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Author: Dr Jacqueline Deen, Dermatology Principal House Officer, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia. DermNet NZ Editor in Chief: Adjunct A/Prof. Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. November 2019.
Calcineurin inhibitors are drugs that work by inhibiting the calcium-dependent protein phosphatase calcineurin, an enzyme that results in activation of T lymphocytes through the upregulation of interleukin-2 and related cytokines, and leads to immunosuppression .
They are commonly used off-label in dermatology for:
Topical calcineurin inhibitors do not cause many of the possible adverse effects of topical corticosteroids, such as striae, cutaneous atrophy, glaucoma, rebound flares, and systemic absorption, or the potential for hypothalamic pituitary–adrenal axis (HPA) suppression.
Indications for topical calcineurin inhibitors
Oral calcineurin inhibitors are commonly used for immunosuppression after solid organ transplantation. Occasionally, systemic ciclosporin and tacrolimus may also be used to treat immune-mediated diseases including psoriasis and atopic dermatitis; however, their use is mainly restricted to patients who have failed to respond to conventional therapy .
The most commonly reported side effect of topical calcineurin inhibitors is local skin irritation (burning, pruritus, and erythema) at the application site. However, this is usually transient and decreases over time (usually within one month).
Other adverse effects may include:
There is no evidence to support the theoretical concern that topical calcineurin inhibitors may increase the risk of malignancy, such as basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma and cutaneous lymphoma. Information reporting this risk is based on data from animal studies, case reports in a small number of patients, and knowledge of how these drugs work [2,4,5].
Potential adverse effects of topical calcineurin inhibitors
The adverse effects of tacrolimus and ciclosporin are generally similar. These include:
Adverse effects of oral calcineurin inhibitors
Calcineurin inhibitors can cause non-cutaneous side effects.
Oral calcineurin inhibitors can cause the following side effects:
Topically applied calcineurin inhibitors do not cause significant systemic side effects as less than 0.1% of the applied dose is absorbed except in conditions with severe skin barrier defects. Large epidemiological studies have not found topical calcineurin inhibitors to be correlated with an increased risk of lymphoma or other malignancies, however a Cochrane review noted such conclusions are affected by lack of reliable data [6, 7].
Cury Martins J, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM. Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev. 2015 Jul 1;2015(7):CD009864. doi: 10.1002/14651858.CD009864.pub2. PMID: 26132597; PMCID: PMC6461158.
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