Increased stratum corneum turnover induced by subclinical irritant dermatitis

The chronic effects of the irritant sodium lauryl sulphate (SLS) on stratum corneum (SC) barrier function, determined by transepidermal water loss (TEWL) measurements and on epidermal cell kinetics, estimated by stratum corneum turnover time (SCTT) determination (dansyl chloride staining method), were investigated in 18 healthy female volunteers. SLS (7.5%) was applied without occlusion for 20 min once daily, over a period of 3 weeks (5 days a week) on dansyl chloride-stained skin and on untreated skin. SCTT of untreated skin (19.3 +/- 0.8 days; mean +/- SEM) was not changed by daily treatment with water (control) (19.3 +/- 2.0) but was significantly reduced by SLS (10.9 +/- 0.6; P less than or equal to 0.0001; compared to controls). However, TEWL was increased in SLS-treated sites 1.5-fold after 4 days of treatment (5.3 +/- 0.6 vs. 3.5 +/- 0.3; P less than 0.001). At the end of the second week, TEWL was increased 2.6-fold and after 3 weeks TEWL was 3.3 times higher than in controls 13.0 +/- 1.6 vs. 3.9, P less than or equal to 0.0001). The intensity of SLS-induced irritation as measured by TEWL was significantly correlated with baseline TEWL (r = 0.50; P less than or equal to 0.02) and significantly negatively correlated with SCTT of SLS treated sites (r = -50; P less than or equal to 0.02) but not with SCTT of untreated skin (r = 0.19).     

Plantar hyperkeratosis: a study of callosities and normal plantar skin

Although callosities of the plantar skin are common and often disabling, little is known of their pathology or the reasons for their persistence. In this study plantar epidermal structure and cell renewal were investigated in patients with callosities and normal, age-, sex- and site-matched control subjects. Tritiated thymidine autoradiographic labeling indices were increased in the calluses but the dansyl chloride fluorescence clearance time was prolonged, reflecting the increased thickness of the stratum corneum. The number of corneocytes that could be removed from the surface of callosities by a standardized stimulus was considerably increased compared to controls but after adhesive tape stripping no such increase was observed. The density of corneocytes as measured on Percoll gradients was decreased in corneocytes from callus compared to normal plantar skin, and their volume was increased. These observations suggest that there are differences in epidermal differentiation due to an increased rate of epidermal cell production in plantar skin affected by callosity.     

应用荧光图像对丹磺酰氯染色后角质层转化时间的评价

目的丹磺酰氯皮肤染色后,应用荧光图像及其灰度值对角质层的转化时间进行评价。方法 30名受试者的前臂内侧应用丹磺酰氯染色,染色后每天在伍德氏灯下肉眼评价染色强度,连续28d。同时每周应用相机摄取荧光图像2次,根据这些图像的染色强度得到荧光图像的肉眼评分。应用Photoshop软件分析摄取图像得到荧光图像的灰度值。结果经过28d的试验,皮肤染色逐渐脱落,而荧光图像的灰度值也随时间逐渐减小。荧光图像灰度值与伍德氏灯下肉眼评分、图像的肉眼评分具有较好的一致性。结论应用荧光图像评分及其灰度值可以客观地评价丹磺酰氯皮肤染色的脱落情况,提高试验评分的敏感性,并可获取数字化的结果。     

UVB-induced epidermal hyperproliferation is modified by a single, topical treatment with a mitosis inhibitory epidermal pentapeptide

A single application of a water-miscible cream base containing the recently identified mitosis inhibitory epidermal pentapeptide pyroGlu-Glu-Asp-Ser-GlyOH (EPP) to hairless mouse skin is followed by a long-lasting period of reduced epidermal cell proliferation. To examine if a similar growth inhibition could be achieved in stimulated and rapidly proliferating epidermis, EPP was applied at two different concentrations, 0.005 or 0.02%, to hairless mouse skin immediately after exposure of the left flank to an erythemic dose of ultraviolet B light (UVB). This dose of UVB alone induces a sustained period of rapid epidermal cell proliferation, starting at about 18 h after the irradiation. Epidermal cell proliferation was followed from 18 to 54 h (0.005% cream) or from 18 to 30 h (0.02% cream) after the treatment by estimating the rate of G2-M cell flux (the mitotic rate) by means of Colcemid, and epidermal DNA synthesis by counting labeled cells after pulse-labeling with 3H-thymidine. The unirradiated side of the mice was used as reference. The results showed that topical treatment with a 0.02% EPP cream partially inhibited UVB-induced epidermal hyperproliferation, while the 0.005% EPP cream inhibited as well as stimulated the UVB-induced hyperproliferation. Thus, EPP is effective even in rapidly proliferating epidermal cell populations, but the outcome is obviously dose-dependent in this test system.     

痤疮消霜对兔耳痤疮模型的作用研究

目的:观察痤疮消霜对兔耳痤疮模型的影响。方法:选取新西兰兔30只,雌雄不限,分为正常对照组、模型组、痤疮消霜高剂量组、痤疮消霜低剂量组、维A酸霜组共5组。正常对照组3只不涂煤焦油,不用药;余下27只分别外涂煤焦油造模2周,并于造模成功后每天外涂乳膏基质、痤疮消霜(高、低剂量)、0.1%维A霜3周。于末次给药后24小时,以打孔器制作涂药处耳片标本,以10%甲醛溶液固定,苏木精-伊红染色,光学显微镜下观察组织病理学改变,并进行显微照相。结果:27只新西兰兔造模成功24只,未造模成功的3只归为正常对照组。经观察,在改善兔耳痤疮反应强度上,痤疮消霜高剂量组与模型组比较(t=2.62,P<0.05),说明痤疮消霜高剂量能明显降低兔耳痤疮反应强度,有很好的治疗痤疮的作用;痤疮消霜高剂量组与维A酸霜组相比较(t=0.06,P>0.05),两者无统计学差异。同时,在兔耳病理改变上,痤疮消霜高剂量组兔耳病变改善明显,其表皮增厚状况明显减轻,毛囊口扩张程度减轻,毛囊四周角化层明显减轻,炎性细胞减少,与模型组相比(χ~2=4.00,P<0.05),有统计学差异。痤疮消霜低剂量组兔耳病变程度与模型组相比(χ~2=1.09,P>0.05),无统计学差异,未见明显改善。维A酸霜组与痤疮消霜高剂量组相比(χ~2=0.34,P>0.05),无统计学差异。结论:痤疮消霜高剂量组对煤焦油所致兔耳痤疮模型有明显改善作用。     

Anti-inflammatory effect of pimecrolimus in the sodium lauryl sulphate test

Background Pimecrolimus is a calcineurin inhibitor used for the topical treatment of inflammatory skin diseases. We have shown previously that pimecrolimus cream is not effective on intact skin in the ultraviolet erythema test. Objective To test the anti‐inflammatory effect of pimecrolimus cream after damage of the skin barrier by sodium lauryl sulphate (SLS) in a randomised, placebo‐controlled, observer‐blinded study. Methods SLS (3% v/v) was applied under occlusion on the back of 36 healthy volunteers for 24 h. Subsequently, the test areas were treated for 24 h with pimecrolimus cream, 1% hydrocortisone in a hydrophilic ointment, and the vehicle alone over three consecutive days. One control area remained untreated. The erythema index and the transepidermal water loss (TEWL) served as readout parameters to assess the SLS‐induced skin irritation. Results Pimecrolimus cream and 1% hydrocortisone cream significantly reduced the SLS‐induced erythema. The two test preparations did not have a significant effect on the TEWL. Conclusion After damage to the skin barrier by SLS, pimecrolimus seems to penetrate into the skin as shown by a reduction of the irritation‐induced erythma. These data further support the notion that pimecrolimus is selectively effective in the treatment of skin disorders with an impaired function of the epidermal barrier.     

The effects of an abrasive agent on normal skin and on photoaged skin in comparison with topical tretinoin

Two studies were designed to assess the effect of abrasive preparations on the skin and to test the specificity of the effect of topical tretinoin in the management of chronic photodamage to the skin. In the first study two abrasive preparations (Brasivol fine and Brasivol medium) were compared with white soft paraffin and no treatment in eight volunteer subjects for their effects on the epidermis. The study was conducted over 3 days and measurements were taken of the effects on dansyl chloride-induced fluorescence to assess desquamation, epidermal thickness, and the tritiated thymidine autoradiographic labelling index. The abrasives were found to increase the desquamation rate significantly and to increase epidermal thickness and the epidermal labelling index compared to white soft paraffin and no treatment. In the second study the effect of one of the abrasive preparations (Brasivol medium) was compared with 0.05% tretinoin cream (Retin A) on the photodamaged skin of the dorsal aspects of the forearms of 12 subjects over an 8-week period. Cutaneous blood flow measured by the laser-Doppler flowmeter was found to be significantly increased in the abrasive-treated sites, but there was only a non-significant trend to increased blood flow in the tretinoin-treated sites. Measurements of skin thickness using pulsed A-scan ultrasound demonstrated that both treatments produced significant increases in thickness over the 8-week period but the increase was greater for the abrasive treated site. Measurements of the skin extensibility at the treated sites were made using a uniaxial extensometer. Forces needed for 30% skin extension were increased in the abrasive-treated sites only. Measurements of epidermal thickness and of [3H]-thymidine autoradiographic labelling indices showed greater increases in the abrasive-treated sites than in tretinoin-treated sites compared to untreated sites, but these increases were not statistically significant. No significant inflammation and no changes in the degree of elastosis or the presence of a 'repair zone' were found in any of the post-treatment biopsies. The results indicate that some of the changes produced in the skin by topical tretinoin that are taken to indicate a specific antiphotoageing effect may not in fact be specific and can be achieved by an abrasive preparation.     

Objective evaluation of the efficacy of daily topical applications of cosmetics bases using the hairless mouse model of atopic dermatitis

BACKGROUND/AIMS: Dry skin (xerosis) is a characteristic change associated with atopic dermatitis (AD) and has often been treated with topical petrolatum applications despite its unfavorable feel. Recently, various therapeutically effective skin-care products with better feel have been introduced. To elucidate the mechanisms underlying the clinical effectiveness of these newer treatments, we used our recently established hairless mouse model of AD. METHODS: We produced AD-like skin lesions in hairless mice with repeated applications of 2,4,6-trinitro-1-chrolobenzene (TNCB) in acetone for 36 days as reported previously. Groups of five mice with AD-like skin were treated once daily with an emollient-type cream containing petrolatum, a moisturizer-type cream containing 10% glycerin, a solution of 0.01% dexamethasone in acetone, or were left untreated. Over the duration of these treatments, we conducted non-invasive measurements of skin surface condition with biophysical instruments and electron microscopic evaluation of the surface area size and density of rear surface villi of superficial corneocytes. We also obtained skin biopsy samples and blood samples at each time point for histopathological evaluation and to assess serum IgE levels, respectively. RESULTS: After cessation of topical TNCB applications, AD-like skin underwent spontaneous resolution with normalization of skin appearance. A similar reduction in skin fold thickness was observed in the cream-treated mice and in the untreated mouse group, whereas a significant decrease in skin thickness was observed in the dexamethasone-treated mice. Transepidermal water loss, a measure of stratum corneum barrier function, rapidly normalized in all groups, without any statistical differences noted among groups. In comparison with untreated skin, skin surface hydration markedly improved after repeated applications of the moisturizer-type cream, whereas it consistently remained low in dexamethasone-treated skin. The skin treated with emollient-type cream appeared similar to skin that received no treatment. Reduced corneocyte surface area size resulting from repeated applications of TNCB returned to control size with cream treatments, while the corneocyte surface area size became much larger following dexamethasone treatment. In addition, the density of villi on the rear surface of corneocytes decreased with application of the creams or dexamethasone. By contrast, no changes were observed in the number of leukocytes in the epidermis or in serum IgE levels among the different treatment groups. In all treatment groups, even after 32 days of treatment, reapplication of TNCB resulted in early-stage skin swelling, but only in the steroid-treated animals did this swelling show a remarkably prolonged time course. CONCLUSIONS: Our present results indicate that the efficacy of skin-care products containing no active ingredients in treating atopic xerosis can be objectively evaluated using the hairless mouse model of AD.     

A simplified method for measurement of desquamation using dansyl chloride fluorescence

A fluorescence comparator has been used to assess quantitatively the skin fluorescence due to applied dansyl chloride. Experiments were performed demonstrating that measurements with the device had a low intra-and inter-observer error, with coefficients of variation of between 4% and 6%Another experiment in which fluorescence photographic photometry was simultaneously performed showed that the comparator provided estimates of stratum corneum renewal similar to the more complex photographic technique Repeated mechanical trauma to the skin and skin stripping showed that the technique can detect alterations in the rate of cell renewal in the epidermis.     

The influence of a topical corticosteroid on short-contact high-dose dithranol therapy

BACKGROUND: Dithranol (anthralin) has been known to be effective in the treatment of psoriasis for more than 80 years. However, perilesional and uninvolved skin often show irritation during dithranol treatment, which limits its use. As the relapse rate of psoriasis is worsened by adding corticosteroids to a dithranol regimen, the use of topical corticosteroids to reduce dithranol irritation is controversial. OBJECTIVES: The aim of the present study was to investigate the clinical and cell biological effect of clobetasol-17-propionate 0.05% ointment on dithranol-treated lesional and perilesional skin. METHODS: For 17 consecutive days, 2% dithranol cream was applied on two test sites. A third site was left untreated on all participating patients (n = 8). All sites consisted of a psoriasis lesion as well as a 3-cm zone of perilesional skin localized on the back. After 1 h, the cream was washed off, and subsequently one of the dithranol-treated sites was treated once a day with clobetasol-17-propionate 0.05% ointment. The second site was treated once daily with the vehicle. On day 17, punch biopsies were taken from all three lesions and from the perilesional zone of all test sites in order to perform an immunohistochemical investigation, using markers to assess proliferation, differentiation and inflammation. RESULTS: The SUM score (erythema + induration + scaling) of the lesion treated with dithranol/clobetasol showed a pronounced reduction, which was significantly greater than the SUM score of the lesion treated with dithranol/vehicle. However, the scores of both sites were equal by 6 weeks of follow-up. Comparing the two treated lesions, we observed a lower number of cycling epidermal cells in the dithranol/clobetasol lesion and a significantly lower perivascular dermal score of T lymphocytes. Comparing the perilesional skin of the two treated sites we observed less cycling epidermal cells in the dithranol/clobetasol-treated site. Regarding perilesional differentiation, the interpapillary involucrin expression was higher in the dithranol/clobetasol-treated site. With respect to perilesional inflammation the expression of dermal polymorphonuclear leucocytes, monocytes, macrophages and T lymphocytes in the dermal infiltrate were significantly lower in the dithranol/clobetasol-treated site. CONCLUSIONS: The addition of clobetasol-17-propionate enhanced the antipsoriatic efficacy of dithranol by interfering with T-cell accumulation and epidermal proliferation. The addition of a corticosteroid reduced perilesional dithranol inflammation at the cellular level, although clinically detectable dithranol erythema was not reduced.     

A double-blind study comparing the effect of glycerin and urea on dry,eczematous skin in atopic patients

Moisturizing creams have beneficial effects in the treatment of dry, scaly skin, but they may induce adverse skin reactions. In a randomized double-blind study, 197 patients with atopic dermatitis were treated with one of the following: a new moisturizing cream with 20% glycerin, its cream base without glycerin as placebo, or a cream with 4% urea and 4% sodium chloride. The patients were asked to apply the cream at least once daily for 30 days. Adverse skin reactions and changes in skin dryness were assessed by the patient and a dermatologist. Adverse skin reactions such as smarting (a sharp local superficial sensation) were felt significantly less among patients using the 20% glycerin cream compared with the urea-saline cream, because 10% of the patients judged the smarting as severe or moderate when using glycerin cream, whereas 24% did so using urea-saline cream (p < 0.0006). No differences were found regarding skin reactions such as stinging, itching and dryness/irritation. The study showed equal effects on skin dryness as judged by the patients and the dermatologist. In conclusion, a glycerin containing cream appears to be a suitable alternative to urea/sodium chloride in the treatment of atopic dry skin.     

The in vivo effects of lymphokines on mitotic activity and keratinization in guinea pig epidermis

Lymphokines may alter epidermal growth and differentiation contributing to changes such as acanthosis and hyperkeratosis. The main in vivo effects of lymphokines on epidermal mitotic activity were therefore investigated. Guinea pigs were injected intradermally with antigen-stimulated lymphocyte culture supernatants and a partially purified lymphokine preparation in phosphate buffered saline (PBS) 18, 24, 36 and 48 hr prior to biopsy. Control sites were injected with unstimulated supernatants and PBS respectively and the mitotic activity determined by use of a stathmokinetic agent. Both lymphokine injected areas and controls showed significantly increased mitotic indices compared to untreated skin which was apparent only at 24 hr. However mitotic activity in lymphokine lesions was significantly higher than in control lesions. There was no difference in the effect on mitotic activity between PBS and unstimulated culture supernatants. Lymphokine lesions at 24 hr also exhibited marked epidermal edema and acanthosis compared to minimal changes in controls. A variable patchy parakeratosis developed between 18 and 24 hr in areas injected with partially purified lymphokine but not in control sites or after injection with unpurified supernatants. The lymphokine-induced inflammatory infiltrate was mild and consisted mainly of neutrophils not differing significantly from that of the control lesions. This strongly suggests that lymphokines induce an alteration in epidermal kinetics and keratinization by a direct effect on keratinocytes and not indirectly via the dermal inflammatory infiltrate.     

Hautschutz‐ oder Hautregenerationscreme? Der Halbseitenversuch in der Bewertung eines hautpflegenden Externums

Summary: It is often said that moisturizers should be used both during and after work with skin irritating substances. However, many products are lacking experimental proof to prevent from skin irritation or to support the regeneration of the skin. Taking a protection cream as an example, we present a test design that enables us to discriminate between a barrier‐supporting effect and a moisturizing effect (“skin recovery cream”) of this product. 30 volunteers performed a repetitive washing on both forearms with a sodium lauryl sulfate solution. One forearm was treated with the cream either 30 minutes prior to washing (15 volunteers) or 30 minutes after washing (15 volunteers).
The other forearm was not treated and served as a control. On the treated forearms we found a lower increase in transepidermal water loss and a higher skin hydration as compared to the untreated arm. Treatment after washing was significantly more effective than treatment before washing.
Hence, this test design was able to discriminate between the barrier and the regeneration effect of the cream. The tested protection cream was most effective as a skin recovery cream.     

Acquired perforating calcific collagenosis after topical calcium chloride exposure

A 24‐year‐old healthy man presented with a 6‐week history of numerous umbilicated coalescing erythematous papules with some scale and crust on his anterior medial thighs. The eruption began 1 to 2 weeks after he spilled calcium chloride rock salts on his pants while salting the sidewalk during a snow storm. The salts dissolved and remained in contact with his skin for at least 4 hours until he was able to change clothes. A skin biopsy shows thick and thin collagen fibers with partial calcification in the papillary and upper reticular dermis associated with a sparse infiltrate of neutrophils, lymphocytes and mononuclear histiocytes. There are foci of transepidermal elimination of calcified fibers with adjacent epidermal hyperplasia and ortho‐ and parakeratosis. Von Kossa stain highlights calcification of the fibers, and trichrome stain confirms the fibers are collagen. A Verhoeff‐van Gieson stain shows no abnormality of elastic fibers. The patient was treated with topical betametasone diproprionate cream twice daily for 3 weeks, as well as a short course of oral levofloxacin and topical gentamicin cream. The lesions resolved over 3 weeks with residual scarring. We report a unique case of acquired perforating calcific collagenosis secondary to topical calcium chloride exposure. Patel RR, Zirvi M, Walters RF, Kamino H. Acquired perforating calcific collagenosis after topical calcium chloride exposure.     

A randomized, double-blind, vehicle-controlled study of a novel liposomal dithranol formulation in psoriasis

Dithranol is infrequently used in psoriasis in spite of excellent efficacy due to its local adverse effects. We have synthesized a novel formulation of dithranol in which the drug is entrapped in phospholipid liposomes. This formulation has shown markedly low irritation and minimal staining of skin and clothes in preliminary studies. Twenty patients with bilaterally symmetrical stable plaque psoriasis applied 0.5% dithranol lipogel to lesions over one side of the body. On the other side, 10 patients were randomized to apply pure liposomal base and 10 applied a conventional cream containing 1.15% dithranol, 1.15% salicylic acid and 5.3% coal tar in a 30-minute, short contact regimen for 6 weeks. Patients were assessed for disease severity, perilesional erythema and skin staining, pruritus and any other adverse effects at baseline, 2, 4 and 6 weeks. Both lipogel and the cream significantly reduced the total severity score compared to the liposomal base at 4 (p = 0.004) and 6 (p = 0.01) weeks. There was no significant difference in the clinical response of dithranol cream and lipogel. Markedly low incidence and severity of perilesional erythema (p<0.001) and skin staining (p<0.05) was seen with the lipogel in comparison with the cream.     

Accelerating effects of epidermal growth factor on skin lesions of pemphigus vulgaris: a double-blind, randomized, controlled trial

BACKGROUND: Pemphigus vulgaris (PV) is a severe blistering disease involving the skin and mucous membranes. The most common causes of death in these patients are adverse effects of drugs, and infection. Skin lesions are one of the important sources of infection. Thus, any local treatment that could reduce healing time of lesions and consequently reduce the total dosage of drugs needed to treat is favourable. OBJECTIVE: To evaluate the efficacy of epidermal growth factor (EGF) in reducing healing time of lesions in patients with pemphigus vulgaris. METHODS: In this randomized, double-blind, within-patient, left/right, controlled trial, 20 hospitalized patients with pathologial and immunohistologial (direct and indirect immunoflourecence) proven pemphigus vulgaris (PV) were chosen. In addition, all patients had at least one appropriate pemphigus lesion on each side of the body that had not healed after 2-week systemic therapy and sterile saline washing. EGF (10 microg/g) in 0.1% silver sulfadiazine cream vs. 0.1% silver sulfadiazine cream alone was applied randomly on one side of the body. RESULTS: Kaplan-Meier survival analysis suggested that median time to heal with application of EGF plus silver sulfadiazine cream was 9 days, in comparison with 15 days for silver sulfadiazine cream alone (log-rank test, P=0.0003). No intervention-related adverse effect was observed during the study. CONCLUSIONS: EGF can significantly reduce healing time of skin lesions in patients with pemphigus vulgaris, at least when this cream base is applied (Cochrane skin group identifier: CSG20).     

Mechanism of action of a lipophilic derivative of salicylic acid on normal skin

Background/aims: Keratolytics are agents used for a very long period of time to improve various skin disorders such as acne, hyperkeratoses, ichtyose etc. Very little is known about their mechanism of action on healthy skin. On man, the chronic application of a cosmetic cream containing a lipophilic derivative of Salicyclic acid (LSA) markedly improves the aspect and texture of the skin. Different methods were used to investigate the mechanisms of action of this new compound, compared to salicyclic acid.
Methods: Both non-invasive and histologic methods were used on the dorsal forearm of human volunteers treated with the products. Concerning the non-invasive methods, TEWL, silflo replica and confocal microscopy were used. On shave biopsies, various histometric parameters were measured by image analysis after different staining. The use of antibody MIB-1 reacting with the proliferating nuclear antigen Ki 67 allows one to measure the epidermis proliferation index.
Results: Compared to the excipient alone, presence of LSA 1% improves smoothness and firmness of the skin. The appearance in terms of clearness and healthy complexion is also improved. The thickening of all the living epidermis layers is obtained by both histometric measurement and confocal microscopy. This acanthosis is only recorded on the LSA-treated zones. The Ki 67 labelling study shows that LSA significantly increases the skin proliferation index.
Conclusions: Salicylic acid, and more markedly its lipophilic derivative (LSA), appear to have a significative effect on the renewal of the living epidermis. This probably explains the cosmetic improvement of the skin obtained after a 1-month treatment with a cream containing this new molecule.     

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.     

Phytomenadione pre‐treatment in EGFR inhibitor‐induced folliculitis

Background Targeted oncology therapy with inhibitors of epidermal growth factor receptor is associated with numerous cutaneous side effects. Acneiform eruptions are the most frequent skin toxicities reported. They may lead to impairment of patients’ quality of life and sometimes may even become severe enough to necessitate the interruption or cessation of therapy. Objective To assess the possible effect of topical phytomenadione (vitamin K₁) pre‐treatment in diminishing the extent and severity of acne‐like follicular rash associated with epidermal growth factor receptor inhibitor therapy. Methods A series of 20 patients with colorectal cancer or head and neck cancer were pre‐treated with phytomenadione cream (0.05% in seven patients and 0.1% in 13 patients), starting morning before the first infusion of cetuximab or panitumumab, and followed up for the development of therapy‐associated folliculitis. The cream was prepared from phytomenadione solution added to a hydrophilic cream base, oil in water, to obtain the concentration of 0.05% or 0.1%. Results Majority of patients (15 out of 20, 75%) pre‐treated with phytomenadione cream experienced only mild, grade I acneiform eruptions. Five patients (25%) had grade II rash, which included two of seven patients pre‐treated with 0.05% phytomenadione cream and three of 13 patients who used 0.1% phytomenadione cream. Topical phytomenadione cream was well tolerated and no abnormalities in blood coagulation were observed. Conclusions Topical pre‐treatment with phytomenadione cream might become useful in epidermal growth factor inhibitor‐associated acneiform eruptions.     

Prevention of changes after UV-irradiation by sunscreen products in skin of hairless mice

Summary Female hairless mice (strain mutant hr/hr) have been irradiated with increasing doses of UV-B over a period of 4 weeks. They were compared with untreated controls. Additional groups of 30 mice were treated with milk base or cream base or milk SPF6 or cream SPF6 or cream SPF8 daily before irradiation. No changes of body weight indicating systemic effects were found. Skin thickness was increased significantly after irradiation. These changes were partially antagonized by cream or milk bases and completely prevented by the corresponding formulations containing sunscreen agents. Under the chosen conditions ultimate load of excised skin samples was increased by irradiation. This effect was not reversed by the bases but by the sunscreen products. Ultimate strain of excised skin samples proved to be the most sensitive indicator. The decrease of ultimate strain after irradiation was partially antagonized by the bases. The sunscreen products had a more powerful effect. Due to the effects on skin thickness and ultimate load tensile strength and modulus of elasticity did not show significant changes under the chosen conditions. Likewise, collagen and elastin content per gram wet weight did not show significant changes. Considering the increase of thickness of skin which is prevented by sunscreen products one may conclude also a prevention of formation of additional intercellular material. The results prove the value of sunscreen products. Furthermore, they demonstrate a new method for evaluation of chemicals and sun protection preparations.