Topical tretinoin for treatment of photodamaged skin. A multicenter study

The clinical and histologic effects of a new emollient cream formulation of topical tretinoin at concentrations of 0.05% and 0.01% were examined in 251 subjects with mild to moderate photodamaged facial skin in a randomized, double-blind, vehicle-controlled, multicenter study. Seventy-nine percent of the subjects who received 0.05% tretinoin for 24 weeks showed overall improvement in photodamaged skin compared with improvement in 48% of the vehicle-treated control subjects. Significant reductions were found in fine wrinkling, mottled hyperpigmentation, roughness, and laxity after 0.05% tretinoin therapy when compared with controls. In addition, histologic changes of increased epidermal thickness, decreased melanin content, and stratum corneum compaction provide independent evidence supporting clinical improvement. Side effects of erythema, peeling, and stinging were usually mild and well tolerated.     

TOPICAL TRETINOIN IMPROVES THE APPEARANCE OF PHOTO DAMAGED SKIN

A multicentre clinical trial has been conducted to assess the efficacy and safety of tretinoin 0.05% cream (Retin-A®) in the treatment of photodamaged Australian skin. Subjects with cutaneous facial photodamage were randomised to treatment with tretinoin (62) or vehicle (63) cream. After an initial two week run-in, all subjects applied the cream to the face, neck and left forearm/hand, once nightly for 24 weeks. Changes in clinical signs of photodamage and parameters of cutaneous irritation were assessed by investigators using a 7 point scale, whilst changes in signs of photodamage were rated by subjects using a 5 point scale. Changes in skin biopsies and silicone skin surface replicas were also assessed. Significant improvements in skin wrinkles, mottled hyperpigmentation, laxity, lentigines and roughness of tretinoin treated subjects were noted by investigators. Subjects receiving tretinoin noted significant improvements in skin wrinkles, tightness, colour and pores. Improvement in overall severity of photodamage was significantly greater for tretinoin treated subjects and was progressive over the study period. Histological findings included a significant increase in mean epidermal thickness. Significant topographical changes were not detected in skin surface replica sets. Cutaneous irritation, the most common side effect, was usually mild and transient. We conclude that tretinoin 0.05% cream significantly improved the appearance of photodamaged skin.     

Adapalene 0·1% gel and adapalene 0·1% cream stimulate retinoic acid receptor mediated gene transcription without significant irritative effects in the skin of healthy human volunteers

A randomized, investigator masked, intra individual comparative study was conducted in 30 healthy volunteers to compare the cutaneous effects of adapalene 0·1% gel and adapalene 0·1% cream with their respective vehicles, using tretinoin 0·05% cream ( n  = 21) or tretinoin 0·1% cream ( n  = 9) and a tretinoin cream vehicle ( n  = 30) as controls. The products were applied to hip/buttock skin for 4 days under occlusive conditions. Cytosolic retinoic acid binding protein-II (CRABP-II) mRNA levels were measured using the RT-PCR technique in punch biopsies taken from 10 subjects. Epidermal thickness was assessed using image analysis of haematoxylin and eosin stained sections from another 11 subjects. Erythema was assessed in all subjects both by a visual scoring system and by chromameter.
  Adapalene 0·1% gel and adapalene 0·1% cream produced similar significant increases in CRABP-II mRNA levels compared to their vehicles ( P < 0·01). The two tretinoin formulations also resulted in similar significant increases in CRABP-II compared to the cream vehicle ( P < 0·001). However, only the two tretinoin formulations resulted in an increase in epidermal thickness and only the tretinoin 0·1% cream resulted in significant erythema.
  Adapalene 0·1% gel and adapalene 0·1% cream induce RAR-mediated gene expression to a similar degree in this model, without the irritant effects of tretinoin.     

Long-Term Efficacy and Safety of Tretinoin Emollient Cream 0.05% in the Treatment of Photodamaged Facial Skin

Background: Long-term (>1 year) placebo-controlled studies of tretinoin in the treatment of photodamaged skin have not been conducted. Recently, we conducted a 2-year placebo-controlled study of tretinoin emollient cream 0.05%, including histopathologic assessment of safety and analysis of markers of collagen deposition. Objective: The objective of the study was to determine the long-term safety and efficacy of tretinoin emollient cream 0.05% in the treatment of moderate to severe facial photodamage. Methods: A total of 204 subjects were treated with tretinoin or placebo (vehicle emollient cream) applied to the entire face once a day for up to 2 years. Clinical and histologic effects were assessed at regularly scheduled clinic visits. Results: Treatment with tretinoin resulted in significantly greater improvement relative to placebo in clinical signs of photodamage (fine and coarse wrinkling, mottled hyperpigmentation, lentigines, and sallowness), overall photodamage severity, and investigator’s global assessment of clinical response (p < 0.05). Histologic evaluation showed no increase in keratinocytic or melanocytic atypia, dermal elastosis, or untoward effects on stratum corneum following treatment with tretinoin compared with placebo. Immunohistochemistry studies, conducted at three study centers, showed a significant increase relative to placebo in facial procollagen 1C terminal, a marker for procollagen synthesis, at month 12 (p = 0.0074). Conclusion: Long-term treatment with tretinoin emollient cream 0.05% is safe and effective in subjects with moderate to severe facial photodamage.     

Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.

OBJECTIVE: To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage. DESIGN: Prospective weekly multicenter, investigator-masked, randomized, parallel-group study. SETTING: University hospitals and clinical research centers. PATIENTS: Three hundred forty-nine subjects with facial photodamage. INTERVENTION: Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream. RESULTS: Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate. CONCLUSIONS: Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.     

HISTOLOGICAL EVALUATION OF THE EFFECT OF 0.05% TRETINOIN IN THE TREATMENT OF PHOTO DAMAGED SKIN

In a randomised double-blind vehicle controlled trial of 0.05% tretinoin cream in the treatment of photodamaged skin, the histological results of paired biopsies from 28 individuals who applied tretinoin for 26 weeks are compared with 28 paired biopsies from a control group applying vehicle alone. There was a significant increase in epidermal thickness in the tretinoin-treated group (P.001). Epidermal atrophy was reversed in ten patients applying tretinoin cream. Baseline biopsies obtained from participants in Melbourne, Victoria (38° latitude) showed significantly less elastosis than those in Sydney (34° latitude) and Newcastle in N.S.W., although the two groups did not show significant differences in age or sex, and the differences could not be correlated with skin type. Tretinoin cream had no effect on the degree of solar elastosis after 26 weeks application. Tretinoin cream appears effective in reversing epidermal atrophy and clinically diminishes fine wrinkling, mottled hyperpigmentation and skin roughness. Tretinoin cream may not offer a solution to the gross solar damage seen in the Australian population who have marked solar elastosis as a principal, clinical and histologie finding. However it is possible that dermal repair and reversal of solar elastosis may require topical application of tretinoin cream for a longer period than the six months used in this trial.     

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.     

Tazarotene 0.1% cream versus tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin: a multicenter,double‐blind,randomized, parallel‐group study

OBJECTIVES: To compare the efficacy and tolerability of tazarotene 0.1% cream and tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin.

METHODS: Subjects were eligible to enroll in this multicenter, double‐blind, randomized, parallel‐group study if they had at least mild levels of facial fine wrinkling and mottled hyperpigmentation, and at least moderate levels of one of these. Subjects were randomly assigned to apply either tazarotene cream or tretinoin emollient cream to their faces once each evening for 24 weeks.

RESULTS: A total of 173 subjects were enrolled, of whom 157 completed. All significant between‐group differences in efficacy measures were in favor of tazarotene – for fine wrinkling at the study endpoint and, at earlier timepoints, for treatment success (≥50% global improvement), and the overall integrated assessment of photodamage, mottled hyperpigmentation, and coarse wrinkling. Both products were comparable in terms of cosmetic acceptability and tolerability except that tazarotene was associated with a transiently higher incidence of a burning sensation on the skin (in the first week of treatment but not thereafter).

CONCLUSIONS: Tazarotene 0.1% cream can offer superior efficacy over tretinoin 0.05% emollient cream in the treatment of facial photodamage, particularly with respect to the speed of improvement.     

Tazarotene 0.1% cream versus tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin: a multicenter, double-blind, randomized, parallel-group study.

OBJECTIVES: To compare the efficacy and tolerability of tazarotene 0.1% cream and tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin. METHODS: Subjects were eligible to enroll in this multicenter, double-blind, randomized, parallel-group study if they had at least mild levels of facial fine wrinkling and mottled hyperpigmentation, and at least moderate levels of one of these. Subjects were randomly assigned to apply either tazarotene cream or tretinoin emollient cream to their faces once each evening for 24 weeks. RESULTS: A total of 173 subjects were enrolled, of whom 157 completed. All significant between-group differences in efficacy measures were in favor of tazarotene - for fine wrinkling at the study endpoint and, at earlier timepoints, for treatment success (> or =50% global improvement), and the overall integrated assessment of photodamage, mottled hyperpigmentation, and coarse wrinkling. Both products were comparable in terms of cosmetic acceptability and tolerability except that tazarotene was associated with a transiently higher incidence of a burning sensation on the skin (in the first week of treatment but not thereafter). CONCLUSIONS: Tazarotene 0.1% cream can offer superior efficacy over tretinoin 0.05% emollient cream in the treatment of facial photodamage, particularly with respect to the speed of improvement.     

A review of skin ageing and its medical therapy

Intrinsic (chronological) skin ageing is characterized hy atrophy of the skin with loss of elasticity and slowed metabolic activity. The superposition of environmental damage, particularly exposure to ultraviolet radiation (photodamage). on the intrinsic ageinj; process results, at least initially, in a hypcrtrophic repair response, with a thickened epidermis and increased melanogenesis. Even more striking changes occur in the dcrmis: massive elastosis (deposition of abnormal elastic libres). collagen degenerafion. and twisted, dilated microvasculature. ReguUir use of a sunscreen alone appears to allow some repair as well as protection from further photodamage. Topical tretinoin has been shown fo partially reverse the clinical and histological changes induced by the combination of sunlight exposure and chronological ageing. A formulation of tretinoin in an emollient cream (Retinova? Renova®). developed speciiically for the treatment of photodamaged skin, has heen extensively investigated in multifenlre. double-blind trials and has been shown to produce significant improvement within 4–6 months of daily use, compared witb vehicle alone, as part of a regimen including sun protection and moisturizer use. Histological changes in the epidermis and dermis noted after 12 months suggest tretinoin repairs photodamage by reconstitution of the rete pegs, repair of kcratinocyte ultrastructural damage, more even distribution of melanocytcs and melanin pigment, deposition of new papillary dermal collagen, and Improvements in vasculature. Alpha-hydroxy acids (AHAs) have also been widely used for therapy of photodamaged skin, and these compotinds have been reported lo normalize hyperkeratlnization and increase viable epidermal thickness and dermal glycosaminoglycans content. The single randomized controlled study now available appears to substantiate AHA efficacy and safety. In summary, recent work has substantially elucidated the ageing processes that alTect the skin and has demonstrated that many of tbe unwanted changes can be improved by topical therapy.     

Tretinoin cream 0.02% for the treatment of photodamaged facial skin: a review of 2 double-blind clinical studies

In extensive clinical studies and practical use since its US Food and Drug Administration approval in 1995, tretinoin emollient cream 0.05% has been shown to be safe and effective in the treatment of fine facial wrinkles, mottled hyperpigmentation, and skin roughness. To provide additional prescribing flexibility for various patient needs, a new lower concentration formulation, tretinoin cream 0.02% was chosen for further development. Two multicenter, randomized, double-blind, vehicle-controlled clinical., studies were conducted to evaluate the safety and efficacy of the lower concentration tretinoin formulation in the treatment of moderate-to-severe facial photodamage. Results indicate statistically significant improvement in fine wrinkling, coarse wrinkling, and yellowing with the use of tretinoin cream 0.02% at week-24 end point, compared with placebo. Therapy with tretinoin cream 0.02% was well tolerated overall and demonstrated a favorable safety profile. Both studies demonstrated that tretinoin cream 0.02% is safe and effective for the treatment of moderate-to-severe photodamaged facial skin.     

Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients

BACKGROUND: One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. OBJECTIVE: To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. METHODS: Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved 'treatment success' (Global Assessment Score 相似文献   

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.     

Histological effects of tazarotene 0.1% cream vs. vehicle on photodamaged skin: a 6-month, multicentre, double-blind, randomized, vehicle-controlled study in patients with photodamaged facial skin

BACKGROUND: Topical tazarotene has been shown to offer efficacy in ameliorating multiple effects of photodamage. OBJECTIVES: To evaluate the histological effects of tazarotene cream on photodamaged skin. METHODS: In this multicentre, double-blind, randomized, vehicle-controlled study, 50 patients with photodamaged facial skin (at least mild fine wrinkling and mottled hyperpigmentation, with at least one of these being moderate) were randomized to apply tazarotene 0.1% cream or vehicle cream to their face, once daily for 24 weeks. RESULTS: Blinded assessments showed that tazarotene was less likely than vehicle to be associated with an increase in keratinocytic and melanocytic atypia, and more likely than vehicle to be associated with a reduction in atypia. Between-group comparisons in distribution of change from baseline categories of severity were in favour of tazarotene (P = 0.055 for keratinocytic atypia, P = 0.034 for melanocytic atypia, and P < 0.001 for the number of granular cell layers). Compared with vehicle, tazarotene was associated with an increase in epidermal polarity (P = 0.008) and epidermal thickness (P = 0.012), and a tendency for stratum corneum compaction. Tazarotene was also associated with widened intercellular spaces (reported as epidermal oedema) relative to vehicle (P < 0.001). CONCLUSIONS: Treatment of photodamaged skin with tazarotene is associated with an amelioration of keratinocytic and melanocytic atypia, an improvement in epidermal polarity, and an increase in epidermal thickness.     

In vivo tretinoin-induced changes in skin mechanical properties

Topical tretinoin has been reported as having anti-aging effects on photodamaged skin. The purpose of this study was to evaluate tretinoin-induced changes in the mechanical properties of the skin of 18 patients (aged 39 +/- 8 years) after 4 months of treatment with topical 0.05% tretinoin on one forearm and a placebo base cream on the other. The biomechanical skin parameters investigated were elasticity, extensibility and hysteresis and data were normalized for skin thickness. A slight but non-significant increase of skin elasticity was detected in the tretinoin-treated sites using low-stressing forces (1.2 X 10(4) Nm-2) and at higher loads (3.8 X 10(4) Nm-2), the increase in skin elasticity was significant (P less than 0.01). This improved skin elasticity was dependent on the increased collagen resulting from topical tretinoin and the replacement of elastotic material. However, topical tretinoin treatment did not improve the responses mediated by elastic fibres.     

Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial

Melasma is a common disorder of cutaneous hyperpigmentation predominantly affecting the faces of women. Little is known about the aetiology of melasma, and treatment is frequently disappointing. Topical tretinoin is of benefit in treating other forms of hyperpigmentation, for example liver spots, and we therefore investigated its effectiveness in melasma. Thirty-eight women completed a randomized, vehicle-controlled study, in which they applied 0.1 % tretinoin (n=19) or vehicle cream (n=19) once daily to the face for 40 weeks. At the end of treatment 13 (68%) of 19 tretinoin-treated patients were clinically rated as improved or much improved, compared with 1 (5%) of 19 in the vehicle group (P=0.0006). Significant improvement first occurred after 24 weeks of tretinoin treatment. Colorimetry (an objective measure of skin colour) demonstrated a 0.9 unit lightening of tretinoin-treated melasma and a 0.3 unit darkening with vehicle (P=0.01); these results correlated with clinical lightening (r=0.55, P=0.0005). Histologically, epidermal pigment was reduced 36% following tretinoin treatment, compared with a 50% increase with vehicle (P=0.002). Reduction in epidermal pigment also correlated with clinical lightening (r=0.41, P=0.01). Moderate cutaneous side-effects of erythema and desquamation occurred in 88% of tretinoin-treated and 29% of vehicle-treated patients. Topical 0.1% tretinoin produces significant clinical improvement of melasma, mainly due to reduction in epidermal pigment, but improvement is slow.     

Topical retinoic acid treatment of photoaged skin: its effects on hyaluronan distribution in epidermis and on hyaluronan and retinoic acid in suction blister fluid.

Topical treatment with retinoic acid (tretinoin, vitamin A acid) has been reported to partly reverse signs of photodamage. To determine whether the histochemical distribution of hyaluronan (hyaluronic acid, HYA) in the epidermis and dermis and the amounts of HYA and retinoic acid in suction blister fluid were influenced by such topical treatment, 14 subjects healthy apart from moderate photodamage were instructed to treat the lateral forearm with 0.01-0.05% retinoic acid cream for 6 months. In a study of the short-term effects, another six subjects applied 0.05% retinoic acid cream for 2 weeks. After 6 months the thickness of the vital epidermis had increased by 23%. The HYA staining was based on a specific immunohistochemical method in which hyaluronan-binding protein is used. Before treatment HYA was seen as a meshwork around the cells in the upper half of the stratum spinosum. After 6 months of treatment this meshwork had increased in thickness by 31% compared with pretreatment specimens. The HYA staining was already intense in the papillary dermis before treatment and no difference was observed after 6 months' treatment. The mean concentration of HYA in blister fluid had increased significantly (43%) after 2 weeks of treatment whereas after 6 months there was no significant difference in this respect between the treated and untreated arm. The increase in the thickness of the epidermal HYA meshwork after 6 months and the blister fluid HYA after 2 weeks may indicate that HYA is involved in the epidermal change induced by topical retinoic acid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds

Pretreatment of skin with all-trans retinoic acid (tretinoin) has been shown to enhance wound healing. Previous studies have mainly used animal models to demonstrate this effect. We wanted to determine whether pretreatment could promote wound healing in severely photoaged dorsal forearm skin. Four elderly men with severely actinically damaged forearms were treated daily for 16 weeks. One arm was treated with 0.05-0.1% tretinoin cream (Retin A®, Ortho), and the other with Purpose® cream (Ortho) as a vehicle control. Four-millimetre punch biopsies were taken from both dorsal forearms prior to treatment. After 16 weeks, full-thickness 2-mm punch biopsies were taken from both sides. Serial photographs were taken, and healing of the wounds quantitatively assessed by image analysis. On the 11th day, the wounds were excised using a 4-mm biopsy punch. Biopsies were processed for light microscopy. After 16 weeks, the tretinoin-treated Forearms showed moderate erythema and scaling. Polarized tight photographs revealed multiple, red, vascularized foci and/or a diffuse network of small vessels. The histological effects were typical for tretinoin, i.e. compaction of the stratum corneum, epidermal acanthosis with correction of atypia, an increase in small vessels, and increased cellularity in the upper dermis. Purpose® cream had no effect, either clinically or historically. On the tretinoin-treated side, the wound areas were 35-37% smaller on days 1 and 4, and 47-50% smaller on days 6, 8, 11, compared with the controls. Clinically and histologically. reepithelialization occurred more rapidly. Thus tretinoin dramatically accelerated wound healing in photodamaged skin.     

Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands

To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5′ and 3′ untranslated region sequences (AREG‐UTR) led to a >10‐fold increase in hAREG expression compared to an otherwise‐identical construct containing only the coding region (AREG‐CDR). AREG‐UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG‐CDR mice. Histologically, AREG‐UTR mice presented with marked epidermal hyperplasia of tail skin (2.1‐fold increase in epidermal thickness with a 9.5‐fold increase in Ki‐67⁺ cells) accompanied by significantly increased CD4+ T‐cell infiltration. Dorsal skin of AREG‐UTR mice manifested lesser but still significant increases in epidermal thickness and keratinocyte hyperplasia. AREG‐UTR mice also developed marked and significant sebaceous gland enlargement, with corresponding increases in Ki‐67⁺ cells. To determine the response of AREG‐UTR animals to a pro‐inflammatory skin challenge, topical imiquimod (IMQ) or vehicle cream was applied to dorsal and tail skin. IMQ increased dorsal skin thickness similarly in both AREG‐UTR and wild type mice (1.7‐ and 2.2‐fold vs vehicle, P < 0.001 each), but had no such effect on tail skin. These results confirm that keratinocyte expression of hAREG elicits inflammatory epidermal hyperplasia, and are consistent with prior reports of tail epidermal hyperplasia and increased sebaceous gland size in mice expressing human epigen.     

Efficacies of a barrier cream and an afterwork emollient cream against cutting fluid dermatitis in metalworkers: a prospective study

We compared the point prevalence of cutting fluid dermatitis and transepidermal water vapour loss (TEWL) changes in groups of new machinists who (a) used a barrier cream; (b) used an afterwork emollient cream; and (c) did not use any cream (controls) over a 6-month period. All machinists handled cutting fluid (neat mineral oil) during their work. There was no significant difference in the prevalence of cutting fluid dermatitis in the 3 groups throughout the study period. The prevalence of cutting fluid dermatitis in all groups increased rapidly during the first 6 weeks and thereafter remained steady throughout the remainder of the study period. The prevalence of cutting fluid dermatitis was slightly lower in machinists using afterwork emollient cream compared to those using barrier cream and controls (not significant). The differences in the mean TEWL changes during the study period among the 3 groups were also not statistically significant. The mean TEWL values in the 3 groups increased rapidly during the first 6 weeks of exposure to cutting fluids and thereafter remained fairly constant throughout the remainder of the study period. Barrier cream and afterwork emollient cream did not appear to have any significant effect against either cutting fluid dermatitis or TEWL changes in machinists exposed to cutting fluid. However, afterwork emollient cream appeared clinically to help reduce the prevalence of cutting fluid irritation.