Antipruritic and thermal sensation effects of hydrocortisone creams in human skin

Few studies evaluate the effect of topical corticosteroids on thermal sensation and in alleviation of itch produced by intradermal injection of histamine. We evaluated the antipruritic effect of hydrocortisone (1% and 2.5%) on histamine-induced itch and sensory effects by measuring itch magnitude, itch duration and thermal thresholds using a computerized thermal sensory analyzer (TSA). This was a double-blind, random, comparative, controlled, single-dose and single-center study. Itch was experimentally induced in both forearms by intracutaneous injection of histamine in 18 subjects. Hydrocortisone 1%, 2.5% and placebo were applied to test sites on both forearms. The thermal threshold for warmth sensation, cold sensation, cold and heat pain was measured with the TSA. Itch magnitude was measured each minute after histamine injection for 10 min with a visual analogue scale (VAS). Itch duration was also recorded. In comparison to placebo, 2.5% hydrocortisone significantly (p = 0.03) reduced itch duration from 12.6 +/- 11.0 min (mean +/- SD) to 8.6 +/- 8.2 min (the reducing rate was 32%) as well as itch magnitude (at minutes 3, 6, 7 and overall). Placebo, 1% and 2.5% hydrocortisone significantly altered (p <0.05) the cold sensation threshold. No treatment altered cold or heat pain thresholds. These data suggest that topical application of 2.5% hydrocortisone may be significantly beneficial for the treatment of histamine-induced itch. The correlation between thermal measurements and antipruritic effects warrants further study.     

Efficacy of skin barrier creams

2 barrier creams (BC) were evaluated against the anionic detergent sodium lauryl sulphate (SLS) using a new human test model. In the repetitive irritation test (RIT) on human skin, the irritant SLS is applied to the ventral forearm of Healthy volunteers daily for 2 weeks. 1%, 5%, and 10% SLS is exposed to the skin for 30 min. using a glass cup 2.5 cm in diameter. The BC is applied 30 min before the irritant. Cutaneous irritation is assessed on a score for erythema (0 to 5+), and quantified by various biophysical techniques: transepidermal water loss (TEWL) by evaporimetry, skin blood flow volume (BFV) by laser-Doppler velocimetry, and -skill colour bi colorimetry (La^* value). 10 subjects were tested with SLS on one forearm without pretreatment (control) and with Taktosan Salbe as BC on the other forearm. A 2nd panel of 10 subjects was tested in the same way with SLS and Marly skin as BC. Taktosan Salbe was extremely effective in reducing the irritation by SLS: there were significant differences regarding all lest parameters for 10% SLS in the 2nd week. The most differentiating parameter was TEWL, revealing statistical differences as early as the 1st week for 10%. SLS and Taktosan Salbe, while the least differentiating sensitivity was found for La^*. In contrast, there was no significant suppression of irritancy in any parameter with Marly skin, either in the 1st week or in the 2nd week with any concentration of SLS. The results show the differentiating potential of the model developed. Results obtained with the previously described animal model are confirmed- Noninvasive biophysical techniques, particularly TEWL measurements, might be extremely valuable in identifying new active ingredients of BC.     

Efficacy of skin barrier creams

An animal model for the evaluation of skin protective creams against chemical irritants is described. The irritants were applied daily for 2 weeks to shaved back skin of young guinea pigs: sodium tauryl sulphate (5% aq.: 30 min), sodium hydroxide (0,5% aq.; 2 min). and toluene (20'i. eth.; 2 mint. "The harrier cream was applied 2 h prior to and immediately after exposure to the irritant. Control animals were treated with the irritant only. The irritant reaction was scored on a 4–point scale for erythema and quantified with regard to transepidennal water loss (TEWL) by evaporime-try and skin blood flow volume (BFV) by laser Doppler velocimetry. A total of 90 guinea pigs, consisting of" individual panels of 5 to 10 animals, was tested. While one barrier cream (Slokoderm) significantly suppressed the irritation due 10 sodium lauryl sulphate and toluene, the other (Contra-Alkalh failed to do so and even aggravated the response, which was particularly evident with sodium hydroxide. This model may be useful in developing more effective barrier creams.     

Ranking of glucocorticoid creams and ointments

20 corticosteroids ointments and 19 corticosteroid creams available on the Swedish market in January 1977 were tested for their blanching effect. Three ointments and three creams showing pronounced blanching were tested only without occlusion. Hydrocortisone preparations were tested only with occlusion. Other preparations were tested with and without occlusion. All ointments and creams were tested at four randomized sites on the flexor aspect of the forearm in each of 11 or 12 subjects. When used occlusion was applied for 6 hours. Repeated readings were made, using scores 0, 1, 2, and 3. The reading at the time when most preparations showed blanching were analysed statistically. The scores for blanching showed a Poisson distribution when the mean score was less than or equal to 1. Classification of preparations according to blanching was facilitated by the fact that statistical methods for Poisson distribution could be used. A ranking of corticosteroids based on vasoconstriction was obtained, and four different groups for ointments and four for creams emerged. The arbitrary nature of any ranking and grouping of steroids is evident from the data presented.     

Enzyme inhibition in human skin homogenates by hydrocortisone,hydrocortisone acetate and hydrocortisone butyrate

Summary In fresh human skin homogenates, the activities of four enzymes, lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), acid phosphatase (AcP), and leucine aminopeptidase (LAP) were assayed following an incubation with hydrocortisone, hydrocortisone acetate, or hydrocortisone-17-butyrate, respectively. Concentration of the three compounds measured 2.75 mMol/l. Hydrocortison butyrate inhibited LDH-, G-6-PDH-, and AcP-activities. Hydrocortisone and hydrocortisone acetate exerted a significant inhibitory action only in the case of G-6-PDH-activity.—On pure G-6-PDH from yeast, the inhibition exerted by hydrocortisone butyrate was significantly stronger than the inhibition exerted by the two other steroids. Time/action diagrams revealed the fact that hydrocortisone butyrate is superior to the other two compounds from the beginning of the incubation period.—The data sustain the assumption that hydrocortisone butyrate exerts biochemical-pharmacological actions of its own and that it may not be considered just as an esterified transport form of hydrocortisone.

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Zusammenfassung In Homogenaten frischer menschlicher Haut wurden die Aktivitäten der Laktatdehydrogenase (LDH), der Glukose-6-phosphat-Dehydrogenase (G-6-PDH), der sauren Phosphatase (AcP) und der Leucinaminopeptidase (LAP) nach Inkubation mit Hydrocortison, Hydrocortison-acetat oder Hydrocortison-17-butyrat bestimmt. Die Konzentration des Steroids betrug in allen drei Fällen 2,75 mMol/l. Hydrocortison-butyrat bewirkte eine signifikante Hemmung der LDH-, G-6-PDH- und AcP-Aktivitäten. Hydrocortison und Hydrocortison-acetat zeigten nur bei der G-6-PDH-Aktivität eine signifikante Hemmwirkung. — An reiner G-6-PDH aus Hefe war die Hemmwirkung von Hydrocortison-butyrat signifikant stärker als die Hemmwirkung von Hydrocortison und Hydrocortison-acetat. Zeit-Wirkungs-Diagramme zeigten, daß Hydrocortison-butyrat vom Beginn der Inkubation an wirksam ist (keine Esterspaltung). — Die Ergebnisse unterstützen die Annahme, daß Hydrocortison-butyrat eigene biochemische-pharmakologische Effekte besitzt und daß es nicht nur als veresterte Transportform von Hydrocortison angesehen werden darf.

     

Water protective effect of barrier creams and moisturizing creams: a new in vivo test method

Frequent exposure to water is an important risk factor for the development of irritant hand eczema. Evaluation of cream efficacy in protecting against water is difficult. A new non-irritant, non-invasive method is introduced, based on evaluation of colour intensities when an aqueous solution of crystal violet is applied to the skin, after pretreatment with different creams. By skin reflectance measurement, differences in colour intensity were objectified. Measurements of transepidermal water loss were also performed. 2 barrier creams and a moisturizer were tested on the dorsal and volar aspects of the handy One barrier cream contained silicone the other solid particles. The moisturizer had a high content of lipid. In one experiment, the immediate effect of the cream in protecting against water was evaluated. In a second experiment, the water resistancy of the creams was tested, using a standard water immersion procedure (4X20 min). The barrier cream with particles gave the best immediate protection (dorsal 76% volar 69%). The moisturizer was intermediately protective (dorsal 57% volar 34%) while very link protection was found for the silicone-containing cream (dorsal 16% volar 10%). The water immersion procedure resulted in only minor changes in protection for each cream. When comparing transepidermal water loss in the treated areas with pretreatment values, a reduction was recorded only for the particle-containing barrier cream. The colour method described may be used as a quick and easy test of the protective effect of creams against water.     

Glass fibre irritation and protective creams

5 commercial products were tested pairwise as prophylaxis against itching and irritation from glass fibres: a commercial cream for glass fibre itching, a silicone spray, an emollient cream, a fatty ointment, and a "cream-ointment". The preparations were found to have very limited value in protection against glass fibre irritation. Some workers even experienced exacerbated itching from all the preparations, including the cream marketed for protection against glass fibre irritation. Only 25% of a group of workers with severe glass fibre itching still used an emollient cream after 12 weeks.     

Ingredients and safety of cellulite creams

There is virtually no knowledge of the ingredients of cellulite creams in the dermatological literature. In the present study, the ingredients of cellulite creams, the frequency of their use and whether the ingredients have been reported to cause allergy were investigated. In the 32 products tested, 263 ingredients were used. On average each product contained 22 ingredients (range 4 to 31). Botanicals and emollients predominated; altogether 44 different botanicals and 39 different emollients were used in the 32 products. Caffeine, present in 14 products was the most common additive, apparently representing an "active" ingredient. In other respects the compositions of the products were similar to those of skin creams. All products contained fragrance. The creams were microbiologically pure. Concentrations of preservatives did not exceed limit values in the regulations. No formaldehyde was present (detection limit 10 ppm). The well-known allergens isothiazolinones or dibromoglutaronitril were declared only in a few products. In spite of the large number of substances used in cellulite creams, their safety seems acceptable for most users. Because, however, one fourth of the substances used have been shown to cause allergy, the risk of adverse effects should be taken into account when using cellulite creams.