Current And Emerging Modalities For Psoriasis

Palmoplantar psoriasis can be a particularly devastating condition, given the condition’s negative effect on quality of life. These authors provide a stepwise guide to therapy, progressing from topical steroids to phototherapy to biologics depending on the severity of the psoriasis.

As podiatrists, we often have patients presenting with a scaly rash on the foot. In these cases, it is important not only to consider tinea pedis as a differential but psoriasis as well.

Psoriasis is an inflammatory disorder of the skin. While it varies in distribution and severity, psoriasis is chronic in nature. The most common type is the generalized plaque variant, which presents as an erythematous base with a micaceous scale. The palmoplantar psoriasis type may also present as a red plaque with a silvery scale, sterile pustules or a combination of both pustules and plaques.^1,2

Palmoplantar psoriasis can be exceptionally debilitating due to its anatomic location. Although the total body surface involved is relatively small in comparison to generalized plaque psoriasis, the plantar surface distributes the entirety of our body weight with each step causing greater irritation and worsening of the condition.³ Palmoplantar psoriasis is a devastating affliction for patients. It has an incredible negative impact on quality of life and overall psychological well-being.

Psoriasis is a clinical diagnosis. For palmoplantar psoriasis, always check the palmar surface of the hands when the plantar surface of the feet is involved. Psoriatic episodes can be triggered by a multitude of events such as infection, trauma, smoking and stress.¹

There are several treatment options for palmoplantar psoriasis. The generally accepted first-line therapy is an integrated use of topical corticosteroids, topical vitamin D analogs and/or an epidermal barrier repair cream. Another possible treatment option for palmoplantar psoriasis is phototherapy with outcomes demonstrating an extended remission period in comparison to other therapies. In cases of severe palmoplantar psoriasis, systemic or biologic therapy are typical considerations for primary therapy.^4–6

Currently, there is no consensus on a specific therapy regimen for palmoplantar psoriasis. Finding a therapy that effectively clears the lesions with minimal adverse effects or contraindications proves to be a challenge. Even a highly potent therapy regimen has variable results among patients. With these issues in mind, let us take a closer look at the evidence-based medicine to elucidate a potential standard of care for your patients.

Key Insights On Topical Therapy For Psoriasis

Topical treatments such as corticosteroids, retinoids, vitamin D analogs, salicylic acid and emollients are the first-line therapy options for palmoplantar psoriasis. In 80 percent of patients diagnosed with palmoplantar psoriasis, topical steroids are the primary treatment option because of their potent anti-inflammatory, immunosuppressive and antiproliferative properties.^3,7 Topical steroids are preferable over systemic steroids for initial treatment due to their lessened adverse effects with local application.⁸

However, prolonged exposure to topical steroids over a large surface area can cause skin atrophy and possible systemic absorption among other characteristic side effects. To minimize potential adverse effects and increase efficacy, treatment should incorporate combination therapy and cycling of topical steroids.⁶ Do not consider oral steroids if you have a psoriasis patient presenting to you as oral steroids can precipitate a worse form of psoriasis and cause a rebound phenomenon.  

Tazarotene, a topical retinoid, is a valuable addition to treating palmoplantar psoriasis by decreasing the rate of differentiation and production of keratinocytes. One can also use tazarotene as an alternate therapy option if the side effects of steroids are too severe.³ However, evidence indicates the use of both a topical tazarotene and steroid together can decrease the chance of skin atrophy as a possible side effect. Utilizing both products in treatment will also produce a synergistic effect, allowing the use of an effective lowered dose.⁹ The drawback of topical retinoid use is the high occurrence of irritation and for this reason, the senior author always pairs retinoids with a topical steroid.⁵                          

Topical keratolytic therapy, such as salicylic acid, in low concentrations is useful in decreasing hyperkeratotic scales involved in palmoplantar psoriasis.⁹ This is particularly advantageous for patients in whom combination therapy with a steroid or retinoid would improve absorption for maximal effectiveness. However, do not use keratolytic therapy with vitamin D analogs or ultraviolet light therapy at the same time due to potential side effects.³    

Vitamin D analogs inhibit keratinocyte production and are therefore another acceptable adjunct treatment for palmoplantar psoriasis with topical steroids.⁶ Previous studies found that the simultaneous use of vitamin D analogs and topical steroids has improved effects in comparison to monotherapy and decreased side effects due to the reduced dose of the steroid.⁷ However, the senior author does not pair calcipotriene and betamethasone together at the same time due to their interaction with each other. There is a topical medication that links the two together as a single use daily treatment. It comes as a topical suspension (Taclonex, Leo Pharma), foam (Enstilar, Leo Pharma) and ointment (generic). If for insurance purposes the senior author must prescribe the medications separately, she has the patients use them at opposite times of the day.  

In addition to prescribing your newly diagnosed plantar psoriatic patient with a topical steroid and a topical vitamin D analog, provide emollients, whether they are over the counter or prescription. Emollients create a protective layer over the epidermis, increasing hydration and lowering the possibility of erythema and scaling.¹⁰ Studies demonstrate that mixing emollients with betamethasone, a class 1 corticosteroid, can increase the efficacy of the steroid and reduce the number of applications needed.¹¹ Combining the three topicals together is ultimately steroid sparing. The goal with these patients is to maintain them on moisturizers and non-steroidal topical therapies while using the topical steroids for flare-ups.  

Topical treatments are a suitable first-line therapy for palmoplantar psoriasis. However, there are drawbacks such as frequency of application and tachyphylaxis (when the medication “stops” working) that are discouraging to patients, especially when they are coupled with incomplete clearance of the lesions. It is also imperative to choose the correct vehicle for application of the thickened stratum corneum of the plantar skin, which can prevent proper absorption. The most successful therapy is an individualized combination of topicals for each patient to limit adverse effects and increase effectiveness. Additionally, provide clearly written and verbal instructions for the patient because the regimen requires adherence over an extended treatment period.⁶   

When Patients Need Phototherapy

Phototherapy is a frequently utilized therapy for psoriasis. However, there is currently no defined regimen of treatment strength or duration for palmoplantar psoriasis. There are various ways to deliver radiation therapy to the skin but the most common are ultraviolet B (UVB) or a combination of ultraviolet A (UVA) with a photosensitizer agent, such as psoralen.^6,11,12 One aspect all phototherapy studies emphasize is the longer periods of remission in comparison to the traditional topical medication treatments for palmoplantar psoriasis. Thus, phototherapy is often an option after failed treatments of topical medications.

A 2017 study by Gianfaldoni and colleagues evaluated treatment with narrowband UVB therapy at 308 nm to reduce collateral damage on non-affected skin.¹³ Patients had this treatment twice a week for four weeks and subsequently once a week for the following four weeks. The duration of treatment started at 15 seconds for the first session and increased five seconds thereafter. After 16 sessions, the patients achieved complete remission in the affected areas and remained clear through 12 weeks of evaluation with no treatment. A major advantage to UVB therapy, as opposed to UVA, is decreased skin penetrance, resulting in little to no risk of skin cancer development and no required chemical adjunctive treatments.

In contrast, a study by Fritsch and coworkers tested the effects of psoralen UVA therapy augmented with another photosensitizer, methoxsalen (Oxsoralen-Ultra, Ortho Dermatologics), and compared it to the administration of standard PUVA therapy as well as administration of only an oral retinoic acid derivative.¹⁴ The study discovered that the addition of methoxsalen resulted in a 30 to 50 percent decrease in the total duration and the number of treatments needed (mean of 10 irradiations in 17 days). Further results showed a 75 percent decrease in the total cumulative UVA energy applied to the patient in comparison to traditional psoralen and ultraviolet A (PUVA) therapy. This significant reduction in exposure and treatment time is considerably more beneficial and safe to the patient. While PUVA therapy with methoxsalen has proven to be a very effective method, the authors acknowledge there is still the long-term risk of developing skin cancer.¹⁴

As with any therapy, consider risk versus benefit. Overall, evidence suggests the use of phototherapy/photochemotherapy is effective for palmoplantar psoriasis as a first-line treatment or after the failure of topical treatments. Patients may obtain this therapy by either going to a physician who offers phototherapy in the office three times per week or by using a home foot phototherapy device (National Biological), which may be partially covered by insurance.

A Guide To Effective Systemic Therapies For Psoriasis

Systemic treatments for psoriasis are often options once a patient fails topical medications and phototherapy. Multiple case studies have illustrated an effective systemic treatment for palmoplantar psoriasis but studies often lack a large sample size.

In a retrospective study, 45 of 62 patients with palmoplantar psoriasis required systemic treatment after failed improvement with topical agents.¹⁵ Many of these patients also required multiple systemic treatments. Marked improvement (> 75 percent area cleared) occurred in 52.9 percent of the palmoplantar psoriasis patients treated with systemic retinoids, PUVA, methotrexate, cyclosporine or a combination of these drugs. This retrospective study helps illustrate the difficulty in treating palmoplantar psoriasis while noting the importance of combination therapy to facilitate significant improvement in the patient’s condition.

One of the most commonly used systemic drugs for palmoplantar psoriasis, outside of women of childbearing age, is an oral retinoid.¹⁶ Acitretin (Soriatane, Steifel Laboratories) combined with PUVA is often the retinoid of choice in patients with palmoplantar psoriasis.³ However, acitretin has known teratogenic effects and systemic abnormalities associated with its use. Other systemic therapies include methotrexate, cyclosporine and dapsone (Aczone, Allergen).  

A more recent study focused on the efficacy and safety of apremilast (Otezla, Celgene), a phosphodiesterase-4 inhibitor (PDE4).¹⁷ In the double-blind, randomized, placebo trial, patients used 30 mg of apremilast twice per day for 16 weeks. Researchers recorded data using the Physician Global Assessment (PGA) scale based on severity from 0 (clear) to 4 (severe, dark red). Of the 1,431 total patients pooled, 427 members had palmoplantar psoriasis with 144 of the cases being moderate or severe (3-4 PGA). After 16 weeks, 48 percent of the apremilast group and 27 percent of the placebo group improved from a 3-4 PGA to a 0-1 PGA. In the mild (PGA 1-2) pool, 46 percent of apremilast-treated patients and 25 percent of placebo patients improved to a completely clear or 0 PGA. No serious systemic side effects such as cellulitis occurred. However, greater than 5 percent of the apremilast-treated patients experienced diarrhea, nausea/vomiting, headaches, upper respiratory infections or nasopharyngitis. Data from Bissonnette and colleagues suggests that apremilast can be effective in patients with mild or severe palmoplantar psoriasis.¹⁷ The senior author has prescribed apremilast to several of her patients with palmoplantar psoriasis. One of the most important aspects of prescribing this systemic medication is titration of the drug to twice daily dosing to lessen the possible gastrointestinal side effects.  

While there is no definitive choice for a single systemic agent in the treatment of palmoplantar psoriasis, there is promising data on their importance in more severe cases. In these cases, research has shown systemic agents, such as an oral retinoid or PDE4 inhibitor, to be both effective and safe.¹⁵ Future studies may be able to help expand on the findings from Adisen and coworkers, and determine a definitive combination of these agents.¹⁵

Assessing The Impact Of Biologics For Patients With Psoriasis

The use of biologics for the treatment of psoriasis is relatively new in comparison to its other indications such as rheumatoid arthritis.¹⁸ Currently, the American Academy of Dermatology (AAD) recommends the use of biologics as third- or fourth-line therapies in conjunction with other medications.^6,19 The recommendation to reserve biologic therapy is due to the high financial burden.^20,21

Patients tolerate biologics well and they “pose little risk of end organ damage” in comparison to other systemic agents.^6,22 Despite this low risk, it is important to consider the patient’s comorbidities and severity of psoriasis before starting a biologic.⁶ Clinical practice guidelines recommend checking for human immunodeficiency virus, hepatitis B, hepatitis C, tuberculosis, other granulomatous infections, and preexisting or previous malignancy.^4,23 Therapy with biologics can reactivate these comorbidities.²⁴

Various biologics have had better results for palmoplantar psoriasis than other treatment options.²⁵ Ustekinumab (Stelara, Janssen Immunology) is a recently approved biologic that can treat plaque psoriasis by inhibiting both IL-12 and IL-23, which stops the inflammatory cascade.^26,27 Research has shown ustekinumab to be just as effective for palmoplantar psoriasis after other conservative treatments failed.²⁸ Similarly, secukinumab (Cosentyx, Novartis) is an anti-interleukin 17A antibody that also is particularly effective in patients with palmoplantar psoriasis.²⁹

Authors have made few comparisons between biologics and other treatment options.¹⁸ There is, however, some insight into the cost efficiency of biologics as treatment can be expensive. The high cost has prompted insurance companies to enact rigid eligibility criteria that patients need to meet, such as previously failing improvement with topical or phototherapies.^20,30 A study by Chi and colleagues compared the commonly used biologics for psoriasis and determined that adalimumab, a tumor necrosis factor (TNF) alpha inhibitor, was the most cost efficient.³⁰ Cost efficiency is particularly important when it comes to psoriasis as it is a condition that requires long-term treatment.^30,31 Despite the cost, treatment with biologics remains an effective second tier agent for the treatment of palmoplantar psoriasis.^4,32   

In Summary

There is no consensus on the standard of care for palmoplantar psoriasis. Evidence shows combination therapy is always more effective than monotherapy in both clearance of the lesions and improvement in quality of life.
Topicals are generally safer and more cost-efficient for long-term use, making them an excellent first-line treatment option. Patients should begin with a combination of a topical steroid, vitamin D analog and emollient. Long-term use of this topical therapy may require cycling of the steroid and utilizing non-steroidal topical medications to avoid adverse effects. If the patient suffers from the plaque form of palmoplantar psoriasis, consider salicylic acid in place of the vitamin D analog to reduce the hyperkeratosis. Phototherapy is also a safe treatment option to use in addition to topical therapy, especially for moderate to severe cases on the feet.

Palmoplantar psoriasis is particularly difficult to treat and due to the significant impact on quality of life, clinicians often resort to systemic treatment in addition to topical/phototherapy. Physicians have utilized acitretin, methotrexate and cyclosporine in these patients. Additionally, apremilast is a successful adjunct to therapy with mild adverse effects.

Biologics such as adalimumab (Humira, AbbVie) are very effective. However, due to the expense of the drug for long-term use, biologics are not a primary treatment option. Pay special attention if the patient has a severe chronic infection or malignancy as biologics are contraindicated. An ideal candidate for biologics is someone who has moderate to severe palmoplantar psoriasis, no chronic infection or malignancy, and is aware of the long-term financial burden.

Approach therapy of palmoplantar psoriasis as a stepwise gradient beginning with topicals and progressing to systemic therapy. Each progression in therapy should build on the previous therapy because combination therapy has consistently proven to be more effective. As always, a review of the patient’s severity of condition, health status and lifestyle is necessary to individualize therapy for the best patient care.

Dr. Vlahovic is a Clinical Professor in the Department of Podiatric Medicine at the Temple University School of Podiatric Medicine.

Mr. Romani, Mr. Biela, Ms. Farr, Mr. Lazar, Mr. Duval and Ms. Trovillion are third-year students at the Temple University School of Podiatric Medicine.

References
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Additional Reference
33.    Mehta BH, Amladi ST. Evaluation of topical 0.1% tazarotene cream in the treatment of palmoplantar psoriasis: an observer-blinded randomized controlled study. Indian J Dermatol. 2011; 56(1):40-3.