Topical corticosteroid vehicle composition and implications for clinical practice.

This narrative review highlights the therapeutic significance of topical corticosteroid (TCS) vehicles and provides subsequent guidance to improve clinical and research outcomes. A greater understanding of the relationship between the topical vehicle, corticosteroid and skin is needed to ensure safer, more effective treatment for patients. Topical vehicles are not inert and can affect TCS bioavailability, due to the ability of their composition to positively or negatively influence skin status and change the physiochemical characteristics of an inherent corticosteroid. However, this principle is not commonly understood, and has contributed to inconsistencies in potency classification systems. This review provides an insight into the research methods and standardization needed to determine TCS product bioavailability. It identifies formulation components responsible for vehicle composition that underpin the quality, stability, compounding and functionalities of vehicle ingredients. This helps to contextualize how topical vehicles can be responsible for clinically significant effects, and how their composition gives products unique properties. In turn, this facilitates a more in-depth understanding of which resources offer information to inform the best selection of TCS products and why products should be prescribed by brand or manufacturer. This review will better equip clinicians and formulary teams to appraise products. It will also inform prescribing of Specials and why products should not be manipulated. The recommendations, accompanied by patient perspectives on using TCS products, assist clinical decision-making. They also identify the need for research into concomitant application of TCS products with other topical therapies.

Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo-controlled, double-blind clinical trial.

BACKGROUND: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety. OBJECTIVES: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability. METHODS: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically. RESULTS: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions. CONCLUSIONS: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment.

Epidemiology of basal cell carcinoma in the United Kingdom: incidence, lifestyle factors, and comorbidities.

BACKGROUND: Little is known about the epidemiology of basal cell carcinoma (BCC). METHODS: Using the Clinical Practice Research Datalink, we calculated annual incidence rates. In a case-control analysis, we examined lifestyle factors and comorbidities. RESULTS: Incidence rose significantly between 2000 and 2011. Basal cell carcinoma risk was increased in alcohol drinkers (slightly) and immunocompromised patients, but reduced in smokers and individuals with abnormal weight. CONCLUSIONS: Basal cell carcinoma places a growing public health burden. Lifestyle factors do not play a major role in pathogenesis, but immunosuppression is important.

Sun protective behaviour of vacationers spending holidays in the tropics and subtropics.

BACKGROUND: The development of malignant melanoma has been associated with intense episodic sun exposure, as it typically occurs during holidays in high ultraviolet (UV)-index countries. OBJECTIVES: To investigate sun protective behaviour and sunburn experience of vacationers spending holidays in the tropics or subtropics. METHODS: Using standardized face-to-face interviews, we conducted cross-sectional surveys among air passengers waiting in the departure or the baggage claim area at the Airport Basel-Mulhouse (Switzerland/France), and among vacationers waiting for pretravel health advice at a travel clinic in Basel (Switzerland). RESULTS: We completed 533, 324 and 308 interviews with departing air passengers, returning air passengers and vacationers at the travel clinic, respectively. The interviews revealed widespread misconceptions about how to prepare the skin for the sun before holidays (e.g. pretanning in the solarium). At the holiday destination, almost all respondents used sunscreen, whereas wearing protective clothing and seeking shade were less practised. Among the returning air passengers, 44% had got sunburnt during their holiday stay. CONCLUSIONS: The sunburn rate among returning vacationers was alarmingly high. Skin cancer prevention campaigns and pretravel health advice should tackle misconceptions regarding the preparation of the skin for the sun, and emphasize the significance of covering up and seeking shade.

Outdoor workers' sun-related knowledge, attitudes and protective behaviours: a systematic review of cross-sectional and interventional studies.

Sun protection is a major concern for outdoor workers as they are particularly exposed to solar ultraviolet radiation and therefore at increased risk of developing some forms of skin cancer, cataract and ocular neoplasm. In order to provide an overview of outdoor workers' sun-related knowledge, attitudes and protective behaviours as reported in the literature and to evaluate the effectiveness of sun-safety education programmes in outdoor occupational settings, we conducted a systematic review of the literature by searching three electronic databases (PubMed, Embase, PsycINFO) from their inception up to 25 April 2012. An extensive hand search complemented the database searches. We identified 34 relevant articles on descriptive studies and 18 articles on interventional studies. Considerable numbers of outdoor workers were found to have sun-sensitive skin types; sunburn rates per season ranged from 50% to 80%. Data concerning outdoor workers' sun-related knowledge and attitudes were scarce and controversial. The reported sun-protective behaviours were largely inadequate, with many workers stating that they never or only rarely wore a long-sleeved shirt (50-80%), sun-protective headgear (30-80%) and sunscreen (30-100%) while working in the sun. However, there is growing evidence that occupational sun-safety education is effective in increasing outdoor workers' sun-protection habits and presumably in decreasing sunburn rates. Occupational sun-safety education programmes offer great potential for improving outdoor workers' largely insufficient sun-protective behaviours. It is hoped that, in the future, committed support from healthcare authorities, cancer foundations, employers and dermatologists will open the way for rapid and uncomplicated implementation of sun-safety education programmes.

Howard I. Maibach: extraordinary leadership in integrating key concepts underpinning our understanding of percutaneous absorption and occupational dermatology.

The purpose of the present article is to briefly highlight some contributions of Prof. Howard I. Maibach to the field of dermatology. After a few introducing remarks regarding Howard's personal career, the article specifically reviews contributions to the understanding of percutaneous absorption and to occupational dermatology. He and his companions/coworkers established and introduced experimental prerequisites to better study and understand percutaneous absorption - both in vitro and in vivo. Not less influential was his contribution to occupational dermatology acting as a founding member of the International Contact Dermatitis Research Group and coinaugurating the North American Contact Dermatitis Group. These groups have been very active ever since. As an academic teacher, he inspired young colleagues to perform original research work and to establish their own working groups. He has done this most successfully with many fellows who worked with him over the years, and who are now leading departments or companies dedicated to dermatological research all over the world. Probably this is his most important and lasting achievement.

Photoprotection in immunocompetent and immunocompromised people.

Ultraviolet radiation (UVR) exposure from the sun and artificial UV sources has been widely acknowledged as the major culprit for skin cancer and premature skin ageing. Skin cancers are among the most dangerous (cutaneous malignant melanoma) and the most numerous (basal cell carcinoma, actinic keratosis and invasive squamous cell carcinoma) of all neoplasms in the caucasian population worldwide. Skin cancers therefore have a significant impact on public health and healthcare costs, and will continue to do so. It is obvious that adequate photoprotection - seeking shade, wearing protective clothing and using sunscreens - is the key to reducing the harmful effects of UVR in both immunocompetent and immunocompromised people. This article provides background information on UVR, photoprotection (including the concept of topical sunscreen formulations), associated concerns regarding efficacy and safety, and behavioural and educational aspects of photoprotection and skin cancer prevention in immunocompetent and immunocompromised people. Certain persistent misconceptions and mistakes regarding photoprotection are also addressed.

Noninvasive stratum corneum sampling and electron microscopical examination of skin barrier integrity: pilot study with a topical glycerin formulation for atopic dermatitis.

INTRODUCTION: Therapy of atopic dermatitis encloses use of medicated and nonmedicated preparations. Results of clinical and biophysical procedures indirectly describe the condition of the impaired skin barrier (SB). Direct evaluation of SB integrity is only possible by electron microscopical visualization, e.g. intercellular lipid lamellae (ICLL) organization of the stratum corneum. METHOD: SB integrity was measured by morphometric analysis of ICLL in healthy and atopic skin and after a 15-day treatment (plus 7-day follow-up) of atopic skin with a glycerin preparation. RESULTS: Significant treatment effect was shown by the restoration of the ICLL. CONCLUSIONS: The study reveals that morphometric analysis of ICLL organization is suitable to differentiate between healthy and diseased skin and to semiquantitatively determine the effect of a nonmedicated glycerin formulation. LIMITATION: Small treatment cohort.

Asthma tests in the assessment of military conscripts.

BACKGROUND: Respiratory diseases such as asthma may affect individuals' fitness for military service. In order to assess fitness for military service in subjects with asthma symptoms at conscription, objective and reliable tests are needed. OBJECTIVE: To prospectively determine the diagnostic value of the mannitol and methacholine bronchial provocation test (BPT) as well as exhaled nitric oxide in assessing physician-diagnosed asthma in a group of Swiss Armed Forces conscripts. METHODS: Questionnaire, spirometry, BPT with methacholine and mannitol, exhaled nitric oxide (FeNO) and skin prick testing were conducted in 18-20-year-old male conscripts. Asthma was diagnosed by a military physician not involved in this study according to the medical record, results of BPT, current respiratory symptoms and use of asthma medication. RESULTS: Two hundred and eighty four subjects participated in the study. Complete data for the BPT with methacholine, mannitol and measurement of FeNO were available on 235 subjects. Forty-two conscripts (17.9%) had physician-diagnosed asthma. The sensitivity/specificity of mannitol to identify physician-diagnosed asthma was 41%/93% and for methacholine it was 43%/92%. Using a cut-off point of 36.5 p.p.b., FeNO had a similar negative predictive value to rule out physician-diagnosed asthma as BPT with mannitol or methacholine. CONCLUSION: BPT with mannitol has a sensitivity and specificity similar to methacholine for the diagnosis of physician-diagnosed asthma in military conscripts but is less costly to perform without the need to use and maintain a nebulizer.

Topical retinoids in the management of photodamaged skin: from theory to evidence-based practical approach.

Skin, being exposed directly to the environment, represents a unique model for demonstrating the synergistic effects of intrinsic and extrinsic factors on the ageing process. Ultraviolet radiation (UVR) is the major factor among exogenous stressors responsible for premature skin ageing. The problem of skin ageing has captured public attention and has an important social impact. Different therapeutic approaches have been developed to treat cutaneous ageing and to diminish or prevent the negative effects of UVR. Topical retinoids represent an important and powerful class of molecules in the dermatologist's hands for the treatment of photodamaged skin. Since their introduction more than 20 years ago, topical retinoids have shown beneficial efficacy and good safety profiles in the management of photodamaged skin, and as therapeutic anti-ageing agents. This review provides a brief retrospective of the development of topical retinoids in the treatment of photodamaged skin, elucidates their mechanism of action, delineates their use and addresses clinical, pharmaceutical and regulatory issues in connection with their intended use.

Children and sun protection.

Sun protection is a central measure to avoid the development of skin cancer and premature aging of the skin. In this context skin protection of children is of particular relevance since children spend a lot of time outdoors and they cannot provide themselves with sun protection measures as adults can. In addition to this sunburn reactions in childhood are particularly important in the development of melanoma skin cancer. This special situation of children with regards to sun protection has not only become aware to dermatologists but also to politicians, which is why a recent recommendation of the European Union explicitly points out the necessity of stringent sun protection of children. This review summarizes the current knowledge about sun protection of children. Underlying mechanisms of skin carcinogenesis in children, available sun protection measures as well as practical advice on daily sun protection of children are discussed.

Glycerol and the skin: holistic approach to its origin and functions.

Glycerol is a trihydroxy alcohol that has been included for many years in topical dermatological preparations. In addition, endogenous glycerol plays a role in skin hydration, cutaneous elasticity and epidermal barrier repair. The aquaporin-3 transport channel and lipid metabolism in the pilosebaceous unit have been evidenced as potential pathways for endogenous delivery of glycerol and for its metabolism in the skin. Multiple effects of glycerol on the skin have been reported. The diverse actions of the polyol glycerol on the epidermis include improvement of stratum corneum hydration, skin barrier function and skin mechanical properties, inhibition of the stratum corneum lipid phase transition, protection against irritating stimuli, enhancement of desmosomal degradation, and acceleration of wound-healing processes. Even an antimicrobial effect has been demonstrated. Topical application of glycerol-containing products improves skin properties in diseases characterized by xerosis and impaired epidermal barrier function, such as atopic dermatitis. The increase of epidermal hydration by glycerol is critical in skin conditions aggravated by dry and cold environmental conditions, e.g. winter xerosis. This paper provides a review on effects of glycerol on the skin, the mechanisms of its action, and the potential applications of glycerol in dermatology.

Individualising drug dispensaries in a university hospital.

BACKGROUND: In hospitals and other healthcare institutions drugs are routinely stored in designated satellite areas on the wards. Often ad hoc decisions are made by clinicians and nurses regarding drug type and quantity to be stored. As a result the number of different drugs and drug packages in storage tends to increase, which may lead to inefficient drug handling and become a potential risk factor in the medication control process. Based on an extended analysis of drug inventories on three different wards it was hypothesized that a ward-individualised formulary (WIF) can halve the number of different drugs and drug packages in a drug dispensary and hence reduce bound capital, money lost through expired drugs, and facilitate safer drug handling. The interdisciplinary intervention described here took place on three 40-bed wards in a 700-bed university hospital housing patients in general internal medicine, haematology, nephrology and oncology. METHODS: A WIF was defined by including all drugs from the hospital formulary ordered at least three times in the past six months. A pharmacist, a nurse and a clinician reviewed the inclusion list of drugs and clinicians were strongly encouraged to prescribe drugs primarily from the WIF. Drugs excluded from the WIF were removed from the drug dispensaries and the number of included drug packages stored in the remote dispensaries was reduced according to their order history. Drug inventory on the wards was monitored from February 2004 to April 2006. RESULTS: The initial drug dispensary inventories on wards A, B and C consisted of 2031, 1667 and 1536 packages with 943, 897 and 831 different drugs valued at h 83 931, h 44 590 and h 57 285. respectively. After adjusting the drug dispensaries according to the WIF drug dispensary inventories on wards A, B and C consisted of 808 (-60%), 600 (-64%) and 485 (-68%) packages with 415 (-56%), 334 (-63%) and 376 (-55%) different drugs valued euro 28 012 (-67%), euro 10 381 (-77%) an euro 17 898 (-69%). The overall reductions the number of packages, the different drugs and the drug value were comparable (>50%) and remained low during the entire observation time (A: 18 months, B: 13 months, C: 8 months). CONCLUSION: Rearranging dispensaries by individualizing the drug inventory according to the needs of the ward by introducing a WIF is a valuable means to significantly (>50%) reduce [1] the number of drug packages, [2] the number of different drugs stored and [3] the capital bound drugs. The positive effects of the WIF are supported by the interdisciplinary interaction of the different professional groups involved in the medication process. The leaner drug dispensaries offer optimal basic conditions for introducing new IT-based systems to further increase the safety of the medication process.

[Ointments and other dermal applications]. / Salben und andere dermale Anwendungsformen.

In dermatopharmacotherapy the choice of the appropriate vehicle is essential. Acuity of the efflorescence, localization, and extent of the affection, skin type, cosmetic preferences of the patient as well as removability with water, cooling and occlusive effects of the vehicle are important criteria for the choice of the appropriate vehicle. Adapted therapeutic and utilization modalities support a successful dermatopharmacotherapy and compliance.

Principles of skin care in the elderly.

With aging, skin undergoes progressive structural and functional degeneration that leaves it prone to a wide variety of bothersome and even serious conditions and diseases. As skin conditions and diseases may affect all ages from cradle to grave, a disproportionate burden will clearly fall on the elderly and may significantly impact on quality of life (QoL). With a reduced ability of the skin to regenerate, the elderly are at an increased risk of skin breakdowns from even the simplest insults. It is therefore vital that skin care in the late adulthood is seen as a priority among both clinicians and caregivers. The scientific literature on diagnosing and assessing age-related skin conditions and diseases is vast; however, when it comes to preventive care and treatment, the scientific data available is less profound, and the recommendations are often based on personal experience, opinions or at best on consensus documents rather than on scientific data retrieved from controlled clinical trials. In addition to the absence of the scientific data, the imprecise terminology to describe the topical products, as well as the lack of understanding the essence of the vehicle, contributes to vague and often unhelpfully product recommendations. This paper aims to elucidate some basic principles of skincare, the choice of skincare products and their regulatory status. The paper discusses adherence to topical therapies, percutaneous absorption in the elderly, and skin surface pH and skin care. Lastly, it also discusses skin care principles in selected age related skin conditions and diseases.

Effect of sodium lauryl sulfate-induced skin irritation on in vitro percutaneous absorption of four drugs.

The influence of irritant contact dermatitis on percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated in vivo for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment animals were sacrificed. Percutaneous penetration was then measured using in vitro diffusion cells and the removed (pretreated) skin. The following parameters were determined: cumulative amount of compound penetrated, steady state flux, lag time, and permeability coefficient, skin concentration per unit area, and the relative amount of drug remaining in the skin (as a percentage of the cumulative amount of compound penetrated through the skin). SLS pretreatment resulted in moderate irritant dermatitis in all animals and increased in vivo transepidermal water loss 4.5 times. Flux was increased in SLS-pretreated skin as compared with controls for all four compounds, with the greatest enhancement for hydrocortisone (HC) (5.9 times), followed by indomethacin (IM) (4.6 times), ibuprofen (IB) (3.9 times), and acitretin (AC) (3.4 times). Skin concentrations increased to a smaller degree from 1.6 times (IB) and 2.6 times (HC) to 3.4 times (IM). However, AC skin concentrations were not different between the two groups. Thus, percutaneous penetration parameters were equivocally influenced by SLS-induced irritation. Increased skin concentrations were paralleled by even higher increases in flux.