Topical calcineurin inhibitors in dermatology. Part I: Properties, method and effectiveness of drug use

Abstract

A Ad dd dr re es ss s f fo or r c co or rr re es sp po on nd de en nc ce e: : Prof. A b s t r a c tTopical calcineurin inhibitors (TCI) are a relatively new class of drugs used in dermatology. There are two drug forms available -tacrolimus 0.03% or 0.1% ointment and 1.0% pimecrolimus cream. The drugs act by inhibiting synthesis of proinflammatory cytokines. The only approved indication for using TCI is treatment of atopic dermatitis. The TCI may be used as an alternative therapy to corticosteroids. Tacrolimus is used to treat moderate-to-severe atopic dermatitis, pimecrolimus -mild-to-moderate atopic dermatitis. Topical calcineurin inhibitors do not cause skin atrophy and the drug absorption through the skin is minimal. The TCI have been well-studied, their efficacy was evaluated in a number of vast, long-term studies. The anti-inflammatory potency of tacrolimus ointment is similar to a corticosteroid with moderate activity, while the latter is clearly more active than pimecrolimus cream. Topical calcineurin inhibitors significantly relieve pruritus in atopic eczema.K Ke ey y w wo or rd ds s: : topical calcineurin inhibitors, tacrolimus, pimecrolimus.

Dexamethasone but not tacrolimus suppresses TNF-α-induced thymic stromal lymphopoietin expression in lesional keratinocytes of atopic dermatitis model

“…On the other hand, the calcineurin inhibitor tacrolimus is a complex macrocyclic compound that binds to the intracellular protein macrophilin-12 and functions as a macrolactam immunomodulator, thereby inhibiting the activity of the phosphorylase enzyme calcineurin [24]. Since not only T-lymphocytes but also epidermal keratinocytes express immunoferrin, calcineurin and NFAT, tacrolimus as well as dexamethasone have the possibility to regulate TSLP expression by direct action on epidermal keratinocytes [37,38].…”

“…Topical glucocorticosteroids and calcineurin inhibitors are commonly used as clinical agents for AD [23][24][25]. However, the effects of these agents on TNF-a-induced TSLP expression in human epidermal keratinocytes have not been studied well.…”

Atopic dermatitis and tacrolimus: Current perspectives

“…The TCI have been well-studied, their efficacy was evaluated in a number of vast, long-term studies. [6] …”

Position statement: topical calcineurin inhibitors in atopic dermatitis

“…The standard approach is the 'Scoring of Atopic Dermatitis' (SCORAD), 10 but another commonly used scale to assess disease severity is the Eczema Area and Severity Index (EASI). 9,10,15 What about the mechanism of action and therapeutic indications in AD? 9 To this end, anti-inflammatory treatment based on topical corticosteroids and TCIs should be used for the management of exacerbations and the proactive therapy of selected cases.…”