A multistep approach to improving biopsy site identification in dermatology: physician, staff, and patient roles based on a Delphi consensus.

IMPORTANCE: Excisional skin cancer surgery is a common procedure, with no formal consensus for mitigating the risk of wrong-site cutaneous surgery. OBJECTIVE: To systematically consider the usefulness and feasibility of proposed methods for correct biopsy site identification in dermatology. EVIDENCE REVIEW: Survey study with a formal consensus process. Item development was via a literature review and expert interviews, followed by 2 stages of a Delphi process to develop consensus recommendations. FINDINGS: In total, 2323 articles were reviewed in the literature search, with data extraction from 14. Twenty-five experts underwent 30-minute structured interviews, which were transcribed and coded. The resulting survey was composed of 42 proposed interventions by multiple stakeholders (biopsying physicians, operating physicians, nurses, ancillary staff, patients, caregivers, and family members) at 3 time points (day of biopsy, delay and consultation period, and day of definitive surgery). Two rounds of a Delphi process with 59 experts (25 academic and 34 private practice) scored the survey. Strong consensus was obtained on 14 behaviors, and moderate consensus was obtained on 21 other behaviors. In addition, a 2-state simultaneous algorithm was developed to model surgeon behavior on the day of definitive surgery based on surgeon and patient perceptions. CONCLUSIONS AND RELEVANCE: When definitive surgery is performed after the initial biopsy and by a different surgeon, procedures can be implemented at several time points to increase the likelihood of correct site identification. The specific circumstances of a case suggest which methods may be most appropriate and feasible, and some may be implemented. The risk of wrong-site cutaneous surgery can be reduced but not eliminated.

Drug-induced photoallergic and phototoxic reactions - an update.

INTRODUCTION: Photoallergic and phototoxic medications continue to be an important concern for dermatologists. In the last 5 years, the list of phototoxic and photoallergic medications has expanded, as well as the testing tools used to screen for potential allergy. Currently available testing methods include the photoprick, photoscratch and illuminated intracutaneous tests. If the causative photosensitizer is not the test substance but a metabolite of the test substance, a systemic photoprovocation test can be utilized. Photodynamic therapy pro-photosensitizers have been shown to be sensitizers to visible light, while most other phototoxins respond to the UVA and/or UVB spectrum. AREAS COVERED: This article reviews the findings of a PubMed search for the key words 'photosensitivity', 'photosensitive', 'phototoxicity', 'phototoxic', 'photoallergy' and 'photoallergic'. Articles published over the last 5 years were compared with those published earlier than this to find updated information on photo-reactions. EXPERT OPINION: With the variety of new monoclonal antibodies, clinicians must remain up to date as to the drugs that can cause photo-reactions. There are new tests that can aid in assessing photo-reactions.

Necrolytic acral erythema: a review of the literature.

Necrolytic acral erythema (NAE) has been described as an early cutaneous marker for hepatitis C virus (HCV) infection. It most commonly presents as a well-defined, dusky, erythematous eruption with marked hyperkeratosis and a dark red rim associated with pruritus or burning. Necrolytic acral erythema bears microscopic and clinical resemblance to other necrolytic erythemas, including necrolytic migratory erythema (NME) and several nutrient-deficient syndromes. It is distinct, however, in its predominantly acral distribution and strong association with HCV infection. The pathogenesis is unknown, but a relationship to metabolic alterations has been hypothesized. Optimal therapy appears to be treatment of the underlying HCV infection using a combination of ribavirin and interferon alfa; oral zinc therapy may be an alternative but useful therapy. Cases of NAE without HCV infection suggest that more work needs to be done defining NAE and its relationship to HCV.

Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy.

Pazopanib, which is being developed by GlaxoSmithKline plc, is an oral, second-generation multi-targeted tyrosine kinase inhibitor that targets VEGFR, platelet-derived growth factor receptor and c-kit, key proteins responsible for tumor growth and survival. Pazopanib exhibited good potency against all of the human VEGFRs and closely related tyrosine receptor kinases in vitro, and demonstrated antitumor activity in several human tumor xenografts, including renal cell carcinoma (RCC), and breast and lung cancer. In phase I and II clinical trials, pazopanib was generally well tolerated with the main side effects being hypertension, fatigue or gastrointestinal disorders. Pazopanib alone caused a decrease in tumor size and stable disease in a significant number of patients, including those with RCC, NSCLC and gynecological tumors. The combination of pazopanib with lapatinib was effective in patients with breast cancer. At the time of publication, pazopanib monotherapy was being evaluated in phase III trials in patients with RCC and as combination therapy with lapatinib in patients with breast cancer. In addition, phase I and II trials were being conducted to assess pazopanib alone or in combination with a range of chemotherapeutics in patients with solid tumors or multiple myeloma.

Talarozole, a selective inhibitor of P450-mediated all-trans retinoic acid for the treatment of psoriasis and acne.

Talarozole, being developed by Barrier Therapeutics Inc under license from Johnson & Johnson, is a potent and selective inhibitor of cytochrome P450 26-mediated breakdown of endogenous all-trans retinoic acid for the treatment of psoriasis and acne. Phase II clinical trials of an oral formulation of talarozole in patients with psoriasis and with acne, and a phase I clinical trial of a topical formulation have been completed. At the time of publication, Barrier Therapeutics had suspended the development of talarozole as part of a series of cost-cutting initiatives; the company had also been acquired by Stiefel Laboratories Inc. No formal announcement had been made regarding the further development of talarozole.

Pramiconazole, a triazole compound for the treatment of fungal infections.

Pramiconazole from Barrier Therapeutics Inc is a new addition to the family of triazole antifungal agents that act by inhibiting fungal cell membrane ergosterol synthesis, thereby leading to increased cell permeability and destruction. Barrier Therapeutics was developing an oral formulation of pramiconazole for the potential treatment of seborrheic dermatitis (erythematosquamous skin disease), onychomycosis and dermatomycosis (including tinea versicolor, tinea pedis and tinea cruris/corporis). In preclinical studies, pramiconazole exhibited similar or superior antifungal activity to ketoconazole and itraconazole, and selectively inhibited ergosterol synthesis with a broad spectrum activity. Pramiconazole was absorbed rapidly and had a long half-life, allowing for once-daily dosing. In phase I and II clinical trials, pramiconazole reduced the growth of Candida albicans, Malassezia globosa, Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum, and was generally well tolerated. At the time of publication, Barrier Therapeutics had suspended the development of pramiconazole as part of a series of cost-cutting initiatives; the company had also been acquired by Stiefel Laboratories Inc. No formal announcement had been made regarding the further development of pramiconazole. The results of studies performed to date suggest that pramiconazole may be useful in the treatment of dermatomycoses when oral treatment is mandated. Promising preclinical and early phase II clinical data warrant the further development of the drug in larger clinical trials.

Drug-induced photoallergic and phototoxic reactions.

Drug-induced photosensitivity involves reactions to medication triggered by exposure of the skin to ultraviolet light. Medications that trigger reactions can be topical or oral. Following interaction of ultraviolet radiation with a chemical present in sufficient amounts in the skin, one of the several reactions may occur in susceptible patients, most commonly photoallergy or phototoxicity. These reactions can be diagnosed separately based on pathogenesis, clinical characteristics and histopathology. Phototoxic disorders have a higher incidence than photoallergic disorders. The action spectra for most photoallergens and phototoxins lie in the ultraviolet A range. Subtypes of drug-induced photosensitivity include dyschromia, pseudoporphyria, photo onycholysis, and lichenoid and telangiectatic reactions.