Compounding topicals in dermatology.

Compounding topical medications is a way for dermatologists to prescribe customized topical treatment options based on the individualized needs of patients. However, there are limited data on the safety of compounded medications and potential systemic absorption. Additionally, there also are limited data on the efficacy of compounded medications given their unique nature.

The Role of Topical Retinoids in Prevention and Treatment of Atrophic Acne Scarring: Understanding the Importance of Early Effective Treatment

Atrophic acne scarring is a frequent occurrence among acne patients. These facial marks are often very emotionally distressing for the patient and can result in adverse impact to quality of life. While most clinicians consider scarring as a sequela of moderate to severe acne, recent studies have found that scars are also associated with mild acne. Risk factors include time to effective treatment, severity of acne, family history, and excoriations. New data shows that early and effective acne treatment can reduce the development of new scars, confirming the widespread perception of this approach in prevention. It is also becoming clear that the inflammatory process drives both the development of acne lesions and atrophic scars. This implies that inhibiting activation of inflammatory pathways early is key to preventing scars. Data also suggests a useful role for adapalene for the treatment of well-established acne scars with scar remodeling accompanied by the production of new collagen and elastic tissue. Acne guidelines and recommendations continue to highlight the central role of retinoids, with fixed-dose combination retinoids being particularly important due to targeting of multiple inflammatory pathophysiologic factors and for patient convenience. Higher concentrations of retinoids such as adapalene 0.3%/benzoyl peroxide 2.5% (A0.3/BPO2.5) have shown increased efficacy, particularly among patients with moderately severe and severe acne ­ a population at high risk for scarring. Further, controlled study of A0.3/BPO2.5 in patients with moderate acne (mean, 40 acne lesions per half face) and mild-moderate scarring demonstrated A0.3/BPO2.5 was significantly superior to vehicle in reducing scar counts from baseline over 24 weeks. While scar counts lessened on the A0.3/BPO2.5 side, counts increased on the vehicle side during the study. This occurred in the setting of active acne, where the efficacy of A/BPO is well known, emphasizing the dual actions of A0.3/BPO2.5 in both treatment and prevention. J Drugs Dermatol. 2019;18(3):255-260.

Skin Care Products for Healthy and Diseased Skin.

The industry offers a vast armamentarium of skin care products (SCP) to cleanse the skin; to reduce/eliminate unpleasant skin symptoms; to restore, reinforce, fortify and protect undamaged, vulnerable or damaged skin; and to provide a pleasant skin and body feel. Skin care products are readily available and their promotions with a variety of tall claims are omnipresent. This text discusses the various interpretations of skin care, the diversity of its comprehensions and the various groups of receivers and their needs for skin care. Skin care is part of our daily routines, the information on the effects of SCP is omnipresent and the purchase of SCP seems straightforward. However, the true essence of SCP remains concealed to many. This is mainly due to that fact that the "physico-chemical anatomy," the nomenclature and the regulatory classification of SCP as well as the role and the significance of active and inactive ingredients within these products are not well understood. This text addresses the different views, interpretations and comprehensions. The final part highlights the current challenges with SCP and gives an outlook on how to improve our mutual understanding of SCP.

Yes to Appropriate Compounding, No to Illegal Compounding.

Dermatology is often described as a "visual" specialty. While it is true that many of our diagnoses can be made based on a relatively quick recognition of morphology, such a characterization of our profession overlooks the reality that dermatologists are "doers" in the clinic. From aesthetic injections to biopsies and cryosurgery, much of our patient care time is spent performing minor and major procedures. We are well known for our in-office efficiency and cost saving practices.

The Practice of Compounding, Associated Compounding Regulations, and the Impact on Dermatologists.

Medication compounding gained national attention in the fall of 2012 after contaminated compounded medications produced in the New England Compounding Center infected 800 people with fungal meningitis and led to several fatalities. This prompted Congress to pass regulations on compounding through the Drug Quality and Security Act (DQSA) in 2013. The act increased oversight of patient-specific drug compounding taking place in compounding pharmacies, created 503(b) outsourcing facilities to obtain compounded drugs, and added regulations for obtaining compounded drugs from traditional 503(a) pharmacies. These regulations also had a broader overall impact by triggering federal and state-specific policies, which have ultimately limited a physician's ability to perform low-risk, in-office compounding. This article provides an overview of the different types of compounding restrictions, reviews the current federal and state regulations and/or guidelines, discusses how newly proposed policies may affect the practice of dermatology, and presents an algorithm on how the practicing dermatologist should approach compounding. J Drugs Dermatol. 2018;17(7 Suppl):s17-22.

Japanese Dermatological Association Guidelines: Guidelines for the treatment of acne vulgaris 2017.

The Guidelines for the Treatment of Acne Vulgaris of the Japanese Dermatological Association was first published in Japanese in 2008 and revised in 2016 and 2017. These guidelines (GL) indicate the standard acne treatments in Japan and address pharmaceutical drugs and treatments applicable or in use in Japan. In these GL, the strength of the recommendation is based on clinical evidences as well as availability in Japanese medical institutions. In the 2016 and 2017 GL, some of the clinical questions were revised, and other questions were added in accordance with approval of topical medicines containing benzoyl peroxide (BPO). Rather than monotherapies of antibiotics, the 2017 GL more strongly recommend combination therapies, especially fixed-dose combination gels including BPO in the aspects of pharmacological actions and compliance in the acute inflammatory phase to achieve earlier and better improvements. The 2017 GL also indicate to limit the antimicrobial treatments for the acute inflammatory phase up to approximately 3 months and recommend BPO, adapalene, and a fixed-dose combination gel of 0.1% adapalene and 2.5% BPO for the maintenance phase to avoid the emergence of antimicrobial-resistant Propionibacterium acnes. The 2017 GL also discuss rosacea, which requires discrimination from acne and a different treatment plan.

Diagnostic criteria, severity classification and guidelines of localized scleroderma.

We established diagnostic criteria and severity classification of localized scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for localized scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of localized scleroderma.

Optimizing the use of topical retinoids in Asian acne patients.

Acne vulgaris is a common disease among people in Asia. International guidelines and treatment recommendations emphasize the central role of topical retinoids in the management of acne. However, topical retinoids remain underutilized in clinical practise, which may be in part due to fear of retinoid-associated dermatitis/lack of experience, particularly in Asian patients. There is a perception that Asian skin has a greater tendency toward sensitivity compared with Caucasian skin. In our clinical experience, topical retinoid therapy can be used with excellent effect to treat Asians with acne. This article discusses available published work regarding the use of topical retinoids in Asian populations, and presents tips for utilizing these important agents in daily practise. Optimizing use of topical retinoids may improve adherence and, in turn, therapeutic outcomes and patient satisfaction.

Developing drugs for treatment of atopic dermatitis in children (≥3 months to <18 years of age): Draft guidance for industry.

Atopic dermatitis is the most common chronic skin disease, and it primarily affects children. Although atopic dermatitis (AD) has the highest effect on burden of skin disease, no high-level studies have defined optimal therapy for severe disease. Corticosteroids have been used to treat AD since the 1950s and remain the only systemic medication with Food and Drug Administration approval for this indication in children, despite published guidelines of care that recommend against this option. Several clinical trials with level 1 evidence have supported the use of topical treatments for mild to moderate atopic dermatitis in adults and children, but these trials have had little consistency in protocol design. Consensus recommendations will help standardize clinical development and trial design for children. The Food and Drug Administration issues guidance documents for industry as a source for "the Agency's current thinking on a particular subject." Although they are nonbinding, industry considers these documents to be the standard for clinical development and trial design. Our consensus group is the first to specifically address clinical trial design in this population. We developed a draft guidance document for industry, Developing Drugs for Treatment of Atopic Dermatitis in Children (≥3 months to <18 years of age). This draft guidance has been submitted to the Food and Drug Administration based on a provision in the Federal Register (Good Guidance Practices).

Lack of pregnancy warnings on over-the-counter dermatologic products containing potentially harmful hydroquinone.

OBJECTIVE: To determine the presence of pregnancy warnings on over-the-counter (OTC) dermatologic products with hydroquinone, a potentially harmful ingredient. STUDY DESIGN: Data were obtained from the Food and Drug Administration National Drug Code Directory and Label Repository to identify OTC dermatologic products containing hydroquinone. Products were stratified based on pregnancy or general warning presence (WP) or absence (WA). Product characteristics were compared between groups: hydroquinone concentration, presence of external packaging, indication and warning statements. RESULTS: Of the 112 products studied, 21 had a pregnancy warning and 3 included a general warning against use: WP (n=24) and WA (n=88) group. External packaging was more prevalent in the WP group compared to WA (62.5% vs 29.5%, P=0.004). CONCLUSIONS: Majority of OTC dermatologic products containing hydroquinone did not have a pregnancy warning. This highlights the need for improved labeling and informs providers caring for pregnant women of OTC labeling limitations.

[Acne and rosacea in pregnancy]. / Akne und Rosazea in der Schwangerschaft.

Acne and rosacea are common chronic inflammatory skin diseases. During pregnancy these skin disorders may become aggravated, in rare cases occurring for the first time. There are no data available for rosacea and little data for acne concerning the course of these skin disorders during pregnancy. Up to 42% of the pregnant women suffer from acne. In 90% of these women the disease existed before pregnancy. In 1/3, however, acne relapsed during pregnancy after a prior disease-free period. In 60% acne deteriorated during pregnancy. Randomized controlled trials for the treatment of acne or rosacea during pregnancy do not exist. In this article the recommendations of current guidelines are modified, so that effective treatments can be recommended without harming the embryo or fetus.

Healing effect of Dillenia indica fruit extracts standardized to betulinic acid on ultraviolet radiation-induced psoriasis-like wounds in rats.

CONTEXT: Dillenia indica Linn. (Dilleniaceae) is traditionally used to treat skin inflammation. OBJECTIVE: This study evaluated the healing effect of Dillenia indica fruit extracts on induced psoriasis-like wounds in Wistar rats. MATERIALS AND METHODS: Extracts were standardized to betulinic acid, including an aqueous ethanolic extract (AEE), ethyl acetate extract (EAE) and petroleum ether extract. Effects against lipid peroxidation were assessed in vitro. Wounds were created at rat tails (n = 12). Topical treatments were applied once daily for 7 days (1 mL of AEE or EAE at 5 or 50 mg/mL). Maximal dose was defined by the extract solubility. A 10-fold lower dose was also tested. Positive and negative controls were treated with clobetasol (0.5 mg/mL) or excipient. Half of each group was euthanized for histology. The remaining animals were observed for 20 days for wound measurements. RESULTS: Yields of AEE and EAE were 4.3 and 0.7%, respectively. Betulinic acid concentrations in AEE and EAE were 4.6 and 107.6 mg/g. Extracts neutralized lipid peroxidation in vitro at 0.02 µg/mL, accelerating healing at 50 mg/mL. Complete healing in mice treated with AEE occurred 16 days after wound induction. This time was 14 and 12 days in mice treated with EAE and clobetasol. Compared to orthokeratosis, parakeratosis was reduced by AEE (25%), EAE (45%) and clobetasol (55%). EAE caused superior protection against biomolecules oxidation of skin compared to AEE. DISCUSSION AND CONCLUSION: EAE exhibited activity closer to that of clobetasol. Betulinic acid may be an active constituent, which should be assessed in future studies.

Topical preparations and their use in dermatology.

The challenges of everyday clinical routine require dermatologists to have a basic knowledge of the composition of topical preparations as well as the regulatory background associated with their prescription. Proper selection, prescription, and application of topical preparations, depending on the respective indication, are key to professional and responsible medical practice. Problems commonly arise with respect to regulatory classifications (medicinal products, medical devices, or cosmetics), eligibility for reimbursement by the statutory health insurances (GKV), and insufficient declaration of vehicle systems. Apart from selecting the appropriate active substance and its proper concentration, choosing a suitable pharmaceutical (galenic) formulation - and thus utilizing the intrinsic effects thereof - is pivotal in enhancing the intended therapeutic effects. When prescribing individual formulations, dermatologists should, to the greatest extent possible, always resort to standardized extemporaneous preparations. Given the multitude of potential ingredients available for pharmaceutical formulations as well as the complexity resulting therefrom, arbitrary changes in quality or quantity of individual components are associated with a high risk of instability, thus jeopardizing safety and the rationale behind any given formulation. Optimal use of topical preparations also requires basic knowledge in pharmacokinetics as well as evidence-based treatment planning.

Evaluation of Ubtan - A traditional indian skin care formulation.

ETHNOPHARMACOLOGICAL RELEVANCE: 'Ubtan' is a traditional herbal formulation in the Indian system of medicine being used in India and its subcontinent for a long time. Several commercial skin care formulations are marketed throughout this region as the name of Ubtan. Therefore, it is worthwhile to evaluate Ubtan in respect of its efficacy as skin care formulation. AIM OF THE STUDY: The present study was designed for the preparation of Ubtan and standardization through the chromatographic techniques by using suitable phyto-markers. Further, its antioxidant, sun protection factor (SPF) and anti-tyrosinase potential have been explored. MATERIALS AND METHODS: Four in-house formulations (UF-1, UF-2, UF-3 and UF-4) were prepared by mixing a varied quantity of each powdered plants, i.e. turmeric (Curcuma longa L.), Chickpea (Cicer arietinum L.) and sandalwood (Santalum album L.). Optimization of the formulations was made by evaluating its biological activity through in vitro assay. Evaluation of physicochemical properties of the optimized formulation (UF-1) has been carried out by analysis of pH, flow properties and stability. Moreover, RP-HPLC (reverse phase - high performance liquid chromatography) and HPTLC (high performance thin layer chromatography) standardization of UF-1 was performed for its quantitative and qualitative analysis. RESULTS: Ubtan formulations (UF-1to UF-4) showed free radical scavenging and ferric reducing potential. It may be due to its high phenolic and flavonoid content. Statistically, significant Pearson's correlation (r) was confirmed the positive correlation between phenolic content and SPF of the formulations. The tyrosinase inhibition study indicated that the formulations showed both diphenolase and monophenolase inhibitory activity. Among four formulations, UF-1 showed notable biological activity (p<0.05). The content of curcumin and ascorbic acid was found to be 1.6% and 2.1% w/w respectively in UF-1 through RP-HPLC estimation. Physiochemical properties of the UF-1 exhibited good flow rate and aqueous solubility. From the stability studies, it can be anticipated that the UF-1 was stable at 40°C for longer periods. Microbial load count and heavy metal content (lead-Pb, arsenic-As, mercury-Hg and cadmium-Cd) of the formulation was also within the permissible limit of a pharmacopeial standard. CONCLUSION: This scientific exploration helps to set the quality and safety standard of traditional cosmetic formulation, Ubtan and its further use as an herbal skin care product.

[Current guidelines in dermatology : A selection of clinically relevant recommendations]. / Aktuelle dermatologische Leitlinien : Eine praxisorientierte Übersicht ausgewählter Empfehlungen.

Guidelines are systematically developed decision aids for specific medical conditions. The German Dermatological Society, together with the German Professional Association of Dermatologists, takes the lead in the development of the guidelines for dermatology in Germany. In addition to national guidelines, European and international guidelines also exist. In 2014 and 2015 German guidelines on the following topics were newly developed or updated: cutaneous larva migrans, anticoagulation during dermatosurgery, pemphigus vulgaris and bullous pemphigoids, Mohs surgery, anal dysplasia, and anal carcinoma in HIV-infected patients. European guidelines on psoriasis vulgaris and hand eczema were updated among others. An international guideline on actinic keratosis was also published. The guidelines are available at www.awmf.org and www.euroderm.org .

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.

An Update of the Brazilian Regulatory Bioequivalence Recommendations for Approval of Generic Topical Dermatological Drug Products.

This note aims to clarify the Brazilian regulatory bioequivalence recommendations for approval of generic topical dermatological drug products, since the legal framework of the "Brazilian Health Surveillance Agency" (ANVISA) is only available in Portuguese. According to Resolutions RE n. 1170 (December 19th 2006) and RDC n. 37 (August 3rd 2011) in Brazil, only in vitro studies are required for registration of generic topical dermatological drug products. Current Regulatory Agenda of ANVISA, which contains possible future resolutions to be revised over 2015-2016, includes a discussion on biowaiver requirements and on possible in vitro and in vivo comparability tests for these products.

[Off-label use and G-BA. Legal framework for off-label use]. / Off-label-Use und G-BA. Rechtliche Rahmenbedingungen für Off-label-Use.

Off-label use of medicinal products, i.e. beyond their submitted, tested and approved indications, lies between 30 and 90%--depending on the indication. In dermatology, off-label use is of special importance, for even guideline-endorsed standard therapeutic approaches for common dermatological diseases like atopic eczema, psoriasis, or malignant melanoma are to some extent not licensed for these indications. In addition, many of the approximately 5000 dermatological diseases have a low prevalence. For many such orphan diseases, there are no approved drugs, and it is not feasible that licensing studies will be performed for these indications within a foreseeable time. A reliable legal framework for the reimbursement of medicinal products that are used off-label is essential both for patients and to allow physicians to choose the most adequate therapy. Therefore, off-label use expert groups have been convened by the Federal Ministry of Health (BMG) in order to improve patient care. So far this new and innovative approach has not provided any reasonable improvement for many patients with dermatological diseases whose treatment can only be off-label since a comprehensive evaluation of all off-label indications is not possible. The following statement of the former Federal Minister of Health, U. Schmidt, is particularly true for dermatological therapy: "Good oncologic care also requires a good drug treatment--especially in the outpatient setting. The use of drugs which are not or not yet approved for this indication is often required here". Federal Minister of Health, Ulla Schmidt, 25th German Cancer Congress, 10 March 2002, Berlin.