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

Taken together, the above studies suggest that treatment with oral PLE together with NB-UVB may improve repigmentation in patients with vitiligo; however, larger trials are warranted to confirm these observations.

De las Heras et al,²⁵ in 1997 sought to evaluate the effect of oral PLE as an adjuvant treatment to PUVA for patients with plaque psoriasis; they found that patients who received PLE in addition to PUVA had a statistically significant decrease in cumulative dosage of PUVA required for clearance (P<0.0001), whereas there was no difference regarding the number of UVA sessions required. Histochemically, they observed the preservation of epidermal CD1a+ dendritic cells in patients who had been treated with oral PLE in addition to PUVA. These results suggest that the addition of oral PLE to PUVA could potentially minimize the adverse effects seen with PUVA photochemotherapy, namely local immunosuppression and photocarcinogenesis.

Additionally, Middlekamp-Hup et al,²⁶ demonstrated that oral PLE significantly decreased the acute PUVA-induced phototoxic reaction and also diminished the subsequent cutaneous pigmentary response. By reducing the hyperpigmentation, the need for increasing the UVA dose was also reduced, thus leading to a lower cumulative UVA dose for clearance of psoriasis. Histologically, they showed that in patients treated with oral PLE and PUVA, there was a significantly lower number of sunburn cells (P=0.05) and less depletion of Langerhans cells (P≤0.01) when compared to skin treated with PUVA alone, confirming oral PLE’s effectiveness as a chemopreventative agent against PUVA-induced phototoxicity.

A study by Ramirez-Bosca et al,²⁷ sought to investigate whether daily treatment with PLE would reduce the use of topical corticosteroids in children and adolescents with moderate atopic dermatitis, in which disease severity was evaluated using the Scoring Atopic Dermatitis (SCORAD) index. They enrolled 105 participants, aged 2-17 years, to a randomized, double-blinded, placebo-controlled trial. The patients were randomized to receive, in addition to their standard treatment, either PLE or placebo for 6 months. Patients were divided into 3 treatment groups according to age, such that children aged 6 years or younger received 240mg daily of PLE, children aged 6 to 12 years received 360mg daily (120 mg in the morning and 240 mg at night), and children over 12 years old received 480mg daily in 2 divided doses. The authors found that subjects in the PLE group demonstrated a reduction in topical corticosteroid use from the first month to second month, and from the fourth month to the fifth month (P=0.012). More notably, they found an overall decrease in oral antihistamine use in the PLE group after the first month of treatment, and this finding became statistically significant after the third month of treatment with PLE (P=0.038). Clinically, the authors found a reduction in the number of flares reported by PLE group, however this was not statistically significant. These results indicate that long-term administration of oral PLE, in addition to standard first-line therapy, may have a beneficial effect in the treatment of atopic dermatitis. Again, more studies are needed, however, to confirm these benefits.

PLE has also been investigated for its effect on infectious processes, particularly in athletes regularly engaged in rigorous physical activity (volleyball, football, athletics, cycling) who may be predisposed to a window of immunosuppression after strenuous activity. In 2012, Solivellas et al,²⁸ conducted an observational study in which they enrolled two groups of patients, of which one group received 480mg PLE twice daily for 3 months and the other did not receive PLE. They subsequently compared the onset of respiratory infection and relapse infection rates in both groups. The participants were followed for a total of 8 months. The authors found that symptomatic improvement was reached quicker, was more favorable in the PLE group, and fewer relapse cases were found in this group as well. The authors attributed this effect to the anti-inflammatory and immunomodulatory properties of PLE; specifically, its ability to stimulate peripheral blood mononuclear cells and its effect on cytokines such as an increase in interleukin-2 (IL-2), IL-10, and interferon-α secretion, and a decrease in tumor necrosis factor (TNF) γ levels.²⁹ Additionally, PLE regulates the expression of adhesion molecules on monocytes and lymphocytes and increases membrane antigen expression on T cells and natural killer cells.³⁰ These changes suggest possible augmentation of cell-mediated immunity, especially against viruses.

Oral PLE has been used in the treatment of dermatologic disease with promising results and no reported side effects. It has multiple mechanisms of action, ranging from anti-inflammatory and immunomodulatory to antioxidative and photoprotective.