The topical corticosteroid classification called into question: towards a new approach

Abstract

ConclusionsTo date, majority of studies on EMT have been carried out on airway epithelial cell (see Supplementary Reference 3) types as well as bronchial cells (see Supplementary Reference 4) and kidney cells (see Supplementary Reference 5) but not with primary keratinocytes that too from vitiligo patient tissues. Therefore, a better insight into the mechanisms underlying EMT during wound healing is highly relevant. However, an unequivocal role for keratinocytes in the repair of wound in vitiligo patients remains unclear. We are not certain whether it is an 'all-or-none' phenomena where all the keratinocytes have phenotypic plasticity or whether only a subpopulation of them is actually pliable. Nevertheless, our study offer convincing evidence that vitiligo patient-derived keratinocytes undergo EMT similar to their normal counterparts and probably contribute to the process of wound repair in skin tissue. AcknowledgementsKrupa Shankar (KS) provided the skin samples; Rajarshi Pal (RP) designed the study; Poulomi Banerjee (PB), Sandhyaa Venkatachalam (SV) and Murali Krishna Mamidi (MMK) performed the research; PB and RP analysed the data; PB wrote the manuscript; RP and Ramesh Bhonde (RB) edited it. Manipal University, Manipal, is gratefully acknowledged for the graduate fellowship to PB. Conflicts of interestThe authors have declared no conflicting interests. Supporting InformationAdditional supporting data may be found in the supplementary information of this article. Figure S1. The schematic depicts a flowchart for isolation of primary keratinocytes and the subsequent experiments to characterize the cells and validate our hypothesis. Figure S2. ( Data S1. Materials and methods. Table S1. Shows the details of the patient samples used for this study. Table S2. Details of antibodies used for this study. Vasoconstrictor assay described in 1962 was an interesting assessment of potency of topical corticosteroids at the beginning of these new therapies, however knowledge and technology have evolved and the classification should follow. A topical corticosteroids with a strong vasoconstrictor effect, as determined by vasoconstrictor assay, has not necessary a strong anti-inflammatory effect. Therefore a specific classification adapted to the therapeutic target is needed to be more efficient and thus reduce side effects and corticophobia.

Anti‐inflammatory potency testing of topical corticosteroids and calcineurin inhibitors in human volunteers sensitized to diphenylcyclopropenone

“…The DPCP model in healthy volunteers is a promising alternative to the vasoconstrictor assay, which is only relevant for corticosteroids. Furthermore, the traditional classification of topical corticosteroids has been questioned due to the fact that a strong vasoconstrictor effect, as determined by the vasoconstrictor assay, is not necessarily equivalent to a strong anti‐inflammatory effect .…”

A Novel Approach to Assess the Potency of Topical Corticosteroids

“…Unlike other therapeutic classes of drugs, such as antifungals or antibacterials, topical corticosteroid products have been ranked and classified depending on their potencies [ 1 ]. The main method to evaluate the potencies of topical corticosteroid products has been through the results of their clinical use and randomized clinical comparative studies [ 2 ].…”

Topical therapy of atopic dermatitis with a focus on pimecrolimus

“…Topical corticosteroids act on immune cells, impeding antigen processing and inflammatory cytokine release 56 . Furthermore, TCS reduce cell proliferation, neutrophil adhesion, human leukocyte antigen expression, chemotaxis, phagocytosis, collagen synthesis, capillary permeability and dilatation, while increasing lipocortin 1 production and protein catabolism 76,77 . In addition to anti‐inflammatory and immunomodulatory effects, TCS may also lead to local adverse effects, such as impairment of skin barrier function, development of striae and skin atrophy, perioral dermatitis, rosacea and allergic contact dermatitis, especially when not used properly 78–80 .…”