Steroids are disproportionately blown
Corticosteroids for topical use on the skin
Since mainly chronic or recurrent skin diseases are treated with local steroids, the risk / benefit ratio or the side effects of a therapy are of particular importance. In recent years, research has been able to uncover some approaches and mechanisms that could make it possible to decouple effectiveness and side effects.(3,8) In addition, the anti-inflammatory effects (via keratinocytes) and atrophoderma (via fibroblasts) can be influenced in different ways.(9)
However, local side effects are rarely reported, so that there are no reliable statistics on the side effects of local steroids.
The most common side effects of local steroids are the following:(10)
Skin atrophy: Telangiectasia - Striae distensae - Purpura - Ulcerations - Star-shaped pseudo-scars
Infections: Masked infections such as tinea incognita - exacerbation of infections such as candida, herpes - granuloma gluteale infantum
Ocular problems: Increased pressure in the eye or glaucoma - cataract
Contact allergy: Against the steroids or against additives
Chronic Administration Problems: Tachyphylaxis - steroid addiction - rebound phenomenon
Systemic side effects: Cushing's Syndrome - Adrenal Insufficiency - Hyperglycemia
Other local problems: Steroid acne - perioral dermatitis - steroid rosacea - hirsutism - hyper- and hypopigmentation - delayed wound healing
Skin atrophy after steroid therapy has been known for years and is discussed again and again, but there are only a few controlled studies. Initial studies with measurements of skin thickness using radiography, 50 MHz skin sonography or profilometry have produced contradicting results.(11,12) However, the thickness of the epidermis to be measured poorly; such studies mainly measured dermal atrophy. It has been known since the 1970s that steroids primarily cause epidermal atrophy and not dermal.(13)
With the so-called “optical coherence tomography” (OKT), with which the epidermal thickness can be measured, it was shown that skin atrophy developed after 4 weeks of use of methylprednisolone aceponate (Advantan®). This is in contrast to company studies that showed no atrophy after 12 weeks. This study also clearly shows that the more potent the local steroid, the greater the risk of skin atrophy.(14) The correlation between desirable and undesirable effects must therefore be reassessed for the various steroids.
Any steroid with an anti-inflammatory effect has an atrophogenic effect. The Application frequency the local steroid appears to play an important role in the development of skin atrophy. If, between the single application of locally applied clobetasol propionate (Dermovate®), an active ingredient-free phase of about 3 days was switched on, the atrophic effect in long-term use was massively reduced.(15)
The epidermal atrophy makes the dermal blood vessels much more visible. This effect, the abnormal expansion of capillaries and arterioles and also the stimulation of endothelial cell proliferation lead to the formation of cosmetically very disturbing telangiectasias. Changes in the dermal matrix lead to striae and, in connection with the vascular changes, to purpura.
Skin infections / acneiform eruptions
Mucocutaneous skin infections are often observed in connection with local steroid therapy and often manifest at the beginning of treatment.(16) The incidence is between 16 and 43%.(17) Common problem germs are Candida sp., Dermatophytes, pityrosporon ovale and herpes simplex.
Local steroids, especially on the face, can lead to an acneiform eruption within 2 to 3 weeks. People with a history of acne are particularly at risk. The same goes for rosacea and perioral dermatitis.
Systemic side effects
Systemic side effects rarely occur when the local steroids are used properly. The absorption of steroids through the skin is not only individually different, but also depends on the anatomical location. While the absorption on the forearm (1%) and on the scalp (4%) is low, up to 35% of the applied steroids are absorbed on the scrotum.(18)
Children in particular are at risk (because of the higher ratio between body surface area and body weight) and old people (because of their mostly atrophic, dry and cracked skin). The persistent inhibition of endogenous cortisol secretion can lead to Cushing's syndrome.(19,20) Severe systemic side effects such as adrenal insufficiency, diabetes and fetal toxicity have been observed in the black population of Paris as a result of abuse of depigmentation creams containing clobetasol propionate.(21)
Some of these creams are sold over the Internet without any control. In a new study, 20 children aged 5-12 received topical treatment with a 0.1% hydrocortisone butyrate cream (Locoid®) three times a day for 4 weeks.(22) No adrenal suppression was observed in any of these children. It must be emphasized, however, that this treatment only lasted 4 weeks and it is not known what would happen after longer treatment.
In recent years it has become more and more apparent that a contact allergy can develop to the various modifications of the corticosteroids. If dermatitis does not react to the local steroids, but becomes more and more inflammatory, then an allergy to steroids or substances in the ointment base should be excluded. Patch testing with various steroids has shown that there are four groups of cross-reacting corticosteroids. These are compiled in Table 3. The most common contact allergies are observed against budenoside, tixocortol pivalate and hydrocortisone-17-butyrate.(24) If an allergy to one or more steroid classes is found in the patch test, a local steroid of a different class should be prescribed and the person concerned must be issued a corresponding allergy passport. It is important that this allergy pass not only describes the steroids to which a reaction occurred, but also that the alternative steroid classes are specified.
Immediate-type allergy to individual steroid preparations is possible, but extremely rare (around 10 known cases).
Tachyphylaxis, addiction and rebound phenomena
Tachyphylaxis is defined by a steadily decreasing effect of the steroids. It can be directly associated with a temporary reduction in glucocorticoid receptors (25) and is measured experimentally by reducing vasoconstriction and inhibiting fibroblast proliferation.(10) As a result, for longer, regular use, increasingly stronger steroids with a higher potential for side effects have to be used. This is also important for long-term treatment with hydrocortisone preparations, in which the effect slowly wears off and leads to a change to stronger steroid classes.
The Addiction of steroids is primarily an issue related to the uncontrolled use of local steroids on the face. After stopping, acne, rosacea, perioral dermatitis may flare up.
The Rebound phenomenon is often observed with psoriasiform dermatoses; here the dermatosis exacerbates with the formation of pustulosis as soon as the steroids are reduced. Rebound phenomena are also observed in other chronic dermatoses, e.g. in atopic dermatitis. The rebound phenomenon can largely be avoided if, after an initial treatment with potent steroids, the strength class of the steroids is reduced (step therapy) and the frequency of use is also slowly reduced. The steroids are slowly tapered off over a period of about 1 month.
The improvement in therapy schemes has led to the fact that tachyphylaxis can now be avoided even with long-term therapy. In the light of the more recent findings on the glucocorticoid receptor (GR), the question of whether tachyphylaxis is related to the quantitative ratio of the two isoforms hGR and hGR is interesting. (3)
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