Skin Therapy Letter

Topical products commonly used to treat acne include retinoids and antimicrobials, due to their effects on different components of pathogenesis. Accordingly, a fixed combination of adapalene 0.1% and benzoyl peroxide (BPO) 2.5% was developed (Epiduo, Galderma) and was approved by the US FDA in December 2008 for the treatment of acne. The superior efficacy of this combination was demonstrated in 2 large randomized controlled trials. This paper reviews the evidence for efficacy and tolerability of the combination of the retinoid adapalene 0.1% and BPO 2.5%, a once-daily gel formulation for the treatment of acne.

Tazarotene (Tazorac, Allergan) has been shown to be effective in reducing the effects of photoaging in short term studies. To determine its effectiveness in the longer term, a 24-week multicenter, double-blind, randomized, vehicle controlled intervention study of 562 patients with facial photodamage was carried out followed by a 28-week open label extension. Patients were treated with one daily application of tazarotene 0.1% cream or vehicle cream to the face for 24 weeks, then tazarotene 0.1% cream for another 28 weeks. At week 24, when compared to vehicle, tazarotene resulted in a significantly greater incidence of patients achieving treatment success (over 50 percent greater improvement) and at least a 1 grade improvement in fine wrinkling, mottled pigmentation, pore size, lentigines, elastosis, irregular depigmentation, tactile roughness, coarse wrinkling and overall integrated assessment of photodamage. Additional clinical improvement occurred with continued tazarotene treatment and had not plateaued by week 52.

Carac (5-fluorouracil 0.5% cream, Aventis Pharma) was approved by the US FDA in October 2000, for the treatment of multiple actinic or solar keratoses involving the face and anterior scalp. The cream should be applied in a thin film once daily to the skin where actinic keratoses (AKs) are present. When it is applied for 1, 2, or 4 weeks, it is significantly more effective than a vehicle in the management of patients with five or more AKs at pretherapy. Pooled data from the two pivotal trials (n=384) indicate that following 4 weeks of therapy the number of subjects with total AK clearance in the Carac and vehicle groups was 52.9% and 1.6% respectively (p<0.001). Furthermore, the corresponding reduction of AK lesion counts in the Carac and vehicle groups was 82.5% and 19.3%, respectively (p<0.001). Treatment should be continued up to 4 weeks as tolerated by the patient. The most common adverse-effect is facial irritation.

Hyperpigmentation disorders of the skin are common and can be the source of significant psychosocial distress for patients. The most common of these disorders are melasma and postinflammatory hyperpigmentation. Sunscreen use and minimizing sun exposure are crucial in all cases. Topical applications are the mainstay of treatment and include phenols, retinoids, corticosteroids, and their combinations.

Eflornithine HCl 13.9% cream is the first topical prescription treatment to be approved by the US FDA for the reduction of unwanted facial hair in women. It irreversibly inhibits ornithine decarboxylase (ODC), an enzyme that catalyzes the rate-limiting step for follicular polyamine synthesis, which is necessary for hair growth. In clinical trials eflornithine cream slowed the growth of unwanted facial hair in up to 60% of women. Improvement occurs gradually over a period of 4-8 weeks or longer. Most reported adverse reactions consisted of minor skin irritation.

Photoaging and skin damage that is caused by solar radiation is well known. We have recently learned that within the solar spectrum this damage not only results from ultraviolet (UV) radiation, but also from longer wavelengths, in particular near infrared radiation. Accordingly, infrared radiation (IR) has been shown to alter the collagen equilibrium of the dermal extracellular matrix in at least 2 ways: (1) by leading to an increased expression of the collagen degrading enzyme matrixmetalloproteinase-1 while (2) decreasing the de novo synthesis of the collagen itself. Infrared-A (IRA) radiation exposure, therefore, induces similar biological effects to UV, but the underlying mechanisms are substantially different. IRA acts via the mitochondria and therefore protection from IR requires alternative strategies.

Acting on keratinocytes to produce antimicrobial peptides and chemokines, which in turn attract neutrophils and other inflammatory cells, interleukin-17 (IL-17) is believed to be a potent driver of plaque psoriasis. Its proinflammatory characteristics make IL-17 an attractive therapeutic target for addressing immune dysregulation. This review examines the role of IL-17 in the pathogenesis of plaque psoriasis and the potential implications of its inhibition. The efficacy and safety results from Phase 2 and 3 trials with monoclonal antibodies targeting IL-17RA (brodalumab), and IL-17A (ixekizumab and secukinumab) validate IL-17 as an effective therapeutic target for the treatment of plaque psoriasis.

Actinic Keratoses (AKs) are epidermal skin lesions that have the potential to develop into squamous cell carcinoma. Many of the treatment options available can cause discomfort, pain or skin irritation. Topical 3% diclofenac in 2.5% hyaluronan gel (Solaraze, Bioglan Pharma) is a relatively new treatment that has been shown to be effective and well tolerated for the treatment of AKs.

Psoriasis is a common chronic inflammatory skin disease that is mediated, in part by the body's T-cell inflammatory response mechanisms. Further insight into the pathogenesis of the disease and the role of various cytokines, particularly interleukin(IL)-12 and IL-23, has led to advances in the treatment of this disease. A relatively new class of drugs that inhibit these interleukins is being developed and studied. Current data regarding the efficacy of these agents show they may have the potential to become the new clinical gold standard for biologic therapy to treat psoriasis.

In the past three decades, major advances have been made in understanding the pathogenesis of psoriasis. The currently accepted theory is that T-cell mediated immune dysregulation triggers keratinocyte hyperproliferation in psoriasis. Recent research indicates that the Th17/interleukin (IL)-23 pathway plays a prominent role in the amplification phase of psoriasis. The discovery of the Th17/ IL-23 pathway provides targets for new drug development. This review focuses on the role of IL-23 in psoriasis pathogenesis and the current therapies targeting IL-23 that are in clinical trials.

Imiquimod 3.75% cream has recently been approved by both the U.S. Federal Drug Administration and Health Canada for the treatment of external genital warts. Herein, we provide an overview of external genital warts, review the phase 3 clinical trials leading to the approval of imiquimod 3.75% cream, and compare its efficacy and clinical use with imiquimod 5% cream. Moreover, therapeutic options have further expanded with the relatively recent introduction of sinecatechins 15% ointment, an extract of green tea leaves.

Psoriasis is a common skin disease affecting 1%-3% of the world's population with significant impacts on quality of life. There is a great need for therapies that are efficacious and safe, not only for the short-term, but also for long-term management. Dovobet/ Daivobet/ Taclonex is a product combining two molecules, calcipotriol and betamethasone dipropionate, that may offer psoriatic patients with an option for maintenance therapy. The efficacy and safety of this combined formulation when used over a 4-week period is well documented. A recent publication in the British Journal of Dermatology discusses the safety of this product when used for 52 weeks.

The latest techniques for endovenous occlusion, i.e., radiofrequency ablation catheters or endoluminal laser targeting water are our preferred methods for the treatment of saphenous-related varicose veins. Clinical experience with endovenous techniques in more than 1,000 patients shows a high degree of success with minimal side effects, most of which can be prevented or minimized with use of tumescent anesthesia. Within the next 5 years, these minimally invasive endovenous ablative procedures involving saphenous trunks should have virtually replaced open surgical strippings.

Wound care after laser skin resurfacing (LSR) is critical for achieving a successful result. The superficial thermal injury created by LSR heals more quickly and with a reduced risk of scarring under occlusion. While open and closed wound care regimens can be employed to expedite reepithelialization, closed methods with semi-occlusive dressings may decrease morbidity. Effective medications and management techniques can help to minimize expected effects of the procedure such as crusting, discomfort, pruritus, erythema, and swelling.

Cutaneous T-cell lymphomas are rare, distinct forms of non-Hodgkin´s lymphomas. Of which, mycosis fungoides (MF) and Sézary syndrome (SS) are two of the most common forms. Careful, clear classification and staging of these lymphomas allow dermatologists to commence appropriate therapy and allow correct prognostic stratification for those patients affected. Of note, patients with more advanced disease will require multi-disciplinary input in determining specialist therapy. Literature has been summarized into an outline for classification/staging of MF and SS with the aim to provide clinical dermatologists with a concise review.

Acitretin over the last 20 years has proven useful in a number of dermatologic diseases. Evidence of efficacy, side-effect profile, and approach to its use will be reviewed.

Acitretin (Soriatane, Roche Pharmaceuticals) is an aromatic retinoid, effective in the treatment of severe psoriasis. This study highlights data from two existing clinical trials to capture PASI 50 and PASI 75 responder rates which represent a common metric used in current psoriasis clinical trials. A review of pharmacokinetics, safety and a discussion of relapse rate establish acitretin as an efficacious, convenient, oral treatment for initial and maintenance therapy of severe psoriasis.

Benzoyl peroxide is one of the most widely used topical agents for acne. It has potent antibacterial and mild anti-inflammatory and comedolytic effects. To treat mild to moderate acne, it can be used alone or in combination with topical antibiotics and topical retinoids. The combination of benzoyl peroxide with either erythromycin or clindamycin is synergistic and well-tolerated. In more severe acne, when oral antibiotics are required, benzoyl peroxide can contribute to suppressing the emergence of resistant strains of Propionibacterium acnes.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. It is typically characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. Women with PCOS often experience dermatologic manifestations of hyperandrogenism, including hirsutism, acne vulgaris, and androgenic alopecia. This article will review the treatments for acne due to androgen excess in PCOS women.

Dapsone 5% gel for the topical treatment for acne vulgaris was recently introduced in Canada. It represents the first new anti-acne agent to gain North American regulatory approval in the past decade. Dapsone's utility is attributable to its anti-inflammatory and antimicrobial properties that improve both inflammatory and non-inflammatory acne, with more prominent effects occurring in inflammatory lesions. Short- and long-term safety and efficacy have been demonstrated. Especially for patients exhibiting sensitivities or intolerance to conventional anti-acne agents, topical dapsone is a novel addition to the treatment armamentarium.

Acne vulgaris can represent a therapeutic challenge in terms of managing ongoing symptoms and preventing scar formation. While the copious variations of available treatments address milder forms of the disease, until recently, therapies for resistant or moderate-to-severe forms were limited to systemic agents that were accompanied by potentially severe side-effects. With the addition of lasers, light sources, and aminolevulinic acid-photodynamic therapy (ALA-PDT) therapies, dermatologists may now have viable new alternatives for treating all grades of acne severity that circumvent the negative side-effects associated with many conventional options.

Clinical studies with topical and systemic agents for acne show remarkable improvement over a 3 month period of time, with continued progress in long-term use. However, in clinical practice it is uncommon to see these favorable results. Clinical experience and recent published data suggest that compliance, perhaps better referred to as adherence, is a major obstacle in achieving these outcomes. This article will review this problem and offer a number of suggestions, including dosing considerations and the use of laser/light devices, to better treat the nonadherent patient.

Acne vulgaris has anecdotally been attributed to diet by individuals affected by this skin condition. In a 2009 systematic literature review of 21 observational studies and 6 clinical trials, the association between acne and diet was evaluated. Observational studies, including 2 large controlled prospective trials, reported that cow's milk intake increased acne prevalence and severity. Furthermore, prospective studies, including randomized controlled trials, demonstrated a positive association between a high-glycemic-load diet, hormonal mediators, and acne risk. Based on these findings, there exists convincing data supporting the role of dairy products and high-glycemic-index foods in influencing hormonal and inflammatory factors, which can increase acne prevalence and severity. Studies have been inconclusive regarding the association between acne and other foods.

Propionibacterium acnes (P. acnes) is an anaerobic bacteria implicated in the pathogenesis of acne. The last 30 years have witnessed an alarming increase in resistance to antibiotics commonly employed to treat acne. Antibiotic resistance in acne represents a significant international public health concern because resistance can occur in more pathogenic bacteria than P. acnes, and an increase in pathogenic P. acnes has been reported. Current treatment guidelines offer strategies to limit the potential for resistance while achieving optimal outcome in the management of inflammatory and non-inflammatory acne.