A new in vitro method to predict in vivo photoprotection of skin hyperpigmentation induced by visible light.

BACKGROUND: Ultraviolet radiation is the main cause of skin pigmentation, but more recently visible light has been shown to be an important contributor especially in melano-competent subjects. Photoprotection from visible light can improve several hyperpigmentation disorders. Recently, a visible light photoprotection assessment method has been proposed based on in vivo pigmentation; the visible light photoprotection factor (VL-PF) is determined by assessment of the change in colorimetry parameter ITA over several days measured using a chromameter. Although in vivo methods remain the most representative of real life, in vitro methods are more suited to screening sunscreen formulations. OBJECTIVE: The aim of this study was to evaluate the correlation between in vivo and in vitro methods in assessing protection against visible light induced pigmentation. METHODS: We first analysed the in vitro protective properties of the 10 commercially available sunscreens using transmission measurements in the visible spectrum. Then, we performed a monocentric, double-blind, randomized controlled study with intra-individual comparisons in 20 healthy subjects and measure the VL-PF in vivo of those sunscreens. The correlation between the VL-PF and the percentage of blocked light was evaluated using the coefficient of determination R2 . RESULTS: A strong significant correlation was demonstrated between in vivo visible light protection factor and in vitro transmittance measurements, with the highest correlation factor at 420 nm and in the spectrum covering from 400 to 469 nm. CONCLUSION: Transmittance measurements were found to be a good predictive tool to evaluate sunscreen visible light photoprotection efficacy and could be used to select formulations for final in vivo testing.

Evaluation of the activity and safety of CS21 barrier genital gel® compared to topical aciclovir and placebo in symptoms of genital herpes recurrences: a randomized clinical trial.

BACKGROUND: Topical or systemic antiviral drugs reduce the duration of genital herpes recurrences but may not always alleviate functional symptoms. OBJECTIVES: To assess the efficacy and safety of oxygenated glycerol triesters-based CS21 barrier genital gel(®) vs. topical aciclovir and placebo (vehicle) in resolving functional symptoms and in healing of genital herpes recurrences. METHODS: A prospective randomized controlled, investigator-blinded trial of CS21 barrier genital gel(®) vs. topical aciclovir (reference treatment) and placebo (vehicle) was designed. The primary endpoint was the cumulative score of four herpes-related functional symptoms (pain, burning, itching and tingling sensations). Secondary endpoints included objective skin changes (erythema, papules, vesicles, oedema, erosion/ulceration, crusts), time to heal, local tolerance and overall acceptability of the treatment as reported by a self-administered questionnaire. RESULTS: Overall, 61 patients were included. CS 21 barrier genital gel(®) was significantly more efficient than topical aciclovir and vehicle for subjective symptoms and pain relief in genital herpes recurrences; additionally, time to heal was significantly shorter with CS 21 than with vehicle, whereas no significantly difference was observed between patients receiving topical aciclovir and vehicle. The treatments under investigation were well tolerated and the adverse events were comparable in the three treatment groups. CONCLUSION: Overall, these results support the interest of using of CS 21 barrier genital gel(®) in symptomatic genital herpes recurrences. Accordingly, this product offers a valuable alternative in topical management of recurrent genital herpes.

Evaluation of the efficacy and safety of a CS20® protective barrier gel containing OGT compared with topical aciclovir and placebo on functional and objective symptoms of labial herpes recurrences: a randomized clinical trial.

BACKGROUND: Topical or systemic antiviral drugs reduce the duration of herpes simplex virus 1 (HSV-1) recurrences but may not alleviate functional symptoms. OBJECTIVES: To assess the efficacy and safety of CS20 (Acura 24(®) ) protective barrier gel versus topical aciclovir and placebo in resolving functional symptoms in HSV-1 labial recurrences. METHODS: A prospective, randomized, single-centre, assessor-blinded study of CS20 versus topical aciclovir or placebo. The primary endpoint was the total score of four herpes-related functional symptoms (pain, burning, itching, and tingling sensations), evaluated by visual analogue scale (VAS). Secondary endpoints encompassed objective skin changes (oedema, crusting and erythema), evaluated by specific clinical scores. RESULTS: In a study of 106 patients, compared with placebo, a significant improvement in total functional symptom score was observed after 1 day of treatment in the CS20 group, but only after 7 days of treatment in the topical aciclovir group. Burning sensations were significantly reduced by CS20 compared with aciclovir (Days 1-2) or placebo (Days 1-7). Compared to placebo, CS20 significantly reduced pain intensity on Days 1-6. CS20 induced significant and early improvements in the clinical scores for oedema and crusting compared with placebo. Time to cure was similar for CS20 and aciclovir. The treatments were well tolerated and adverse events were comparable in the three treatment groups. Limitations The single-centre and single-blind design of the study and the preselection of patients. CONCLUSION: CS20 showed superior effectiveness against functional symptoms (pain and burning) associated with HSV-1 labial recurrences and was similar to aciclovir for time to cure.

Clinical evidence of benefits of a dietary supplement containing probiotic and carotenoids on ultraviolet-induced skin damage.

BACKGROUND: Lactobacillus johnsonii (La1) has been reported to protect skin immune system homeostasis following ultraviolet (UV) exposure. OBJECTIVES: To assess the effects of a dietary supplement (DS) combining La1 and nutritional doses of carotenoids on early UV-induced skin damage. METHODS: Three clinical trials (CT1, CT2, CT3) were performed using different UV sources: nonextreme UV with a high UVA irradiance (UV-DL, CT1), extreme simulated solar radiation (UV-SSR, CT2) and natural sunlight (CT3). All three clinical trials were carried out in healthy women over 18 years of age with skin type II-IV. In CT1, early markers of UV-induced skin damage were assessed using histology and immunohistochemistry. In CT2, the minimal erythemal dose (MED) was determined by clinical evaluation and by chromametry. Chromametry was also used to evaluate skin colour. Dermatologists' and subjects' assessments were compiled in CT3. RESULTS: A 10-week DS intake prevented the UV-DL-induced decrease in Langerhans cell density and the increase in factor XIIIa+ type I dermal dendrocytes while it reduced dermal inflammatory cells. Clinical and instrumental MED rose by 20% and 19%, respectively, and skin colour was intensified, as shown by the increase in the ΔE* parameter. The efficacy of DS was confirmed by dermatologists and subjects under real conditions of use. CONCLUSIONS: Nutritional supplementation combining a specific probiotic (La1) and nutritional doses of carotenoids reduced early UV-induced skin damage caused by simulated or natural sun exposure in a large panel of subjects (n=139). This latter result might suggest that DS intake could have a beneficial influence on the long-term effects of UV exposure and more specifically on skin photoageing.

Cellulite and skin ageing: is there any interaction?

OBJECTIVE: This study aimed to identify the characteristics of cellulite in women of different age and to appreciate whether cellulite could interfere with skin ageing or not. METHODS: 94 Healthy females, divided into three age groups (21-30yrs; 31-40yrs; 51-60yrs) and two grade groups of cellulite (grade 2; grade 0 or control group), were investigated using non invasive techniques. The "orange peel appearance" was quantified by measuring the shadowed surfaces under low angle light. The biomechanichal properties were measured (extensibility-retractability-elasticity). The thicknesses of the skin structures were also evaluated using ultrasound. Echogenicity of the dermis was recorded and dermis density determined in two bands (superficial and low dermis). RESULTS: In grade 2, the shadowed surfaces are significantly different according to age; i.e. smaller and more numerous after age of 30; the total skin thickness including hypodermis is increased of about 30% irrespective to age, compared to control group. The biomechanical properties of the skin are significantly modified as age increases without any grade effect. In grade 2, retractability and elasticity parameters are altered from age 30 whilst only from age 50 in the control group. Echogenicities of the superficial and deep dermis also decrease from age 30 and become significantly lower than the ones of grade 0. CONCLUSION: Population with cellulite presents earlier skin ageing characteristics than the control population. Two sub-populations may exist: the under 30 age with large dimpled surfaces, normal biomechanical and density properties; and the over 30 age with smaller and numerous dimpled surfaces and already altered dermis properties. This premature skin ageing should be prevented accordingly.

Evaluation of efficacy and safety of rucinol serum in patients with melasma: a randomized controlled trial.

BACKGROUND: Melasma is a hyperpigmentation disorder predominantly affecting sun-exposed areas in women, which is often refractory to treatment. Most commercially available treatments incorporate inhibitors of tyrosinase, a key enzyme in melanin production within the melanocyte. In general, however, the efficacy of these therapies is somewhat limited. Recent studies have identified other enzymes that play an important role in melanogenesis, including tyrosinase-related protein-1 (TRP-1), which catalyses the oxidation of the melanogenetic intermediate 5,6-dihydroxyindole-2-carbolylic acid. Rucinol (4-n-butylresorcinol) has been shown to inhibit the activity of both tyrosinase and TRP-1. OBJECTIVES: To assess the efficacy of rucinol serum 0.3% vs. the corresponding vehicle as a treatment for melasma. Secondary objectives were to evaluate local and general tolerability and to assess the skin acceptability of rucinol serum in the target population. METHODS: In this prospective, single-centre, double-blind, randomized, vehicle-controlled, bilateral (split-face) comparative trial, 32 women with melasma were provided with two identical tubes containing rucinol serum 0.3% or vehicle. The products were each applied to one-half of the face, according to the randomization scheme, twice daily for 12 weeks (phase 1). A broad-spectrum sunscreen (sun protection factor 60) was also applied daily. Assessments at baseline, 4, 8 and 12 weeks included clinical evaluations by a dermatologist, chromametry, ultraviolet and standard photography, and assessments of skin acceptability and tolerability. After 12 weeks, patients were given the option of an additional 3-month treatment period of open full-face rucinol treatment, with reviews at 16, 20 and 24 weeks (phase 2). RESULTS: Twenty-eight patients completed phase 1 and 26 patients completed phase 2. After 12 weeks, the clinical pigmentation score for rucinol-treated skin was significantly lower than for vehicle-treated skin (P = 0.027). During phase 2, rucinol induced a significant reduction in mean pigmentation score on the half of the face previously treated with vehicle. There was also a further, significant improvement on the rucinol-treated side of the face. Chromametry measurements showed that skin was significantly lighter and less yellow, with a strong trend towards reduced redness, following rucinol therapy compared with vehicle. Rucinol serum showed good tolerability and acceptability and was considered to have good or fair efficacy by 78% of the patient population. CONCLUSIONS: Rucinol serum was shown to have significant efficacy compared with vehicle alone in improving melasma after 3 months of treatment, according to clinical and objective assessments of skin colour.

[Assessment of the photosensitization potential of zinc gluconate]. / Evaluation du potentiel photosensibilisant du gluconate de zinc.

INTRODUCTION: Tolerance and clinical efficacy of zinc gluconate are well documented, however, no study have evaluated its photosensitizing potential. It is well known that many treatments of acne are photosensitizing. Evaluation of the photosensitizing potential of zinc gluconate was the aim of this study. PATIENTS AND METHOD: Two open, monocentric studies were carried out with acneic volunteers. The methodology used in this study was an adaptation from that existing for the evaluation of the photosensitizing potential of topical products. In the study of phototoxic potential, volunteers were exposed to 20 J/cm2 UVA and to 0.75 times MED, before and after administration of zinc gluconate. Clinical and colorimetric evaluations of reactions were then carried out 1, 24, 48 and 72 hrs after exposure. In the photoallergic potential study, during the first week of the induction phase, the volunteers were exposed to 2 times MED, and to 3 times the MED during the second and third week. Then during the challenge phase, they were exposed t o4 J/cm2 UVA and to 0.75 times MED. Zinc gluconate was administered throughout the study. Clinical and colorimetric evaluations of reactions were carried out 24, 48 and 72 hrs after exposure, only during the challenge phase. RESULTS: The majority of clinical scores measured on scales at 6 and 5 levels were equal to 0 and 0.5 (evaluation of the phototoxic potential) or all equal to 0 (evaluation of the photoallergic potential). Thus zinc gluconate did not induce phototoxic or photosensitive reactions, whatever the ultraviolet type used. DISCUSSION: Since zinc gluconate does not induce any photosensitive reaction, it could be prescribed during periods of exposure to sun.

A randomized, controlled study of the safety and efficacy of topical corticosteroid treatments of sunburn in healthy volunteers.

Topical glucocorticosteroids are frequently used for the treatment of sunburn despite the scarcity of randomized, double-blind controlled trials to support this indication. This randomized, intra-individually controlled trial compared the efficacy and safety of two topical glucocorticosteroids, 0.1% methylprednisolone aceponate milk (MPA) and 0.1% hydrocortisone 17-butyrate emulsion (HCB), for treatment of sunburn in 24 healthy volunteers of skin type III. After irradiation of the skin by simulated sunlight, treatments were blinded and randomly allocated to 36 cm2 test areas on both sides of the spine. Volunteers were treated twice daily for 7 days and assessed daily with 1-day follow-up. The untreated area was not blinded. Primary efficacy measures were sum score and sunburn reaction based on erythema, oedema, burning and itching. Secondary efficacy measures were physician's global assessment, individual signs/symptoms, colorimetry, dermatological improvement, and time to healing. Intra-individual comparisons were made. Differences in sum score were apparent on days 3-4 and significant on days 4-5 for corticosteroids compared with nontreatment. Treated areas had significantly lower sunburn reaction than untreated areas (P = 0.1% and P = 0.5% for MPA and HCB, respectively). Differences between treatments were not significant. Secondary efficacy measures were in line with these findings. None of the three adverse events reported were considered to be related to treatment. We conclude that MPA and HCB are safe and effective in the treatment of sunburn.

The safety of calcitriol 3 microg/g ointment. Evaluation of cutaneous contact sensitization, cumulative irritancy, photoallergic contact sensitization and phototoxicity.

Vitamin D analogues are widely used for the treatment of psoriasis. A new topical formulation of calcitriol (3 microg/g ointment) has been shown to be effective in the treatment of stable plaque-type psoriasis. This paper reports the results of four separate studies designed to evaluate specific local-safety parameters: cumulative irritancy, cutaneous contact sensitization, potential photoallergic contact sensitization and phototoxicity. Calcitriol 3 microg/g ointment was classified as non-irritant when compared to calcipotriol, tacalcitol and white petrolatum. Petrolatum and tacalcitol were slightly irritant and calcipotriol moderately irritant. No sensitization was observed with calcitriol 3 microg/g ointment. With regard to phototoxic potential, sites treated with calcitriol 3 microg/g ointment or vehicle ointment were less irritated than those treated with white petrolatum or those that were untreated. Using standard photoallergenicity testing methodology, there were no skin reactions of a photoallergic nature to the study material. These studies showed that calcitriol 3 microg/g ointment is a well-tolerated treatment for stable plaque-type psoriasis.

The new topical ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin for 4 weeks: a randomized, double-blind controlled study.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of inflammatory cytokines released from T lymphocytes and mast cells, which has been developed for the treatment of inflammatory skin diseases. OBJECTIVES: In the present study, the atrophogenic potential of SDZ ASM 981 1% cream in humans was compared with that of medium and highly potent topical steroids, and vehicle. METHODS: Four different preparations, SDZ ASM 981 1% cream, the corresponding vehicle of SDZ ASM 981 1% cream, betamethasone-17-valerate 0.1% cream and triamcinolone acetonide 0.1% cream, were applied to the volar aspect of the forearms of 16 healthy volunteers, twice daily, 6 days a week, for 4 weeks. Skin thickness was evaluated by ultrasound examination, clinical signs of atrophy by stereomicroscopy, and epidermal thickness was assessed by histology. RESULTS: Both topical corticosteroids induced a significant reduction in skin thickness, as compared with SDZ ASM 981 1% cream and vehicle, which were shown to be equivalent. The difference in skin thickness (measured by ultrasound examination) between patients treated with SDZ ASM 981 1% cream and those receiving either of the two topical steroids was significant from day 8 onwards. Histological analysis performed at day 29 showed significant epidermal thinning with topical steroids compared with SDZ ASM 981 1% cream or the vehicle. Conclusion The lack of atrophogenic properties of SDZ ASM 981 1% cream in this short-term study demonstrates its potential as long-term treatment for inflammatory skin diseases, thus overcoming a major drawback of topical steroids. This may also be important for the treatment of children, and sensitive areas of skin, such as the face and skin-folds.

Echographic assessment of corticosteroid-induced skin-thinning, including echogenicity measurement.

BACKGROUND/AIMS: Skin atrophy is one of the main side effects of long-term topical corticosteroid therapy. It has already been studied through ultrasound skin-thickness measurement. In this study, the quantification of dermal echogenicity was introduced to provide new information on this phenomenon. METHODS: Skin thinning induced by topical application (without occlusion) of the superpotent corticosteroid clobetasol propionate (0.05% lotion), was assessed by means of ultrasonography in terms of thickness and echogenicity. 15 healthy volunteers were treated for 6 weeks, 1 daily, 5 days a week on the forearms. RESULTS: The thinning showed a biphasic pattern, with a 1st period of rapid change (about 15% of thinning in a week) followed by a period of slower but significant change. Skin thickness returned to baseline values 3 weeks after the end of treatment. Dermal echogenicity, which represents the mean intensity of the ultrasound signals reflected by the dermis, was found to follow the same variations, increasing strongly during the 1st week, then more slowly. The 2 parameters are correlated and probably reflect the same physiological modifications responsible for skin thinning, i.e., a reduction in glycosaminoglycan synthesis (leading to a drastic fall in dermal water content) and vasoconstriction. CONCLUSION: This sensitive and non invasive method enables us to identify the effects of clobetasol propionate on the healthy dermis in the absence of any clinical signs of thinning.

Colorimetric assessment of the effects of azelaic acid on light-induced skin pigmentation.

A 20% azelaic acid (AZA) cream is currently used as a therapeutic agent in the treatment of acne vulgaris. Therefore, this product is intended to be applied on frequently or continuously sun-exposed skin. In certain disorders of hyperpigmentation, AZA has been reported to have a depigmenting effect as well, while showing no significant activity on normal skin. It has been suggested that AZA selectively inhibits hyperactive or malignant melanocytes. Knowing that light-stimulated melanocytes are in a state of hyperactivity, it seemed worthwhile to investigate AZA activity on light-induced skin pigmentation. This study aimed to assess the activity of 20% AZA cream on light-induced skin pigmentation in 10 subjects. There were 5 test zones, all located on the middle of the back: 2 were treated with AZA cream, 2 others with the vehicle and 1 was left untreated. Each product was applied twice daily, 5 days a week, for 4 weeks on one zone, and for 5 weeks on the other. In the middle of the fourth week, the tested zones were exposed to ultraviolet B (UVB) + UVA + visible light, with a total of 3 times the minimal erythema dose distributed progressively over 3 consecutive days. Seven and 10 days after the last irradiation, the induced photopigmentation was assessed by colorimetric and visual means. Compared with its vehicle, the AZA cream had neither a depigmenting effect nor a preventive effect on the light-acquired skin pigmentation. Moreover, interrupting or continuing the AZA treatment after skin irradiation had no influence on the resulting pigmentation.

Processing and statistical analysis of laser Doppler data applied to the assessment of systemic anti-inflammatory drugs.

Continuous laser Doppler measurements of methyl nicotinate-induced skin inflammation have been used to evaluate the activities of three oral non-steroidal anti-inflammatory drugs, indomethacin 50 mg (Indocid), tiaprofenic acid 100 mg (Surgam) and sodium acetylsalicylate 1 g (Catalgine). They were compared in a single-blind, randomized, intra-individual comparison (N = 16) versus placebo (lactose). One hour after each drug was ingested, four concentrations of methyl nicotinate were applied to the subject's forearms. Simultaneous skin blood flow (SBF) measurements were then carried out on the four tested zones, by use of four calibrated laser Doppler flowmeters. Computerized processing of recorded SBF levels provided data related to flow amplitude, kinetics and magnitude (area under the curve) of the reactions. A detailed statistical analysis was performed to establish the selectivity of this type of test and the following points were demonstrated: adjustment of SBF data to baseline did not improve precision, data had to be log-transformed before analysis, and magnitude data gave the best product discrimination. Under the conditions of this study, i.e. one hour after oral administration and for the indicated doses, the tested products could be classified, in terms of anti-inflammatory activity, as follows: Lactose less than Indomethacin 50 mg = Tiaprofenic acid 100 mg less than Sodium acetylsalicylate 1 g.

[Clinical trials in dermatology. The phase I trials]. / Les essais cliniques en dermatologie. Les essais de phase I.

Application of the new topical product on the diseased skin should be preceded by its safety evaluation on the healthy skin in human volunteers. We propose here guidelines for the evaluation of the irritation, sensitization, phototoxicity and photoallergy potentials for topical products. The methods for evaluation of percutaneous absorption are also discussed. The studies presented here are not the object of any regulations. Therefore, we propose here an approach for the safety evaluation of topical products in human volunteers.

[Clinical trials in dermatology. Evaluation of the tolerability and efficacy of a topical antifungal agent in the treatment of superficial mycoses]. / Les essais cliniques en dermatologie. Evaluation de la tolérance et de l'efficacité d'un antifongique topique dans le traitement des mycoses superficielles.

There is no single method for evaluating topical antifungal drugs. The localisation and the type of fungal, determine the treatment duration (from few days to several months). The main methodological characteristics of clinical trials in tinea pedis treatment (athlete's foot type) are reported. Aspects related to other clinical forms such as tinea versicolor and onychomycosis are also described. In any case, the main criteria of activity remains the mycological examination based on KOH microbiology and culture performed at the end of the treatment and again afterwards.

[Clinical trials in dermatology. Statistical support]. / Les essais cliniques en dermatologie. Support statistique.

To determine the efficacy or safety of new topical treatments, more or less standardized studies must be performed. This article presents several examples of statistical analyses of the data currently seen in the dermatology area, and some guidelines for study sample size determination. More importantly, it indicates, for as soon as phase I studies, the need for preliminary informations such as development strategy, historical data, literature references or pilot studies, to determine or adapt appropriate designs and sample sizes. This need can be filled by close collaboration among clinicians, statisticians and sponsor.

Objective assessment of topical corticosteroids and non-steroidal anti-inflammatory drugs in methyl-nicotinate-induced skin inflammation.

The aim of this study was to compare the activities of the two main classes of topical anti-inflammatory drugs in methyl-nicotinate-induced skin inflammation, using a new methodology based on laser-Doppler velocimetry. Six topical non-steroidal anti-inflammatory drugs (NSAIDs) (bufexamac, diclofenac, ibuprofen, indomethacin, phenylbutazone and niflumic acid) and three topical corticosteroids (clobetasol propionate, hydrocortisone and hydrocortisone butyrate) were tested. Drugs were commercially available (except indomethacin) and were applied under occlusion for 4 h to the forearms of 16 healthy male volunteers. Thirty minutes after excess drug removal, skin inflammation was induced by a 1-min application of methyl nicotinate (3 mM). This was repeated 44 h later. Each methyl-nicotinate application was followed by continuous skin blood flow recordings over 1 h. Overall, NSAIDs proved more effective than corticosteroids in inhibiting methyl-nicotinate-induced increases in skin blood flow. Diclofenac and indomethacin showed a potent prolonged inhibitory effect. Different types of activity were observed in the corticosteroid group: (a) At 30 min, hydrocortisone and hydrocortisone butyrate moderately inhibited methyl-nicotinate reactions whereas clobetasol propionate produced no detectable effects; (b) at 44 h, clobetasol propionate produced a significant inhibition whereas hydrocortisone butyrate and hydrocortisone exhibited either weak or no inhibitory action at all. These pharmacodynamic discrepancies between the corticosteroids tested could be related to differences in drug affinity to cutaneous receptors and in vasoconstrictive potency.

Objective assessment of topical anti-inflammatory drug activity on experimentally induced nickel contact dermatitis: comparison between visual scoring, colorimetry, laser Doppler velocimetry and transepidermal water loss.

Four topical anti-inflammatory drugs were investigated for their effect on allergic contact dermatitis. Nickel dermatitis was chosen for its high incidence in European healthy volunteers. Experimental lesions were treated twice daily with two steroids, two non-steroidal anti-inflammatory drugs and a blank base for 4.5 days without occlusion. The influence of treatments was assessed by daily visual grading and one site was left untreated for comparison over the same period. To quantify drug activities objectively, skin colour (colorimetry), skin blood flow (laser Doppler velocimetry) and transepidermal water loss (evaporimetry) were measured before drugs were first applied, then 6 hr after the last application. As expected, only Dermoval cream significantly improved the spontaneous clinical evolution in comparison with the other creams (Hydrocortisone Aster à 1%. Parfenac, indomethacin 2.5% and Skinbase) and the untreated site. Colorimetric parameter a* (redness) and L* (luminance) showed more differences between treatments than the other criteria and a close relationship was obtained between these two parameters and skin blood flow, all three being highly correlated to visual grading. Transepidermal water loss appeared less related to clinical improvement but this parameter could prove helpful for detecting compounds which could be irritant to diseased skin.