatment is control of the disease. Although treatment can provide patients with high degrees of disease improvement, there is no cure for psoriasis. <\/p>\n
Educating the patient about psoriasis is important and referral to an organization such as the National Psoriasis Foundation (www.psoriasis.org) is often helpful. <\/p>\n
Psoriasis may affect patients' perceptions of themselves and this can potentially initiate or exacerbate psychological disorders such as depression [4,5]. Patients with limited skin disease may still have significant psychosocial disability [6]. Some patients with psoriasis may benefit from counseling and\/or treatment with psychoactive medications. <\/p>\n
Choice of therapyFor most patients, the initial decision point around therapy will be between topical and systemic therapy. However, even patients on systemic therapy will likely continue to need some topical agents. Topical therapy may provide symptomatic relief, minimize required doses of systemic medications, and may even be psychologically cathartic for some patients. <\/p>\n
For purposes of treatment planning, patients may be grouped into mild-to-moderate and moderate-to-severe disease categories. Limited, or mild-to-moderate, skin disease can often be managed with topical agents, while patients with moderate-to-severe disease may need phototherapy or systemic therapy. The location of the disease and the presence of psoriatic arthritis also affect the choice of therapy. Psoriasis of the hand, foot, or face can be debilitating functionally or socially and may deserve a more aggressive treatment approach. The treatment of psoriatic arthritis is discussed separately. (See \"Treatment of psoriatic arthritis\".) <\/p>\n
Moderate-to-severe psoriasis is typically defined as involvement of more than 5 to 10 percent of the body surface area (the entire palmar surface, including fingers, of one hand is approximately 1 percent of the body surface area [7]) or involvement of the face, palm or sole, or disease that is otherwise disabling. Patients with more than 5 to 10 percent body surface area affected are generally candidates for phototherapy or systemic therapy, since application of topical agents to a large area is not usually practical or acceptable for most patients. Attempts to treat extensive disease with topical agents are often met with failure, can add cost, and lead to frustration in the patient-clinician relationship. <\/p>\n
There is ample evidence of efficacy of the newer systemic therapies (\"biologics\"); however, cost is a major consideration with these agents. Established therapies such as methotrexate and phototherapy continue to play a role in the management of moderate to severe plaque psoriasis. (See 'Biologic agents' below.) <\/p>\n
The management of patients with extensive or recalcitrant disease is a challenge even for experienced dermatologists. However, the availability of biologic medications has reduced the challenge considerably. <\/p>\n
The concept that many patients with psoriasis in the United States do not receive sufficient treatment to control the disease is suggested by an analysis of surveys performed by the National Psoriasis Foundation between 2003 and 2011 [2]. Among the 5604 survey respondents with psoriasis, 52 percent expressed dissatisfaction with their treatment. Many patients received no treatment, including 37 to 49 percent of respondents with mild psoriasis, 24 to 36 percent of respondents with moderate psoriasis, and 9 to 30 percent of respondents with severe psoriasis. Further studies will be useful for clarifying the reasons for these observations and for determining the value of interventions to increase the accessibility of treatment. <\/p>\n
Widespread pustular disease requires aggressive treatment, which may include hospitalization. Therapeutic approaches to generalized pustular psoriasis and psoriatic arthritis are discussed separately. (See \"Pustular psoriasis: Management\" and \"Treatment of psoriatic arthritis\".) <\/p>\n
Mild-to-moderate diseaseLimited plaque psoriasis responds well to topical corticosteroids and emollients. Alternatives include vitamin D analogs, such as calcipotriene and calcitriol, tar, and topical retinoids (tazarotene). For facial or intertriginous areas, topical tacrolimus or pimecrolimus may be used as alternatives or as corticosteroid sparing agents, though improvement may not be as rapid. Localized phototherapy is another option for recalcitrant disease. <\/p>\n
Combinations of potent topical corticosteroids (table 1) and either calcipotriene, calcitriol, tazarotene, or UVB phototherapy are commonly prescribed by dermatologists. Calcipotriene in combination with Class I topical corticosteroids is highly effective for short-term control. Calcipotriene alone can then be used continuously and the combination with potent corticosteroids used intermittently (on weekends) for maintenance. A combination product containing calcipotriene and betamethasone dipropionate is available for this use. With proper adherence, considerable improvement with topical therapies may be seen in as little as one week, though several weeks may be required to demonstrate full benefits. <\/p>\n
Because adherence to topical treatment can be a major hurdle, keeping the treatment regimen simple and using treatment vehicles that the patient finds acceptable is often beneficial. <\/p>\n
Severe diseaseSevere psoriasis requires phototherapy or systemic therapies such as retinoids, methotrexate, cyclosporine, apremilast, or biologic immune modifying agents. Biologic agents used in the treatment of psoriasis include the anti-TNF agents adalimumab, etanercept, and infliximab, the anti-interleukin (IL)-12\/23 antibody ustekinumab, and the anti-IL-17 antibody secukinumab. Improvement usually occurs within weeks. Patients with severe psoriasis generally require care by a dermatologist. <\/p>\n
Intertriginous psoriasisIntertriginous (inverse) psoriasis should be treated with class VI and VII low potency corticosteroids (table 1) due to an increased risk of corticosteroid-induced cutaneous atrophy in the intertriginous areas. Topical calcipotriene or calcitriol and the topical calcineurin inhibitors tacrolimus or pimecrolimus are additional first-line treatments [8,9]. These agents may be used alone or in combination with topical corticosteroids as corticosteroid sparing agents for long term maintenance therapy. Calcipotriene, tacrolimus, and pimecrolimus are more expensive options than topical corticosteroids. Some concerns have been raised about the safety of the calcineurin inhibitors (see 'Calcineurin inhibitors' below and \"Epidemiology, clinical manifestations, and diagnosis of psoriasis\", section on 'Inverse psoriasis'). <\/p>\n
Scalp psoriasisThe presence of hair on the scalp can make topical treatment of psoriasis challenging because patients may find certain products messy or difficult to apply. Recognizing the patient's preference for a drug vehicle may help to improve adherence to therapy. For many patients, lotion, solution, gel, foam, or spray vehicles are preferable to thicker creams or ointments. <\/p>\n
Topical corticosteroids are the primary topical agents used for psoriasis on the scalp [10]. Support for the use of these agents is evident in a systematic review of randomized trials that found that very potent or potent topical corticosteroids are more effective treatments for scalp psoriasis than topical vitamin D analogs [11]. Combining a corticosteroid and vitamin D analog may offer additional benefit; in the systematic review, combination treatment with a potent topical corticosteroid and a vitamin D analog appeared slightly more effective than potent topical corticosteroid monotherapy. However, in clinical practice, complicating the treatment regimen with more than one topical product may reduce the likelihood of consistent adherence to the treatment regimen. Thus, we usually prescribe a topical corticosteroid alone as initial therapy. A commercially available betamethasone dipropionate-calcipotriene combination product is available, but is more expensive than most topical corticosteroid preparations. <\/p>\n
Other topical therapies used for psoriasis (eg, tazarotene, coal tar shampoo, anthralin) and intralesional corticosteroid injections also may be beneficial for scalp involvement, though data on efficacy specifically in scalp disease are limited [10]. Salicylic acid can be a helpful adjunctive treatment because of its keratolytic effect. Phototherapy (eg, excimer laser) and systemic agents are additional treatment options for patients who cannot achieve sufficient improvement with topical agents [10]. <\/p>\n
Guttate psoriasisThe management of guttate psoriasis is reviewed separately. (See \"Guttate psoriasis\", section on 'Treatment'.) <\/p>\n
Generalized pustular psoriasisThe management of generalized pustular psoriasis is reviewed separately. (See \"Pustular psoriasis: Management\".) <\/p>\n
Localized pustular psoriasisLocalized pustular psoriasis (palms and soles) is difficult to treat. Approaches include potent topical corticosteroids and topical bath psoralen plus UVA phototherapy (PUVA). (See \"Psoralen plus ultraviolet A (PUVA) photochemotherapy\".) <\/p>\n
Data are limited on the use of systemic retinoids for localized pustular psoriasis. However, these drugs appear to be particularly effective in the treatment of pustular psoriasis, and we consider them first line therapy. Acitretin is the retinoid that is used most often for this indication. Acitretin is a potent teratogen and should not be used in women who might become pregnant. Pregnancy is contraindicated for three years following acitretin therapy. (See 'Retinoids' below.) <\/p>\n
Nail psoriasisAlthough nail involvement alone is uncommon, many patients with psoriasis have disease that involves the nails. The management of nail psoriasis is reviewed in detail separately. (See \"Nail psoriasis\", section on 'Treatment'.) <\/p>\n
Erythrodermic psoriasisThere is no high quality evidence to support specific recommendations for the management of erythrodermic psoriasis. Based upon data from open-label or retrospective studies and case reports, a panel of experts suggested that patients with severe, unstable disease should be treated with cyclosporine or infliximab due to the rapid onset and high efficacy of these agents [12]. Patients with less acute disease can be treated with acitretin or methotrexate as first-line agents. The panel advised against the use of systemic glucocorticoids due to the perceived potential for these drugs to induce a flare of psoriasis upon withdrawal of therapy. (See 'Systemic therapies' below.) <\/p>\n
Data are limited on the efficacy of biologic agents other than infliximab for the treatment of erythrodermic psoriasis. Etanercept was effective in an open-label study of 10 patients [13], and case reports have documented successful treatment with adalimumab and ustekinumab [14,15]. <\/p>\n
In general, patients with erythrodermic psoriasis should be cared for by a dermatologist and may require hospitalization and\/or combinations of systemic treatments. Topical therapies, such as mid-potency topical corticosteroids, emollients, wet dressings, and oatmeal baths can be used in concordance with systemic treatment to manage symptoms [12]. Long-term maintenance therapy for psoriasis is required. <\/p>\n
ChildrenThe immediate and long-term adverse effects of therapies for psoriasis are of particular concern in the pediatric population. Many agents used in the treatment of adult psoriasis have also been used for children [16]. However, high quality studies on the efficacy and safety of therapies for psoriasis in children are limited. Guidelines for the treatment of children based upon the available evidence have been published [17]. <\/p>\n
Special populationsThe treatment of psoriasis in pregnant women and patients with hepatitis B, hepatitis C, human immunodeficiency virus infection, latent tuberculosis, or malignancy is reviewed separately. (See \"Treatment selection for moderate to severe plaque psoriasis in special populations\" and \"Management of psoriasis in pregnancy\".) <\/p>\n
ReferralReferral to a dermatologist should be considered in the following settings: <\/p>\n
Confirmation of the diagnosis is needed. <\/p>\n
The response to treatment is inadequate as measured by the clinician, patient, or both. <\/p>\n
There is significant impact on quality of life. <\/p>\n
The primary care clinician is not familiar with the treatment modality recommended such as PUVA, phototherapy, or immunosuppressive medications. <\/p>\n
The patient has widespread severe disease. <\/p>\n
In cases of psoriatic arthritis, referral and\/or collaboration with a rheumatologist is indicated. (See \"Treatment of psoriatic arthritis\".) <\/p>\n
TOPICAL THERAPIESPatient adherence may be the largest barrier to treatment success with topical therapies; early patient follow-up (within a week of initiating treatment) may improve adherence. Published guidelines for the treatment of psoriasis with topical therapies are available [18]. <\/p>\n
EmollientsHydration and emollients are valuable and inexpensive adjuncts to psoriasis treatment. Keeping psoriatic skin soft and moist minimizes the symptoms of itching and tenderness. Additionally, maintaining proper skin hydration can help prevent irritation and thus the potential for subsequent Koebnerization (development of new psoriatic lesions at sites of trauma). <\/p>\n
The most effective are ointments such as petroleum jelly or thick creams, especially when applied immediately after a hydrating bath or shower. <\/p>\n
CorticosteroidsTopical corticosteroids remain the mainstay of topical psoriasis treatment despite the development of newer agents [19]. The mechanism of action of corticosteroids in psoriasis is not fully understood. Corticosteroids exert antiinflammatory, antiproliferative, and immunosuppressive actions by affecting gene transcription. <\/p>\n
The inherent potency of a topical corticosteroid is frequently reported using a I to VII scale based on vasoconstrictive assays (table 1). Although ointments are sometimes thought to be inherently more effective because of their occlusive properties, this is not uniformly correct. In practice, the efficacy\/potency of a topical corticosteroid is dependent on many factors including skin type, plaque thickness, and, perhaps most importantly, compliance. <\/p>\n
To minimize adverse effects and maximize compliance, the site of application needs to be considered in choosing the appropriately potent corticosteroid: <\/p>\n
On the scalp or in the external ear canal, potent corticosteroids in a solution or foam vehicle (eg, fluocinonide 0.05% or clobetasol propionate 0.05%) are frequently indicated. Clobetasol 0.05% shampoo or spray can also be used for scalp involvement. <\/p>\n
On the face and intertriginous areas, a low potency cream (eg, hydrocortisone 1%) is often sufficient. <\/p>\n
For thick plaques on extensor surfaces, potent preparations (eg, betamethasone 0.05% or clobetasol propionate 0.05%) are often required. <\/p>\n
The typical regimen consists of twice daily application of topical corticosteroids. Most patients will show a rapid decrease in inflammation with such therapy, but complete normalization of skin or lasting remission is unpredictable. <\/p>\n
Topical corticosteroids generally can be continued as long as the patient has thick active lesions. Skin atrophy from topical corticosteroids usually is not a problem unless the medication is continuously applied after the skin has returned to normal thickness. Once clinical improvement occurs, the frequency of application should be reduced [18]. For patients in whom lesions recur quickly, topical corticosteroids can be applied intermittently (such as on weekends only) to maintain improvement. The addition of non-corticosteroid topical treatments can also facilitate the avoidance of long-term daily topical corticosteroids. (See 'Mild-to-moderate disease' above.) <\/p>\n
The risks of cutaneous and systemic side effects associated with chronic topical corticosteroid use are increased with high potency formulations. Data support limiting the continuous application of Class I topical corticosteroids to two to four weeks; thus, close clinician supervision should be employed if longer treatment durations are required (table 1) [18]. Data are less clear regarding treatment durations for less potent topical corticosteroids. Side effects of topical corticosteroids, including the potential for suppression of the hypothalamic axis, are discussed separately. (See \"Pharmacologic use of glucocorticoids\" and \"General principles of dermatologic therapy and topical corticosteroid use\".) <\/p>\n
The cost of topical corticosteroids varies widely. The price of a 60 gram tube of a potent corticosteroid brand name product can be hundreds of dollars. There are generic preparations in each potency class that have reduced the cost somewhat, though generic prices in the United States are rising [20]. Examples of available generics include, in order of increasing potency, hydrocortisone 1%, triamcinolone 0.1%, fluocinonide 0.05%, betamethasone dipropionate 0.05%, and clobetasol 0.05%. <\/p>\n
Different formulations have been developed in an effort to enhance the delivery of topical corticosteroids. Betamethasone valerate in a foam had superior efficacy for scalp psoriasis and was preferred by patients when compared with betamethasone valerate lotion [21]. The foam becomes a liquid on contact with skin and is also well tolerated by patients with trunk and extremity psoriasis [22]. A clobetasol propionate spray is also available; like foams, sprays are easy to apply to large areas [23]. The main advantage of these newer preparations is likely greater patient acceptance, which may translate into greater adherence; the main disadvantage is cost. <\/p>\n
Topical vitamin D analogsTopical vitamin D analogs for the treatment of psoriasis include calcipotriene (calcipotriol), calcitriol, and tacalcitol. Although topical vitamin D analogs are effective as monotherapy for some patients, a systematic review found that combination therapy with a topical corticosteroid is more effective than either treatment alone [24]. <\/p>\n
Until 2009, calcipotriene was the only topical vitamin D analog available in the United States. Calcipotriene is obtainable as a cream, solution, ointment, or foam, or as a combination ointment, suspension, or foam with betamethasone dipropionate. Topical calcitriol ointment has been prescribed in Europe for years, and is now available in the United States. When compared with calcipotriene, calcitriol appears to induce less irritation in sensitive areas of the skin (eg, skin folds) [25]. <\/p>\n
CalcipotrieneCalcipotriene (calcipotriol) is an established therapy in psoriasis. The precise mechanism is not clear, but a major effect is the hypoproliferative effect on keratinocytes [26]. An immune modulating effect has been postulated for calcipotriene, but has not been shown to be significant in psoriasis to date [27]. <\/p>\n
In a systematic review of randomized controlled trials, calcipotriene was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5% [28]. Only potent topical corticosteroids appeared to have comparable efficacy at eight weeks. Skin irritation is the main adverse event associated with calcipotriene. <\/p>\n
Combined use of calcipotriene and superpotent corticosteroids has demonstrated increased clinical response and tolerance in clinical trials compared with either agent used alone [29-31]. One regimen employed daily use of both calcipotriene ointment and halobetasol ointment for two weeks, followed by weekend use of the halobetasol ointment and weekday use of calcipotriene [29]. This regimen produced six-month remission maintenance in 76 percent compared with 40 percent with weekend halobetasol alone. A similar regimen with calcipotriene ointment and clobetasol propionate foam also appears to be effective [32]. <\/p>\n
In addition, a randomized trial found that a preparation that combines calcipotriene with betamethasone dipropionate (0.064%) was effective with once daily usage, and more effective than once daily therapy with either betamethasone or calcipotriene [33]; this combination preparation typically costs more than $400 for a 60 g tube. Patients who use topical corticosteroids in combination with calcipotriene must be monitored for adverse effects as with corticosteroid monotherapy. (See 'Corticosteroids' above.) <\/p>\n
Thus, topical calcipotriene may be used as an alternative or adjunct to topical corticosteroid therapy. It is applied twice daily when used as monotherapy. No controlled trials guide how best to use topical corticosteroids in conjunction with calcipotriene. Once daily use of each may be adequate. Acidic products can inactivate topical calcipotriene, and some topical corticosteroids may be acidic. A reasonable approach to combination therapy is to have patients apply topical calcipotriene and topical corticosteroids each once daily at different times of day. <\/p>\n
Other than skin irritation, side effects of topical calcipotriene are usually minimal; the risk of hypercalcemia is low when the drug is used appropriately [34]. However, topical calcipotriene is more expensive than many generic potent corticosteroids. <\/p>\n
CalcitriolThe mechanism of action of calcitriol is thought to be similar to that of calcipotriene and involves the drug's ability to inhibit keratinocyte proliferation and stimulate keratinocyte differentiation [35]. In addition, calcitriol inhibits T-cell proliferation and other inflammatory mediators [35]. In two randomized trials with a total of 839 patients with mild to moderate plaque psoriasis, calcitriol 3 mcg\/g ointment was more effective than vehicle [36]. At the end of the study periods (up to eight weeks), 39.6 and 32.7 percent of the calcitriol groups versus 21.2 and 12 percent of the vehicle groups exhibited at least marked global improvement. <\/p>\n
In a systematic review, calcipotriene and calcitriol were equally effective [24]. However, on sensitive areas of the skin, calcitriol appears to be less irritating than calcipotriene. An intraindividual randomized trial of 75 patients compared treatment with calcitriol 3 mcg\/g ointment to calcipotriene 50 mcg\/g ointment for mild to moderate psoriasis on facial, hairline, retroauricular, and flexural areas [25]. Perilesional erythema, perilesional edema, and stinging or burning sensations were significantly lower in the areas treated with calcitriol. A 52-week open-label study of the safety of calcitriol ointment did not reveal an adverse effect on calcium homeostasis [37]. <\/p>\n
Similar to calcipotriene, calcitriol ointment is more expensive than many generic potent topical corticosteroids. The drug is applied twice daily. <\/p>\n
TarThe use of tar is a time-honored modality for treating psoriasis, although newer (and less messy) treatment options have reduced its popularity. The precise mechanism of action of tar is not known; it has an apparent antiproliferative effect. <\/p>\n
Tar can be helpful as an adjunct to topical corticosteroids. There are no commercially available corticosteroid\/tar combinations. Tar products are available without a prescription in the form of shampoos, creams, lotions, ointments, and oils. Newer products include a solution and a foam. Some patients may prefer the less messy formulations. <\/p>\n
Tar can also be compounded into creams and ointments. A commonly used compound is 2% or 3% crude coal tar in triamcinolone cream 0.1% applied twice daily to individual plaques. An alternative is 4 to 10% LCD (liquor carbonis detergens, a tar distillate) in triamcinolone cream or ointment, used similarly. A preparation of 1% tar in a fatty-acid based lotion may be superior to conventional 5% tar products [38] and appears to have efficacy similar to that of calcipotriene [39]. <\/p>\n
Topical tar preparations, including shampoos, creams, and other preparations, can be used once daily. Patients should be warned that tar products have the potential to stain hair, skin, and clothing. It may help to use them at night and wear inexpensive night clothes (eg, old pajamas) as they tend to be messy. Patients may also find the odor of tar products unpleasant. <\/p>\n
For shampoos, the emphasis should be on making sure the product reaches the scalp. Tar shampoo should be left in place for 5 to 10 minutes before rinsing it out. <\/p>\n
TazaroteneTazarotene is a topical retinoid that was safe and effective in two randomized, vehicle-controlled trials that included 1303 patients with psoriasis [40]. The 0.1% cream was somewhat more effective than 0.05% cream, but with a slightly higher rate of local side effects. Another study found that once daily administration of tazarotene gel, 0.05% or 0.1%, compared favorably with the twice daily administration of topical fluocinonide 0.05% [41]. Absorption of tazarotene was minimal over the 12-week course of the study, suggesting that systemic toxicity is unlikely during long-term therapy. A small uncontrolled study of short contact tazarotene found that a 20 minute application followed by washing appeared to be less irritating than traditional use, and seemed to have similar efficacy [42]. Irritation limits use of tazarotene by itself; the irritation is reduced by concomitant treatment with a topical corticosteroid [43]. <\/p>\n
Calcineurin inhibitorsTopical tacrolimus 0.1% and pimecrolimus 1% are effective in the treatment of psoriasis [44-47]. Facial and intertriginous areas may be well suited to these treatments, which can allow patients to avoid chronic topical corticosteroid use: <\/p>\n
An eight-week randomized trial in 167 patients ages 16 and older found that twice daily treatment to intertriginous and facial lesions with tacrolimus 0.1% ointment resulted in more patients achieving clearance of lesions or excellent improvement compared with placebo (65 versus 32 percent) [48]. <\/p>\n
An eight-week randomized trial in 57 adults with moderate to severe inverse psoriasis found that twice daily treatment with pimecrolimus 1% cream resulted in more patients clearing or almost clearing lesions compared with placebo (71 versus 21 percent) [49]. <\/p>\n
Topical tacrolimus and pimecrolimus are generally well tolerated when used to treat facial and intertriginous psoriasis [48,49]. However, corticosteroid therapy may be more effective, at least compared with pimecrolimus. This was suggested in a four-week randomized trial in 80 patients with intertriginous psoriasis that compared various therapies applied once daily [50]. Betamethasone valerate 0.1% was more effective than pimecrolimus 1%. <\/p>\n
In 2005, the US Food and Drug Administration (FDA) issued an alert about a possible link between topical tacrolimus and pimecrolimus and cases of lymphoma and skin cancer in children and adults [51], and in 2006 placed a \"black box\" warning on the prescribing information for these medications [52]. No definite causal relationship has been established; however, the FDA recommended that these agents only be used as second line agents for atopic dermatitis. Subsequent studies have not, however, found evidence of an increased risk of lymphoma [53,54]. (See \"Treatment of atopic dermatitis (eczema)\", section on 'Topical calcineurin inhibitors'.) <\/p>\n
AnthralinTopical anthralin (also known as dithranol) is an effective treatment for psoriasis that has been utilized since the early 20th century [55-57]. The mechanism of action of anthralin in psoriasis is not well understood, but may involve antiinflammatory effects and normalization of keratinocyte differentiation [18]. <\/p>\n
Skin irritation is an expected side effect of anthralin that can limit the use of this therapy. This side effect and the ability of anthralin to cause permanent red-brown stains on clothing and temporary staining of skin have contributed to a decline in the use of anthralin therapy. <\/p>\n
In order to minimize irritation, anthralin treatment is usually prescribed as a short-contact regimen that is titrated according to patient tolerance. For example, treatment may begin with concentrations as low as 0.1% or 0.25% applied for 10 to 20 minutes per day, with weekly step-wise increases in duration to reach a total contact time up to one hour [58]. Then, weekly, serial increases in the concentration of anthralin can be performed (eg, 0.5, 1, and 2%) based upon patient tolerance and lesion response. <\/p>\n
In the United States, anthralin is commercially marketed only as a 1% or 1.2% cream or a 1% shampoo. Thus, in the outpatient setting in the United States, the initial treatment regimen often consists of 1% or 1.2% anthralin applied for 5 to 10 minutes per day. Subsequently, the application time is titrated up to 20 to 30 minutes as tolerated. <\/p>\n
Application to surrounding unaffected skin should be avoided to minimize irritation. For patients with well-defined plaques, petrolatum or zinc oxide may be applied to the surrounding skin as a protectant prior to application. After the desired contact period has elapsed, anthralin should be washed off the treated area [18]. <\/p>\n
Benefit from anthralin therapy is often evident within the first few weeks of therapy. When administered by patients in the outpatient setting, anthralin is less effective than topical vitamin D or potent topical corticosteroid therapy [24,59,60]. <\/p>\n
ULTRAVIOLET LIGHTUltraviolet (UV) irradiation has long been recognized as beneficial for the control of psoriatic skin lesions. As an example, patients often notice improvement in skin lesions during the summer months. UV radiation may act via antiproliferative effects (slowing keratinization) and anti-inflammatory effects (inducing apoptosis of pathogenic T-cells in psoriatic plaques). In choosing UV therapy, consideration must be given to the potential for UV radiation to accelerate photodamage and increase the risk of cutaneous malignancy. <\/p>\n
Phototherapy and photochemotherapy require the supervision of a dermatologist trained in these treatment modalities. The American Academy of Dermatology has provided guidelines for the treatment of psoriasis with ultraviolet light [61]. Despite high efficacy and safety, the use of office-based phototherapy has declined in the United States because of administrative issues and the development of new systemic medications [62]. <\/p>\n
ModalitiesTherapeutic doses of ultraviolet light can be administered in several ways: <\/p>\n
Ultraviolet B (UVB) radiation (290 to 320 nm) is used in patients with extensive disease, alone or in combination with topical tar. The mechanism of action of UVB is likely through its immunomodulatory effects [63]. Patients receive near-erythema-inducing doses of UVB at least three times weekly until remission is achieved, after which a maintenance regimen is usually recommended to prolong the remission. <\/p>\n
Narrow band UVB (311 nm) is an alternative to standard (broadband- 290 to 320 nm) UVB in the treatment of psoriasis. Suberythemogenic doses of narrow band UVB are more effective than broadband UVB in clearing plaque psoriasis [64]. Apoptosis of T cells is also more common with 311 nm than with broadband UVB. <\/p>\n
Photochemotherapy (PUVA) involves treatment with either oral or bath psoralen followed by ultraviolet A (UVA) radiation (320 to 400 nm) under strict medical supervision. UVA penetrates deeper into the dermis than UVB and does not have the latter's potential for burning the skin. A number of possible mechanisms have been postulated to explain PUVA's effects [65]. With oral PUVA, patients ingest the photosensitizing drug, 8-methoxypsoralen, followed within two hours by exposure to UVA; this sequence is performed three times weekly in increasing doses until remission, then twice or once weekly as a maintenance dose. With bath PUVA, the psoralen capsules are dissolved in water, and affected skin (hands, feet, or total body) is soaked for 15 to 30 minutes prior to UVA exposure. There are few data on the comparative efficacy of oral and bath PUVA for psoriasis. A small open randomized trial of 74 patients with moderate to severe psoriasis did not find a significant difference in efficacy between the two treatments [66]. Additional studies are necessary to confirm this finding. <\/p>\n
Some patients take psoralen prior to coming into the office or clinic for PUVA. Increased photosensitivity is typically present starting one hour after an oral dose and resolves after eight hours. Pre and post treatment photoprotection (eg, hat, sunscreen, sun protective goggles) are critical in preventing serious burn injury to the skin and eyes from being outside. (See \"Psoralen plus ultraviolet A (PUVA) photochemotherapy\".) <\/p>\n
Pretreatment emollients have long been thought to improve results with UVB. However, while thin oils do not impede UV penetration, emollient creams can actually inhibit the penetration of the UV and should not be applied before treatment [67]. Gentle removal of plaques by bathing does help prior to UV exposure. <\/p>\n
Uncertainty remains about the comparative efficacy of UVB phototherapy and PUVA photochemotherapy for plaque psoriasis. Randomized trials comparing the efficacy of narrowband UVB to PUVA have yielded inconsistent findings [68]. The convenience of not needing to administer a psoralen prior to treatment is a favorable feature of UVB phototherapy. <\/p>\n
Home phototherapyAn alternative to office-based phototherapy is the use of a home ultraviolet B (UVB) phototherapy unit prescribed by the treating clinician [69]. This option may be preferred by patients who are not in close proximity to an office-based phototherapy center, whose schedules do not permit frequent office visits, or for whom the costs of in-office treatment exceed those of a home phototherapy unit. Home units cost about $3000, but may prove cost-effective in the long term, particularly when compared with biologic therapies. Insurance coverage of these units varies. <\/p>\n
For some dermatologists, uncertainty regarding the safety of home units has led to a reluctance to prescribe them. Some have expressed concern for the potential for improper or excessive usage of these devices [70]. In contrast, a randomized trial of 196 subjects found that narrowband UVB administered via home units was as safe and effective as office-based treatments [70]. Home phototherapy units that are equipped with electronic controls that allow only a prescribed number of treatments are available and may help to mitigate clinician concerns. <\/p>\n
Commercial tanning beds can improve psoriasis and are occasionally used for patients without access to medical phototherapy [71,72]. However, data are limited on this mode of treatment, and clinicians and patients should be cognizant that there is significant variability in the UV output of tanning beds [73]. <\/p>\n
Excimer laserAnother development in ultraviolet therapy for psoriasis involves use of a high energy 308 nm excimer laser. The laser allows treatment of only involved skin; thus, considerably higher doses of UVB can be administered to psoriatic plaques at a given treatment compared with traditional phototherapy. Uncontrolled trials suggest that laser therapy results in faster responses than conventional phototherapy [74,75]. As an example, one study of excimer laser therapy involved 124 patients with stable mild to moderate plaque psoriasis, of whom 80 completed the entire protocol [74]. Treatments were scheduled twice weekly. After 10 or fewer treatments, 84 and 50 percent of patients achieved the outcomes of 75 percent or better and 90 percent or better clearing of plaques, respectively. This number of treatments was far fewer than that typically required of phototherapy (25 or more). Side effects of laser therapy included erythema and blistering; these were generally well tolerated, and no patient discontinued therapy because of adverse effects. <\/p>\n
A common sequela of excimer laser therapy is the induction of UV-induced hyperpigmentation (tanning) in treated areas, which can be cosmetically distressing for some patients. Hyperpigmentation resolves after the discontinuation of treatment. <\/p>\n
Like 311 nm UVB, the excimer laser represents a therapeutic advance toward specific wavelength therapies for psoriasis. While both the excimer laser and narrow band UVB are approved for use in psoriasis, inconsistencies in third party coverage for these treatments limit their utilization. <\/p>\n
Cancer riskA concern with PUVA is an increased risk of nonmelanoma skin cancer and melanoma. Ongoing monitoring is indicated in patients who have received prolonged courses of PUVA. In general, phototherapy is contraindicated in patients with a history of melanoma or extensive nonmelanoma skin cancer. (See \"Psoralen plus ultraviolet A (PUVA) photochemotherapy\", section on 'Skin cancer'.) <\/p>\n
Folate deficiencyFolate deficiency has been associated with health disorders such as neural tube defects in fetuses of affected pregnant women, anemia, and hyperhomocysteinemia (a risk factor for cardiovascular disease). In an in vitro study, exposure of plasma to UVA led to a 30 to 50 percent decrease in the serum folate level within 60 minutes [76]. However, folate deficiency secondary to UVA exposure has not been proven to occur in vivo. In a small randomized trial of healthy subjects, no difference in serum folate levels was identified between subjects irradiated with UVA for six sessions and untreated subjects [77]. In addition, an observational study of 35 psoriasis patients found that narrow band UVB had no effect on serum folate levels after 18 treatment sessions [78]. <\/p>\n
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More: Literature review current through: Feb 2016. Continue reading
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