Application Of Clobetasol Propionate Research Articles

PEMPHIGUS VULGARIS AFFECTING GENGIVAL MUCOSA IN A PEDIATRIC PATIENT: CLINICAL CASE REPORT

A 7-year-old female patient reporting burning and pain in the gingiva for 1 year was seen in the clinic. Medical history was without relevance. The person responsible for the child reported that her father was diagnosed with pemphigus foliaceus. Intraoral examination showed atrophy in the upper and lower gingival mucosa associated with vesicles and ulcerations. The diagnostic hypotheses were pemphigoid mucous membranes and pemphigus vulgaris (PV). Incisional biopsy was performed and the histopathology was inconclusive but suggestive of PV. Topical application of clobetasol propionate (0.05%) was prescribed for the patient, with partial resolution. The patient was referred to a specialized medical center, and direct immunofluorescence testing was performed, which was positive for PV. After the evaluation of G6PD test, the patient started dapsone (50 mg/day) treatment. There is difficulty in the diagnosis of immune-mediated diseases, especially in children, so direct immunofluorescence may be necessary for a conclusive diagnosis.

Topical Applications of a Heparinoid-Containing Product Attenuate Glucocorticoid-Induced Alterations in Epidermal Permeability Barrier in Mice

Introduction: Either systemic or topical glucocorticoids (GCs) can cause significant adverse effects on cutaneous structure and function. Although some products and ingredients can improve GC-induced abnormalities in epidermal permeability barrier, the efficacy is moderate. Prior studies in normal mice showed that topical applications of a heparinoid-containing product, Hirudoid® cream, improve epidermal barrier function by upregulation of epidermal proliferation, expression of mRNA for epidermal differentiation, and lipid production. Objective: The objective of this study was to assess whether topical applications of this product could prevent GC-induced changes in epidermal function in murine skin. Materials and Methods: One group of C57BL/6J mice was treated topically with 0.05% clobetasol propionate twice daily for 6 days, while another group was treated topically with Hirudoid® cream 30 min after each application of clobetasol propionate. Untreated mice served as normal controls. Transepidermal water loss (TEWL) rates, stratum corneum hydration, and skin surface pH were measured using respective probes connected to an MPA5 physiology monitor. qPCR was used to measure the expression levels of mRNA for keratinocyte differentiation-related proteins and lipid synthetic enzymes. Results: Co-applications of Hirudoid® cream with GC minimally, but significantly, increased skin thickness in comparison to GC treatment alone (p < 0.05), in parallel with increased expression levels of mRNA for PCNA in both the dermis and the epidermis. Moreover, Hirudoid® cream largely prevented GC-induced elevation in basal TEWL (p < 0.001) and delay in barrier recovery (p < 0.05), accompanied by upregulation in the expression levels of mRNA for epidermal involucrin, HMGCoA, and SPT1. However, both stratum corneum hydration and skin surface pH were comparable in the skin treated with GC alone versus GC + Hirudoid® cream. Conclusion: Topical heparinoid-containing product can partially prevent GC-induced alterations in some epidermal functions.

Effect of Curcumin versus Hyaluronic Acid on Glucocorticoid Induced Skin Atrophy and Subsequent Skin Abrasions in Rats

Background: Skin is the largest organ of the body in surface area and weight. One of the most important side effects of topical glucocorticoids therapy is skin atrophy. This study aimed to evaluate the possible therapeutic effects of curcumin versus aftamed gel (Hyaluronic Acid) on glucocorticoid-induced skin atrophy, as well as on subsequently induced abrasion wounds. Methods: Forty two adult male albino rats were divided into 4 groups: Group1 (Control group) of 6 rats, Group II (Steroid-Exposed Group), Group III (Curcumin-Treated Group) and Group IV (Aftamed-treated group). Each of group II, III and IV were subdivided into two subgroups IIA, IIIA, IVA (subjected to clobetasol propionate cream) each included 6 rats and IIB, IIIB, IVB (subjected to clobetasol propionate cream, then exposed to skin abrasion) each included 6 rats. Skin biopsies were taken from the dorsum of rats 12th days from the stoppage of clobetasol propionate application. Sections were stained with hematoxylin and eosin, Masson's trichrome and immunohistochemichal stain for PCNA & CK19. Epidermal thicknesses, mean area percent of collagen fibers and mean number of PCNA & CK19 immunopositive cells were measured. Results: Steroid-exposed group showed thinning of epidermal and dermal layers with scanty hair follicles and sebaceous glands as well as delay in wound healing. Increased epidermal thickness and reorganized dermal structural elements with increased PCNA & CK19 immunopositive cells were more obvious in curcumin treated group than aftamed treated group. Conclusion: topical application of curcumin had more improving effect on skin and its abrasions rather than aftamed gel.

Cortisol homeostasis in the epidermis is influenced by topical corticosteroids in patients with atopic dermatitis

Background:The skin produces cortisol by itself and regulates its own proliferation and differentiation. There is a possibility that topical corticosteroids (TCSs) influence the cortisol homeostasis in the skin.Aims and Objectives:The author described the density and distribution of cortisol and its parties in the epidermis after application of topical steroids immunohistologically.Materials and Methods:The forearm skin was biopsied before and after 2 weeks’ application of clobetasol propionate 0.05% two times a day in one healthy volunteer. The biopsied skin was stained immunohistologically by ant-MLN64, StAR, CPY11A1, cortisol, HSD11B1, HSD11B2, glucocorticoid receptor alpha, glucocorticoid receptor beta (GRB), and mineralocorticoid receptor (MCR) antibodies. The skin biopsy was performed similarly in 19 adult patients with atopic dermatitis who had used TCS for a considerable period. They were 4 TCS present users (TCS+), 12 TCS nonusers with skin manifestation on the biopsied site (TCS-E+) and 3 TCS nonusers without skin manifestation on the biopsied site (TCS-E−).Results:The staining density increased during TCS application in MLN64, cortisol and HSD11B2 in a healthy volunteer. The staining density was stronger in HSD11B2 of the basal layer and MCR of the spinous layer in the TCS-E+ patients than in the TCS+ and TCS-E− patients. The staining density was weaker in MLN64 of the basal and granular layers, HSD11B1 of the basal layer and GRB of the whole layer in the TCS-E+ patients than in the TCS+ and TCS-E− patients.Conclusion:The hypertrophy of the epidermis and insufficient keratinization recognized in the TCS-E+ patients might be caused by the decreased cortisol synthesis regulated by MLN64 and the increased cortisol inactivation by HSD11B2. Decreased GRB and increased MCR might enhance the reactivity of cortisol in the keratinocytes.

Topical corticosteroid has no influence on inflammation or efficacy after ingenol mebutate treatment of grade I to III actinic keratoses (AK): A randomized clinical trial

Ingenol mebutate (IngMeb) is approved for treatment of actinic keratoses (AK) and may cause unpredictable local skin responses (LSR). We sought to investigate whether IngMeb-induced LSR, pain, and pruritus could be alleviated with a topical glucocorticoid and, further, to assess efficacy, cosmetic outcome, and patient satisfaction in patients with severe photodamage. In this blinded, randomized controlled clinical trial, patients with multiple AK and field cancerization of the face or scalp were treated in 2 areas with IngMeb (0.015%) daily for 3 days. After finalized IngMeb treatment, 1 area was randomized to receive topical clobetasol propionate (0.05%) twice daily for 4 days. Assessments included LSR (0-24; days 1, 4, 8, 15, 57), pain (0-10) and pruritus (0-3; days 1-15), AK clearance (days 15, 57), and cosmetic outcome (0-3; day 57). Clobetasol propionate application had no influence on LSR (P = .939), pain (P = .500), pruritus (P = .312), or AK cure rate (P = .991). Overall, IngMeb cleared 86% of all AK lesions, exerting a therapeutic effect on all AK severity grades; cure rates were 88%, 70%, and 60% for grade I, II, and III AK, respectively. Skin texture improved significantly in remedied areas (2.0 vs 1.0; P < .001); no hypopigmentation, hyperpigmentation, or scarring were observed. These results do not provide safety and efficacy beyond 2 months of follow-up. Application of clobetasol propionate does not alleviate IngMeb-induced LSR after 3 days of IngMeb treatment.

First randomized trial on clobetasol propionate and mometasone furoate in the treatment of vulvar lichen sclerosus: results of efficacy and tolerability

A 3-month topical application of clobetasol propionate (CP) represents the recommended and accepted first-line treatment for vulvar lichen sclerosus (VLS); however, to date, no randomized controlled trials have compared the efficacy and safety of CP with other topical corticosteroids. To compare the effectiveness and tolerability of two different topical corticosteroids, CP 0·05% ointment and mometasone furoate (MMF) 0·1% ointment, in the treatment of VLS. Fifty-four patients with VLS were enrolled in a 12-week active treatment phase (ATP) and randomized to apply either CP or MMF in a tapering regimen. The main efficacy parameters were the response rate, the rate of patients achieving an improvement from baseline of ≥75% in the subjective and objective scores, and the mean reduction in subjective and objective scores throughout the treatment. By the end of the 12-week ATP, 24 (89%) patients were considered to be responders among the CP patients and 24 (89%) among the MMF patients; 59% and 37% of patients in the CP group and 67% and 48% in the MMF group achieved an improvement of at least 75% in subjective and objective scores, respectively. The decrease in mean symptom and sign scores was significant compared with baseline with both treatments. No significant differences were found in any of the assessed efficacy endpoints between CP and MMF. Both treatments were well tolerated. Clobetasol propionate and MMF appeared similarly efficacious and well tolerated for the treatment of VLS and both may represent the first-line treatment for the disease.

Reversal of Murine Epidermal Atrophy by Topical Modulation of Calcium Signaling

Cytosolic Ca(2+) signals are performed by Ca(2+) releases from the endoplasmic reticulum and Ca(2+) influx from the extracellular medium. Releases rely on the refilling of the intracellular Ca(2+) stores by the Ca(2+) influx "Store-Operated Calcium Entry" (SOCE) via the channel Orai1. Here we show that Orai1 expression, SOCE amplitude, and epidermal proliferation are decreased in the epidermis of patients with skin fragility when compared with aged nonatrophic skin. Epidermal atrophy was induced in mice by the inhibition of Orai1 with small interfering RNA and the topical application of a SOCE blocker BTP2. The inhibition of Orai1 impaired the heparin-binding epidermal growth factor (HB-EGF)-induced Ca(2+) influxes and fully prevented the mitogen effect of HB-EGF in primary human keratinocytes. Importantly, epidermal proliferation correlated with Orai1 expression in mice. Conversely, the topical application of an Orai1 activator, the benzohydroquinone (BHQ), increased the epidermal thickness and proliferation, whereas the pro-proliferative effect of BHQ was prevented by the inhibition of Orai1. Finally, the topical application of BHQ reversed the epidermal atrophy induced by corticosteroids in mice. The topical modulation of Ca(2+) signals may thus be a promising therapeutic strategy in dermatology.

Topical tacrolimus does not negatively impact acute skin wound healing

Despite the increasing use of topical tacrolimus, there is little information about its effect on skin wound healing. To determine effects on acute cutaneous wound healing, two full-thickness skin wounds were imparted on the backs of 45 hairless mice, which were then divided into vehicle-, topical tacrolimus- and topical steroid-treated group. Each drug was topically applied once daily. The wound area was assessed by using dermoscopic images every two days after wounding. At 3, 7 and 11 days after wounding, 10 wounds in each group were collected for semi-quantitative analysis of histological features including re-epithelialization, polymorphonuclear leucocytes, fibroblasts and collagen. We also checked the mRNA expression levels of EGF, TGF-β, TNF-α and IL-1α. While topical application of clobetasol propionate was found to delay re-epithelialization and infiltration of polymorphonuclear leucocyte, topical treatment with tacrolimus showed patterns similar to that of the vehicle. In the tacrolimus-treated group, mRNA expression levels of IL-1α and TGF-β were slightly decreased, while the others were similar with the vehicle-treated group. Unlike steroid, topical tacrolimus, therefore, did not disturb the wound healing process in a murine skin wound model.

Fluorescence spectroscopy as a tool to detect and evaluate glucocorticoid-induced skin atrophy

Topical glucocorticoid (GC) therapy has been successfully used in the treatment of several common cutaneous diseases in clinical practice for a long time, and skin atrophy is one of the most typical cutaneous side effects of this therapy. The aim of this study was to evaluate the potential of noninvasive fluorescence spectroscopy (FS) technique in the detection and classification of GC-induced skin atrophy. A total of 20 male Wistar rats were used in the experimental protocol under controlled environmental conditions and with free access to food. One group received topical application of clobetasol propionate 0.05% for 14days to induce cutaneous atrophy (atrophic group) and the other (control) group received only vehicle application following the same protocol and schedule. Histological analyses and FS measurements with laser excitation at both 532nm and 408nm were obtained on days 1 and 15. The FS results were classified as "normal" or "atrophic" according by histological analysis. Fluorescence spectra obtained with excitation at 408nm allowed a clear distinction between the control and atrophic groups, and were more informative than the those obtained at 532nm. Our results reveal that, if correctly applied, FS allows noninvasive evaluation of corticosteroid-induced skin atrophy, and thus represents an important step towards better monitoring of undesirable side effects of cutaneous therapy.

Efficacy of Combined Peroxisome Proliferator-Activated Receptor-α Ligand and Glucocorticoid Therapy in a Murine Model of Atopic Dermatitis

Although topical glucocorticoids (GCs) display potent anti-inflammatory activity in inflamed skin, they also can exert numerous harmful effects on epidermal structure and function. In contrast, topical applications of ligands of peroxisome proliferator-activated receptor-α (PPARα) not only reduce inflammation, and also improve cutaneous barrier homeostasis. Therefore, we examined whether sequential topical GCs followed by topical Wy14643 (a ligand of PPARα) might be more effective than either alone for atopic dermatitis (AD) in a hapten (oxazolone)-induced, murine model with multiple features of AD (Ox-AD). Despite expected anti-inflammatory benefits, topical GC alone induced: i) epidermal thinning; ii) reduced expression of involucrin, loricrin and filaggrin; and iii) allowed outside-to-inside penetration of an epicutaneous tracer. While Wy14643 alone yielded significant therapeutic benefits in mice with mild or moderate Ox-AD, it was less effective in severe Ox-AD. Yet, topical applications of Wy14643 after GC was not only significantly effective comparable to GC alone, but it also prevented GC-induced structural and functional abnormalities in permeability barrier homeostasis. Moreover, rebound flares were largely absent after sequential treatment with GC and Wy14643. Together, these results show that GC and PPARα ligand therapy together is not only effective but also prevents development of GC-induced side effects, including rebound flares, in murine AD.

Oral lichen planus and dental hygiene: a case report

The presence of atrophic-erosive lesions among gingival tissues makes oral hygiene procedures difficult for several reasons. Plaque control and rigorous oral hygiene are a fundamental requisite for the treatment of any oromucosal disease. A patient suffering from a mixed atrophic-erosive form of oral lichen planus (OLP), with serious gingival involvement, was also treated with the topical application of clobetasol propionate 0.05% using gingival trays. The highest hygiene standards of both patient and trays were of fundamental importance. The management of the patient suffering from gingival atrophic-erosive OLP requires the synergic treatment of both dentist and dental hygienist, whose contribution supports the corticosteroid and/or immunosuppressive treatment.

Ultrasound evaluation of clobetasol propionate 0.05% foam application in psoriatic and healthy skin: a pilot study

The aim of the present study was to evaluate through ultrasound imaging the response to treatment of twice and once daily application of clobetasol propionate 0.05% foam on psoriatic skin as well as the atrophogenic potential of once daily application of the foam on healthy skin. The study included a total of 40 participants, 30 affected by Psoriasis vulgaris and 10 healthy volunteers. Patients with psoriasis were branched in two groups of 15 subjects: in the first group, clobetasol propionate 0.05% foam was applied twice daily for up to 2 weeks on targeted plaques, in the second group, it was applied once daily for up to 4 weeks. Ten healthy adult volunteers were instructed to apply the foam to a 4 x 4 cm area on the volar aspect of the forearm once daily for 4 weeks. Ultrasound evaluation was performed in all treated areas using a 20-MHz B-mode high-resolution system (EasyScan Echo), Business Enterprise, Trapani, Italy). At the end of the study, ultrasound showed a reduction of psoriatic skin thickness, with values equal to those of adjacent healthy skin, in all treated plaques. No differences in treatment efficacy between the two groups of patients with psoriasis were observed. As regards the healthy group, no ultrasound variations in skin thickness were observed at the end of the study. Ultrasound imaging, allowing an objective and reproducible measurement of skin thickness, is a useful technique for a noninvasive evaluation both of the efficacy of psoriasis treatment and of the potential side effects of topical corticosteroids.

Evaluation of the effects of topical clobetasol propionate by visual score, electrical impedance and laser Doppler flowmetry

The intensity of steroid-induced skin blanching is usually evaluated subjectively by a trained observer using a visual score although a few methods have been described for doing this objectively. In this study we wished to establish whether the effects of topical steroids can be detected by measuring the electrical impedance of the skin. Ten healthy volunteers were treated with three concentrations of clobetasol propionate (0.005, 0.05, and 0.5 mg/mL) on the forearm covered by a dressing overnight. On the following morning, we assessed dermal blanching using a visual score, laser Doppler flowmetry and electrical impedance. Using the visual score, we found dose-response blanching at all concentrations of clobetasol propionate. The laser Doppler flow values declined significantly after the application of clobetasol propionate (0.005 mg/mL (P<0.01) and 0.5 mg/mL (P<0.05)), as compared with the test site treated with the vehicle alone. Electrical impedance showed a significant increase in phase index after the application of 0.05 mg (P<0.01) and 0.5 mg (P<0.01) of clobetasol propionate, and a significant reduction in real part index after of 0.05 mg/mL (P<0.05) and 0.5 mg/mL (P<0.05) compared with the test site treated with the vehicle alone. The magnitude index and imaginary part index were not affected by this steroid. Our findings indicate that the dermal blanching induced by topical corticosteroids can be evaluated with a skin impedance spectrometer.

Effect of topical corticosteroid application frequency on histamine‐induced wheals

Very few studies have been conducted to assess the effect of corticosteroid application frequency to attain maximum benefit with minimum side-effects. Compare the efficacy of twice-daily, once-daily and alternate-day applications of clobetasol propionate (0.05%) and compare whether an initial once-daily application followed by a subsequent alternate-day application is as effective as a once-daily application. The ability of corticosteroids to suppress histamine-induced wheals on human skin was used as a human bioassay model. Of the 26 subjects included, 21 completed the 1st phase. In the 2nd phase, 11 subjects were included and all completed the study. Four sites were chosen on the left forearm. Clobetasol propionate (0.05%) was applied twice daily, once daily, and on alternate days, and on the control site a color, texture and odour-matched vehicle was applied. Prick test with histamine was carried out after 10 days. In the 2nd phase, clobetasol propionate (0.05%) was applied once daily for 14 days and compared with the initial once daily for 7 days and the subsequent alternate-day application for 7 days. Prick test was carried out after 14 days. The once-daily application of clobetasol propionate (0.05%) was as effective as the twice-daily application, but the alternate-day application was less effective than the once-daily application (P < 0.01). Also, the initial-daily and subsequent alternate-day applications were not as effective as the continuous once-daily application (P < 0.05). A once-daily application of clobetasol propionate (0.05%) is likely to provide the required therapeutic effect.

Clobetasol propionate 0.05% shampoo in the treatment of seborrheic dermatitis of the scalp: Results of a pilot study

Seborrheic dermatitis (SD), a common dermatosis associating hyperseborrhea, erythema, itching, and dandruff, has frequent scalp involvement. Malassezia furfur infection seems to play an important role in the condition's etiopathology. Treatment of SD usually consists of corticosteroids or antifungals, such as ketoconazole. The aim of this multicenter, randomized, investigator-blinded, parallel-group pilot study was to evaluate the efficacy and safety of clobetasol propionate shampoo 0.05% after different short-contact application times compared with its vehicle and ketoconazole foaming gel 2% in the treatment of SD of the scalp. For 4 weeks, 55 subjects received one of the following treatments twice weekly: clobetasol propionate shampoo for 2.5, 5, or 10 minutes; clobetasol propionate vehicle for 10 minutes; or ketoconazole foaming gel for 5 minutes before rinsing off. Efficacy criteria included total severity score (TSS) and individual scores of signs such as itching and global improvement. Safety included reporting of burning, overall tolerance, and adverse events. Results showed that an application of clobetasol propionate for 5 and 10 minutes provided a similar mean percentage decrease of TSS, and the mean percentage decrease of TSS for all active groups was significantly superior to that of the vehicle (P < .01). Overall and local safety were good for all treatment groups. The present pilot study demonstrated that a short-contact application of clobetasol propionate shampoo is effective and safe in the treatment of SD of the scalp.

Anatomical region variations on the in vitro skin permeation of clobetasol propionate formulations

The effects of topical drugs are influenced by the absorption rate into skin, which in turn can be influenced by the anatomical sites of application. Clobetasol propionate foam has been shown in the clinic to be effective in reducing erythema, plaque thickness and scaling scores on the extremities and trunk regions. It is hypothesized that the hydroethanolic foam vehicle, which enhances the permeation of clobetasol propionate (shown in both in vivo and in vitro studies), can overcome regional variation in different anatomical sites compared to other vehicles, such as cream and ointment. Objective: To assess the in vitro skin permeation of clobetasol propionate in three different formulations on different anatomical regions. Method: In vitro permeation through human split-thickness skin (∼0.5mm) was measured using flow-through diffusion cells. Radio-labeled clobetasol propionate 0.05% formulations (foam, cream, ointment) were applied to different anatomical regions (elbow, thigh, scalp, abdomen, back, palm, and sole) of different strateum corneum thickness on three or four replicate skin sections from each of three human donors. Receptor fluid was collected at 4 hour intervals. At 24 hours after application, the skin was washed and split into epidermis and dermis to measure drug content within these layers. The drug content in the samples was measured by liquid scintillation. Results: The permeation profile of clobetasol propionate foam shows consistently faster onset of delivery than cream or ointment in all anatomical regions (elbow, thigh, scalp, abdomen, back, palm, and sole), especially in the first 12-hour period. Conclusions: Foam application of clobetasol propionate on different anatomical body regions generally overcomes the site differences more effectively than cream or ointment. This is in agreement with other study results showing that the foam vehicle follows a vehicle-skin non-interactive pathway. Foam vehicle needs the least time to overcome anatomical region variations that can be correlated to the thickness of stratum corneum, whereas cream and ointment take longer time for the onset of delivery.

Treatment of severe erosive gingival lesions by topical application of clobetasol propionate in custom trays.

We sought to describe the response of patients with severe erosive gingival lesions to treatment with clobetasol propionate in Orabase paste administered in trays. The adverse effects were also recorded. A descriptive pretest/posttest clinical study with no control group (33 patients total) was developed. All patients received repeated applications of 0.05% clobetasol propionate plus 100,000 IU/cc of nystatin in Orabase paste. Over the 48-week period, the pain levels, ulcerations, presence of atrophy, and the patients' daily activities were recorded, and Likert scales were used to classify each outcome as either a complete recovery, excellent, good, poor, or failed. The presence of any adverse effect was also noted. At the end of the study period, the pain and ulceration had disappeared (complete response) in 100% of the sample (33/33; 95% confidence interval = 89.4%-100%), and there was a complete recovery of daily activities and remission of atrophy in 93.9% (31/33; 95% confidence interval = 79.8%-99.3%) and 21.2% (7/33; 95% confidence interval = 9.0%-38.9%) of the patients, respectively. No adverse effects related to the treatment were observed. The application of an Orabase paste of 0.05% clobetasol 17-propionate plus 100,000 IU/cc of nystatin by means of a tray appears to be an efficacious treatment for severe erosive gingival lesions.

Anti-CD11a Ameliorates Disease in the Human Psoriatic Skin–SCID Mouse Transplant Model: Comparison of Antibody to CD11a with Cyclosporin A and Clobetasol Propionate

The present study assesses the applicability of human skin–SCID (severe combined immunodeficiency) mouse chimeras in testing antipsoriatic therapeutics. Three agents were examined: (1) a monoclonal antibody to the alpha subunit of leukocyte function associated antigen-1 integrin (CD11a); (2) Cyclosporin A; and (3) clobetasol propionate (Temovate), a potent topical corticosteroid used clinically in the treatment of psoriasis. Skin transplanted to SCID mice from normal human volunteers or from psoriatic lesional skin was allowed to heal for 3 to 5 weeks before application of test reagents. During this period, psoriatic skin, which was 3.8-fold thicker than the corresponding normal skin before transplantation, maintained its phenotype (ie, increased epidermal thickness, rete ridges with blunted ends, and intralesional presence of T lymphocytes). Transplanted normal human skin, however, underwent a hyperplastic response during this period, resulting in a 2.4-fold increase in epidermal thickness. After the healing period, animals transplanted with normal or psoriatic skin were treated for 14 days by daily intraperitoneal injection of either Cyclosporin A or a monoclonal antibody to human CD11a, or by topical application of clobetasol propionate. At the end of the treatment period, the mice were killed and the tissue evaluated morphometrically for changes in epidermal thickness and immunohistologically for the presence of T lymphocytes. Both Cyclosporin A and anti-CD11a reduced the epidermal thickness of transplanted psoriatic skin, whereas neither reagent significantly reduced the thickness of transplanted normal skin. T lymphocytes were detected in the skin from treated animals; there did not seem to be any reduction in the number of T lymphocytes. Clobetasol propionate reduced the epidermal thickness of both normal and psoriatic skin. These data indicate that, in this model, therapies directed against pathophysiologic mechanisms that contribute to psoriasis can be distinguished from treatments that block epidermal hyperplasia occurring as a consequence of xenografting. Our observations provide evidence for the activity of anti-CD11a in an animal model of human psoriasis.

The effect of topical steroids on cutaneous oxygen tension.

The precise mode of action of topically applied steroids is unknown. We have applied clobetasol propionate 0.05% ointment (Dermovate; Glaxo Pharmaceuticals) under occlusion to the forearm skin of 10 healthy volunteers for 6 h and monitored transcutaneous oxygen tension at the site for 19 h after its removal. Compared to the ointment base, the steroid-treated area was significantly hypoxic up to 13 h after application. The profound hypoxia present at the site of application of clobetasol propionate 0.05% ointment may account for some of its anti-inflammatory effects, and its atrophogenicity.

Strain differences in the induction of mono-oxygenase activity in mouse skin by topical clobetasol propionate: Evidence of a role for the hr locus

The effect of the topical application of clobetasol propionate on cutaneous ethoxycoumarin O'dealkylation (EOD) has been studied in various strains of mice. Clobetasol propionate markedly increased cutaneous EOD activity in adult hairless mice only. Similar treatment of adult haired C57BL/6J mice, or adult haired DBA/2J mice had no significant effect on cutaneous EOD activity. In contrast 3 methylcholanthrene induced cutaneous EOD activity in both hairless and C57 strains to a far greater extent than in the DBA strain. EOD activity in hairless mice non-responsive to polycyclic hydrocarbons, derived by selective breeding of hairless and DBA strains was induced by clobetasol propionate to a similar extent to that observed in responsive hairless strains. Hepatic EOD activity was not induced by clobetasol propionate in any of the strains tested. Strain differences in the induction of EOD by clobetasol propionate were not related to differences in either the concentration of cytosolic glucocorticoid receptor in the skin, the dissociation constant of the cytosolic receptor, or differences in percutaneous absorption. Polycyclic hydrocarbons did not compete with triaminolone acetonide for binding to the cytosolic glucocorticoid receptor. Strain differences in the induction of EOD activity by clobetasol propionate appear therefore not to be related to strain differences in either the Ah receptor or the glucocorticoid receptor, but to be regulated by the hr locus.