D07: Corticosteroids, dermatological preparations
D07 holds the corticosteroids for use on the skin, either plain (D07A) or combined with antiseptics, antibiotics or other drugs (D07B, D07C and D07X). The plain corticosteroids are grouped by potency, from weak (group I, D07AA) to very potent (group IV, D07AD). Hydrocortisone (D07AA02) is in group I, and clobetasol (D07AD01) in group IV [1].
How do topical corticosteroids work?
Glucocorticoids change which proteins a cell makes, either by acting directly on DNA or indirectly by modulating specific transcription factors. Several enzymes induced in inflammation are sites of their inhibitory action. Exactly how they act in the skin was still uncertain in 1998 [2].
Efficacy
The clinical scores for the diseases these drugs treat are described under D05 and D11.
Topical corticosteroids blanch the skin where they are applied, and this response has been correlated with clinical efficacy. Blanching is an accepted pharmacodynamic measure for establishing bioequivalence between corticosteroid formulations, but the approach cannot be applied to all drugs [3].
In the Stoughton-McKenzie vasoconstriction assay, trained observers grade the blanching on a 0 to 4 intensity scale, an ordered categorical observation, or it is measured with a quantitative method, such as reflectance spectroscopy. The FDA accepts the assay as a surrogate method for the bioequivalence of topical corticosteroid products. The intensity of blanching depends on the vehicle, the concentration, the application site, posture and covering of the treated skin (occlusion) [4].
Rath and colleagues fitted an Emax model to blanching from the FDA vasoconstrictor assay to compare two marketed creams. The clobetasol cream came out more potent than the mometasone (D07AC13) cream, although mometasone had the greater inherent potency when the two corticosteroids were tested on their own. The authors suggest that this reversal may be due to formulation factors [5].
Safety
Skin (cutaneous) adverse effects occur regularly with prolonged treatment, and depend on the drug, the vehicle and where it is applied. The most frequent are thinning of the skin (skin atrophy), stretch marks (striae), persistent facial redness (rosacea), a rash around the mouth (perioral dermatitis), acne and purple spots from bleeding under the skin (purpura) [6]. In a systematic review of topical treatments for eczema (atopic dermatitis) in children, topical corticosteroids were the only class associated with reports of skin atrophy [7].
Systemic reactions, such as high blood glucose (hyperglycemia), glaucoma and too little cortisol from the adrenal glands (adrenal insufficiency), have also been reported after topical application. Children are more prone to systemic reactions, because of their higher ratio of body surface area to body weight [6].