Optimizing topical combination therapy for the treatment of acne vulgaris

Given the multifactorial and complex contributors to acne development, combination therapy is standard of care. By addressing multiple pathogenic factors, combination therapy provides a quicker and more efficacious treatment outcome than monotherapy. Topical retinoids normalize follicular keratinocyte differentiation and are anti-inflammatory. Their use is limited by the potential for cutaneous irritation. Antimicrobials reduce Propionibacterium acnes colonization on the skin and reduce the bacteria's proinflammatory effects. Topical antibiotics and benzoyl peroxide (BPO) are commonly employed in fixed-dose combination products or two separate medications. BPO has the added benefit of being comedolytic and can minimize the risk for bacterial antibiotic resistance. Like topical retinoids, BPO may cause skin irritation, burning, erythema, and peeling. Managing cutaneous side effects when using multiple products that cause irritation can be a challenge. Careful product selection, dose titration, and patient-directed regimens can help to optimize outcomes. This review presents the latest data on two topical acne products that have demonstrated excellent efficacy and tolerability profiles. In addition, their in vitro profiles suggest the potential for combination use, affording greater dosing flexibility.     

The role of topical retinoids in the treatment of photoaging

Aging of the skin is a complex biological process which is influenced by the interaction of several intrinsic and extrinsic factors. Intrinsic or chronological aging is an inevitable, genetically programmed process, of unclear underlying mechanism, for which no prevention or effective treatment is currently available. Photoaging refers to the gross and microscopic cutaneous changes that are induced by cumulative exposure to UV radiation and are superimposed on the background of chronological aging. Although primarily an aesthetic problem with significant psychological effects, photoaging constitutes the background for the development of precancerous and cancerous skin lesions.Overwhelming clinical and histological evidence indicate that certain structural changes induced by excessive sun exposure can be reversed, to some extent, by the use of topical retinoids. A number of retinoid compounds, for example tretinoin, isotretinoin, retinaldehyde and tazarotene, have been employed for the treatment of photoaged skin, and demonstrate beneficial clinical and histological effects. Adverse effects have been limited to an irritant reaction of variable intensity presenting with dryness, scaling and erythema. Ongoing research will enhance our understanding of the molecular mechanisms that determine the effects of retinoids on photodamaged skin and contribute to the employment of new, more effective and less irritating retinoid compounds.     

Truncal acne vulgaris: the relative roles of topical and systemic antibiotic therapy

Information is limited on the management of truncal acne vulgaris. Survey results suggest that most dermatologists commonly prescribe oral antibiotic therapy when treating acne involving the chest and back. This article reports therapeutic outcomes based on an investigator-blinded, randomized, 10-week observational trial completed in patients presenting with moderate or severe truncal acne vulgaris. One group received treatment with benzoyl peroxide (BP) 9% cleanser daily, clindamycin 1% foam daily, and doxycycline 100 mg twice daily. The other group received BP cleanser 9% daily and doxycycline 100 mg twice daily without clindamycin 1% foam. Baseline, week 6, and week 10 evaluations were completed. Efficacy parameters included inflammatory and total lesion count reduction, and investigator global assessment. Global evaluations of treatment response were recorded and skin tolerability was also evaluated. This trial was designed to capture observational experience reflective of treatment of patients with truncal acne in a private practice dermatology setting.     

The modern age of acne therapy: a review of current treatment options

This review of current acne treatments begins with the crucial discovery in 1979 of isotretinoin treatment for nodulocystic acne. This drug s approval in 1982 revolutionized therapy, since it was the first oral acne-specific drug, and it provided prolonged remissions. In addition, it may prevent the emergence of resistant bacteria, a problem linked to the traditional use of antibiotics for acne. Patients who are not candidates for isotretinoin therapy may benefit from one of the other drugs or drug combinations reviewed, including the third-generation topical retinoids adapalene and tazarotene, retinoic acid reformulated in new vehicles, azelaic acid, and topical antibiotics. Proper selection and education of patients are essential, since serious consequences may result from poorly monitored use of antibiotics and retinoid.     

Transdermal penetration of topical drugs used in the treatment of acne

Acne vulgaris is a very common skin disease. Most patients present with mild to moderate acne comedonica or papulopustulosa grade I-II. The first-line treatment for these cases is generally via the topical route, whereas systemic medication is indicated when higher severity grades with small nodes or scarring occur. There are several topical agents available that affect at least one of the main pathogenetic factors responsible for the development of acne: hyperseborrhoea, hyperkeratosis, microbial colonisation and inflammatory and immunological reactions. Topical retinoids have a comedolytic and anticomedogenic activity, and some of them have anti-inflammatory potency. Azelaic acid and benzoyl peroxide have a moderate to strong antibacterial effect without inducing bacterial resistance, which is becoming a significant problem with the increasing use of topical antibacterials. Topical antiandrogens may soon be available for the treatment of the pathogenetic factor hyperseborrhoea. The transdermal penetration and the resulting systemic bioavailability of the various topical agents has not been widely considered. Apart from the retinoids, which can be associated with the risk of embryotoxicity/teratogenicity, and clindamycin, which might cause pseudomembranous colitis, information on the systemic pharmacokinetics of other topical agents is not readily available. There is still no consensus on the safe use of topical retinoids in pregnancy, and the occurrence of pseudomembranous colitis after the topical use of clindamycin does not appear to be of clinical relevance. In general, topical anti-acne agents are well tolerated and, as would be expected from their limited transdermal uptake, other significant safety concerns have not so far arisen.     

Vitamin A acid: a review of its pharmacological properties and therapeutic use in the topical treatment of acne vulgaris.

Vitamin A acid (retinoic acid: tretinoin) is a vitamin A derivative used in the topical treatment of acne. It acts by 'unseating' comedones, improvement developing slowly over a period of 2 to 3 or more months, and is also said to prevent the formation of new lesions. About three-quarters of patients with acne vulgaris benefit from treatment. In controlled studies, results achieved after a 3 to 4 months course of treatment were superior to those with sulphur-resorcinol-salicylic acid. When compared with benzoyl peroxide, results were variable and appear to depend on the length of treatment, the types of formulations used, and the concentrations compared. Application of vitamin A acid should be continued until the patient has been free of new lesions for several months. Further continued application at a less frequent interval or using a less active dosage form may help to prevent exacerbations of acne. A systemic antibacterial agent such as tetracycline can be given as well as in patients with moderate to severe lesions. Vitamin A acid is used in conjunction with gentle washing (to remove surface oil) but should be applied to a dry skin to avoid unnecessary irritation. Patient education and encouragement are crucial during the initial phase of treatment when microcomedones may be converted to pustules prior to desquamation.     

Psychiatric disorders,acne and systemic retinoids: comparison of risks

Background: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids.

Materials and methods: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest.

Results: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin.

Conclusion: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.     

5-氨基酮戊酸光动力疗法治疗寻常痤疮临床应用进展

寻常痤疮(acne vulgaris)是一种毛囊皮脂腺单元的慢性炎症性皮肤病,好发于青年人群,病因及发病机制复杂.临床上多根据皮损性质将痤疮分为轻、中、重度分级治疗.近年来,5-氨基酮戊酸光动力疗法(5-aminolevulinic acid photodynamic therapy,ALA-PDT)被广泛应用于中、重...     

Effective topical combination therapy for treatment of lichen striatus in children: a case series and review

Lichen striatus (LS) is an uncommon linear dermatosis that is primarily seen in children from 4 months to 15 years of age. While some of these eruptions are asymptomatic, others can be quite pruritic. In darker-skinned individuals, post-inflammatory hypopigmentation can be significant and may provide a cause for concern for the patients and/or their parents. In our case series of 4 patients, we observed rapid resolution of LS by combining a topical retinoid with a topical steroid. To our knowledge, this is the first report of successful treatment with this kind of combination therapy in the English literature. The patients not only achieved satisfying cosmesis, but also complete resolution of their pruritus. The most common side effect of topical tazarotene is localized irritation at treatment sites, but the patients in this particular series tolerated the treatment well.     

Mechanism-based treatment of acne vulgaris: the value of combination therapy

Acne vulgaris has multiple pathogenic mechanisms that act in concert to produce disease. Effective therapy addresses more than one pathogenic factor to speed resolution of disease. Typically, retinoids are used to inhibit comedo formation and an antibacterial is used to suppress Propionibacterium acnes (P. acnes). Using combinations of agents can enhance efficacy, but increase side effects. Therefore, the tolerability of a topical retinoid is important. Strategies to enhance retinoid tolerability include the use of new retinoids such as adapalene, new delivery systems such as the tretinoin microsphere delivery system, or alternative dosing schedules such as short contact or every other day (QOD).     

RU 58841-myristate--prodrug development for topical treatment of acne and androgenetic alopecia

Acne and androgenetic alopecia are linked to androgen effects and therefore should improve following topical application of antiandrogens. We present a new antiandrogen prodrug, RU 58841-myristate (RUM) for topical therapy. Almost devoid of affinity to the androgen receptor, as derived from investigations in the mouse fibroblast cell line 29 +/GR +, RUM is rapidly metabolised to the potent antiandrogen RU 58841 by cultured human foreskin fibroblasts and keratinocytes, male occipital scalp skin dermal papilla cells, and by cells of the sebaceous gland cell line SZ95. In order to improve a specific targeting of the hair follicle, RUM was loaded on solid lipid nanoparticles (SLN), which are already known to support dermal targeting effects. Physically stable RUM loaded SLN were produced by hot homogenization. Penetration/permeation studies carried out using the Franz diffusion cell proved only negligible permeation of reconstructed epidermis and excised porcine skin within 6 h, implying a more topical action of the drug. Targeting to the hair follicle using SLN was visualised by fluorescence microscopy, following the application of Nile Red labelled SLN to human scalp skin. Transmission electron microscopy (TEM) allowed to detect intact silver labelled SLN in porcine hair follicles of preparations applied to the skin for 24 h. RUM loaded SLN should be considered for topical antiandrogen therapy of acne and androgenetic alopecia.     

Adapalene: a review of its use in the treatment of acne vulgaris

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favourable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a role in the first-line treatment of acne vulgaris.     

Novel vesicular and particulate drug delivery systems for topical treatment of acne

BACKGROUND: The efficacy of the antiacne topical drugs is well established. The local side effects, however, mainly cutaneous irritation, erythema, dryness, peeling and scaling, remain major problems. Novel vesicular and particulate drug delivery systems have been proposed to reduce the side effects of drugs commonly used in the topical treatment of acne. OBJECTIVE: This review focuses on the development and evaluation of antiacne drug-loaded vesicular and particulate delivery systems (liposomes, polymeric microspheres and solid lipid nanoparticles) for topical treatment, their advantages and challenges. METHODS: All the literature available was reviewed to highlight the potential of these novel systems for the topical treatment of acne. CONCLUSION: The encapsulation of antiacne drugs in vesicular and particulate delivery systems represents an innovative alternative to minimize side effects, while preserving their efficacy. This can be obtained by the capacity of these systems to provide controlled release or to improve the drug penetration into skin or even into the pilosebaceous unit.     

The new therapy schema of the various kinds of acne based on the mucosa-skin side effects of the retinoids

The most common adverse effects of oral isotretinoin (>1/10) are: cheilitis, skin dryness, erythema, itching, scaling, bruising, skin atopy, conjunctivitis, dry eyes and eyelid inflammation. The aim of this work was to define an optimal dose regime of the oral isotretinoin allowing for effective reduction of sebum production and minimalization of adverse effects such as decreased skin moisturization, increase in TEWL and intensified erythema. The skin parameters were assessed using the MPA 5 diagnostic apparatus. Moisturization together with an increase in TEWL and erythema during treatment with isotretinoin seem to be crucial factors responsible for patient discomfort. The decrease in the pigment content in the skin during retinoid treatment is a favourable symptom, due to the frequent tendency of skin pigmentation disturbances in the sites after acne changes. On the basis of performed analyses it was concluded that the new therapy schema is the most advantageous form of isotretinoin dosing and it involves the use of a constant drug dose – 0.4–1.0?mg/kg body mass/day without modification during treatment.     

The new therapy schema of the various kinds of acne based on the mucosa-skin side effects of the retinoids

The most common adverse effects of oral isotretinoin (>1/10) are: cheilitis, skin dryness, erythema, itching, scaling, bruising, skin atopy, conjunctivitis, dry eyes and eyelid inflammation. The aim of this work was to define an optimal dose regime of the oral isotretinoin allowing for effective reduction of sebum production and minimalization of adverse effects such as decreased skin moisturization, increase in TEWL and intensified erythema. The skin parameters were assessed using the MPA 5 diagnostic apparatus. Moisturization together with an increase in TEWL and erythema during treatment with isotretinoin seem to be crucial factors responsible for patient discomfort. The decrease in the pigment content in the skin during retinoid treatment is a favourable symptom, due to the frequent tendency of skin pigmentation disturbances in the sites after acne changes. On the basis of performed analyses it was concluded that the new therapy schema is the most advantageous form of isotretinoin dosing and it involves the use of a constant drug dose - 0.4-1.0 mg/kg body mass/day without modification during treatment.     

A review of the chemopreventive and chemotherapeutic effects of topical and oral retinoids for both cutaneous and internal neoplasms

Retinoids, a group of compounds encompassing Vitamin A and its analogs, have been shown to inhibit tumor growth in laboratory studies. Based on these findings, a number of clinical trials have been conducted to investigate the chemoprotective and chemotherapeutic effects of retinoids. This paper reviews the current database regarding the use of oral and topical retinoids in the prevention and treatment of cutaneous and internal malignancies. Clinical studies have shown that retinoids have beneficial effects in the prevention and treatment of certain neoplasms. In view of the heightened concern of malignancy associated with the use of biologic agents in the treatment of psoriasis, retinoids may be an attractive option for combination therapy with the biologic agents. Future clinical investigations are needed to precisely define how this combination will fit into the treatment algorithm for moderate-to-severe psoriasis.     

Atopic dermatitis: a review of topical treatment options

Abstract

Background:

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease with a wide range of severity, and is usually the first manifestation of atopic disease. It is one of the most common skin disorders in developed countries, affecting approximately 20% of children and 1–3% of adults. Symptoms such as eczematous papules, plaques, and itch, and their associated consequences, such as sleep disturbance, can significantly impact the quality of life of the patient and family.     

Combination topical therapy for the treatment of psoriasis

Dermatological research continues to move toward the goal of developing an effective psoriasis treatment that would rapidly clear lesions and provide long-term freedom from visible signs and symptoms. Currently, topical corticosteroids remain a pivotal treatment due to their effective anti-inflammatory properties; however, potential adverse effects associated with chronic application limit long-term continuous therapy. Vitamin D analogues provide another mechanism of action, reducing lesions through effects on both keratinocytes and on the cytokine environment. A topical combination of corticosteroid and vitamin D derivative appears to provide a balanced approach to psoriasis treatment. The development of clobetasol propionate foam 0.05% (clobetasol propionate foam/Olux) offers a convenient topical corticosteroid that can be used concomitantly, that is, immediately followed by application of calcipotriene ointment 0.005% (Dovonex). This regimen has been shown to offer an increased short-term efficacy compared with either agent alone. Continued application of calcipotriene ointment on weekdays supplemented by long-term clobetasol propionate foam pulse therapy on weekends appears to provide an enhanced maintenance of remission compared with calcipotriene monotherapy.