BACKGROUND:Itraconazole, approved for treatment of toenail fungal infection onychomycosis, provides antifungal activity at a dosage requiring once-daily (QD) administration of 2 100-mg capsules for 12 weeks. Utilizing the Meltrex® technology delivery system, a novel 200-mg formulation of itraconazole was developed delivering the same dosage as 2 capsules in a single tablet.METHODS:This phase 3, randomized, placebo-controlled trial investigated the noninferiority of 1 itraconazole 200-mg tablet to 2 itraconazole 100-mg capsules dosed QD for 12 weeks, with a 40-week follow-up period. Clinical Cure (Investigator's Global Assessment plus mycological examination) was the primary outcome measure and Clinical Improvement was a secondary endpoint. Safety and efficacy of itraconazole 200-mg tablets were also compared with placebo.RESULTS:Significantly more patients in the intent-to-treat per-protocol populations on itraconazole (200-mg tablet or 2 100-mg capsules) achieved Complete Cure and Clinical Improvement compared with placebo. For both endpoints, itraconazole 200-mg tablet QD was noninferior to itraconazole 100-mg capsules and superior to placebo. All treatment groups demonstrated a similar safety profile with no new safety signals identified.LIMITATIONS:Absolute patient blinding was not possible; the number of tablets versus capsules differed, and the appearance of the active drugs could not be masked. However, efficacy was based on objective assessments from blinded investigators.CONCLUSIONS:Once-daily itraconazole 200-mg was well-tolerated, and may be an effective alternative to 2 itraconazole 100-mg capsules for the treatment of toenail onychomycosis. The convenience of a simpler dosing regimen may improve patient compliance

The tremendous success of botulinum toxin type A (BOTOX ® , Allergan Inc.) in the cosmetic arena has acted as a stimulus for the development of other neurotoxins. After more than 2 decades of use, BOTOX ® has become synonymous with wrinkle reduction and is considered to be the one of the most common non-surgical cosmetic procedures performed worldwide. Because of its vast popularity among patients seeking non-invasive methods to achieve facial rejuvenation, physicians from diverse specialties have integrated botulinum toxin injections into their existing practices. Herein, we present an overview of botulinum toxin products for cosmetic applications that have received regulatory approval or are under development.

The choice of treatment for psoriasis in children, as in adults, is determined by disease acuity, morphology, distribution, severity, and the presence of comorbidities, such as psoriatic arthropathy. Fortunately, most patients present with mild disease that responds adequately to topical medications. A minor subset of children will present with severe, rapidly evolving disease that requires more aggressive interventions. Advanced medical treatment with systemic and phototherapy is challenging and primarily anecdotal, as these modalities are neither well-studied nor approved for use in children. Part II of this 2-part series features an overview of systemic and light therapies including their varying degrees of effectiveness, potential side-effects and applications in clinical practice.

Psoriasis represents a potentially life-altering disease that can profoundly impact physical, emotional and social functioning, and overall quality of life. The majority of cases are mild and managed adequately with topical medications. A minor subset of children present with severe, rapidly evolving disease that requires systemic therapy. The choice of treatment in children, as in adults, is determined by disease acuity, morphology, distribution, severity and the presence of comorbidities such as psoriatic arthropathy. Practical considerations such as ease of use, patient acceptability, accessibility, risk to benefit ratio, cost and individual perceptions of disease and quality of life are factored into treatment decisions. Part I of this 2-part series will focus on topical agents, their varying degrees of effectiveness, potential side-effects and applications in clinical practice.

Ultraviolet (UV) radiation is a carcinogen that also compromises skin appearance and function. Since the UV action spectra for DNA damage, skin cancer, and vitamin D photosynthesis are identical, and vitamin D is readily available from oral supplements, why has sun protection become controversial? First, the media and, apparently, some researchers are hungry for a new message. They have also drawn attention to the emerging evidence of possible vitamin D benefits other than for bone health. Second, the controversy is fueled by a powerful special interest group: the tanning industry. This industry does not target the frail elderly or inner-city ethnic minorities, which are the groups at greatest risk of vitamin D deficiency, but rather fair-skinned teenagers and young adults, who are at highest risk of UV photodamage. Third, evolution does not keep pace with civilization. When nature gave humans the appealing capacity for cutaneous vitamin D photosynthesis, life expectancy was less than 40 years of age; long-term photodamage was not a concern, and vitamin D deficiency, with its resulting skeletal abnormalities (rickets), was likely to be fatal in early life. This article briefly reviews the “pseudo-controversy”, as well as the data supporting a revision of the recommendations for vitamin D supplementation. It concludes with a suggested message for patients, many of whom are understandably confused by recent media coverage of the topic.

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.

Human papillomavirus (HPV) infection is the known cause of almost all cases of cervical cancer. An understanding of the HPV genome has allowed the development of two prophylactic vaccines capable of protecting against both persistent HPV infection and cervical intraepithelial neoplasia (CIN) with 100% efficacy in fully vaccinated women. The vaccines, manufactured by Merck (Gardasil ® , which was approved by

Atypical presentations of typical dermatological conditions are common in human immunodeficiency virus (HIV). This article will focus on three specific topics: eosinophilic folliculitis, psoriasis, and cutaneous mycoses. Their unique presentations in HIV and treatments are discussed.

Etanercept is a tumor necrosis factor antagonist with anti-inflammatory effects. It is currently approved in the US for psoriasis, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis and juvenile rheumatoid arthritis. Clinical trials have shown this agent to have an excellent safety profile and to be well tolerated by both adult and pediatric patients.

Atypical presentations of typical dermatological conditions are common in human immunodeficiency virus (HIV). This article will focus on three specific topics: eosinophilic folliculitis, psoriasis, and cutaneous mycoses. Their unique presentations in HIV and treatments are discussed.

Tacrolimus ointment (Protopic ® , Fujisawa) is an effective agent in a class of topical immunomodulators. Its mechanism of action is based on calcineurin inhibition, which results in decreased T-cell activation and inflammatory cytokine release. Tacrolimus ointment is safe and effective for short- and long-term treatment of atopic dermatitis (AD) in pediatric and adult patients. The most common adverse events associated with its use are a transient burning sensation and pruritus at the site of application. Unlike topical corticosteroid agents, tacrolimus ointment does not cause a reduction in collagen synthesis or skin thickness. Because tacrolimus ointment does not cause skin atrophy, it may be safely used for months or years on all skin areas, including the face and intertriginous areas.

Disorders of hyperpigmentation are difficult to treat, particularly in dark-skinned individuals. The goal is to reduce the hyperpigmentation without causing undesirable hypopigmentation or irritation in the surrounding normally pigmented skin. The psychosocial impact caused by these disorders must be considered. Although there are many effective therapeutic modalities available, there are potentially significant side-effects associated with treatment. The most commonly used treatment is topical hydroquinone. There are other phenolic agents, such as Nacetyl-4-cystaminylphenol (NCAP), that are currently being studied and developed. The nonphenolic agents, which include tretinoin, adapalene, topical corticosteroids, azelaic acid, arbutin, kojic acid, and licorice extract, are also used for hyperpigmentation disorders.

Postherpetic neuralgia (PHN) is a serious complication of herpes zoster that has a predilection for older individuals. PHN is often associated with significant morbidity, and it can cause insomnia, fatigue, depression and interference with daily activities in affected individuals. Treatment for PHN is initiated with anitvirals during the acute herpes zoster outbreak. Acyclovir, valacyclovir or famciclovir can be used to treat herpes zoster, and all three have been shown to reduce the duration of the herpetic rash and zoster-associated pain. These antivirals are most effective when used within the first 72 hours of the onset of the rash. Side-effects of these antivirals are low and include nausea, vomiting, abdominal pain and headache. Other treatment options for PHN include topical analgesics, opioid analgesics, tricyclic antidepressants and gabapentin. Because of the complexity of PHN,

Atopic dermatitis (AD) is a chronically relapsing eczematous disorder of the skin that occurs in persons of all ages but is more common in children. AD is associated with other atopic diseases such as allergic rhinoconjunctivitis or bronchial asthma. Nearly 80% of children with AD eventually develop allergic rhinitis or asthma. AD can be classified as “mixed” (cases associated with respiratory allergies) and “pure”. Pure AD has “intrinsic” and “extrinsic” variants. In the extrinsic type, interleukin-4 is secreted by T-cells isolated from spontaneous lesions and skin-derived T-lymphocytes express more IL-13. Due to the different immunopathogenesis, it has been suggested that antileukotriene agents may be more successful in the treatment of the extrinsic subgroup. Leukotrienes (LTs) are a class of potent biological inflammatory mediators derived from arachidonic acid through the 5-lipoxygenase pathway. There is evidence of enhanced LT production in the pathogenesis of AD. Evidence in the literature provides a pathophysiological rationale for the use of cysLT receptor blockers in the treatment of AD. However, the exact mechanism of action of leukotriene receptor antagonists in AD is not known. In small clinical and case studies, montelukast was found to be a safe and effective alternative or steroid-sparing therapy in the management of patients with atopic dermatitis.

Oral isotretinoin, since its introduction more than 20 years ago, has been and still is the "gold standard" in the treatment of acne and its variants. This is the only approach to acne with the possibility of a permanent "cure" or long term remission. The role of isotretinoin has evolved with higher dosage schedules and use earlier in the course of the disease. The frequency of laboratory monitoring has diminished along with associated costs based on 2 decades of experience. Pregnancy-associated safeguards have become a more prominent facet of oral retinoid therapy leading to increased safety for its use in females of child- bearing potential.

Etanercept (Enbrel ® , Amgen and Wyeth), a tumor necrosis factor (TNF) antagonist, was approved in January 2002, for the treatment of psoriatic arthritis (PsA). The anti-inflammatory effects of etanercept are due to its ability to bind to the pro-inflammatory cytokine TNF, preventing it from interacting with cell-surface receptors and rendering it biologically inactive. Etanercept was evaluated for the treatment of PsA and psoriasis in a preliminary study of 60 patients and in a confirmatory phase III study of 205 patients. In both studies, etanercept was shown to be significantly superior to placebo for the treatment of PsA, evaluated by Psoriatic Arthritis Response Criteria (PsARC) and American College of Rheumatology (ACR) criteria. It also was superior to placebo in improving psoriatic skin lesions, evaluated by the Psoriasis Area and Severity Index (PASI) and target lesion scores. Side-effects were minimal; mild injection site reactions, which resolved during continued therapy, were experienced by approximately onequarter of the patients. Overall, etanercept is highly effective and well tolerated by patients with PsA, with a safety profile similar to that seen in rheumatoid arthritis.