Cosmetic retinoid use in photoaged skin: A review of the compounds, their use and mechanisms of action.

The inevitable attrition of skin due to ultraviolet radiation, termed photoaging, can be partially restored by treatment with retinoid compounds. Photoaged skin in lightly pigmented individuals, clinically presents with the appearance of wrinkles, increased laxity, and hyper- and hypopigmentation. Underlying these visible signs of ageing are histological features such as epidermal thinning, dermal-epidermal junction flattening, solar elastosis and loss of the dermal fibrillin microfibrillar network, fibrillar collagen and glycosaminoglycans. Retinoid compounds are comprised of three main generations with the first generation (all-trans retinoic acid, retinol, retinaldehyde and retinyl esters) primarily used for the clinical and cosmetic treatment of photoaging, with varying degrees of efficacy, tolerance and stability. All-trans retinoic acid is considered the 'gold standard' for skin rejuvenation; however, it is a prescription-only product largely confined to clinical use. Therefore, retinoid derivatives are readily incorporated into cosmeceutical formulations. The literature reported in this review suggests that retinol, retinyl esters and retinaldehyde that are used in many cosmeceutical products, are efficacious, safe and well-tolerated. Once in the skin, retinoids utilize a complex signalling pathway that promotes remodelling of photoaged epidermis and dermis and leads to the improvement of the cutaneous signs of photoaging.

L'altération inévitable de la peau due aux rayons ultraviolets, appelée photovieillissement, peut être partiellement restaurée par un traitement à base de composés rétinoïdes. Chez les personnes à la pigmentation claire, le photovieillissement de la peau se manifeste au plan clinique par l'apparition de rides, un relâchement accru et une hyperpigmentation ou hypopigmentation. Ces signes visibles du vieillissement sont sous­tendus par des caractéristiques histologiques telles que l'amincissement de l'épiderme, l'aplatissement de la jonction dermo­épidermique, l'élastose solaire et la perte du réseau microfibrillaire de fibrilline dermique, du collagène fibrillaire et des glycosaminoglycanes. Les composés rétinoïdes sont constitués de trois générations principales, la première génération (acide tout­trans rétinoïque, rétinol, rétinaldéhyde et esters de rétinyle) étant principalement utilisée pour le traitement clinique et cosmétique du photovieillissement, avec des degrés variables d'efficacité, de tolérance et de stabilité. L'acide tout­trans rétinoïque est considéré comme la référence en matière de rajeunissement de la peau; il s'agit toutefois d'un produit délivré uniquement sur ordonnance, dont l'utilisation est largement limitée au domaine clinique. Les dérivés rétinoïdes sont donc volontiers incorporés ds formulations cosméceutiques. La littérature citée dans cette synthèse bibliographique laisse penser que le rétinol, les esters de rétinyle et le rétinaldéhyde, utilisés dans de nombreux produits cosmétiques, sont efficaces, sûrs et bien tolérés. Une fois dans la peau, les rétinoïdes utilisent une voie de signalisation complexe qui favorise le remodelage de l'épiderme et du derme photovieillis, et conduit à l'amélioration des signes cutanés du photovieillissement.

[Translated article] Iberia Consensus on Strategies to Prevent and Manage Irritation by Topical Retinoids in Facial and Trunk Acne.

OBJECTIVE: To assess the level of agreement on various prevention and management strategies for irritation caused by topical retinoids in facial and trunk acne in an attempt to alleviate it and minimize treatment discontinuations as much as possible. METHOD: After reviewing the scientific medical literatura currently available, 4 different areas of uncertainty in the management of irritation caused by topical retinoids in acne were identified. A questionnaire with 34 recommendations was created and evaluated by a group of 133 dermatologists (Delphi methodology). RESULTS: In 82.3% of the recommendations (28 out of 34), some level of agreement was reached (≥85% agreement in 22 recommendations and≥70% agreement in 6). The results with the highest level of agreement focused on specific patient education strategies (explaining that irritation is an expected reaction at the beginning of treatment and tends to decrease over time), gradual and/or spaced application of topical retinoids (at night time to prevent and/or reduce skin irritation), and the importance of using adjuvant products, specific for acne-prone skin, hydration, photoprotection, and skin cleansing. These recommendations reflect a comprehensive approach to managing irritation associated with topical retinoids and promoting long-term adherence. CONCLUSIONS: Skin irritation caused by topical retinoids in facial and trunk acne is an expected, mild, and controllable reaction if proper prevention and management guidelines are followed, meaning that it should not be a reason for treatment discontinuation.

Iberia Consensus on Strategies to Prevent and Manage Irritation by Topical Retinoids in Facial and Trunk Acne. / Consenso Iberia sobre estrategias de prevención y manejo de la irritación por retinoides tópicos en acné localizado en cara y tronco.

OBJECTIVE: To assess the level of agreement on various prevention and management strategies for irritation caused by topical retinoids in facial and trunk acne in an attempt to alleviate it and minimize treatment discontinuations as much as possible. METHOD: After reviewing the scientific medical literatura currently available, 4 different areas of uncertainty in the management of irritation caused by topical retinoids in acne were identified. A questionnaire with 34 recommendations was created and evaluated by a group of 133 dermatologists (Delphi methodology). RESULTS: In 82.3% of the recommendations (28 out of 34), some level of agreement was reached (≥85% agreement in 22 recommendations and≥70% agreement in 6). The results with the highest level of agreement focused on specific patient education strategies (explaining that irritation is an expected reaction at the beginning of treatment and tends to decrease over time), gradual and/or spaced application of topical retinoids (at night time to prevent and/or reduce skin irritation), and the importance of using adjuvant products, specific for acne-prone skin, hydration, photoprotection, and skin cleansing. These recommendations reflect a comprehensive approach to managing irritation associated with topical retinoids and promoting long-term adherence. CONCLUSIONS: Skin irritation caused by topical retinoids in facial and trunk acne is an expected, mild, and controllable reaction if proper prevention and management guidelines are followed, meaning that it should not be a reason for treatment discontinuation.

Management of Acne Vulgaris With Trifarotene.

Topical retinoids have an essential role in treatment of acne. Trifarotene, a topical retinoid selective for retinoic acid receptor (RAR) γ, is the most recent retinoid approved for treatment of acne. RAR-γ is the most common isoform of RARs in skin, and the strong selectivity of trifarotene for RAR-γ translates to efficacy in low concentration. Trifarotene, like other topical retinoids, acts by increasing keratinocyte differentiation and decreasing proliferation, which reduces hyperkeratinization. Retinoids have also been shown to inhibit inflammatory pathways via effects on leukocyte migration, toll-like receptors, and Activator Protein (AP)-1. Large-scale randomized, controlled clinical trials have demonstrated trifarotene to be safe, well tolerated, and efficacious in reducing both comedones and papules/pustules of acne. However, unlike all other retinoids, trifarotene is the first topical retinoid with rigorous clinical data on safety and efficacy in truncal acne. Data supporting use of trifarotene to manage acne are reviewed in this publication.

Prescription patterns and costs of acne/rosacea medications in Medicare patients vary by prescriber specialty.

BACKGROUND: Prescription patterns for acne/rosacea medications have not been described in the Medicare population, and comparisons across specialties are lacking. OBJECTIVE: To describe the medications used for treating acne/rosacea in the Medicare population and evaluate differences in costs between specialties. METHODS: A cross-sectional study was performed of the 2008 and 2010 Centers for Medicare and Medicaid Services Prescription Drug Profiles, which contains 100% of Medicare part D claims. RESULTS: Topical antibiotics accounted for 63% of all prescriptions. Patients ≥65 years utilized more oral tetracycline-class antibiotics and less topical retinoids. Specialists prescribed brand name drugs for the most common topical retinoids and most common topical antibiotics more frequently than family medicine/internal medicine (FM/IM) physicians by 6%-7%. Topical retinoids prescribed by specialists were, on average, $18-$20 more in total cost and $2-$3 more in patient cost than the same types of prescriptions from FM/IM physicians per 30-day supply. Specialists (60%) and IM physicians (56%) prescribed over twice the rate of branded doxycycline than FM doctors did (27%). The total and patient costs for tetracycline-class antibiotics were higher from specialists ($18 and $4 more, respectively) and IM physicians ($3 and $1 more, respectively) than they were from FM physicians. LIMITATIONS: The data might contain rare prescriptions used for conditions other than acne/rosacea, and suppression algorithms might underestimate the number of specialist brand name prescriptions. CONCLUSION: Costs of prescriptions for acne/rosacea from specialists are higher than those from primary care physicians and could be reduced by choosing generic and less expensive options.

Trends in prescribing behavior of systemic agents used in the treatment of acne among dermatologists and nondermatologists: A retrospective analysis, 2004-2013.

BACKGROUND: Despite recommendations to limit the use of oral antibiotics and increasing support for hormonal agents in the treatment of acne, it is unclear whether there have been any significant changes in practice patterns. OBJECTIVE: To characterize changes in prescribing behavior for systemic agents in the treatment of acne in the United States between 2004 and 2013. METHODS: We conducted a retrospective analysis using the OptumInsight Clinformatics DataMart (Optum, Eden Prairie, MN). RESULTS: The number of courses of spironolactone prescribed per 100 female patients being managed for acne by dermatologists and nondermatologists increased from 2.08 to 8.13 and from 1.43 to 4.09, respectively. The median duration of therapy with oral antibiotics was 126 and 129 days among patients managed by dermatologists and nondermatologists, respectively, and did not change significantly over the study period. LIMITATIONS: The OptumInsight Clinformatics DataMart lacks information on acne severity and clinical outcomes. CONCLUSIONS: Additional work to identify patients who would benefit most from alternative therapies such as spironolactone, oral contraceptives, or isotretinoin represents a potential opportunity to improve the care of patients with acne.

Duration of oral tetracycline-class antibiotic therapy and use of topical retinoids for the treatment of acne among general practitioners (GP): A retrospective cohort study.

BACKGROUND: Guidelines recommend limiting the duration of oral antibiotic therapy in acne to 3 to 6 months and prescribing concomitant topical retinoids for all patients. OBJECTIVE: We sought to evaluate the duration of therapy with oral tetracyclines and the use of topical retinoids among patients with acne treated primarily by general practitioners in the United Kingdom. METHODS: We conducted a retrospective cohort study using the Health Improvement Network database. RESULTS: The mean duration of therapy was 175.1 days. Of antibiotic courses, 62% were not associated with a topical retinoid; 29% exceeded 6 months in duration. If all regions were to achieve uses similar to the region with the shortest mean duration of therapy, approximately 3.3 million antibiotic days per year could be avoided in the United Kingdom. LIMITATIONS: The Health Improvement Network does not include information on acne severity and clinical outcomes. CONCLUSIONS: Prescribing behavior for oral antibiotics in the treatment of acne among general practitioners is not aligned with current guideline recommendations. Increasing the use of topical retinoids and considering alternative agents to oral antibiotics when appropriate represent opportunities to reduce antibiotic exposure and associated complications such as antibiotic resistance and to improve outcomes in patients treated for acne.

Duration of oral antibiotic therapy for the treatment of adult acne: a retrospective analysis investigating adherence to guideline recommendations and opportunities for cost-savings.

BACKGROUND: The duration of oral antibiotic acne therapy for adolescents compared with guidelines was recently investigated; however it was uncertain if duration of antibiotics for adult acne therapy differed. OBJECTIVE: This study aimed to evaluate duration of oral antibiotics for adult acne compared with guidelines and determine possible cost-savings. METHODS: This was a retrospective cohort study of MarketScan Commercial Claims and Encounters database that incorporated claims data to determine duration and costs of antibiotic treatment among adults ages 21 years and older. RESULTS: Of 17,448 courses, 84.5% (14,737) aligned with duration guidelines, although 12,040 (69.0%) courses did not include concomitant topical retinoid therapy. Mean savings of $592.26 per person could result if prolonged courses met guidelines. Mean (median) costs of generic and branded formulations for the most frequent course duration (90-179 days) were $103.77 ($54.27) and $1421.61 ($1462.25), respectively. LIMITATIONS: Actual patient prescription adherence is uncertain and database lacks information regarding acne severity, patient physical characteristics, and clinical outcomes. CONCLUSIONS: The majority of oral antibiotic course durations follow guidelines, although topical retinoids are underused. Costs of antibiotic therapy were lower for shorter courses and those using generic medications; the cost-effectiveness of these modifications has not been investigated.

Isotretinoin: Mechanism of Action and Patient Selection.

Oral isotretinoin is a highly effective treatment for appropriately selected patients with acne. This medication is the only treatment that targets all four of the identified factors underlying acne pathogenesis. In addition to the approved indication of resistant nodular scarring acne, clinical studies and experience have shown that other categories of patients benefit from isotretinoin therapy, including those with resistant scarring papular acne, those with resistant acne that interferes with normal living, those who have severe acne-related psychological sequelae, and those with acne who have a skin picking habit or compulsion. Semin Cutan Med Surg 34(supp5):S86-S88© 2015 published by Frontline Medical Communications.

Pharmacologic Treatment Options in Mild, Moderate, and Severe Acne Vulgaris.

Most patients with acne have a disease that responds to acute treatment and can be controlled long term with a maintenance regimen of topical therapy. It is the minority of patients-generally, but not exclusively-the most severely affected, who respond poorly to acute therapy and require continued systemic therapy. The goals of therapy are resolution of visible lesions, prevention of new lesions, avoidance of scarring, and improvement of patient quality of life. Treatment choices are made on the basis of lesion type, number, and size, with consideration given to the presence of physical and psychological scarring. Semin Cutan Med Surg 34(supp5):S82-S85.

Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin.

INTRODUCTION: The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. AIMS: To determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. PATIENTS AND METHODS: Prospective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. RESULTS: Although the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. CONCLUSIONS: This new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne.

A retrospective analysis of the duration of oral antibiotic therapy for the treatment of acne among adolescents: investigating practice gaps and potential cost-savings.

BACKGROUND: Duration of oral antibiotic therapy in acne has not been widely studied. Recent guidelines suggest it should be limited to 3 to 6 months. OBJECTIVE: We sought to compare the duration of oral antibiotic use with recent guidelines and determine the potential cost-savings related to shortened durations. METHODS: This is a retrospective cohort study from the MarketScan Commercial Claims and Encounters database. Claims data were used to determine duration and costs of antibiotic therapy. RESULTS: The mean course duration was 129 days. The majority (93%) of courses were less than 9 months. Among the 31,634 courses, 18,280 (57.8%) did not include concomitant topical retinoid therapy. The mean (95% confidence interval) duration with and without topical retinoid use was 133 (131.5-134.7) days and 127 (125.4-127.9) days, respectively. The mean excess direct cost of antibiotic treatment for longer than 6 months was $580.99/person. LIMITATIONS: Claims cannot be attributed to a specific diagnosis or provider. The database does not provide information on acne severity. CONCLUSIONS: Duration of antibiotic use is decreasing when compared with previous data. However, 5547 (17.53%) courses exceeded 6 months, highlighting an opportunity for reduced antibiotic use. If courses greater than 6 months were shortened to 6 months, savings would be $580.99/person.

Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions.

Both mycosis fungoides (MF) and Sézary syndrome (SS) have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies. Treatment is aimed at the clearance of skin disease, the minimization of recurrence, the prevention of disease progression, and the preservation of quality of life. Other important considerations are symptom severity, including pruritus and patient age/comorbidities. In general, for limited patch and plaque disease, patients have excellent prognosis on ≥1 topical formulations, including topical corticosteroids and nitrogen mustard, with widespread patch/plaque disease often requiring phototherapy. In refractory early stage MF, transformed MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose immunomodulators (eg, interferon or bexarotene) may be effective. Patients with advanced and erythrodermic MF/SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination--including immunomodulators and histone-deacetylase inhibitors--are tried first, with more immunosuppressive therapies, such as alemtuzumab or chemotherapy, being generally reserved for refractory or rapidly progressive disease or extensive lymph node and metastatic involvement. Recently, an increased understanding of the pathogenesis of MF and SS with identification of important molecular markers has led to the development of new targeted therapies that are currently being explored in clinical trials in advanced MF and SS.

Topical and Systemic Retinoids in the Management of Hidradenitis Suppurativa: A Comprehensive Literature Review.

Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.

Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances.

Background: Globally, Acne Vulgaris is a widespread, chronic inflammatory condition of the pilosebaceous follicles. Acne is not fatal, but depending on its severity, it can leave the sufferer with scars, irritation, and significant psychological effects (including depression). In the current review, we have included various factors for acne and their treatment explained. It also narrated the current medicament and the new investigation dosage forms with clinical phases information provided. Main body of the abstract: Acne's pathophysiology involves four important factors: excessive sebum production, hyperkeratinization of pilosebaceous follicles, hyperproliferation of propionibacterium acnes (P. acnes), and inflammation. Identifying both inflammatory (Papule, pustule, nodule, and cyst) and non-inflammatory (black heads, white heads) acne lesions is necessary for diagnosing and treating acne vulgaris. Short conclusion: In this review, traditional therapy approaches such as topical (i.e., retinoids and antibiotics), systemic (i.e., retinoids, antibiotics, and hormonal), and physical therapies are briefly discussed. In addition, we highlight the issues posed by P. acne's resistance to the antibiotics used in commercially available medications and the necessity for novel therapeutic techniques. Finally, we examined a few innovative acne therapies pending clinical trial approval and commercial acne medications.

Guidance for the pharmacological management of acne vulgaris.

INTRODUCTION: Many international guidelines and expert consensuses are available to help the clinician diagnose and treat acne vulgaris; however, a simplified practical guidance that integrates current existing published recommendations is still lacking. This article aims to give practical and simplified insight into the treatment of acne. AREAS COVERED: Herein, the author discusses the treatment of comedonal, papulopustular, and nodular/cystic/conglobate acne. The author also proposes a simplified treatment escalation strategy that is based on disease severity and extension, starting with topical treatments for mild cases and progressing over to systemic therapies in more severe cases. EXPERT OPINION: The ideal acne treatment would simultaneously and safely target all the pathogenic factors implicated in the appearance of acne lesions with minimal side effects. Since no such treatment currently exists, combination therapies are usually recommended for most types of acne. A major limitation in choosing an appropriate treatment plan is the discrepant use of classification systems across the published literature making it difficult to draw clear and succinct conclusions about the recommendations given. Acne is not a traditional infectious disease and so while antibiotics may improve symptoms, they do not reliably resolve the condition. Thus, there is currently a tendency to opt for antibiotic-sparing treatment strategies whenever possible.

Topical treatments in dermatology.

Topical medications are key agents in treating a range of skin conditions, as they allow affected areas to be targeted while avoiding systemic side effects. Although there is a wide range of topical agents available, it is helpful to be familiar with a few commonly used formulations. This article describes how to select appropriate agents, prescribe appropriate quantities, and counsel patients on safe and effective treatment regimens.

Acne in the first three decades of life: An update of a disorder with profound implications for all decades of life.

Acne vulgaris is a chronic, inflammatory, skin condition that involves the pilosebaceous follicles and is influenced by a variety of factors including genetics, androgen-stimulation of sebaceous glands with abnormal keratinization, colonization with Cutibacterium acnes (previously called Propionibacterium acnes), and pathological immune response to inflammation. Acne can occur at all ages and this discussion focuses on the first three decades of life. Conditions that are part of the differential diagnosis and/or are co-morbid with acne vulgaris are also considered. Acne in the first year of life includes neonatal acne (acne neonatorum) that presents in the first four weeks of life and infantile acne that usually presents between 3 and 6 months of the first year of life with a range of 3 to 16 months after birth. Acne rosacea is a chronic, inflammatory, skin condition that is distinct from acne vulgaris, typically presents in adults, and has four main types: erythemato-telangiectatic, papulopustular, phymatous and ocular. Treatment options for acne vulgaris include topical retinoids, topical benzoyl peroxide, antibiotics (topical, oral), oral contraceptive pills, isotretinoin, and others. Management must consider the increasing impact of antibiotic resistance in the 21st century. Psychological impact of acne can be quite severe and treatment of acne includes awareness of the potential emotional toll this disease may bring to the person with acne as well as assiduous attention to known side effects of various anti-acne medications (topical and systemic). Efforts should be directed at preventing acne-caused scars and depigmentation on the skin as well as emotional scars within the person suffering from acne.