Insights Into Treating Palmoplantar Psoriasis
A review. Psoriasis is a chronic, inflammatory, immune-mediated, multi-system disease with a prevalence of approximately 1% to 3% worldwide.1 Chronic stable plaque psoriasis, or psoriasis vulgaris, is the most common form of disease, accounting for 85% to 90% of cases. Joint involvement is common, affecting anywhere from 6% to 42% of patients with psoriasis. 2 Other phenotypes include intertriginous, scalp, palmar, plantar and seborrheic, and patients may present with multiple forms. 3,4 At present, there is no curative therapy available and the clinical course is typically chronically remitting and relapsing disease with well circumscribed, erythematous, indurated plaques with scale.
Health-Related Quality of Life
Given the physical impact of PPP, and its difficulty to treat, complete clearance of lesions may not be essential to some patients if symptomatic relief is obtained. Though debated, many reports state that the physical restrictions of PPP are greater than in patients without hand and foot involvement.11,17 Fissuring of the soles of the feet and palms, especially when the dominant hand is affected, make every day activities difficult secondary to pain.3,39 Conversely, some publications have maintained that impact on health-related quality of life (HRQL) is not greater in those with PPP than in those with generalized psoriasis, and instead, that physical disability caused by palmar and plantar lesions is most important.8 Thus, if practitioners can achieve some clearance of plaques and thereby reduce pain and physical disability, complete clearance is not necessarily required. Therefore, increasing the dose of systemic medications leading to unwanted adverse drug reactions may be avoidable.8 Additionally, non-traditional therapies including radiotherapy or interferential current may be options in therapy-refractory palmoplantar disease. As these modalities have not been studied in large clinical trials or for long-term side effects, these are not considered first line and should be used only after the risks and benefits have been weighed.
Palmoplantar psoriasis (PPP) is a localized form of psoriasis and can manifest in many different morphologic patterns, from predominantly pustular lesions to thickened, hyperkeratotic plaques and anything in between. 5 PPP is characterized by erythema, hyperkeratosis with surrounding lichenification and coarse scale, resulting in peeling, blistering, crusting, fissures and bleeding. These symptoms may significantly interfere with activities, inhibiting patients from closing their hands or walking comfortably on their feet, leading to major disability and reduction in quality of life. 3,5,6,7 PPP lesions are frequently associated with psoriatic plaques elsewhere, but can occur in isolation. 5,8 In the absence of generalized psoriasis, PPP may present similarly to eczematous forms of dermatitis, such as irritant and/or allergic contact dermatitis, dyshidrotic eczema, atopic dermatitis, mycosis fungoides, tinea infections, and palmoplantar keratoderma, making diagnosis difficult. 3,9 This form of psoriasis can start with or be exacerbated by the Koebner phenomenon and patients should be told not to remove the scale physically. 10 Distinction between PPP and hand dermatitis is also difficult histologically, with considerable overlap of histologic findings. 9 PPP can result in functional and social disability, which in some trials is thought to be greater than plaque psoriasis because of the marked morbidity associated with the disease. 6,8,11 Given the physical restrictions of having psoriasis on the soles or feet, these patients often suffer from great physical disability and discomfort. 5,7,12 While the palms and soles represent a relatively small body surface area, their involvement may lead to severe disease. Although PPP has devastating effects on quality of life, there are very few large scale randomized controlled clinical trials studying this condition. 10,13 Treatment selection is determined by the severity and location of the psoriasis, as well as medication side effects, patient preferences, and financial constraints. This review aims to explore the available data on treatment of palmoplantar psoriasis and its unique challenges.
Topical therapy can be challenging in certain areas of the body, particularly in the scalp, palms and soles, and intertriginous areas, and treatment regimens must be tailored to these areas. 14,15 In particular, PPP is relatively resistant to even the most potent topical therapies, likely due in part to the thickness of palmar and plantar skin. 3,5,11,16,17 Commonly used topical medications for psoriasis include corticosteroids, vitamin D analogues, keratolytics, anthralin, coal tar, and tazarotene. They may be used individually or in various combinations, and may be used under occlusion. 18 Tars have been used for PPP, and crude coal tar ointment with or without a topical steroid under occlusion has been reported to be efficacious.19,20 In one study by Kumar et al, 76.5% of patients treated with 6% crude coal tar ointment under occlusion nightly for 8 weeks showed greater than 50% improvement with no reported side effects. This was compared to only 45.5% of patients treated with white petrolatum and salicylic acid. 19 Similarly, 39 patients with PPP were given either twice weekly calcipotriol ointment under occlusion overnight or twice-daily topical nonocclusive application of the same ointment for 6 weeks. At the end of treatment, analysis of the results showed that twice-weekly occlusive calcipotriol ointment was as effective as twice-daily application. Furthermore, there were no significant adverse effects noted. 21 The activity of calcipotriene relates to a dose-dependent decrease in proliferation of keratinocytes, making it a good option for disorders of epidermal hyperproliferation. 22 Topical methotrexate gel has also been studied for the treatment of PPP, with disappointing results. 23
PUVA and NB-UVB
Light therapy is a well-established treatment modality for psoriasis, including broadband UVB (BB-UVB) and narrowband UVB (NB-UVB) in the range of 311 nm to 313 nm. 24 However, few clinical trials exist examining these modalities in PPP. Local psoralen plus ultraviolet A (PUVA) therapy has also been shown to be effective in the treatment of PPP, though little is known about the efficacy and safety of local NB-UVB. 6 In one bilateral comparison study, NB-UVB and PUVA were given three times a week over a 9-week period. The PUVA treated side showed a 61% improvement compared with 43% for the NB-UVB treated side (n = 25). 6 These results were corroborated in a similar small trial by Nordal et al in which 11 patients reported moderate to marked improvement with local PUVA treated sides. 25 In another trial by David et al, topical psoralen-ultraviolet A therapy effectively cleared 40% of patients after a mean of 2.8 months and 27.3 treatments. Furthermore, another 40% of patients had improvement in their disease with this treatment. 26 Efficacy of NB-UVB and PUVA have been compared in plaque-type psoriasis and have less disparity in clinical efficacy, a result that may be explained by lower penetration of NB-UVB compared to PUVA through the thickened stratum corneum of palmoplantar skin. 27 Side effects of PUVA include the risk of phototoxicity and pigmentary changes, including hyper and hypopigmentation. 27,28 The major risk of NB-UVB is carcinogenesis, specifically nonmelanoma skin cancers. However, carcinogenicity with NB-UVB is a controversial topic.
Monochromatic excimer light (MEL) emitting at 308 nm is a form of NB-UVB with a variety of applications. Several studies have validated the use of MEL as an effective therapy for PPP. MEL has many advantages, including more accurate lesion targeting, avoiding unwanted UV damage to areas of healthy skin, shorter treatment time and faster clearance, and high patient compliance. 29,30 Proposed hypothetical mechanisms of action of the MEL include alterations in apoptosis-related molecules, significant T-cell depletion, and decreased proliferation of keratinocytes. 31 Nistico et al reported a complete remission rate in more than 50% of patients with PPP. 31 An average of one session per week for 12 weeks and a total dose range of 4 J/cm2 to 12.5 J/cm2 was required for a clinical response. Han et al showed a similar improvement in 30 patients with PPP who completed either 16 treatments with the 308 nm MEL twice a week or 25 treatments administered once weekly. 30 Better results were obtained by Cappugi et al and Campolmi et al, which showed an improvement ranging from 75% to 100% with MEL in patients with PPP with no relapse during a 16-week follow-up period. 32,33 In another report, 17 patients with palmoplantar pustular psoriasis showed a mean improvement of 79%, which was significantly higher than those with plaque-type psoriasis.29 The MEL ranged from 250 mJ/cm2 to 350 mJ/cm2 and a mean of 5.3 treatments. In these studies, MEL was able to be used at a higher fluency due to its ability to target the psoriatic plaque more selectively, resulting in shorter treatment duration and a lower minimal erythema dose than that of previous light therapy modalities such as NB-UVB. 24,34 Though more recently contradicted by the work of Goldinger et al, the positive results of these small trials have yet to be validated by larger scale studies. 35
Traditional Systemic Therapies: Methotrexate, Cyclosporine, Retinoids
Palm and sole disease frequently requires the use of systemic therapies such as retinoids, cyclosporine and methotrexate. 3,5 Traditional systemic therapies for psoriasis, including retinoids, cyclosporine and methotrexate have shown some benefit, but patients are subject to the same systemic toxicities associated with generalized psoriatic treatment with these therapies. 6,17 In one retrospective study by Adisen et al, the charts of 62 patients with PPP and 52 patients with palmoplantar pustular psoriasis were reviewed, and 17 of 62 patients showed marked improvement to topical corticosteroids (n=12) or to calcipotriol (n=5). The remaining patients were treated with systemic therapies. Acitretin (n=24) was the most common agent used initially, while local PUVA (n=12) and methotrexate (n=9) were less often prescribed. Marked improvement was seen in 53%, 47% and 53% of patients treated with acitretin, methotrexate, and oral PUVA, respectively. Cylosporine was not used first-line. 5
PPP is often resistant to conventional therapy. Although there are no head-to-head trials, it is generally believed that biologic agents, such as adalimumab, etanercept and alefacept (Humira, Enbrel, and Amevive, respectively), offer more targeted therapy with improved tolerability over traditional agents such as acitretin, methotrexate and cyclosporine. 17,36,37 Multiple trials were also conducted examining the treatment of refractory PPP with efalizumab (Raptiva), which has since been pulled from the market based on an association with an increased risk of progressive multifocal leukoencephalopathy (PML), a rare and usually fatal disease of the central nervous system. 11,38,39 Though not available at this time, this drug resulted in clearance of lesions in an often short amount of time (27% to 33% achieved PASI 75 after 12 weeks of treatment and 44% of treated patients achieved PASI 75 after 24 weeks of treatment). 40,41 It is important to note that many trials were conducted examining the effects of biologic agents such as etanercept, alefacept and adalimumab on patients with palmoplantar pustulosis, which is a distinct entity not covered in this paper. 42-46 Because patients with PPP make up a small percentage of the total population of psoriasis patients, and because disease is limited and often falls below the 10% inclusion criteria for systemic trials, much work is needed in this area.
In addition to traditional systemic agents and biologics, many medications have been used off-label, including colchicine. 16,47 There have also been isolated case reports showing efficacy of interferential current and radiotherapy. 7,48 Given the paucity of literature for treating PPP with these therapies, providers may not be aware of these options or have the facilities to provide them. Large clinical studies evaluating systemic therapy palmoplantar disease do not exist, in part because pure PPP without involvement elsewhere affects less than 5% body surface area, a criteria that falls short of the 10% body surface area requirement for most systemic trials, and in part because this form of psoriasis is so recalcitrant to treatment. 3 While there is no algorithm for treating PPP, it is generally agreed that patients are treated initially with topical medications, including topical corticosteroids in combination with non-steroidals such as vitamin D analogues, much as plaque-type psoriasis is treated. 7 If satisfactory treatment is not achieved in a timely manner, systemic retinoids such as acitretin, are added as first-line therapy. 5 Success rates of up to 53% have been achieved. 5 PUVA can be added to the regimen if the former is not effective, although the literature is ambivalent about its efficacy. 5 Additionally, methotrexate or cyclosporine therapy can be considered, although these systemic therapies are associated with significant toxicity and are not generally considered first-line. Alternatively, biologics have been shown in many small trials and case reports to be effective for PPP. Most recently, lasers such as the excimer laser, are gaining popularity and can be used in conjunction with topical or systemic therapy. 49
In conclusion, PPP is a pleomorphic, historically difficult-to-treat form of psoriasis that was formerly called “recalcitrant eruption of the palms and soles. 3” The majority of patients will require a systemic therapy, and the success rates of acitretin, methotrexate and oral PUVA in the literature are approximately 53%, 47% and 53% respectively. Biologics such as alefacept, adalimumab, and etanercept can also be useful, although the majority of studies completed for PPP examined efalizumab, which is no longer on the market. Alternative therapies, such as interferential current and radiotherapy, may also be attempted in treatment refractory cases, although these alternatives may not be readily available. Often, a combination therapy is required to achieve significant clearance, though whether achievement of plaque remission is as important as reduction in disability has yet to be flushed out in the literature. One thing is certain, more large scale randomized controlled clinical trials are needed to provide a treatment algorithm for practitioners treating this difficult disease. Dr Frankel is a clinical dermatopharmacology fellow in the Department of Dermatology at Mount Sinai Medical Center, New York, NY. Dr. Goldenberg is Assistant Professor of Dermatology and Pathology, Medical Director of the Dermatology Faculty Practice, Mount Sinai School of Medicine in New York. He is Board Certified in Dermatology and Dermatopathology. Disclosures: The authors have no conflicts of interest with any material found in this article.