Organ of the
GD Society for Dermopharmacy
Hope for atopical Dermatitis
A therapy of the atopical dermatitis with systemical and topical glucocorticosteroids is connected with the risk of numerous side effects. Tacrolimus recently discovered, represents a non-steroid topical principle which not only influences the disease in a very effective manner by its immunomodulatory effect but moreover contributes to an improvement of quality of life. Thus Tacrolimus constitutes a real progress in the treatment of the atopical dermatitis.
Clinical Effectiveness Proven
discovered by Fujisawa Pharmaceutical Company in 1984 is a macrolide which
is mainly used in transplantation medicine as immunosuppressant. As
could be shown however, the substance cannot only be applied systemically
with success but it also supplies good results in the treatment of inflammatory
dermatoses in topical application.
In view of the fact that Tacrolimus is in fact an immunosuppressant the question arises whether its positive effect at the diseased skin is at the expense of safety, i.e. whether a systemical immunosuppression takes place after percutaneous absorption. Or else a real immunomodulation comes about - as has been hoped for - which brings back the immunologic process into the right tracks?Even if final answers are still pending due to the insufficient experience at present it could be shown in long-term studies that for 75 per cent of the patients the substance could not be proven in the peripheral blood; the speculi of the remaining have been very low. In addition, the uptake of the drug into the systemic circulation gets lower and lower the more the skin condition improves. Healthy skin is not penetrated.
A clinical sign for a systemical immunosuppression is the increase of the number of pigmented naevi as can be observed under the treatment with immunosuppressants after organ transplantations. In a one-year study regarding Tacrolimus in Helsinki the number of naevi did not change.
This allows coming to the conclusion that there is no systemical immunosuppression. The memory-antigen-tests equally underpin this assumption.
A known problem of the atopical dermatitis represents the colonisation of skin lesions with staphylococcus aureus. In the course of the Tacrolimus treatment a distinct reduction of the staphylococcus-colonies has been achieved. This effect again indicating a lack of immunosuppression probably comes about by the amelioration of skin. For a direct anti-bacterial effect which could be quite conceivable due to the structural relationship with erythromycin, the therapeutically used Tacrolimus concentrations are probably too low.
No Skin Atrophy
An essential advantage
of Tacrolimus compared with halogenated glucocorticosteroids lies in the
fact that there is no process of skin thinning. In a double-blind placebo-controlled
study, Tacrolimus has been compared with betamethasonvalerat. When applying
the steroid a distinct reduction of the collagen synthesis and thus a
decrease of the skin thickness has been entailed whereas Tacrolimus has
not shown any influence on any of the two parameters. Additional investigations
have shown that patients having got a marked atrophy of the skin following
a steroid therapy, a distinct reduction of the atrophy and an increase
of the skin thickness could be observed after a twelve month's treatment
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