Topical therapy of psoriasis: Where do we stand?
DM Thappa, M Malathi
Department of Dermatology and STD, JIPMER, Puducherry, India
D M Thappa
Department of Dermatology and STD, JIPMER, Puducherry
|How to cite this article:|
Thappa D M, Malathi M. Topical therapy of psoriasis: Where do we stand?.J Postgrad Med 2017;63:210-212
|How to cite this URL:|
Thappa D M, Malathi M. Topical therapy of psoriasis: Where do we stand?. J Postgrad Med [serial online] 2017 [cited 2022 Nov 29 ];63:210-212
Available from: https://www.jpgmonline.com/text.asp?2017/63/4/210/216436
Psoriasis, an immune-mediated inflammatory disorder with genetic and environmental influences, is a common, chronic, disfiguring, inflammatory, and proliferative condition of the skin, characterized by well-defined erythematous, scaly indurated plaques predominantly affecting the scalp, and extensor surfaces. Despite psoriasis being a benign and noncontagious condition, it significantly affects the quality of life of patients owing to the cosmetically disfiguring nature of the lesions. Based on the extent of involvement and affection of quality of life, the treatment of psoriasis is individualized with either topical therapy for mild-to-moderate cases and phototherapy or systemic therapy for moderate-to-severe cases.
The majority of patients with psoriasis have limited disease, which can be managed with topical therapies alone. Thus, topical therapy plays a very important role in the therapeutic armamentarium of psoriasis, and it is not only limited as monotherapy in the treatment of mild and localized lesions but also has an adjuvant role in the treatment of lesions in specific locations and for residual lesions during or after treatment with phototherapy or systemic therapy including biologics. This strategy of combining topical therapy with systemic and phototherapy results in additional and immediate symptom relief, reduction in the dose of systemic medications, and better psychological comfort to patients.,,,,
The various topical therapeutic agents used in psoriasis include emollients, keratolytic agents such as salicylic acid, coal tar, dithranol, corticosteroids, Vitamin D analogs, retinoids, and immunomodulators such as tacrolimus and pimecrolimus.,,,,, Recommendations based on evidence-based data suggest class I corticosteroids, Vitamin D analogs, tazarotene, and combinations of either corticosteroids and Vitamin D analog or corticosteroids and tazarotene as class A rank drugs (evidence based on large, prospective, double-blind studies and consistent and good-quality patient-oriented evidence) that are statistically superior to other topical therapies., Other agents that have been tried in topical therapy of psoriasis include 5-fluorouracil, ascomycin derivative, methotrexate, and leukotriene inhibitors.
Despite their proven efficacy and safety in psoriasis, there is a continued need for more effective and better tolerated agents with different mechanisms of action for the treatment of recalcitrant lesions and for improved patient adherence. These newer developments include newer combinations, better formulations, newer investigational agents, or a comeback of older traditional therapies.
The need for newer and better formulations to improve topical drug-delivery systems cannot be understated owing to the unique nature of drug delivery across the skin which affects the pharmacokinetics of the drug. This is of special relevance in psoriasis, wherein the heterogeneity of the skin lesions with both thickened and markedly thinned epidermis can increase the variability in drug permeation and systemic absorption, thereby posing challenges in formulation development. Reduced drug concentration can also occur due to presystemic metabolism of the drug in the skin. High variability in in vitro and in vivo skin permeability also adds to the obstacle in formulation development. Hence, failure to choose the optimal topical formulation appropriate for the morphology and site might contribute to poor treatment outcomes. Thus, newer topical formulations should have improved drug-delivery mechanisms with appropriate cosmetic elegance which can be used on many areas of the body including hair-bearing sites to ensure therapeutic efficacy and improved adherence. Liposomes, microemulsions, solid lipid nanoparticles, nanostructured lipid carriers, and micelles may have the potential to encapsulate antipsoriatic drugs for topical application. In addition, techniques such as iontophoresis, electroporation, and lasers can be used to enhance penetration of the stratum corneum.
The investigational topical agents for psoriasis target the small molecules that modulate proinflammatory cytokines and selectively inhibit signaling pathways which include inhibitors of phosphodiesterase 4, integrin, Janus kinase (JAK) 1/JAK2 (ruxolitinib, tofacitinib), and tyrosine kinase., AN2728, a boron-based phosphodiesterase 4 inhibitor with anti-inflammatory property, has been administered topically in phase 2 studies to patients with psoriasis. JAK inhibitors, being small molecules, can easily penetrate the epidermal barrier and hence are used in topical formulations. Tofacitinib, a pan-JAK inhibitor with predominant anti-JAK3 effect, and ruxolitinib, a JAK1/2 inhibitor, have shown promising results in the topical treatment of mild-to-moderate psoriasis. CT327, a tyrosine-kinase A inhibitor in a topical formulation, has been reported to be safe and well tolerated, causing a significant reduction in pruritus. Methotrexate, the dihydrofolate reductase, has been developed as a nanogel composed of methotrexate-loaded nanostructured lipid carrier for topical application and has been reported as a promising alternative to the existing methotrexate formulation in treating psoriasis.
The traditional therapy with immunomodulatory property which is being currently investigated in the topical therapy of psoriasis is Saint John's wort (SJW) (Hypericum perforatum). It is a traditional herbal medicine which has been used topically as oils or tinctures for the treatment of minor wounds and burns, sunburns, abrasions, bruises, contusions, ulcers, and myalgia and orally for the treatment of depression with pharmacologic research supporting its use in these indications. Owing to the antioxidant, anti-inflammatory, anticancer, antimicrobial, and photosensitizing properties as well as the effect on keratinocyte proliferation and differentiation, SJW has been investigated in the treatment of dermatological disorders such as atopic dermatitis, psoriasis, herpes infections, and nonmelanoma skin cancer. These properties are attributed to the active constituents of SJW, namely, the naphthodianthrone derivative hypericin and the phloroglucin derivative hyperforin. The effect of SJW in psoriasis is due to the hyperforin derivative which displays anti-inflammatory activity on T-cells and stimulation of keratinocyte differentiation. These effects of hyperforin are mediated by the effects on cell signaling or production of cytokines, rather than merely toxic effects especially by regulation of CD8-mediated cytotoxicity and inhibition of tumor necrosis factor (TNFα)-induced apoptosis. Moreover, owing to the photosensitizing property of hypericin, SJW can be considered as a viable investigational agent for photodynamic therapy in psoriasis. SJW was reported to be effective in reducing psoriasis area severity index scores in mild plaque-type psoriasis when compared to placebo in a case series. However, large, well-conducted trials are required to provide conclusive evidence.
Taking cue of these facts, Mansouri et al. have formulated an ointment with added extract of H. perforatum in vaseline, propylene glycol, and avicel for the treatment of mild-to-moderate psoriasis. They have conducted a double-blind placebo controlled study to investigate the effects of topical H. perforatum on TNF levels in psoriatic lesions for possible identification of the mechanism by which Hypericum reduces inflammation and modulates the disease in patients with plaque-type psoriasis. They have observed that H. perforatum in the ointment decreases the TNFα levels in psoriatic lesions, thereby proving that the beneficial effect of SJW in psoriasis is probably directly or indirectly associated with its effects on lowering cytokines including TNFα. Although the study design selected was appropriate, the study was not sufficiently powered due to the small sample size. The results obtained from their study need to be validated with a larger sample size. If the efficacy of this topical agent is proven in future studies, it can be included in the armamentarium of topical agents used for the management of mild-to-moderate plaque type of psoriasis.
To conclude, topical therapeutic agents in psoriasis have come a long way from traditional therapies to newer investigational therapies owing to advances in the understanding of the pathogenesis of psoriasis. In addition, significant efforts have been made to improve the efficacy, tolerability, and patient adherence by implementing better drug combinations and formulations. Despite all the developments, symptom reduction, cosmetic clearing of the skin, and better quality of life still remain a challenge for dermatologists warranting continuous research for identifying newer treatments.
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