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Calcineurin inhibitors are ascomycin macrolactam derivatives with immune-modulating and anti-inflammatory properties. Topical preparations on the market to date are:
They have the following immune-modulating effects:
Tacrolimus may also have direct effects on skin cells (keratinocytes). It appears to reduce the number of IL-8 cytokine receptors on the keratinocyte, hence reducing inflammation.
In New Zealand only pimecrolimus is approved for use for the short-term and long-term treatment of atopic dermatitis in patients that are over 3 months of age. However both drugs are proving helpful for many other skin conditions, usually those that also respond to topical steroids.
As these drugs do not cause skin atrophy, they may be applied to all skin surfaces including the head, face, neck, around the eyes, and skin folds. They are best used twice daily at the earliest sign of inflammation.
Because it is unfunded and expensive in New Zealand, current use of pimecrolimus cream is mainly for areas in which there are serious concerns about corticosteroid atrophy especially face, genitals and flexures. To date it has not been directly compared with hydrocortisone cream or other topical steroids, but is thought to be of mild to moderate potency. Tacrolimus appears to be more potent.
Topical pimecrolimus and tacrolimus are usually well tolerated. There are low levels of systemic absorption. The most common side effect at the site of application is a mild to moderate feeling of warmth or a sensation of burning.
Oral tacrolimus is a powerful immunosuppressive, so there are concerns that long term use may increase the risk of cutaneous carcinogenesis. However, this is less of a concern for pimecrolimus, which has no effect on Langerhans cells. Although there's no definite evidence that these drugs lead to more severe bacterial, fungal and viral skin infections, current recommendations are that they are temporarily discontinued if infection arises. At this time, sun protection is strongly advocated, in case they do promote skin cancer, and they should be discontinued when the eczema has cleared.
Describe the evidence that pimecrolimus cream is effective and safe in the treatment of childhood atopic dermatitis.
Developed in collaboration with the University of Auckland Goodfellow Unit in 2007.
Author: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, 2008.
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