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Issue 2 (2004)

Interview with Professor Dr. Thomas Luger on the Therapy of the Atopical Eczema

Topical glucocorticoids are no longer the drug of first choice in either case

In December 2003 the guideline „Topical Dermatotherapy based on Glucocorticoids - Therapeutical Index“ was published in the guideline registry of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) (Working Group of Scientific Medicinal Departments). The guideline has been established by the Deutsche Dermatologische Gesellschaft (DDG) (German Dermatological Society) under the auspices of the DDG’s Secretary General professor Dr. med. Thomas Luger, director of the University Dermatological Clinic of Münster. Professor Luger explained the guideline in a conversation with DermoTopics’ editor-in-chief, Dr. Joachim Kresken, and furthermore introduced a novel concept for the treatment of the atopical eczema.

Professor Luger, a therapeutical index (TIX) for glucocorticoids was introduced together with the DDG guideline published in December 2003. What is the definition of the index? On which criteria is it based?

Professor Luger:
As is generally known, topical glucocorticoids may induce besides their wanted anti-inflammatory effect also unwanted local and possibly also systemic effects. The TIX expresses the relation between the summation of the wanted and the summation of unwanted effects of a topical glucocorticoid thus reflecting the benefit-risk relationship of the substance in question. The higher the TIX value, the more favourable is the benefit-risk relationship. Criteria for an assessment of wanted effects are the vaso constriction and effectiveness at the atopical eczema in comparison to other glucocorticoids. Criteria for an evaluation of unwanted effects are skin atrophy, the suppression of the hypophysis-cortex of suprarenal gland-axis and the allergenic potential of the substance. The data drawn on for the determination of the TIX values have been taken from the literature available.

Which topical glucocorticoids have been considered and what are the results?

Professor Luger:
Regarded were betamethasonvalerate, clobetasolpropionate, hydrocortisone, hydrocortisone butyrate, mometasonfuroate, methylprednisolonaceponate, prednicarbate and triamcinolonacetonide. They represent the 8 glucorticoids which are most frequently prescribed in Germany. The results reveal that topical glucocorticoids are better than their reputation. The unwanted effects outperformed the wanted ones for none of the investigated substances. The TIX values determined for all checked substances were between 1.0 and 2.0.

When comparing the results of the individual substances it can be noticed that TIX values of 2.0 respectively have been determined for mometasonfuorate, methylprednisolonaceponate and prednicarbate whereas hydrocortisone butyrate, to which equally a relatively favourable benefit-risk relationship is ascribed only obtained the value of 1.4. How can the difference be explained?

Professor Luger:
The TIX value indicated in the guideline for hydrocortisone butyrate is, as only turned out retrospectively not entirely correct. In fact the value is also at 2.0 and not at 1.4. A correction will be made in the process of the actualization of the guideline which is due in brief. The error is caused by a too low assessment of the wanted vaso-constrictorical effect and a too high assessment of the allergenic potential. The allergenic potential has been over-evaluated due to the fact that remarkably more positive epicutaneous test reactions have been described for this glucocorticoid compared to other investigated substances. We know, however, today that this diagnostic finding is not due to a higher allergenic potential but merely caused by the fact that there is a higher frequency of use of hydrocortisone butyrate in epicutaneous tests compared with the other substances.

Professor Dr. med. Thomas Luger, director of the University Dermatological Clinic Münster (archive photograph, taken on the occasion of 7th GD Annual Meeting in Bonn on 1 and 2 April 2003)

Which therapeutic consequences should in your opinion be drawn from the TIX values determined? Should from now on only topical glucocorticoids with a TIX of 2.0 be applied or are also substances with lower values in certain cases further indicated?

Professor Luger:
From the TIX values determined, a general conclusion in the sense of a classification of „recommendable“ respectively „not recommendable“ should not be drawn. The attention should rather be directed to which strengths and weaknesses the individual substances exhibit. Thus for example clobetasolpropionate, for which a TIX of 1.5 has been determined due to its strong antiphlogistic effect, is a substance of first choice in the short-term therapy of the severely pronounced eczema and other corticoid-sensitive dermatoses. This in particular applies to the treatment of hand palms, soles of feet and the scalp where the strongly atrophogenic potential of the substance does not take effect in contrast to the face for example. Hence the localization influences to a great extent the side-effect risk of the selected glucocorticoid.

You appealed to the short-term therapy, however which strategies do you recommend for the long-term therapy of an atopical eczema? Which topical glucocorticoids are here indicated?

Professor Luger:
If the application of a topical glucocorticoid is considered for the long-term therapy of the atopical eczema, then a substance with a favourable benefit-risk relationship is to be selected if so possible. However, altogether the frame for the topical glucocorticoids in the long-term therapy of the atopical eczema has narrowed, since the topical immuno-modulators Tacrolimus and Pimecrolimus are available as further therapy option which are in some aspects more advantageous than the topical therapy with glucocorticoids.

Which drawbacks are there in your opinion for the topical glucocorticoids in comparison to the topical immuno-modulators in particular in the long-term therapy of the atopical eczema?

Professor Luger:
Unlike the topical immuno-modulators, the topical glucocorticoids entail a damaging of the epidermal barrier in long-term application. We know from recent investigations that they cause a loosening of the horny layer and are able to change the physiological lipid pattern of the barrier. These effects explain the phenomenon of the tachyphylaxy often observed in long-term therapy. Moreover, the topical glucocorticoids negatively affect the skin immune system. To quote an example in this respect is their effect of inducing the apoptosis of Langerhans cells.

In the preamble of the mentioned DDG guideline, the local treatment with glucocorticoids is nevertheless still described as substance of first choice for the treatment of eczema. To what extent can this classification be further maintained today?

Professor Luger:
For the short-term treatment of an acute eczema this classification is unrestrictedly valid, however this does not apply to the long-term treatment of the atopical eczema. Here, in analogy to the treatment of the asthma bronchiale, a gradual therapy is to be performed targeting at prevention of the emerging of eczema attacks by early intervention.

What are your recommendations for the gradual therapy of the atopical eczema in detail?

Professor Luger:
When the eczema cannot be suppressed by the sole application of the caring preparations for external application, the first medicinal step of treatment should be a topical mono therapy with Pimecrolimus or in particular in case of a more severe pathology it should be started with Tacrolimus. In the further progressed stage, this treatment can be combined with a topical glucocorticoid applied in alternation before a systemical therapy for example with a glucocorticoid or ciclosporine is considered in the last stage.

Professor Luger, thank you for the conversation.


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