Parallel intraindividual evaluation of the vasoconstrictory action and the anti‐allergic activity of topical corticosteroids

Abstract

The human skin blanching assay is a well established method for ranking the efficacy of corticosteroids after epicutaneous application. Vasoconstriction is a pharmacological activity, which correlates well with the clinical efficacy, the intensity of skin blanching after a single application under occlusion corresponding, generally, to the clinical efficacy after repeated application without occlusion. However, in studies dealing with the comparison between the vasoconstriction assay and the evaluation of the clinical effects on inflammatory skin diseases, some exceptions to this correlation have been reported. Therefore, in a pre-clinical phase, it would be useful to combine the blanching assay with at least one anti-inflammatory assay. In the present study the blanching assay and the allergic contact dermatitis inhibition test were performed in parallel, in order to compare the two testing procedures in the same group of subjects, utilizing standardized study designs supported by objective means of evaluation. Three commercial preparations of corticosteroids containing clobetasol propionate (CP), clobetasone butyrate (CB) and hydrocortisone acetate (HA), respectively, were employed both to treat nickel-induced positive patch test responses on the volar forearms, and to perform a vasoconstrictor assay on normal forearm skin in 16 nickel-sensitized healthy volunteers. For evaluating skin blanching, we employed colorimetric measurements, whereas for the quantitative determination of the inhibition of the intensity of allergic patch test reactions, 20 MHz B-scanning supported by image analysis was used. Both colorimetric and echogenicity values enabled us to distinguish between the three corticosteroids (at the 17 h evaluation and the 64 h assessment, respectively). A fair correlation was noted between colorimetric and echogenicity values. Both testing procedures ranked the three corticosteroids in the expected order. Corticosteroid preparations should be compared using methods which allow different effects to be simultaneously monitored, without involving a high number of patients. We are proposing this double procedure for the parallel intraindividual evaluation of the vasoconstrictory action and the anti-allergic activity of topical steroids.

An overview of the efficacy of topical corticosteroids in experimental human nickel contact dermatitis

“…De Lacharriere et al (6), Seidenari et al (8,10) and Di Nardo et al (9) compared the effect of corticosteroid to sensitized, untreated skin. They did not include a vehicle control.…”

“…Echographic evaluation assumes that increased inflammation and edema will result in increased skin thickness and hypoechogenic area (8,10). Accordingly, the decrease should be positively correlated with the potency of corticosteroid tested.…”

“…Accordingly, the decrease should be positively correlated with the potency of corticosteroid tested. However, echographic evaluation is not sensitive enough to evaluate the efficacy of low-potency corticosteroids: in the reviewed studies there was no significant difference between hydrocortisone acetate and untreated skin (9,10). The echographic technique is also influenced by the timing of corticosteroid application and the test site (5,33).…”

Increased bioavailability of hydrocortisone dissolved in a cream base

“…6 Clinical studies have established that the intensity of skin blanching produced by the topical application of corticosteroids is usually correlated with clinical efficacy, and can be used as a valuable bioassay to determine the bioavailability of steroids from topical vehicles. [6][7][8][9][10] The term bioavailability here refers to the relative absorption efficiency as determined by the release of the steroid from the formulation, followed by its penetration through the stratum corneum and viable epidermis into the dermis to produce the characteristic vasoconstrictor effect. 11 Hydrocortisone, as a weak steroid, is rarely associated with undesirable effects and is the steroid of choice for infants, the face, mucous membranes and for individuals with sensitive skin, or possibly when the steroid-responsive condition is not severe.…”

Activity of Different Desoximetasone Preparations Compared to Other Topical Corticosteroids in the Vasoconstriction Assay

“…The classification reflects their relative efficacy. The vasoconstriction assay (blanching test), first described by McKenzie and Stoughton [3] in 1962, is a test known to be suitable to determine the activity of topically applied corticosteroids [3][4][5] . Vasoconstriction is a pharmacolog-ical activity, which correlates well with clinical efficacy.…”