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Cinchocaine hydrochloride (CIN) and betamethasone valerate (BMV) are co-formulated in pharmaceutical formulations that could be used for local treatment of hemorrhoids. Both drugs are susceptible to hydrolytic degradation. Two sensitive and precise stability-indicating chromatographic methods were developed for the simultaneous determination of both active pharmaceutical ingredients. The developed methods were applied for quantitation of CIN and BMV in their pure forms, in presence of their corresponding degradation products and in their pharmaceutical formulation. The first method was a high performance liquid chromatographic (HPLC) one, separation and quantitation was achieved using a Waters Spheriosorb® 5 μm ODS2 C18 analytical column and an isocratic mobile phase formed of acetonitrile-acetate buffer (pH 6.5 ± 0.1) in a ratio of (55:45, v/v). The mobile phase was pumped at a flow rate of 1.2 mL/min. UV-detection was done at 240 nm using photodiode array detector. The second method was based on thin layer chromatography (TLC) fractionation coupled with densitometric determination. Separation was done on high performance thin layer chromatography (HPTLC) silica gel 60F254 plates using a developing system formed of chloroform-toluene-ethanol-acetic acid in a ratio of (4.5:4.5:1:1, by volume). The separated bands were scanned densitometrically at 240 nm. For the HPLC method, linearity was confirmed over concentration ranges of 4-300 and 4-350 μg/mL for CIN and BMV, respectively. For the HPTLC-densitometric method, the obtained ranges were 0.5-12 and 0.5-10 μg/band for CIN and BMV, respectively. The developed methods were optimized and validated according to the ICH guidelines. CIN acid degradation products were separated and identified by mass spectroscopy. The developed HPLC method was used to study the kinetics of acid and alkali degradation of the both drugs. The results obtained were statistically analyzed and compared with those obtained by applying the official methods for both drugs. more...

A topical pharmaceutical cream containing the active pharmaceutical ingredients (APIs) betamethasone-17-valerate and fusidic acid has been developed for the treatment of inflammatory skin conditions and associated secondary infections. In this work, a novel stability-indicating RP-HPLC method has been developed for the simultaneous quantitation of impurities of both APIs present in this cream. The HPLC column was a 150 mm × 4.6 mm I.D. YMC-Pack Pro C18 column with 3 µm particles. The column-oven temperature was maintained at 40°C and UV detection at 235 nm was used. A gradient programme was employed at a flow rate of 0.7 mL/min. Mobile phase A comprised of a 16:21:21:42 (v/v/v/v) mixture of methanol, 10 g/L phosphoric acid, HPLC grade water and acetonitrile. Mobile phase B comprised of a 24:5:5:66 (v/v/v/v) mixture of methanol, 10 g/L phosphoric acid, HPLC grade water and acetonitrile. The method has been validated according to current International Conference on Harmonisation (ICH) guidelines and applied during formulation development and stability studies. The procedure has been shown to be stability-indicating for the topical cream. more...

Summary Background Atopic dermatitis (AD) is an inflammatory skin disease arising as a result of immune system and skin barrier defects. Topical corticosteroids are safe and effective treatments for AD, when used in short courses. Prolonged use is associated with skin barrier damage. Topical calcineurin inhibitors are alternative immune-modulating treatments for AD purported to have no negative effects on the skin barrier. Objectives To compare the effects of betamethasone valerate 0·1% cream (BMVc) and tacrolimus 0·1% ointment (TACo) on the skin barrier. Methods Twenty volunteers with quiescent AD (no active signs for 6 months) participated in a randomized observer-blind study, wherein BMVc was applied to one forearm and TACo to the other, twice daily for 4 weeks. The biophysical/biological properties of the stratum corneum were assessed before and after treatment. Nine volunteers with active disease and 10 with healthy skin were assessed at untreated sites. Results BMVc significantly reduced skin barrier function, integrity and cohesion, and the levels of pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA) towards the subclinical barrier defect observed in patients with AD (nonlesional sites). TACo preserved skin barrier function, integrity, cohesion and PCA and UCA levels, while significantly increasing skin hydration to levels comparable with healthy skin. Both treatments reduced skin surface pH and trypsin-like protease activity, with TACo doing so to a significantly greater degree. Conclusion In quiescent AD, 4 weeks of BMVc treatment adversely affected the biophysical properties of the skin and reduced the levels of natural moisturizing factor, whereas TACo improved the condition of the skin barrier. more...

Summary Background. Discoid lupus erythematosus (DLE) is commonly treated with topical agents, the most important of which are glucocorticosteroids. However, prolonged use of these agents, especially on sensitive areas such as the face, may result in side-effects (e.g. atrophy and telangiectases) by altering collagen synthesis. Therefore, alternative treatments are needed for these patients. Aim. To investigate and compare the efficacy of topical pimecrolimus 1% cream and topical betamethasone 17-valerate 0.1% cream on facial lesions of DLE. Methods. This was a randomized double-blind pilot study, performed in outpatient clinics of two major referral hospitals. Ten patients aged 20–53 years with moderate to severe DLE of the face were randomized into two groups for 8 weeks of treatment and 8 weeks of follow-up after treatment. In this double-blind study, one group applied pimecrolimus 1% cream twice daily and the other group applied betamethasone valerate 0.1% cream twice daily to facial lesions. Efficacy end-points included a combined score based on evaluation of erythema, infiltration and presence of scale. Results. Efficacy end-points showed significant improvement in both groups. A decrease of 86% and 73% in clinical severity scores was obtained for pimecrolimus and betamethasone, respectively (P = 0.043). There was no significant difference between the two groups in terms of efficacy (P = 0.1). No adverse effect was found at the end of the 8-week trial in any of our patients. Conclusions. The efficacy of pimecrolimus 1% cream is comparable with that of betamethasone valerate 0.1% cream in treating facial DLE. more...

Summary Background The cosmetic properties of topical formulations are important parameters for the adherence to treatment, where modern oil-in-water emulsions are considered more acceptable compared with ointments. After application of an emulsion to the skin, the concentration of active ingredients in the formulation residue on the skin will increase, due to evaporation of volatile ingredients. Objectives The aim of the present study was to investigate the effect of changes in vehicle fatty content on the skin penetration of two active ingredients: benzyl nicotinate (BN) and betamethasone valerate (BV). Methods Formulations containing 0·5% BN and 0·3% BV in vehicles with different lipid content (10–80%) were applied in a randomized and double-blind manner to the forearm of healthy volunteers. The changes in skin colour (erythema and blanching) were then monitored visually and with a new noninvasive instrument. Results The BN formulation containing 10% fat induced erythema more rapidly and with higher intensity than the formulations with higher fat content. Increased efficacy was also observed from the low-fat content formulation of BV, which gave more blanching than the formulations with high fat content. Conclusions The rate of penetration of the active ingredients was inversely related to the lipid content, i.e. simple changes of the cosmetic properties by modifications of the lipid content may affect the efficacy of a formulation. more...

The influence of organic solvents on artificial membranes when assessing drug release from topical formulations is, generally, poorly characterised yet current guidelines require no characterisation of the membrane before, during or after an experiment. Therefore, the aim of this study was to determine the effect of solvent-membrane interactions when using in-vitro Franz cell methods for the assessment of corticosteroid release and to assess compliance or otherwise with Higuchi's equation. The rate of beclometasone dipropionate monohydrate (BDP) and betamethasone 17-valerate (BMV) release across a regenerated cellulose membrane (RCM), from both saturated solutions and commercial formulations, was determined. Increasing the ratio of organic solvent, compared with aqueous phase, in the donor fluid (DF) resulted in up to a 416-fold increase in steady-state flux. Further, alterations in the receiver fluid (RF) composition caused, in some cases, 337-fold increases in flux. Analysis indicated that the RCM remained chemically unchanged, that its pore size remained constant and that no drug partitioned into the membrane, regardless of the DF or RF employed. However, it was observed that the organic solvents had a thinning effect on the RCM, resulting in enhanced flux, which was potentially due to the variation in the diffusional path length. Such findings raise issues of the veracity of data produced from any membrane release study involving a comparison of formulations with differing solvent content. more...

Psoriasis is a common chronic inflammatory skin disease, characterized by epidermal hyperplasia, immune cell infiltration, increased dermal angiogenesis and local up-regulation of a variety of inflammatory mediators. Psoriasis is thought to be driven primarily by CD4(+) T cells with a T(h)1 and/or T(h)17 phenotype. Transgenic keratin 14 (K14)/vascular endothelial growth factor (VEGF) mice have previously been reported to develop a psoriasis-like phenotype. The aim of this study was to further characterize the model for validation as an in vivo screening model of psoriasis. Inflammation was induced in the ear skin with five topical applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and a significantly increased inflammation was found in TPA-induced K14/VEGF transgenic animals compared with wild-type mice. The amount of VEGF in the ear tissue was significantly elevated resulting in increased dermal angiogenesis. Furthermore, intense epidermal hyperplasia, CD3(+) infiltration and significantly increased amounts of (TNF) tumor necrosis factor alpha, IL-1 beta, IL-6, IL-12/23p40, IL-12p70, IL-22 and IL-17 were detected in the inflamed ear skin. This cytokine profile strongly suggests a T(h)17-mediated inflammation. All findings were a result of induced over-expression of VEGF. Topical treatment with betamethasone-17-valerate (BMS) significantly reduced ear skin inflammation and epidermal hyperplasia and also decreased the CD3(+) infiltration. In conclusion, the TPA-induced phenotype in K14/VEGF animals displayed several features of psoriasis, including a T(h)17 cytokine profile and a chronic-like progression, and can be used as an in vivo screening model of psoriasis. more...

Summary In inflammatory skin disease, hydrocortisone and prednisolone double esters are about equipotent to conventional medium potency topical glucocorticoids, such as betamethasone valerate. Local adverse effects, in particular skin atrophy, are a potential problem with topical glucocorticoids. Recently, cell cultures have shown promise as a means of assessing local tolerance. To investigate the toxic potential of hydrocortisone, hydrocortisone-17-butyrate, hydrocortisone aceponate, prednicarbate, triamcinolone acetonide, betamethasone valerate and desoximethasone, human keratinocytes and fibroblasts were exposed to these agents in vitro, using a modified neutral red release assay. In addition, the morphology of these cells was assessed by light microscopy. Although all the topical glucocorticoids tested proved toxic to both cell types, there were major differences between glucocorticoids in their effect on fibroblasts. Hydrocortisone and the nonhalogenated double-ester-type glucocorticoids were less toxic than the conventional medium potency topical glucocorticoids tested (betamethasone valerate and desoximethasone). In particular, hydrocortisone aceponate was less toxic than betamethasone valerate (P 0.05). In general, the effect of topical glucocorticoids on the cells, based on neutral red release, was more marked with keratinocytes than with fibroblasts. Although the ranking order with respect to the toxic potential was similar, a clear-cut difference was not observed between non-halogen a ted double-ester-type glucocorticoids and betamethasone valerate. Morphological changes due to glucocorticoid exposure followed the same pattern with both keratinocytes and fibroblasts. The neutral red release assay is able to discriminate between the cytotoxic effects of chemically differing topical glucocorticoids on human keratinocytes and fibroblasts. The present data support the hypothesis of an increase in benefit/risk ratio with the new double esters of hydrocortisone and prednisolone. more...

Poor adherence with therapy is a major cause of treatment failure in atopic dermatitis. Reasons given are multifactorial, and include fear of real or imaginary side-effects, under-prescribing, failure to renew prescriptions on time, lack of time, and child refusal of therapy. Most important, however, is lack of knowledge about treatment, in particular the use of topical corticosteroid (TCS) therapy. We conducted a questionnaire-based study to determine the level of use and knowledge of commonly prescribed TCS preparations amongst parents or carers of 100 children attending paediatric outpatient clinics. Weakly potent TCSs were the most commonly used (86%), but poorly understood. Only 35 (41%) who had used hydrocortisone were aware that it was weakly potent, and 44% graded it as moderately potent. Of 65 who had used the moderately potent TCS clobetasone butyrate 0.05% (Eumovate); Glaxo Wellcome, Uxbridge, UK), 19 (29%) graded it as potent and eight (12%) as weak. Of 50 who had used betamethasone valerate 0.1% (Betnovate); Glaxo Wellcome, Uxbridge, UK), 42% did not grade it as potent. Understanding of TCS/antimicrobial combinations was generally worse. The hydrocortisone 1%/fusidic acid 2% combination (Fucidin H(R); Leo, Risborough, Bucks, UK) was graded as moderate or strong by 88% of the 74 who had used it. Over half (53%) of the 34 using the combination of clobetasone butyrate 0.05%/nystatin 100000 i.u./g tetracycline 3% (Trimovate); Glaxo Wellcome, Uxbridge, UK) assumed that it was a potent TCS. Forty-nine had used Fucibet (betamethasone valerate 0.1%, fusidic acid 2%; Leo, Risborough, Bucks, UK) but 34.5% did not grade it as potent. There was poor knowledge of the strengths of some of the most commonly used TCSs, and all steroid/antimicrobial combinations were perceived as being of greater potency than the constituent steroid alone. Fusidic acid was thought to be a steroid by almost half (46.9%) of the respondents. The packaging of the different products by some pharmaceutical companies is remarkably similar and labelling contains information on the compound and percentage rather than potency of the TCS. This may be a source of confusion. We recommend that manufacturers clearly label TCS products by potency as mild, moderate, potent or very potent and that packaging is sufficiently different for each strength of TCS or emollient to avoid confusion. In order to achieve optimal topical treatment for atopic dermatitis, patients and their carers must receive adequate information and training in how and when to use topical therapies in conjunction with written care plans. more...

SummaryBackground Most studies investigating steroid allergy have been performed with tixocortol pivalate, hydrocortisone butyrate and budesonide. Betnovate® and Dermovate® are widely prescribed in the U.K. but little is known about the frequency of sensitization to them. Objectives To determine the optimum method to detect contact allergy to betamethasone valerate (BV) and clobetasol propionate (CP). Methods Seven centres tested consecutive patients attending for investigation of suspected allergic contact dermatitis to these steroids at a range of concentrations in different vehicles. Results Of 1562 patients tested, 16 (1%) reacted to either BV or CP. Ten patients (0·7%) reacted to BV and 13 (0·8%) to CP. Two patients of a further centre were included in analysis of dilutions and vehicles. Sixteen of a total of 25 reactions (64%) were identified with a 1% dilution in ethanol. Conclusions Consideration should be given to adding BV and CP to a standard allergy series, given that both are frequently used in the treatment of eczema and that most patients sensitized to them are not identified with currently used markers of steroid allergy. If patch tests to BV and CP are initially negative, but an allergy is suspected, the patient should be further investigated. Further studies are required to identify the ideal patch test material. more...

The use of vitamin D analogues for the treatment of chronic plaque psoriasis is well documented. Of importance now is their comparability and compatibility with other established treatments for psoriasis. This paper reviews five studies with calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories). Calcitriol applied twice daily was found to be as effective as short-contact dithranol in terms of global improvement and PASI scores. However, patients favoured calcitriol over dithranol when both quality of life and treatment acceptability were assessed. Two studies provide evidence of the benefit of combining calcitriol with other antipsoriatic therapies. Combination with ultraviolet (UV) B phototherapy proved as effective as UVB alone over an 8-week period; however, the combination had a radiation dose-sparing effect, thus reducing the risk of adverse events. Likewise, calcitriol combined with betamethasone valerate (each applied separately, once daily) was as efficacious as twice-daily betamethasone, thereby achieving a corticosteroid-sparing effect. Finally, two studies confirm that calcitriol 3 microg g(-1) ointment can be used safely in patients with psoriasis of the head and confirm the high level of clinical efficacy achieved with this compound. more...

Summary Background Recent studies have established the pivotal role of irritants and allergens in development of chronic paronychia and the significant improvement with corticosteroid therapy. Objectives The objective of this randomized, unblinded, comparative study was to compare the efficacy of tacrolimus ointment 0·1% vs. betamethasone 17-valerate 0·1% in the treatment of chronic paronychia. Methods Forty-five patients with chronic paronychia were randomized 1 : 1 : 1 to apply twice daily either betamethasone 17-valerate 0·1% or tacrolimus 0·1% ointment or emollient. Protective measures were counselled to all patients. Treatment duration was 3 weeks and patients were followed for an additional 6 weeks. Results Eight patients in the betamethasone group were considered as cured, two as improved and four as nonresponders at the end of the treatment period. Thirteen patients in the tacrolimus group were considered as cured and one as improved at the end of the treatment period. Nine patients in the emollient group were considered as stable and six failed to respond. Both betamethasone and tacrolimus groups presented statistically significantly greater cure or improvement rates when compared with the emollient group (P more...

A clinical study was conducted to determine whether, in the topical treatment of psoriasis, a combination of calcipotriol and betamethasone valerate after previous treatment with calcipotriol alone was more effective than the continuation of the monotherapy with calcipotriol, especially in 'low responders'. Patients (n = 169) with the clinical diagnosis 'chronic plaque-type psoriasis' were treated twice daily for 2 weeks with calcipotriol, followed by a 4-week treatment with calcipotriol monotherapy in 87 patients or combined calcipotriol/betamethasone valerate in 82 patients; all patients were followed for 8 weeks. The psoriasis area and severity index (PASI) was used to compare the two treatment groups. The overall therapeutic result was also assessed by the investigators and patients. The combination therapy was more effective, as assessed by all evaluated variables; moreover, patients showing insufficient response to calcipotriol alone after 2 weeks showed a regression of psoriatic lesions using the combination regimen. Thus, the combination of calcipotriol and topical steroids is recommended as the therapy of first choice for patients who do not respond well to treatment with 2 weeks of calcipotriol alone. Furthermore, this combination reduces the hazards associated with the long-term use of topical corticosteroids (atrophy and rebound) as well as the irritation associated with calcipotriol. more...

Several reversed-phase high-performance liquid chromatographic methods for the baseline separation of some glucocorticoid alcohols and their derivatives (esters and acetals) have been developed. These methods involve fluorocortisone and fluorocortisone acetate, triamcinolone and triamcinolone acetonide, dexamethasone and dexamethasone phosphate, 21-hydroxydeflazacort and deflazacort, betamethasone and betamethasone valerate using deoxycorticosterone or methylprednisolone as an internal standard, a Hypersil C 18 column, several mobile phases containing acetonitrile, and ultraviolet detection. These sensitive methods are used for a further hydrolysis study in an aqueous medium using standard solutions, which allowed the simultaneous monitoring of glucocorticoid derivatives and their hydrolysis products. In this study, the main variables that can affect the hydrolysis (pH and temperature) are also studied. Several applications to pharmaceuticals containing glucocorticoids are also reported. more...

The effects of topical tretinoin on collagen synthesis and degradation were studied in 29 volunteers. The subjects applied 0.1% tretinoin cream on their non-sun-exposed abdominal skin once a day for 1 week (n = 10) (experiment 1) or twice a day for 2 weeks (n = 8) (experiment 2) or once a day for 2 months (n = 11) (experiment 3). After the treatments, suction blisters were induced and amino-terminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) (experiments 1 and 3) and carboxy-terminal propeptide of type I procollagen (PICP) (experiment 2) were assayed as an index of de novo collagen synthesis by radioimmunoassays. Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) were assayed by the zymography method in experiment 2. In experiment 3, histology, immunohistochemistry of type I and III procollagens, tenascin, mRNA levels of type I collagen alpha 1-chain [alpha 1 (I)], interstitial collagenase (MMP-1), MMP-2, MMP-9 by slot-blot analysis and the levels of alpha 1 (I) collagen mRNA by a quantitative polymerase chain reaction method were studied. The proportional area of elastic fibres visualized in Verhoeff-stained sections was analysed by computerized digital image analysis. The results indicated that treatment with topical tretinoin does not markedly induce de novo synthesis of collagen in vivo or affect matrix metalloproteases. In the immunohistochemical staining, tenascin was increased in the papillary dermis. As it has been suggested that tretinoin could counteract the atrophogenic effect of corticoids on the dermis, the effect of a combination of betamethasone-17-valerate (once a day) and tretinoin (once a day) on the propeptide levels was also studied. Betamethasone alone caused a 60% decrease in the concentrations of PINP and PIIINP, and a similar decrease was found after the combination treatment, indicating that topical tretinoin administered during short treatment periods does not counteract the inhibitory effect of a potent corticoid on collagen propeptides. more...

Summary In the present study, the recovery of the collagen synthesis rate after topical potent glucocorticoid treatment in the human skin in vivo was investigated. In the first experiment, two age groups were compared: young subjects with an age range of 21–26 years (mean 23), and old subjects, aged 55–70 years (mean 64). Twenty healthy male volunteers applied betamethasone-17-valerate to their abdominal skin for 3 days twice a day. Suction blisters were induced on the treated areas, and on the opposite side (healthy non-treated skin), of the abdominal skin on the day following the discontinuation of the treatment, and on the second and seventh day. In another experiment, suction blisters were induced after the treatment and 2 weeks later on the treated area and on healthy skin, in eight male volunteers. In both experiments, the aminoterminal propeptides of type I and III collagens (PINP and PIIINP, respectively) were measured radioimmunologically from the suction blister fluid. Corticosteroid treatment decreased the collagen synthesis in both age groups after a 3-day treatment period, and essentially no recovery in the collagen synthesis could be seen during a 1-week corticoid-free period. The inhibition and downregulation of collagen synthesis in the corticoid-treated skin was similar in both young and old subjects, up to 7 days after the treatment. During the 2-week corticoid-free period, collagen synthesis was recovered to about 50% of the level seen in the non-treated skin. Indicating that collagen synthesis is not completely normalized in the human skin even during a 2-week corticoid-free period. more...

We report a 6-month-old boy with an unusual form of cutaneous histiocytosis. The lesions were noticed shortly after birth, and there was no evidence of systemic disease. This histiocytic disorder could not be classified according to the Histiocyte Society classification, and was therefore designated an 'unclassified' group II histiocytic disorder. The clinical picture was characterized by dark-red papulonodules with a tendency to coalesce into plaques. Histologically, the infiltrate was characterized by non-epidermotropic histiocytes showing varying degrees of differentiation, eosinophils and lymphocytes, and by the absence of foamy cells and Touton giant cells. As a most conspicuous feature, electron microscopic examination revealed laminated dense bodies, whereas Birbeck granules and comma-shaped bodies were absent. This further distinguished this uncommon variant from the well-known class II histiocytoses. During a 6-month follow-up period all the lesions showed marked regression. more...

Cutaneous vasoconstriction induced by topical corticosteroids was investigated using non-invasive bioengineering techniques. Corticosteroids of different potency in alcoholic solution were applied topically, under occlusion, and cutaneous blanching was investigated using visual scoring, reflectance spectroscopy (RS) and laser-Doppler flowmetry (LDF). The RS technique allowed separation of cutaneous haemoglobin content into arterial oxygenated (OH) and venous deoxygenated haemoglobin (DOH) components. Application of alcohol decreased total haemoglobin by 10%, with a corresponding 8% increase in blood flow (BF). Clobetasol propionate was the most potent vasoconstrictor, inducing significant visible blanching and decreasing DOH (30%), OH (33%) and BF (18%) (P < 0.01). Fluocinolone acetonide, betamethasone-17-valerate and dexamethasone also caused visible blanching (P < 0.01). There was no significant decrease in BF, but reflectance spectroscopy showed a decrease in DOH (P < 0.01). Tixocortol, CMJ and hydrocortisone acetate did not produce significant blanching, although DOH was decreased compared with the alcohol control. Measured by reflectance spectroscopy, corticosteroid-induced blanching was predominantly venoconstriction and only the most potent corticosteroid caused a significant decrease in OH and blood flow. This may explain why previous attempts to improve cutaneous vasoconstriction assays using laser-Doppler flowmetry have been unsuccessful. more...

Summary Topical betamethasone-17-valerate inhibits the vasodilatation response to local non-pathological heating of rat skin.1 We have shown that this effect can also be demonstrated in man. Topical betamethasone-17-valerate significantly inhibited the increase in human forearm cutaneous blood flow in response to heat of 44°C, as measured by laser-Doppler velocimetry. This suggests that the effects of topical steroids upon skin blood flow in the rat and in man are similar, and supports the use of the animal model as a paradigm for studying human skin blood flow, and changes in response to anti-inflammatory steroids. more...

Changes in epidermal immunocytes and cytokeratins were investigated during treatment of psoriasis with calcipotriol and betamethasone valerate. Skin biopsies were obtained from 10 subjects on each treatment from lesional and non-lesional skin at baseline, and from treated lesions after 4 weeks. In each subject, changes in expression of cytokeratins K5, K10 and K16, and changes in epidermal immunocyte counts were assessed. Responses were compared with a separate histological parameter of improvement, epidermal thickness. Both treatments produced a marked normalization of cytokeratins. The reduction of K16 expression was similar on each treatment and correlated significantly with reduction in epidermal thickness. Expression of both K5 and K10 improved less than thickness with betamethasone valerate but more than thickness with calcipotriol, although these differences did not reach statistical significance. With calcipotriol there was an increase in K5 and K10 responses with increasing response of epidermal thickness, which was not seen with betamethasone valerate. T6+ cells, HLA-DR+ dendritic cells and T lymphocytes were all reduced by betamethasone valerate. There was a remarkable similarity in the level of normalization between cell types and also between cellular response and reduction in thickness. Calcipotriol produced a similar consistent reduction in cell numbers and in thickness, with the exception of T6+ cells which increased in some subjects during treatment. Only in subjects in whom thickness had virtually returned to normal was there a marked decrease in T6+ cells. more...

Summary In 10 patients with chronic plaque type psoriasis one or two plaques affected equally with psoriasis were chosen for study. Five punched out rings of a hydrocolloid dressing were applied to the psoriasis plaque(s). In each circular test area 20 mg of one of the following creams was applied: base, 1% hydrocortisone (DAK), 0·1% triamcinolone acetonide (Kenalogue®), 0·1%, betamethasone-17-valerate cream (Betnovate®), and 0·05% clobetasol proprionate cream (Dermovate®). The areas were occluded with a thin Him of transparent hydrocolloid dressing (Comfeel® P Transparent Dressing), for 1 week. Non-invasive measurements (ultrasound skin thickness, laser-Doppler flowmetry, colorimetry) were performed before and after treatment. Therapeutic response was evaluated blindly by clinical score. The measurements showed a decline in blood How, a decrease in skin thickness, and normalization of colour approaching that of normal skin, the more potent the corticosteroid used. The clinical scores showed the same: the more potent a corticosteroid used, the closer to the score of normal skin. Data on variability and applications of the methods are presented. The study concludes that potent corticosteroids occluded with a hydrocolloid dressing can clear psoriasis in 1 week. Short-course corticosteroid therapy appears harmless and relevant for clinical dermatology. more...

Summary Topical corticosteroids are used extensively to treat inflammatory skin diseases. Long-term use, however, may be associated with adverse effects such as skin atrophy. New steroids have been developed with the objective of increasing efficacy and reducing the incidence of adverse effects. Mometasone furoate (MMF) is one of these new derivatives. The aim of our study was to compare the effects of MMF and betamethasone-17-valerate (BM-17-valerate) on collagen synthesis in human skin in vivo. Fifteen healthy male volunteers applied MMF, BM-17-valerate and vehicle for 1 week to different areas of abdominal skin. Suction blisters were raised on these areas, and a control site, and procollagen propeptide (PICP, PINP, PIIINP) levels in the suction blister fluid were measured by radioimmunoassay. Skin thickness was measured ultrasonically by Dermascan A at the end of the treatment period. The levels of the three propeptides in suction blister fluid were reduced to a similar extent by MMF and BM-17-valerate. The 1-week treatment period had no detectable influence on skin thickness. We conclude that MMF and BM-17-valerate decrease collagen synthesis to the same extent in human skin in vivo. more...

The effect of topical n-6 essential fatty acids in the form of evening primrose oil on the epidermal atrophy caused by a potent topical steroid was studied in 24 normal volunteers by measuring epidermal thickness and cross-sectional area and by histological examination. Epidermal thickness and cross-sectional area were significantly lower in normal forearm skin treated with 0.1% betamethasone valerate twice daily without occlusion for 3 weeks when compared with placebo-treated skin. The addition of evening primrose oil to the topical steroid did not prevent steroid-induced epidermal atrophy suggesting that steroid-induced epidermal atrophy is not mediated by the inhibition of essential fatty acid release from cell membranes. more...

Cicatricial pemphigoid or benign mucous membrane pemphigoid is an autoimmune bullous disease predominantly affecting the mucosal surfaces and healing with scar formation. Localized cicatricial pemphigoid of the vulva in children is rare. We present a child with this rare condition who was initially investigated on suspicion of her being subjected to child sexual abuse, and discuss its management. more...

Aims This study aimed to determine whether a 3-day burst of a potent steroid is more effective than a weak preparation used for 7 days in treating disease exacerbations and in maintaining remissions in children with atopic eczema. Methods A randomized, double-blind, parallel group study of 18 weeks' duration. 174 patients with mild or moderate atopic eczema were recruitment from 13 general practices in the Nottingham area. Two primary outcomes were evaluated: (i) the total number of scratch-free days and (ii) the number of disease relapses. Secondary outcomes included the median duration of the 1st disease relapse; the number of nights when sleep was not disturbed; disease severity (SASSAD), two quality-of-life measures (CLQI and DFI) and the number of treatment ‘failures’ in each arm. Skin thickness was measured using B-mode ultrasound. Results We found no differences between the two groups for any of the outcome measures used. The median number of scratch free days was 118.0 for the hydrocortisone group and 117.5 for the betamethasone valerate group (95% CI median difference −2–4, P = 0.53). The median number of relapses for both groups was 1. Both groups showed clinically significant improvements in disease severity and quality-of-life compared to baseline. No significant changes in skin thickness were observed. Conclusions For children with mild or moderate atopic eczema in the community, both 1% hydrocortisone used for 7 days, or betamethasone valerate 0.1% used for 3 days, are effective in controlling disease symptoms. more...

The inflammatory dose-response to anthralin was measured in human skin 24 h after pretreatment with topical corticosteroids and anthralin, and 48 h after removal of the stratum corneum with adhesive tape. Anthralin inflammation was increased after 1% hydrocortisone application and decreased by 0.1% betamethasone valerate and 0.05% clobetasol propionate; although the difference between these effects was not significant, the difference between the effect of hydrocortisone and clobetasol propionate was. Anthralin inflammation was not significantly affected by pretreatment with anthralin and was reduced, although not significantly by removal of the stratum corneum. The finding that anthralin inflammation is not altered in skin in which aryl hydrocarbon hydroxylase (AHH) activity is increased and that anthralin inflammation may be altered in situations in which AHH activity is unchanged, excludes a direct relationship between anthralin inflammation and AHH activity. more...

SUMMARY The bio-availability of betamethasotie-17-valerate (Betnovate® ointment) in emulsifying ointment (1 in 4 dilution) was investigated in ten subjects using a single-application vasoconstrictor assay; the blanching induced was measured using a skin reflectance spectrophotometer. The vasoconstrictor activity of the diluted preparations decreased with age. There was no significant difference between the vasoconstrictor activity of freshly made Betnovate 1 in 4 in emulsifying ointment and undiluted Betnovate® ointment, and between 3–4 week old diluted Betnovate and emulsifying ointment base. Blanching induced by freshly prepared 4, 8 and 16-fold dilutions was not significantly different but a large reduction in blanching occurred on diluting 32-fold with emulsifying ointment. The degradation of betamethasone-17-valerate in emulsifying ointment was quantified by high performance liquid chromatography. More than 60% of the betamethasone-17-valerate underwent degradation within 6 h. There was a simultaneous increase in the concentration of betamethasone-21 -valerate which peaked within 2 days and was followed by a slow degradation (half-life 8 days) to betamethasone free alcohol. more...

SUMMARY Nineteen patients with symmetrically distributed patches of vitiligo took part in a double-blind trial comparing 0·1% betamethasone valerate in 50% isopropyl alcohol with the unmedicated base. Fifteen patients responded to the medicated application, none to the base alone. Two patients failed to respond and two patients defaulted from the trial. more...

SUMMARY In order to quantify the intensity of skin blanching and thus predict the bioavailability of topical corticoids, a physical device allowing the measurement of light reflected from skin without any contact between the probe and the skin was used (Leveque et al., 1984). Three series of experiments were carried out: firstly, to assess the vasoconstrictor potency of four corticoids; secondly, to show the influence of the vehicle on the bioavailability of the same drug under various galenic forms, such as fatty ointments or water in oil (W/O) and oil in water (O/W) creams; thirdly, to determine the reservoir effects, if any, of some of these formulations. The results confirm previous findings about the potency of hydrocortisone acetate, triamcinolone 17-acetonide, betamethasone 17-valeratc, diflucortolone valerate and clobetasol 17-propionate. more...

We have investigated the mechanisms by which topical corticosteroids modulate cutaneous immune reactions in man. Volunteers applied clobetasone butyrate 0.05% (Eumovate; EV), betamethasone valerate 0.1% (Betnovate; BV), clobetasol propionate 0.05% (Dermovate; DV), and control vehicles twice daily to forearm skin for 7 days. Steroid therapy significantly decreased the number of HLA-DR/T6 (CD1a) positive Langerhans cells (LCs) per mm2 in suction blister-derived epidermal sheets, expressed as a mean percentage of controls, as follows: EV 69.2%; BV 67.3%; DV 37.8%. LC antigen presenting capacity was determined in the allogeneic and autologous epidermal cell-lymphocyte reactions. The LC-dependent allostimulatory capacity of epidermal cells, expressed as a mean percentage of controls, was also significantly reduced by steroid therapy: EV 45.1%; BV 41.9%; DV 23.4%. Following therapy with clobetasol propionate 0.05%, the capacity of epidermal cells to present tetanus toxoid to, and to augment concanavalin A mediated lymphocyte stimulation of, autologous lymphocytes was reduced to 33.6% and 19.7% respectively of controls. Depression of epidermal cell allostimulatory capacity was not the result of a steroid-induced decrease in the production of epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1 by keratinocytes, since it could not be reversed by addition of exogenous interleukin 1. Indomethacin, added to block any potential prostaglandin synthesis during the culture period, did not restore the allostimulatory capacity of epidermal cells from steroid-treated sites. Addition of epidermal cells from DV-treated sites depressed the capacity of control epidermal cells to stimulate lymphocytes in the allogeneic epidermal-lymphocyte reaction. Our results demonstrate that the anti-inflammatory action of topical corticosteroids in man is associated not only with a reduction in the number of HLA-DR/T6 positive LCs, but also with a marked decrease in Langerhans cell-dependent T lymphocyte activation. The effects of the different steroids on both of these parameters correlated with their potency as determined in the standard occlusive vasoconstrictor assay. Topical corticosteroids are widely used for the treatment of inflammatory skin disorders, and inhibit not only the elicitation phase, but also the induction phase, of allergic contact dermatitis reactions.(ABSTRACT TRUNCATED AT 400 WORDS) more...

SUMMARY The ability of topical corticosteroids to reduce the size of weals induced with histamine on human skin was used as a human bioassay model to assess their relative efficacy. Histamine was introduced by the pinprick method and various topical corticosteroids were assessed. It is a simple, easy and reliable procedure which can be used on both white and dark people. Even though it is a non-clinical assay, it possesses close similarity to processes involved in the development of clinical dermatoses. more...

SUMMARY Twelve patients with symmetrical psoriasis were studied for a period of 6 months. Clobetasol propionate 0.05% ointment was applied to the lesions on one side and betamethasone valerate 0.1% ointment to those on the other side as a double-blind controlled trial of these two treatments. All the patients showed a relative improvement on the side treated with clobetasol propionate. Clobetasol propionate-treated lesions tended to clear for longer than the corresponding betamethasone valerate treated lesions. The condition of five of the patients was better at the end of the study period than at the beginning. more...

SUMMARY The rate of relapse after dithranol therapy is significantly less than when betamethasone valerate under occlusion is combined with dithranol in the treatment of psoriasis. It is also argued that local steroids are inferior to dithranol in the management of psoriasis. more...

Twenty-two patients were treated with desoximetasone emollient cream 0.25% twice daily without occlusion for 6 months. Patients applied the medication to approximately one-third of their body over psoriatic lesions. Corticosteroid plasma cortisol values decreased to below normal limits in nine patients before the 6-month study was terminated. In four of these the plasma cortisol spontaneously returned to normal despite therapy; in four other patients, however, the plasma cortisol was still suppressed at the end of 5 months of continual therapy but returned to normal within 7 days of discontinuation of the medication. In one patient, lost to further follow-up at 5 1/2 months of therapy, the trend at the fourth month was an increase in plasma cortisol to within one unit of normal range. Betamethasone 17-valerate 0.1% cream applied twice daily did not suppress plasma cortisol in twenty-three patients similarly tested. The clinical response to desoximetasone emollient cream was significantly better than to betamethasone valerate cream. This study closely approximates the way in which many patients with steroid-responsive dermatoses use potent topical steroids, namely over a long time period and without occlusion. more...

This double-blind study of an antibiotic coritcosteroid combination, the antibiotic alone and the corticosteroid alone, compared their clinical and microbiological effect in infected atopic dermatitis. Combination therapy reduced the mean scores for infection, inflammation and overall severity to a greater extent than the antibiotic or corticosteroid alone. The clinical and microbiological date are discussed in terms of relevance to clinical use. more...

SUMMARY The effect of five anti-inflammatory corticosteroids, i. e. hydrocortisone, hydrocortisone 17-butyrate, betamethasone 17-valerate, nicocortonide acetate and nicocortonide, on the synthesis of hyaluronic acid, sulphated glycosaminoglycans and collagen by cultured skin fibroblasts was studied. As inhibitors of all these parameters the steroids could be arranged in order hydrocortisone < hydrocortisone 17-butyrate < betamethasone 17-valerate, nicocortonide acetate and nicocortonide. The corticosteroid concentrations required for inhibition of hyaluronic acid were very low as compared to those required for inhibition of sulphated glycosaminoglycan and collagen synthesis. more...

Summary Epidermal Langerhans cells (LC) stained by antibodies to Ia, T6 and S-100 showed sustained reduction in numbers following the application of betamethasone-17-valerate 0·05% cream to normal human skin. An initial decrease in cell numbers after 24 h reached a plateau phase after 7 days which remained until a return to almost normal cell numbers following cessation of the steroid. Epidermal Langerhans cells were also reduced in the normal skin of patients receiving cytotoxic chemotherapy for solid tissue tumours. The Langerhans cell numbers rapidly returned towards normal when the chemotherapy ceased; the increase in numbers tended to parallel the recovery in drug-induced bone marrow suppression. These findings arc further evidence in humans that bone marrow replacement may be important in the return of LC numbers following their loss by various insults. This also occurs in association with local recovery of LC which are damaged, but not lost. more...

The non-occluded vasoconstrictor test under thermodynamic control assessed the effect of penetration enhancers on the topical bioavailability of a model steroid betamethasone 17-benzoate, using aqueous dimethylisosorbide (DMI) as a standard solvent. The aqueous potential penetration enhancers used were at 10% steroid saturation i.e. ideally at identical steroid thermodynamic activity. In the vasoconstrictor test, 2-pyrrolidone, N-methyl-2-pyrrolidone, propylene glycol with oleic acid, propylene glycol with azone and dimethylformamide (DMF) increased the steroid bioavailability compared with that from DMI, while propylene glycol alone produced borderline improvement. Azone and oleic acid in combination with DMI or Betnovate cream did not increase the steroid bioavailability indicating the importance of the correct cosolvent. The pyrrolidones established superior stratum corneum reservoirs compared with DMI, the other vehicles being similar to DMI. It was concluded that excepting DMI, the solvents tested were penetration enhancers for the model steroid betamethasone 17-benzoate and are worthy of further study. However, irritant effects may make some of them unacceptable for clinical use. more...

Summary A double-blind, cross-over study was undertaken to compare inhalation of betamethasone valerate (BV, 800 microgram daily) with sodium cromoglycate (SCG, 80 mg daily) in twenty children requiring bronchodilators for perennial asthma. Each treatment period lasted 4 weeks but statistical comparisons were made only in respect of the last 14 days of each therapy. When the children were using BV they required not only less of the bronchodilator drugs but had fewer symptoms and higher daily peak expiratory flow rates when taking SCG. Statistically, all these differences were highly significant. For 2 weeks before the main trial each child was given a placebo aerosol (single-blind) to assess severity of asthma. In comparison with this period, SCG was associated with a significantly increased peak expiratory flow rate a lower symptom score by day but not by night, but their usage of bronchodilators followed a similar pattern. When the BV period was compared with the placebo period, patients had an even more significant rise in peak expiratory flow rate, less day and night symptoms, and took hardly any bronchodilators. The response to the two drugs did seem to depend upon which was given first. No monilial infections were found, nor any measurable defect in adrenal response from either treatment. Betamethasone valerate is considered to be superior to sodium cromoglycate as a treatment for childhood asthma insufficiently controlled on bronchodilators. more...

A new human model for the evaluation of the atrophogenicity of topical corticosteroids is proposed. Formulated corticosteroids (creams and ointments) were applied occlusively to normal forearm skin of human volunteers for 3 weeks using Duhring chambers. Visible atrophy and telangiectasia were rated under a stereomicroscope on a histologically validated five-point scale. There was a close correlation between the parameters of atrophy and telangiectasia. Atrophogenicity varied considerably among the tested corticosteroids, ranging from none (1% hydrocortisone) via moderate (0.1% betamethasone valerate) to very severe (0.05% clobetasol propionate). A dose-response relationship with exposure time and concentration of the corticosteroid could be demonstrated. Furthermore, the vehicle influenced the resulting atrophy and telangiectasia. Fatty ointments seem to pose less risk than oil in water creams. more...

SUMMARY A modified behavioural method called habit-reversal, in combination with potent and weak corticosteroid cream, was compared with the use of the creams alone in the treatment of 45 patients with atopic dermatitis. The patients were randomly assigned to four groups, which received two different cream regimes in combination with the habit-reversal treatment. The patients' skin was assessed before, during and after treatment, and they recorded the amount of scratching during the study. The skin condition improved in all groups, but to a significantly greater degree in the habit-reversal groups. A strong correlation was found between the reduction in scratching and the improvement in skin status. more...

SUMMARY A number of studies describing the effects on pituitary adrenal function of topically applied corti-costeroids are reviewed. It is concluded that the adrenal function of the majority of out-patients is little affected by treatment with correctly prescribed topical corticosteroids. However, where patients need brief periods of treatment with large quantities of potent topical corticosteroids for extensive disease, clinicians should be aware of the possibility of transient adrenal suppression. more...

In the oxazolone-induced delayed hypersensitivity inflammation in the rat ear, betamethasone 17-valerate, in contrast to other topical corticosteroids, is incapable of suppressing oedema. When given in combination with triamcinolone acetonide, betamethasone 17-valerate competitively antagonizes the anti-inflammatory action of the active steroid. When tested in the mouse, betamethasone 17-valerate behaved as an anti-inflammatory agent 15 and 80 times as potent as betamethasone and hydrocortisone respectively. In an in vivo lymphocyte culture system in which preincubation with corticosteroids prevents subsequent phytohaemagglutinin induced DNA synthesis, betamethasone 17-valerate was less active than even hydrocortisone when rat lymph node cells were used, but with human cell preparations it was more potent than either hydrocortisone or betamethasone. Betamethasone 17-valerate behaves uniquely in the rat as an anticorticosteroid; in mouse and in man the compound behaves as a normal corticosteroid. more...

Four corticosteroids were tested in vitro for effect on the proliferation of four strains of fibroblasts from scleroderma skin, four strains from normal adult skin and four strains of rheumatoid synovial cells. Significant effects on fibroblasts occurred only at the highest steroid concentration tested (10 microgram/ml) where the inhibitory ranking of the steriods was clobetasol propionate greater than clobetasone butyrate greater than betamethasone valerate greater than hydrocortisone. Hydrocortisone and betamethasone valerate stimulated proliferation of two normal strains, had no certain effect on the scleroderma group, and inhibited growth of synovial cells. Clobetasone butyrate and clobetasol propionate inhibited growth of all cells. All four steroids substantially reduced acid mucopolysaccharide secretion by scleroderma fibroblasts. These results suggest that fibroblasts from normal and abnormal skin show only small differences in their responses to corticosteroids in vitro, but contrast sharply with the mouse L-929 fibroblasts previously used in some assays of topical corticosteroid potency. more...

SUMMARY.— The vasoconstrictor activity of betamethasone 17-benzoate at a concentration of 0.025% was studied in several ointment bases. Preparations containing betamethasone 17-benzoate in white soft paraffin/propylene glycol or in white soft paraffin/isopropyl myristate both gave rise to significantly higher total vasoconstriction than the other 5 ointments tested (P more...

Summary.— Data for 9 selected patients were used to show that rosacea-like dermatitis (RLD) is to be regarded as an intolerance reaction of seborrhoeic skin to topically-applied strong corticosteroids, such as betamethasone valerate and fluocinolone acetonide. A comparison of the geographical ranges of RLD and the use of strong corticosteroids shows that, in all countries considered, strong corticosteroids had been introduced long before RLD was observed. RLD can be cured by use of a powder suspension that is free from corticosteroids or fatty substances. more...