Psoriasis can commonly appear on the lower extremities but much of the literature does not address this condition in this anatomic area. Accordingly, this author shares three recent studies and their results regarding a novel formulization of halobetasol and its potential for psoriasis of the lower extremities.
Psoriasis is a chronic, recurring disease that can vary both in severity and in the area of the body it affects. It is commonplace in dermatology and podiatry practices with an estimated one to three percent of the general population having psoriasis. It can primarily involve the extremities, including the feet, nails and hands. An estimated three to 41 percent of patients have chronic plaque psoriasis of the hands and/or feet with almost 50 percent of patients with psoriasis having some nail involvement.1,2 A European transversal study of 1,236 patients diagnosed with psoriasis reported lower limb involvement in 60 percent of patients at the moment of clinical inspection with more than 80 percent having multiple skin lesions.3
What The Literature Reveals About Lower Extremity Psoriasis
Psoriasis on the lower extremities, including the feet, can cause significant embarrassment due to its unsightly appearance. Unlike other areas of the body, such as the trunk, the amount of body surface area affected can be relatively small but quality of life is often disproportionately low due to pain, discomfort and physical limitations.4,5
Published clinical data relating to treatment is sparse and has focused mainly on palmoplantar psoriasis. These patients typically have lower body surface area involvement (less than five percent).1 Although there is no consensus on standard of care, topical treatments such as corticosteroids, retinoids, vitamin D analogs and salicylic acid are considered first-line in the majority of cases because of their potent anti-inflammatory, immunosuppressive and antiproliferative properties. However, palmoplantar psoriasis can be resistant to treatment and prolonged topical corticosteroid (TCS) use can have undesirable side effects such as skin atrophy and delayed wound healing.6,7 Topical corticosteroids also have label restrictions limiting consecutive use to two to four weeks.
There are few studies evaluating psoriasis affecting particular locations. In most cases, the severity of psoriasis is assessed through a global severity assessment and body surface area involvement. The efficacy of an individual treatment is determined through changes in these assessments, and changes in signs of psoriasis such as erythema, plaque elevation and scaling evaluated at a specific target lesion. It is not unusual for areas such as the palms and soles to be excluded from overall efficacy assessments, and for target lesions covering bony prominences such as elbows and knees to also be excluded.
Emerging Research On A New Formulation Of Topical Treatment For Psoriasis
Recently, researchers on three clinical studies investigating a novel formulation of halobetasol propionate (HP) for plaque psoriasis published their results.8-10 This formulation utilizes a polymeric emulsion technology to afford efficient delivery of halobetasol propionate into the dermal layers of the skin. In the first study, Kerdel and colleagues compared halobetasol propionate 0.01% lotion with halobetasol propionate 0.05% cream in a label-restricted (in the case of HP 0.05% lotion) two-week study.8 The efficacy of the two formulations was comparable despite the fivefold difference in halobetasol propionate concentration, demonstrating the clinical value of the polymeric emulsion technology.
The subsequent phase 3 studies investigated once-daily treatment of moderate or severe plaque psoriasis with halobetasol propionate 0.01% lotion or vehicle over an eight-week treatment duration.9,10 By week eight, 37 percent of patients achieved treatment success (at least a two grade improvement in disease severity and ‘clear’ or ‘almost clear’) and a 35 percent decrease of mean body surface area affected in comparison to 10 percent treatment success and a six percent decrease of body surface area effected with vehicle.9 Treatment-related adverse events (AEs) were rare with no event occurring at an incidence of greater than or equal to one percent. The most common treatment-related adverse event with halobetasol propionate 0.01% lotion was application site dermatitis (0.7 percent).
Although the location(s) of the plaque psoriasis treated successfully with halobetasol propionate 0.01% lotion is not known, 56 percent of the investigators selected a target lesion on the leg affording an ideal opportunity to assess the efficacy of halobetasol propionate 0.01% lotion in treating psoriasis on the lower extremities.9 Researchers noted rapid and significant improvements in erythema and scaling from week two. By week eight, 52.1 percent, 55.5 percent, and 58.2 percent of patients achieved at least a two grade reduction in erythema, plaque elevation and scaling severity on the leg in comparison with 15.8 percent, 23.0 percent and 22.2 percent of patients treated with vehicle.8-10 Whereas other studies have shown efficacy (with adalimumab) to be greater for psoriasis on the trunk and head than the upper or lower extremities, there was no difference between those patients when the target lesion was on the leg treated with halobetasol propionate 0.1% lotion and the overall study population.11
Assessing Quality Of Life In Patients With Psoriasis
Patients suffering from psoriasis on the lower extremities exhibit disproportionately poor quality of life due to the embarrassment of the unsightly appearance of scales and fissures on the skin. Quality of life assessment has become an important outcome measure in clinical trials and it is likely very useful in assessing the benefits of halobetasol propionate 0.01% lotion in podiatry practice. The interpretation of a change in score of a QoL measure is less intuitive than a clinical measure, such as reduction in body surface area. This highlights the need to define for quality of life measures the minimal change in score considered important by patients and the podiatrist.
The Dermatology Life Quality Index (DLQI) is the most common measure researchers use to assess a patient’s quality of life in clinical trials investigating dermatology-related products.12-16 The minimal clinical important difference (MCID) has been defined as the smallest difference in score in the domain of interest which patients perceive as beneficial and which would mandate, in the absence of troublesome side effects and excessive cost, a change in the patient’s management. Authors of a longitudinal study to assess the MCID of the dermatology life quality index in inflammatory skin diseases (with 51 percent of patients having psoriasis) recommended a MCID of 4.0.
The phase 3 studies with halobetasol propionate 0.01% lotion assessed the dermatology life quality index at baseline, weeks four and eight, and four weeks post-treatment.9 At baseline, the mean dermatology life quality index score was 9.4. By week four, patients receiving treatment with halobetasol propionate 0.01% lotion achieved a MCID with a mean dermatology life quality index score of 4.7, which decreased to 3.8 by week eight. Researchers also noted significant differences between the treatment group and the vehicle group from baseline to week eight on a variety of individual questions related to the dermatology life quality index ranging from questions about itchiness and embarrassment to questions about ease of treatment and impact on social activities.9
In conclusion, psoriasis on the lower extremities is a common problem we see in podiatric practice with a disproportionate quality of life impact. While topical corticosteroids are well suited to treating the majority of cases, safety concerns and labelling restrictions limit use. A new lotion formulation of halobetasol propionate has been developed with polymeric emulsion technology to provide a more efficient delivery into the dermal layers of the skin. Researchers have shown that halobetasol 0.01% lotion is highly effective and well tolerated in treating psoriatic lesions on the leg following once-daily treatment over eight weeks. In addition, the benefits are clinically important from week four. Further study for use in treating palmoplantar psoriasis is warranted.
Dr. Vlahovic is a Clinical Professor in the Department of Podiatric Medicine at the Temple University School of Podiatric Medicine.
- Kumar B, Saraswat A, Kaur I. Palmoplantar lesions in psoriasis: a study of 3065 patients. Acta Derm Venereol. 2002;82(3):192–195.
- Jiaravuthisan MM, Sasseville D, Vender RB, Murphy F, Muhn CY. Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy. J Am Acad Dermatol. 2007;57(1):1–27.
- Chiriac A, Podoleanu C, Azoicai D.I Clinical and epidemiological factors predicting the severity of psoriasis. In: Chiriac A, ed. An Interdisciplinary Approach to Psoriasis. London: InTechOpen; 2017:123-162. Available at: https://www.intechopen.com/books/an-interdisciplinary-approach-to-psoriasis/clinical-and-epidemiological-factors-predicting-the-severity-of-psoriasis. Accessed October 31, 2019.
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- Pettey AA, Balkrishnan R, Rapp SR, Fleischer AB, Feldman SR. Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am Acad Dermatol. 2003;49(2):271–275.
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- Handa S. Newer trends in the management of psoriasis at difficult to treat locations: scalp, palmoplantar disease and nails. Indian J Dermatol Venereol Leprol. 2010;76(6):634–644.
- Kerdel FA, Draelos ZD, Tyring SK, Lin T, Pillai R. A phase 2, multicenter, double-blind, randomized, vehicle- controlled clinical study to compare the safety and efficacy of halobetasol propionate 0.01% lotion and halobetasol propionate 0.05% cream in the treatment of plaque psoriasis. J Dermatolog Treat. 2019;30(4):333-339.
- Sugarman JL, Weiss JS, Tanghetti EA, et al. Safety and efficacy of halobetasol propionate 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis: Pooled analysis of two phase 3 studies. Cutis. 2019;103(2):111-116.
- Green LJ, Kerdel FA, Cook-Bolden FE, et al. Safety and efficacy of halobetasol propionate 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis: Results of 2 phase 3 randomized controlled trials. J Drugs Dermatol. 2018;17(10):1062-1069.
- Armstrong AW, Quintero DGV, Echeverria CM, Gu Y, Karunaratne M, Reyes Servin O. Body region involvement and quality of life in psoriasis: analysis of a randomized controlled trial of adalimumab. Am J Clin Dermatol. 2016;17(6):691-699.
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