1. INTRODUCTION: 

(1.1) Background

Palmoplantar psoriasis is a variant of psoriasis that characteristically affects the skin of the palms and soles. It features hyperkeratotic, pustular, or mixed morphologies. Palmoplantar psoriasis has an average age of onset between 20 and 60 years of age and has a  predilection for females 1. Though the incidence has not been determined, the palmoplantar variant of psoriasis comprises 3% to 4% of all cases of psoriasis, which affects 2% to 5% of the population 4-5.It is mostly characterized by well-demarcated, erythematous, scaly plaques of the palms and/or soles. The pathogenesis of palmoplantar psoriasis is similar to psoriasis in that there is an interplay between genetic factors and antigenic triggers. The most commonly associated human leukocyte antigen in psoriasis is HLA-Cw6 4. Psoriasis is related to the psoriasis-susceptibility [PSORS1] locus on chromosome 6p21, though the relation of this gene in palmoplantar psoriasis remains unclear.Thus it has a huge impact on patients quality of life, as it is a chronic recurring condition.5 

(1.2) Need of the study:

Many treatments have been used for decades, but palmoplantar psoriasis is resistant to conventional treatments and therefore requires the use of systemic medications, which has a wide range of adverse effects. Topical drug therapy is the cornerstone in the treatment of mild to moderate psoriasis. It offers a direct targeting of affected skin by avoiding systemic adverse events. 1 

Several topical therapies are available for the treatment of psoriasis such as topical steroid , topical vitamin D3 analogues (calcipotriol),tar, anthraline, topical tacrolimus (a non-steroidal calcineurin inhibitor) and tazarotene (a third-generation retinoid) however, they do not provide an adequate response owing to the inadequate percutaneous absorption and poor patient compliance caused by greasiness and stickiness of some formulations, and some patients even remain untreated .So that, patient satisfaction with available topical treatments remains modest.6

As many topical agents have poor permeability,hence the need for use of penetration enhancers (or accelerants) iontophoresis is the use of a direct electric current to increase the penetration of ionic substances into the body for therapeutic purposes has shown good efficacy and allows a higher concentration of the drug to be delivered to a limited area however it leads to ,disruption of epidermis,loss of appendages and fractured collagen in the dermis and could even lead to irreversible skin damage.8-9

Conventionally, steroids have been used for palmoplantar psoriasis for periods up to 6-8 weeks and sometimes even longer while patients treated with vitamin D analogues, tazarotene and tacrolimus combination treatments primarily experienced an irritant contact dermatitis, subjects receiving topical corticosteroids reported a broad spectrum of adverse events, ranging from viral infection, headache, and hypertrichosis to skin atrophy.7

 In recent years, the new biological therapies (monoclonal antibodies, receptor fusion proteins and similar) have been developed to manage psoriasis in its inner mechanisms of immune regulation. However, the legal (i.e. FDA and EMA-approved use of biologics in psoriasis) and scientific limitations (i.e. guidelines) for the use of biologics, together with the major possible medical involvements connected to this category of therapeutic agents and their expensive cost, make of them a treatment dedicated to a few well-chosen patients. 10

(1.3) Study drug and permeation enhancers:

Methotrexate is an oral or parenteral drug used for the treatment of extensive psoriasis. It is a folic acid antagonist. It is an inhibitor of the enzyme dihydro folatereductase. It inhibits DNA synthesis, acting primarily at the S-phase of the cell cycle. The activity of methotrexate in psoriasis is to inhibit epidermal mitosis. However due to its poor permeability its use as a topical agent is limited, thus in our study we are using it with surfactants for enhancing its permeability.2

Surfactants partition into the skin, and interact with the Stratum corneum constituents to induce a temporary increase in skin permeability without causing  Nonionic surfactant Transcutol was able to enhance transdermal absorption of MTX and the higher enhancement ratio was obtained with 2% (w/w) concentration of transcutol and addition of salicylic acid increased this ratio 1.Thus the current formulation contains transcutol 2% (w/w) and salicylic acid 6 % (w/w) showed higher enhancement property and can be used clinically for local treatment of psoriasis.Thereby achieving an equivalent permeability as that of iontophoresis without causing irreversible damage of skin.