Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BACKGROUND: Once-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments. OBJECTIVES: To evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed. METHODS: In two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose. RESULTS: Among 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant. CONCLUSIONS: Assessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity.

Applying the phenotype approach for rosacea to practice and research.

BACKGROUND: Rosacea diagnosis and classification have evolved since the 2002 National Rosacea Society expert panel subtype approach. Several working groups are now aligned to a more patient-centric phenotype approach, based on an individual's presenting signs and symptoms. However, subtyping is still commonplace across the field and an integrated strategy is required to ensure widespread progression to the phenotype approach. OBJECTIVES: To provide practical recommendations that facilitate adoption of a phenotype approach across the rosacea field. METHODS: A review of the literature and consolidation of rosacea expert experience. RESULTS: We identify challenges to implementing a phenotype approach in rosacea and offer practical recommendations to overcome them across clinical practice, interventional research, epidemiological research and basic science. CONCLUSIONS: These practical recommendations are intended to indicate the next steps in the progression from subtyping to a phenotype approach in rosacea, with the goals of improving our understanding of the disease, facilitating treatment developments and ultimately improving care for patients with rosacea.

Systemic therapy for rosacea: focus on oral antibiotic therapy and safety.

Although potentially significant adverse reactions and drug interactions have been reported in association with erythromycin, oral tetracyclines, and trimethoprim-sulfamethoxazole, overall these agents are associated with excellent safety profiles, especially considering their widespread use over many years. It must be considered that when these antibiotics are used for the treatment of rosacea and also for acne vulgaris, their use is on a long-term basis rather than their typical short-course regimens for most infectious diseases. As a result, dermatologists prescribing these agents may feel assured that most patients will not encounter any significant problems, but they do need to be aware of potential adverse reactions to allow for early recognition and discontinuation of the offending drug when needed. Early recognition also allows for favorable management of adverse reactions. In addition, potentially significant drug interactions may be recognized by obtaining a thorough medical history and avoiding combinations of drugs that may interact unfavorably. Fortunately, there are several choices that allow us to individually select a treatment regimen that is optimal for the individual patient, allowing for effective control of rosacea.

Verruciform xanthoma of the glans penis: a benign clinical simulant of genital malignancy.

Verruciform xanthoma is a benign disorder affecting skin and mucosa. Although most cases have been reported to occur in the mouth, other sites may be affected, most notably the genitalia. A large, exophytic verruciform xanthoma involving the glans penis is reported. The clinical similarity to a malignancy, especially verrucous carcinoma, is emphasized. The differential diagnosis and histologic features are reviewed along with a summary of the literature regarding this uncommon condition.

Advances in the treatment of superficial fungal infections: focus on onychomycosis and dry tinea pedis.

Onychomycosis is one of the most stubborn superficial mycoses. With few exceptions, oral antifungal therapy is needed to achieve resolution. Before oral itraconazole, fluconazole, and terbinafine hydrochloride became available, physicians had to rely on prolonged therapy with griseofulvin or oral ketoconazole. Of the newer oral agents, itraconazole appears to have the broadest spectrum of action, with therapeutic activity against dermatophytes, yeasts, and some nondermatophyte molds. Tissue pharmacokinetics accounts for significantly greater efficacy and much shorter treatment courses for fungal infections of the skin and nails. In general, oral itraconazole, fluconazole, and terbinafine are very well tolerated. The newer oral agents offer improved efficacy over griseofulvin and ketoconazole for onychomycosis and dry tinea pedis.

Treatment of onychomycosis and tinea pedis with intermittent itraconazole therapy.

A 40-year-old woman had a 10-year history of dermatophyte-related toenail onychomycosis (tinea unguium) and dry-type tinea pedis, which had failed to respond to previous therapy with topical antifungal agents or oral griseofulvin. The patient was successfully treated with four cycles of intermittent itraconazole therapy (that is, 400 mg/d for 1 week per month for 4 months). At the end of this time, the tinea pedis had resolved and the onychomycosis improved significantly after four cycles were completed. Twelve months after the onset of therapy, both conditions had resolved completely according to both clinical and mycologic criteria. Itraconazole was well tolerated, with no side effects reported. These observations suggest that itraconazole intermittent dosing is a highly effective therapy for the treatment of onychomycosis caused by dermatophyte organisms, because it provides a high cure rate after only a short course of therapy.

Itraconazole in the treatment of superficial cutaneous and mucosal Candida infections.

Superficial cutaneous and mucosal Candida infections are common and widely affect both the immunocompromised as well as the immunocompetent populations. Common infections may include Candida paronychia, cutaneous candidiasis, oral candidiasis, vulvovaginal candidiasis, and Candida onychomycosis. Although C albicans has been considered to be the most common pathogen, other Candida species have emerged as potential causes of certain infections. Currently, a variety of antifungal agents is available to treat these infections. They include fluconazole, ketoconazole, and itraconazole. These agents have been widely used to treat fungal infections, including superficial and systemic candidiasis. However, some concerns exist regarding safety associated with long-term use of ketoconazole, and emerging issues of Candida resistance to fluconazole in some patient subsets have been reported. Itraconazole has proven efficacy in treating cutaneous and mucosal Candida infections. Additionally, studies have demonstrated that itraconazole may have increased efficacy and an excellent safety profile when administered in a pulse-dose, or intermittent fashion, for superficial mycotic infections. Itraconazole is an effective agent that warrants consideration when selecting treatment for Candida infections.

Management of tinea capitis. A status report.

Tinea capitis is the most common pediatric fungal infection, usually affecting school-age children. It is caused by a dermatophyte from the genus Trichophyton or Microsporum. The predominant pathogens vary according to geographic location. Infection rates are higher in urban regions, especially those with overcrowded living conditions. In the United States, the incidence is highest among African-American children and appears to be significantly lower among Asian Americans. Tinea capitis may persist into adulthood, especially in females with Trichophyton tonsurans infection. Tinea capitis also has been reported in neonates, infants, and elderly patients.

Onychomycosis in children: prevalence and management.

Onychomycosis in children is often accompanied by tinea pedis and a family history of onychomycosis. The prevalence of onychomycosis in children is substantially lower than that of adults; therefore it is important to confirm the clinical diagnosis. The most common presentation of onychomycosis is the distal and lateral subungual type. The organism most commonly isolated in North America is Trichophyton rubrum. Oral antifungal therapy is required, especially when the onychomycosis is of moderate to severe intensity, with nail matrix involvement. The new oral antifungal agents itraconazole, terbinafine, and fluconazole are being increasingly used for the treatment of onychomycosis. Review of the literature suggests that these agents are effective and safe in managing onychomycosis in children. The short duration of therapy required with these drugs should help improve compliance. The data suggest that the new oral antifungal agents have a role in the treatment of onychomycosis in children. Further experience will help us better position these drugs when evaluating the management of onychomycosis in children.

Hepatitis associated with terbinafine therapy: three case reports and a review of the literature.

Terbinafine is an allylamine antifungal agent first launched in the USA in May 1996 with an estimated 7.5 million individuals worldwide having used the drug. Given orally it is effective for the treatment of dermatophyte infections and is prescribed predominantly for the superficial mycoses. Adverse effects have been reported in 46.7% of patients receiving the oral drug (compared with 29.2% receiving placebo, the attributable risk to terbinafine being 17.5%). Thus, oral terbinafine is associated with the rare development of symptomatic idiosyncratic hepatobiliary dysfunction (1:45,000-1:54,000) and we now describe three patients who developed this disorder whilst taking the medication. The hepatitis produced has the features of both hepatocellular necrosis (with elevations of hepatic enzyme concentrations) and cholestatic injury (with elevations of alkaline phosphatase and cholesterol levels), the latency period between the start of medication and the development of liver injury being approximately 4-6 weeks. The US terbinafine product monograph recommends that serum hepatic enzymes should be assessed in individuals receiving terbinafine for more than 6 weeks, as a result of which some physicians monitor these values at baseline and at 4-6 weeks.

Cutaneous adverse effects associated with terbinafine therapy: 10 case reports and a review of the literature.

Terbinafine is an allylamine antifungal agent widely used to treat dermatophyte onychomycosis and dermatomycoses. We report 10 severe cutaneous adverse reactions associated with terbinafine therapy which required discontinuation of the antifungal agent: erythema multiforme (five patients), erythroderma (one), severe urticaria (one), pityriasis rosea (one) and worsening of pre-existing psoriasis (two patients). The spectrum of cutaneous adverse effects associated with terbinafine therapy is reviewed. Patients should be counselled about discontinuing terbinafine at the onset of a cutaneous eruption and about seeking medical advice about further management.