Role of Oral Polypodium Leucotomos Extract in Dermatologic Diseases: A Review of the Literature

February 2014 | Volume 13 | Issue 2 | Original Article | 148 | Copyright © February 2014

Samreen Z. Choudhry MD,a Neal Bhatia MD,b Roger Ceilley MD,c Firas Hougeir MD,d
Robert Lieberman MD,e Iltefat Hamzavi MD,a and Henry W. Lim MDa

aDepartment of Dermatology, Henry Ford Hospital, Detroit, MI
bAssociate Clinical Professor, Harbor-UCLA Medical Center, Los Angeles, CA
cClinical Professor of Dermatology, University of Iowa, Private Practice, West Des Moines, IA
dAtlanta, GA
eThomas Dermatology, Inc. Las Vegas, NV

A study by Tanew et al,18 also evaluated the effect of oral PLE in PMLE. Of the 35 patients studied, 30 developed PMLE lesions after irradiation with UVA and 18 after UVB irradiation. After two-week treatment with oral weight-based dosing of daily PLE (≤55kg: 720mg/day; 56-70kg: 960mg/day; >70kg: 1200mg/day), 9(30%) patients and 5(28%) patients were unresponsive to repeated UVA and UVB exposure, respectively. The mean number of exposures required to induce PMLE lesions in remaining patients showed a statistically significant increase for both UVA (P=.005) and UVB (P=.047), demonstrating the suppressive effect of oral PLE on photoinduction of PMLE.
Oral PLE has been reported as an adjuvant therapy in SCLE. A recent publication reported a patient with biopsy-proven SCLE, moderately controlled on hydroxychloroquine sulfate 200mg BID and daily use of zinc oxide sunscreen; this patient achieved near total remission of his SCLE with addition of oral PLE 240 mg daily.19 Within four months, the patient demonstrated clinical improvement on the face and neck as well as complete clearance of the skin on his back, and in 37 months of daily oral PLE use, he only had 3 flares, which were all in the summer months. Clearly, more studies are needed to confirm this finding.

PLE and Melasma

The ability of PLE to provide systemic photoprotection has lead to the study of PLE as an adjunctive treatment of melasma (Table 1). A study presented as a poster (but yet unpublished) by Martin et al,20 reported that oral PLE is an effective and well-tolerated agent in reducing melasma severity. In this double-blind placebo controlled trial, 21 females were randomized to receive either placebo plus sunscreen with SPF 45 or oral PLE plus sunscreen with SPF 45 for 12 weeks, and participants rated their perceived improvement at the end of 12 weeks. The authors found a statistically significant improved mean Melasma Area and Severity Index (MASI) scores in the oral PLE group. Additionally, photographic assessment by a blinded investigator revealed mild improvement in 43% of subjects receiving PLE as compared to 17% of patients receiving placebo, and marked improvement in 14% of subjects receiving PLE as compared to 0% of patients receiving placebo.
A recently published randomized, double-blinded study by Ahmed et al,21 found no difference in improvement of melasma in patients taking oral PLE versus placebo. In this study, forty Hispanic females were randomized to receive either placebo or oral PLE 240 mg three times daily for 12 weeks, in addition to a “standard topical sunscreen”. Treatment outcomes were measured by determining melanin intensity via reflectance spectrophotometry of affected as well as adjacent normal skin, and MASI scores. Although the authors found a statistically significant improvement from baseline to week 12 in both PLE and the placebo group, there was no significant difference between the two groups using either outcome measure. They concluded that oral PLE was no better than placebo as an adjunct to topical sunscreen for the treatment of melasma.
Given limited data on treatment of melasma with oral PLE, more studies with a larger sample size are needed to further evaluate the efficacy of oral PLE for the treatment of melasma.

PLE and Vitiligo

Oral PLE has also been studied as a treatment for repigmentation in vitiligo. PLE’s antioxidant effects as well as a shift from a Th1 T-cell cytokine profile to a Th2 T-cell cytokine profile—namely a decreased production of IL-2, IFN-γ and TNF-α and increased production of anti-inflammatory cytokine, IL-10 - are thought to play a role in its use in vitiligo.7 A poster presentation by Pacifico et al,22 at the American Academy of Dermatology meeting in 2009 suggests that oral PLE 480 mg daily in combination with NB-UVB was more effective in repigmentation of patients with generalized vitiligo than treatment with twice weekly NB-UVB alone (40% vs 22%, P<0.0005). The authors concluded that oral PLE in conjunction with NB-UVB can improve response to treatment both in terms of extent and rapidity of repigmentation.
Another study by Reyes et al,23 compares PUVA alone to PUVA plus oral PLE as a treatment for generalized vitiligo. In this randomized, double-blinded clinical trial, nineteen patients underwent randomization to receive either PUVA alone or PUVA with oral PLE, and repigmentation rates were assessed by independent dermatologists. The authors found a higher rate of moderate to excellent repigmentation in the PUVA and oral PLE group compared to the PUVA alone group. They also demonstrated that oral PLE+PUVA normalizes expression of activation markers by T cells and suppresses proliferation of peripheral blood mononuclear cells versus PUVA alone. This study underscores the immunomodulatory effects of oral PLE as an adjuvant to phototherapy in treatment of vitiligo.
Another study by Middlekamp et al,24 investigated the effect of oral PLE and NB-UVB in repigmentation in patients with vitiligo. Fifty patients were randomized to receive either PLE 250mg orally TID or placebo, both in conjunction with NB-UVB treatments twice weekly for 25-26 weeks, with the primary outcome measure being percentage of repigmentation at week 26. Although they did not find a statistically significant difference, they observed higher repigmentation rates in PLE group, specifically in the head and neck areas (44% vs 27%, P=0.06). They also found that lighter skin types (Fitzpatrick skin types II and III) showed significant increased repigmentation in the head and neck areas compared to placebo group (47% vs 21%, P=0.01). Secondary outcome measures included quality of life changes measured with Skindex 29; there were no significant differences between the PLE group and placebo group. Moreover, patient self-assessment at week 26 indicated no differences between PLE group and placebo group.