Topical Therapy for Psoriasis

Introduction

Treatment of psoriasis with topical medication is the first line of therapy for almost all psoriasis patients. Although psoriasis is a disease of systemic immune activity, the clinical manifestations are local to the skin. As the plaques are visible and accessible for application of topical medications, it makes intuitive sense to deliver treatment directly. However, while there are clear advantages to the delivery of medication directly to the psoriatic plaques, there are local, systemic and patient adherence effects that should be considered when using topical treatments. Nonetheless, topical therapy is used in almost all psoriasis patients with active disease and needs to be understood by any physician who actively treats psoriasis.

Prior to an examination of the specific topical treatments of psoriasis, it is important to understand the specific goals associated with this type of therapy (Table 9-1). While the goal of therapy may always seem clearance of active disease, the benefits of topical treatments can be more subtle but equally important. Improvement or clearance of active lesions is usually applicable only to patients with limited disease and relatively few plaques, usually covering <5% of the BSA. Areas greater than that are quite difficult for patients and result in a significant loss of adherence to therapy and drug efficacy.

However, the potential benefits of topicals go beyond being the primary treatment modality of psoriasis. Topicals can provide comfort from signs and symptoms of psoriasis, including scaling, itching, and pain, even if lesions do not fully resolve. These medications can also be used as adjuvants to phototherapy or systemic therapy to give patients more rapid relief. The key rule to remember when using topical therapies is that the greatest success is achieved when topicals are used over limited BSA for relatively short intervals.

There are two general classes of topical treatments (Table 9-2). The first is the large class of medications meant to provide local relief of symptoms or scaling by physically altering the local environment. This class would include the large numbers of emollients or keratolytic agents that can diminish scale or improve barrier function of the skin. The second class is those topical agents that act intracellularly to decrease the inflammatory response or cellular proliferation. Among these agents are tar products, topical corticosteroids, vitamin A and D agents, the aryl hydrocarbon receptor modulator tapinarof and the phosphodiesterase-4 (PDE4) inhibitor roflumilast. It is critical to remember that most of these agents can be used by themselves but that many used in some combination to achieve greater efficacy

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Emollients and Keratolytics

Emollients

Emollients and moisturizers are commonly used to improve symptoms and signs of psoriasis. While these agents are frequently used, data on the effect of these treatments are relatively sparse. The most commonly described evidence for the efficacy of emollients is from placebo-controlled trials of topical agents. These trials will include a control group of a vehicle that acts primarily as an emollient. In these studies, there is indeed an improvement in association with use of the control vehicle. However, this effect is generally relatively small. Controlled clinical trials of emollients with obvious problems of blinding of these trials have been mixed, with alternative demonstration of effect and of no benefit. Emollients are generally considered to be safe and are used in nearly all circumstances in psoriasis. However, specific consideration must be made to some potential adverse situations. The most important consideration is the presence of ingredients in emollients, including preservatives and fragrance, that can induce allergic contact dermatitis reactions. These, through the Koebner phenomena described above, can induce a paradoxical worsening of psoriasis with the use of emollients.

Keratolytics

Keratolytic agents, including those most commonly used such as salicylic acid, urea and lactic acid, are used extensively to help remove scale in psoriasis. There are some who argue that these agents can effectively increase the penetration of coadministered topical agents as well. However, the data on these agents remain extremely limited. Salicylic acid has been used in combination with both topical corticosteroids and topical tacrolimus. In both cases, the addition of the keratolytic added to the efficacy of the primary agent. Additionally, open-label studies have suggested that there is benefit of salicylic acid and lactic acid in scalp psoriasis. While there is little downside to the use of keratolytic agents, some caution should be exercised. Extensive use can lead to systemic absorption at measurable levels, thus some caution should be used when applied to large areas. Also, as with all topical treatments, in children where the surface area to volume ratio is increased, there is a greater chance for increased blood levels of medication.

Physiologic Agents

Topical Corticosteroids

By far the most frequently prescribed medications for psoriasis are topical corticosteroids. These are a variety of topical corticosteroids that can be differentiated by their vehicle and potency. Corticosteroids all work primarily by diminishing multiple levels of the inflammatory process along with other potential effects in the psoriasis pathway. Because it is impossible to understand all the subtle differences between the various preparations, it is important to be aware of the general principles that govern proper usage of corticosteroids.

The most important distinguishing factor of topical corticosteroids is their potency. Typically, this is measured by a rabbit ear assay measuring vascular blanching. Corticosteroids are typically classified from 1 (most potent) to 7 (least potent). The potency class corresponds loosely to both efficacy and side effects. Because a higher classified corticosteroid will generally be more effective, the choice of corticosteroid for a patient will depend on the body surface area (BSA) and specific areas involved.

The most commonly considered side effect of topical corticosteroids is cutaneous atrophy. Corticosteroids thin both the epidermis and dermis, effects that may be permanent. Therefore, appropriate selection of topical corticosteroid is determined by the anatomic site to be treated. Palms and soles, for example, have extremely thick skin, making use of class 1 corticosteroids reasonable. Groin, axillary, and facial skin are much thinner and susceptible to atrophy, thus only the mildest potency can be used in these areas. Of great concern with application to the face are potential ocular side effects associated with topical corticosteroids. These include increased incidence of cataracts and increased intraocular pressure. These concerns make it even of greater importance to avoid the more potent topical corticosteroids on the face.

The area to be treated can also impact the choice of the class of topical corticosteroid. The amount of BSA treated can correlate to blood levels of these medications. Thus when large areas are to be treated, the potency of topical corticosteroids can lead to effects associated with systemic corticosteroids, including adrenal insufficiency. It is likely that class 1 and 2 corticosteroids should not be applied to greater than 10% to 20% of the BSA for more than a few weeks.

Any discussion of the area to be treated requires consideration of the means of delivery of the medication. Topical corticosteroids come in a wide variety of delivery systems that play a major role in clinical efficacy, not because of the strength of the preparation but because of the adherence of the patient to the treatment. Patients frequently avoid application of ointment-based medications as they can feel greasy and stain clothes. On the opposite extreme, the use of alcohol-based gels or foams on areas that are highly inflamed or cracked can lead to stinging and burning and prevent appropriate dosing. This issue of patient adherence to medications is considered by some to be the most important issue in the efficacy of topicals and needs to be considered for every patient.

Considering a few basic points in using topicals for all patients can lead to greater success:

• Fewer applications are better than greater frequency of application. A patient may need 10 to 20 minutes to apply medications, even with limited disease. It is less likely that a patient will want to do this multiple times per day.
• Fewer medications are better than many medications. A single topical may not be appropriate for the extent of disease of a patient. However, finding the perfect agent for each body area will frequently lead to a medicine cabinet filled with bottles and tubes and a highly confused patient who will use the medications inappropriately or not at all.
• Most importantly, consider the cosmetic implications of the medicine. Applying a greasy, thick ointment to the scalp that cannot be easily removed with washing will be cosmetically unacceptable and thus the patient will not use the medication. Topical medication not applied will never be helpful.

While these rules are important for topical medications, they are critical for topical corticosteroids due to the wide variety of strengths and vehicles that are available for these medications.

Tapinarof

The limitations of corticosteroid therapy and the important role of topical agents in psoriasis treatment have prompted a search for novel topical treatments. Tapinarof a, first-in-class topical aryl hydrocarbon receptor (AhR)-modulating molecule that downregulates multiple interleukins and promotes skin barrier normalization, received FDA approval in May 2022.

Tapinarof Mechanism of Action

As a ligand-dependent transcription factor, AhR plays an important role in maintaining skin homeostasis; dysregulation of AhR expression has been demonstrated in patients with psoriasis. Higher serum levels of AhR were observed in patients with psoriasis compared to healthy individuals, while in vitro treatment of skin cells with AhR ligands increased the expression of genes involved in psoriatic pathogenesis. Although not fully understood, the therapeutic effect of tapinarof is thought to result from several mechanisms, primarily the suppression of IL-17 and IL-22 expression, which happens downstream of AhR activation, itself effected by the binding of tapinarof to the receptor. Another potential mechanisms of therapeutic efficacy is increased expression of filaggrin and loricrin (induced by tapinarof binding to AhR and demonstrated in vitro and ex vivo), skin barrier proteins associated with keratinocyte differentiation that are downregulated in psoriasis. Finally, tapinarof has been shown to increase antioxidant activity via both direct scavenging of reactive oxygen species (ROS) and through the Nrf2 transcription factor pathway, which leads to expression of antioxidant enzymes. The proposed mechanism of action of tapinarof are shown in Figure 9-1.

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Tapinarof Efficacy

The efficacy of tapinarof was assessed in two identical, randomized, double-blind, vehicle-controlled phase 3 trials – PSOARING 1 and 2. The PSOARING trials enrolled adults between the ages of 18 and 75 with a baseline PGA score of 2 to 4 and a total affected BSA of 3 to 20%. A total of 692 (PSOARING 1) and 674 (PSOARING 2) patients were randomized (2:1) to either tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary efficacy endpoint was PGA response, defined as a PGA score of 0 or 1 and a decrease of at least 2 points at week 12. The secondary efficacy end points included the percentage of patients with a ≥75% and ≥90% in the PASI score, mean change in the percent of total affected BSA, and the percentage of patients with a PGA score of 0 to 1 at week 12.

In PSOARING 1, 35.4% of the patients in the tapinarof group achieved the primary endpoint at week 12, compared to 6.0% in the vehicle group (P<0.001; Figure 9-2). The primary endpoint results were similar in PSOARING 2, with 40.2% of tapinarof-treated patients and 6.3% of patients who received vehicle cream achieving a PGA response (P<0.001; Figure 9--2). Tapinarof also demonstrated superiority in several secondary endpoints. A PASI 75 response was achieved by 36.1% of patients in the tapinarof group and 10.2% of patients in the control group (P<0.001) in PSOARING 1; in PSOARING 2, 47.6% and 6.9% of patients in tapinarof and vehicle group, respectively, achieved a PASI 75 response (P<0.001). The proportion of patients achieving a PASI 90 response was 18.8% in the tapinarof group and 1.6% in the vehicle group in PSOARING 1 (P<0.001), and 20.9% and 2.5% (tapinarof and vehicle, respectively) in PSOARING 2 (P<0.001). A PGA score of 0 or 1 was achieved by 37.8% of tapinarof-treated and 9.9% of vehicle-receiving patients in PSOARING 1 (P<0.001), with similar results in PSOARING 2 - 43.6% and 8.1% for tapinarof and vehicle, respectively (P<0.001). Finally, the mean change from baseline in the percent of total affected BSA was also significantly greater with tapinarof in both trials: -3.5% and -0.2% in PSOARING 1 (tapinarof vs vehicle, respectively; P<0.001) and -4.2% and 0.1% in PSOARING 2 (P<0.001).

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Tapinarof Safety

Safety assessments in PSOARING 1 and 2 included evaluation of application site events, laboratory assessments, vital signs, electrocardiograms, physical examinations, and monitoring of adverse event (AE) incidence and frequency. No relevant differences between the tapinarof and vehicle groups were reported in non-adverse event safety parameters. Adverse events were more common in the tapinarof-treated group in both trials: 50.3% (tapinarof) vs 22.4% (vehicle) in PSOARING 1, and 54.5% (tapinarof) vs 26.2% (vehicle) in PSOARING 2. Notable tapinarof-related adverse events included folliculitis (23.5% vs 1.2% with tapinarof and vehicle, respectively, in PSOARING 1; and 17.8% vs 0.6% in PSOARING 2), contact dermatitis (5.0% vs 0.6% with tapinarof and vehicle, respectively, in PSOARING 1; and 5.8% vs no patients in PSOARING 2), and headache (3.8% vs 2.4% with tapinarof and vehicle, respectively, in PSOARING 1; and 3.8% vs 0.6% in PSOARING 2). Irritation of the treated skin was reported to be very mild, even on sensitive skin areas, and there were minimal differences between trial groups and across visits.

Roflumilast

Roflumilast, a PDE4 inhibitor that was originally approved in an oral formulation for the reduction of risk of chronic obstructive pulmonary disease, received FDA approval in July 2022 as a novel topical therapeutic option for psoriasis. It is indicated for topical treatment of plaque psoriasis in patients 6 years of age and older. As a PDE4 inhibitor, roflumilast regulates intracellular cyclic AMP (cAMP) levels to suppresses inflammatory cytokine production.

Roflumilast Mechanism of Action

Activated by G-protein and adenylyl cyclase signaling, cAMP in turn (via protein kinase A and the cAMP response element-binding [CREB] transcription factor) modulates transcription of psoriasis-associated genes (including IL-2, IL-6, IL-10 and TNFα). As discussed in Nonbiologic Therapy, PDE4, the most prominent phosphodiesterase in immune cell (lymphocytes, granulocytes, and monocytes/macrophages), degrades cAMP. It is predominantly found in skin cells (e.g., keratinocytes), neutrophils, Langerhans cells, and T lymphocytes, cell types associate with psoriatic plaque formation. Inhibition of PDE4 by roflumilast leads to the accumulation of intracellular cAMP, which, through CREB activation, both suppresses inflammatory cytokines and promotes anti-inflammatory cytokines. However, the specific mechanisms by which roflumilast achieves its therapeutic action are still not well understood.

Roflumilast Efficacy

The efficacy of roflumilast was assessed in two identically designed studies – DERMIS 1 and DERMIS 2. These two multicenter, randomized, double-blind, vehicle-controlled phase 3 trials enrolled patients 2 years of age or older with plaque psoriasis involving a BSA of 2 to 20% (excluding the scalp, palms, and soles). Patients had to have a baseline Investigator Global Assessment (IGA) score of at least 2 (the scale ranges from 0-4; 0 – clear, 1 – almost clear, 2 – mild, 3 – moderate, 4 – severe) and a PASI score of 2. A total of 439 and 442 patients were enrolled in DERMIS 1 and DERMIS 2, respectively. Eligible patients were randomized (2:1) to receive either roflumilast 0.3% cream or vehicle cream once daily for 8 weeks. The primary efficacy endpoint was IGA success, defined as an IGA score of 0 or 1 and a decrease of at least 2 points, assessed at week 8. Secondary efficacy end points included intertriginous IGA (I-IGA) success (an I-IGA score of 0 or 1 and at least 2-grade improvement) and I-IGA clear status at week 8, time to achievement of 50% reduction in the PASI score, percentage of patients achieving a 75% reduction in the PASI score at week 8, a reduction of at least 4 points from baseline on the Worst Itch Numeric Rating Scale (WI-NRS) at weeks 2, 4, and 8, and change from baseline on the 16-item Psoriasis Symptom Diary (PSD) at weeks 4 and 8.

In the DERMIS 1 trial, 42.2% and 6.1% of patients achieved IGA success at week 8 in the roflumilast-treated and the vehicle-treated group, respectively (P<0.001) (Figure 9.3A). Similarly, 37.5% of patients in the roflumilast group achieved IGA success at week 8 in DERMIS 2, compared to 6.9% in the vehicle group (P <0.001) (Figure 9.3B). Roflumilast also demonstrated efficacy in the reduction of I-IGA, PASI, WI-NRS and PSD scores. At week 8, 71.2% (DERMIS 1) and 68.1% (DERMIS 2) of patients receiving roflumilast achieved I-IGA success, compared with 13.8% (DERMIS 1) and 18.5% (DERMIS 2) of patients receiving vehicle cream (P<0.001 for both comparisons). An I-IGA status of clear was attained by significantly more roflumilast-treated patients (63.4% in DERMIS 1 and 57.4% in DERMIS 2) than patients in the vehicle group (10.3% in DERMIS 1 and 7.4% in DERMIS 2)(P<0.001). The time to achievement of 50% reduction from baseline in PASI score was a median of 31.0 days for roflumilast and 104.0 days for the vehicle in DERMIS 1 (P<0.001); in DERMIS 2, the median time was 30.0 days for roflumilast and not estimable for the vehicle group (P<0.001). The proportion of patients achieving a 75% reduction from baseline in PASI score was 41.6% in the roflumilast group and 7.6% in the vehicle group in DERMIS 1 (P<0.001), and 39.0% and 5.3% (roflumilast and vehicle group, respectively) in DERMIS 2 (P<0.001). Roflumilast significantly increased the portion of patients achieving a reduction in WI-NRS, with 34.9%, 50.2%, and 67.5% of subjects in DERMIS 1 attaining at least a 4-point reduction at week 2, 4, and 8, respectively, compared to 22.0% (P=0.12), 18.0% (P<0.001), and 26.8% (P<0.001) of patients who received the vehicle. In DERMIS 2, 41.9%, 56.6%, and 69.4% of roflumilast-treated patients achieved an at least 4-point reduction in WI-NRS at the 2, 4, and 8-week follow-up, compared to 21.1% (P=0.003), 21.9% (P<0.001), and 35.6% (P<0.001) of vehicle-receiving patients. Finally, the total PSD score was significantly improved in the roflumilast group when compared with vehicle in both DERMIS 1 (-43.5 vs -17.7 at week 4 [P<0.001], and -50.1 vs -19.2 at week 8 [P<0.001]) and DERMIS 2 (-42.7 vs -16.7 at week 4 [P<0.001], and -49.3 vs -22.8 at week 8 [P<0.001]).

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Roflumilast Safety

Safety – treatment-emergent AEs (TEAEs), physical examinations, vital signs, weight, clinical laboratory results, Columbia Suicide Severity Rating Scale, and depression – was assessed in both DERMIS trials, with assessments at screening, baseline, week 4, and week 8. The rate of treatment discontinuation due to AEs was 1.0% for patients receiving roflumilast cream (1.7% in DERMIS 1 and 0.3% in DERMIS 2), compared to 1.3% for patients in the vehicle cream group (1.3% in both trials). The primary AE leading to the discontinuation of roflumilast was application site urticaria, with an incidence of 0.3%. In DERMIS 1, serious AEs occurred in 0.7% of subjects using roflumilast and 0.7% using the vehicle, while in DERMIS 2, the rates were 0% with roflumilast and 0.7% with the vehicle. Adverse reactions observed in at least 1% of roflumilast-treated patients, surpassing the rate for vehicle, included diarrhea (3.1% with roflumilast vs 0% with vehicle), headache (2.4% with roflumilast vs 1.0% with vehicle), insomnia (1.4% with roflumilast vs 0.7% with vehicle), nausea (1.2% with roflumilast vs 0.3% with vehicle), application site pain (1.0% with roflumilast vs 0.3% with vehicle), upper respiratory tract infection (1.0% with roflumilast vs 0.3% with vehicle), and urinary tract infection (1.0% with roflumilast vs 0.7% with vehicle).

Other Topical Agents

Due to the significant side effects of using potent topical corticosteroids, alternative agents have been developed to give patients alternatives in topical medications. In particular, the concerns for systemic absorption, skin thinning and difficulties with facial use, along with incomplete responses, have led to a series of alternative medications that can be used without or in conjunction with topical corticosteroids. Some of these agents are extremely old, including tar and anthralin, and some are newer including vitamin A and D derivatives and topical macrolides. However, they all play a role in conjunction with topical corticosteroids.

Tar and Anthralin

Both coal tar and anthralin have, in the past, been mainstays of psoriasis therapy. Unfortunately, there are limited clinical trial data to support their use. Both have limited trials that show benefit and are frequently used in conjunction with phototherapy and topical corticosteroids. There are a wide variety of preparations of these agents, often trying to limit the associated odor and color of these agents that limit their use. Other limitations include staining of the skin and irritation that is unacceptable to many patients. Of great importance, particularly for coal tar, it needs to remembered that this agent is a extract of crude coal and microscopic elements of coal have been found in the circulation of patients using these agents over wide areas. Little is known about the effects of these microparticulates in the circulation and special care.

Vitamin D Derivatives

The most frequently prescribed class of non-corticosteroid topical medication for psoriasis are the vitamin D derivatives. In the United States, there are two available compounds, calcipotriene and calcipotriol. Both come in an ointment base, although calcipotriene also is available in a cream base and solution. In clinical studies, the efficacy of these agents is significant. They have not been compared head to head. Calcipotriene is indicated for usage twice daily, while calcipotriol is used once daily. Importantly, the concerns for corticosteroids such as skin thinning and ocular abnormalities are absent with the use of vitamin D derivatives, making them a helpful adjuvant in patients with inverse and facial disease.

Unfortunately, this benefit of vitamin D derivatives may be outweighed by the most significant side effect, limited tolerability. Small numbers of patients report irritation and discomfort with the application of these medications, particularly in the locations of greatest concern. Calcipotriol seems to be slightly less irritating in these areas than calcipotriene but the same considerations exist. Because these effects are unpredictable, patients will often start with a trial of these medications prior to dedicating themselves to long-term use. More significant concerns, considered early after their release, for alteration in calcium metabolism due to extensive systemic absorption have not been borne out in clinical use. Still, it is recommended that patients not use more than 100 g weekly and that special consideration be given to patients with renal disease prior to use.

Combination Agents

Vitamin D and Topical Corticosteroids

The ability to maintain patients with psoriasis on limited different topical agents is a major advantage in the treatment of psoriasis. In addition, many investigators have promoted the idea that combining topical vitamin D agents and corticosteroids can be beneficial in increasing efficacy, while limiting the amount of exposure to corticosteroids. To solve this dilemma, a combination ointment of betamethasone dipropionate, a potent class II corticosteroid, with calcipotriene has been created. This combination shows good short-term efficacy, although these benefits may be marginal compared with potent topical corticosteroids alone. Additionally, this medication is recommended to be applied only once daily, a potentially significant advantage. The biggest hindrance to use of this combination medication is cost in the United States, which is markedly elevated compared with similar combinations available in the rest of the world.

Topical Vitamin A Agents: Retinoids

Due to the common use of retinoids systemically for the treatment of psoriasis, topical application was thought to be of potential benefit. Only one topical retinoid, tazarotene, has been approved by the FDA for the treatment of psoriasis. Although tazarotene has been shown to be of some clinical efficacy as a single agent, this limited effect has been clouded by local intolerance to the medication.15 Local dermatitic reactions with irritation, pruritus, and burning can be pronounced, so this agent should generally be used in conjunction with topical corticosteroids to increase tolerability. Care must be taken to avoid retinoids during pregnancy as they are classified as category X for pregnancy.

Special Case: Inverse and Facial Psoriasis

Treatment of areas with thinner skin and potentially greater side effects limit the potential benefits of topical corticosteroids on the face and inverse areas, including the groin and axilla. Additionally, the application of heavy ointments to these areas can be uncomfortable. Since these areas are frequently the most uncomfortable for patients, these limitations present special challenges for topical therapy. There are some helpful considerations for the use of alternatives in these areas.

Topical Macrolides: Tacrolimus and Pimecrolimus

Topical macrolide medications, tacrolimus and pimecrolimus, have demonstrated efficacy in inverse areas and on the face. While they have never demonstrated a significant impact on plaque psoriasis, their efficacy in these special areas has been clearly demonstrated in the literature.16,17 Moreover, the special concerns in these areas, including atrophy and ocular manifestations, are not associated with topical macrolides. Thus, to many practitioners, topical macrolides are the treatment of choice for inverse psoriasis.

Two cautions are needed with tacrolimus and pimecrolimus. First, there are some issues with tolerability that can occur. These are limited to what seems to be an idiosyncratic burning sensation that will usually, but not always, diminish within the first week of use. Secondly, the FDA has placed a black box warning on the use of these medications for cancer risk. Importantly, no clinical data either before or after the approval of these medications have ever shown any evidence of increased cancer risk with these medications.18-20 Moreover, the animal data associated with these warnings are likely not applicable to the clinical situations in which these medications are used. Nonetheless, there is significant public awareness of these warnings that needs to be properly explained to patients.

If topical macrolides are not used in inverse psoriasis, it is still possible to rely on traditional agents, including topical corticosteroids and vitamin A and D agents. In these areas, class 6 and 7 topical corticosteroids are indicated rather than the stronger versions. Lotions or foams may be preferable in the areas as well. Additionally, steroid alternatives can be used but care must be taken to avoid associated skin irritation. For example, the use of calcitriol on the face is probably preferable to calcipotriene but the combination medication cannot be used due to the strength of the betamethasone. Tazarotene is frequently used on the face as well, as it is also an approved medication for acne. However, due to the irritation associated with tazarotene, caution should be taken when starting this medication, with use two or three times per week slowly building to daily application.

2020 Joint American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) Guidelines for the Treatment of Psoriasis with Topical Therapy

In 2020, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) jointly issued a set of guidelines on the use of topical agents for the treatment of psoriasis. Separate recommendations are provided for each class of topical agent, including:

• Emollients: Recommended in conjunction with topical corticosteroids for 4 to 8 weeks to help reduce itching, desquamation and total body surface area and prevent quick relapse of psoriasis when topical corticosteroids are discontinued.
• Salicylic acid: Recommended as monotherapy for 8-16 weeks for the treatment of mild to moderate psoriasis, or in combination with topical corticosteroids for the treatment of moderate to severe psoriasis (body surface area ≤20%).
• Topical corticosteroids: Class 1-5 agents are recommended for up to 4 weeks for the treatment of plaque psoriasis not involving intertriginous areas; Class 1-7 agents are recommended for a minimum of up to 4 weeks as initial and maintenance treatment of scalp psoriasis.
• Anthralin and coal tar: Recommended for the treatment of mild to moderate psoriasis. Short contact (up to 2 hours per day) anthralin is recommended to limit adverse side effects.
• Vitamin D analogues: Long-term use (up to 52 weeks) is recommended for the treatment of mild to moderate psoriasis; Vitamin D analogues may also be combined with potent topical corticosteroids for the treatment and maintenance treatment of psoriasis.
• Topical tazarotene: Recommended for the treatment of mild to moderate psoriasis and nail psoriasis. Combination use with a high-potency topical corticosteroid is recommended over monotherapy and use with narrow-band UV therapy is recommended to decrease the total amount of UV therapy received.
• Topical pimecrolimus and tacrolimus: The guidelines state that the use of these agents is off-label, but that 0.1% tacrolimus can be considered for psoriasis involving the face as well as inverse psoriasis for up to 8 weeks, and recommend the use of pimecrolimus for inverse psoriasis for 4-8 weeks.

More information and further recommendations can be found in the current AAD/NPF guidelines.