A seamless phase I/II dose-finding trial assessing ingenol disoxate (LEO 43204) for field treatment of actinic keratosis on the scalp.

BACKGROUND: Actinic keratosis (AK) is a common sun-related skin condition, which can progress to squamous cell carcinoma and occur in cancerized fields. OBJECTIVES: To investigate in a phase I/II trial the safety and efficacy of ingenol disoxate as topical field therapy for patients with AK on the balding scalp. METHODS: Part 1 was a phase I, open-label, dose-escalation trial investigating up to six doses of ingenol disoxate to determine the maximum tolerated dose (MTD). Part 2 was a phase II, randomized, double-blind, parallel group, vehicle-controlled trial. Patients were randomized 2 : 2 : 1 to receive ingenol disoxate 0·037%, 0·05% or vehicle gel once daily for two consecutive days. Percentage reduction in AK count from baseline, complete clearance (AKCLEAR 100) and partial clearance (≥ 75% AK count reduction; AKCLEAR 75) were assessed at week 8. RESULTS: The MTD in part 1 was 0·075% based on a dose-dependent increase in the number and severity of adverse events. Two lower doses of ingenol disoxate gel (0·037%, 0·05%) were assessed in part 2, which showed a reduction in AK count from baseline to week 8 (0·037%, 72·7%; 0·05%, 78·5% vs. vehicle 12·6; P < 0·001), and rates of AKCLEAR 100 and AKCLEAR 75 were significantly higher in active treatment groups compared with vehicle (P ≤ 0·007). Local skin responses peaked at day 3 and declined rapidly. Adverse events were generally mild to moderate in intensity, and were most commonly application site pain/pruritus. CONCLUSIONS: Ingenol disoxate 0·037% and 0·05% gel was effective and superior to vehicle, and well tolerated as field therapy for AK on the balding scalp.

AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery.

The appropriate use criteria process synthesizes evidence-based medicine, clinical practice experience, and expert judgment. The American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery has developed appropriate use criteria for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered based on tumor and patient characteristics. This document reflects the rating of appropriateness of MMS for each of these clinical scenarios by a ratings panel in a process based on the appropriateness method developed by the RAND Corp (Santa Monica, CA)/University of California-Los Angeles (RAND/UCLA). At the conclusion of the rating process, consensus was reached for all 270 (100%) scenarios by the Ratings Panel, with 200 (74.07%) deemed as appropriate, 24 (8.89%) as uncertain, and 46 (17.04%) as inappropriate. For the 69 basal cell carcinoma scenarios, 53 were deemed appropriate, 6 uncertain, and 10 inappropriate. For the 143 squamous cell carcinoma scenarios, 102 were deemed appropriate, 7 uncertain, and 34 inappropriate. For the 12 lentigo maligna and melanoma in situ scenarios, 10 were deemed appropriate, 2 uncertain, and 0 inappropriate. For the 46 rare cutaneous malignancies scenarios, 35 were deemed appropriate, 9 uncertain, and 2 inappropriate. These appropriate use criteria have the potential to impact health care delivery, reimbursement policy, and physician decision making on patient selection for MMS, and aim to optimize the use of MMS for scenarios in which the expected clinical benefit is anticipated to be the greatest. In addition, recognition of those scenarios rated as uncertain facilitates an understanding of areas that would benefit from further research. Each clinical scenario identified in this document is crafted for the average patient and not the exception. Thus, the ultimate decision regarding the appropriateness of MMS should be determined by the expertise and clinical experience of the physician.

Poly-L-lactic acid as a facial filler.

Poly-L-lactic acid is a filler recently approved by the US FDA for the correction of facial lipoatrophy in patients infected with the human immunodeficiency virus (HIV). Currently, poly-L-lactic acid, sold under the brand name Sculptratrade mark (Dermik), is the only product approved by the FDA specifically for this indication. The market for poly-L-lactic acid will likely be larger than the HIV-infected population, as physicians use poly-L-lactic acid off-label to correct lipoatrophy associated with the normal aging process in non-HIV-infected patients. The benefits of poly-L-lactic acid are limited by the fact that multiple treatments are necessary to achieve the desired correction; its results are temporary and its cost is high.

Unilateral acquired nevus flammeus in women.

Congenital nevus flammeus is a benign vascular tumor characterized by pink to pale red patches that thicken as the patient ages, producing a dull red to reddish blue, cobblestone-textured plaque. We present the cases of 3 women with unilateral acquired nevus flammeus on the cheek whose lesions resolved after minimal treatment with a 585-nm pulsed dye laser. The etiology of acquired nevus flammeus is reviewed and tumor response rates to laser surgery are discussed.

A history of dermatologic surgery in the United States.

BACKGROUND: Dermatologic surgery has a long and distinguished history in the United States. OBJECTIVE: To examine the specific contributions of American dermatologic surgeons. METHOD: The medical literature on cutaneous reconstructive and cosmetic surgery for the last century and a half was researched. RESULTS: Numerous American dermatologic surgeons have had a major impact on scientific and technological discoveries in cutaneous surgery. Dermatologic surgeons have been significantly involved in cutaneous surgery since the second half of the 19th century. Dermatologic surgeons have contributed many important advances to the fields of chemical peeling, cryosurgery, dermabrasion, electrosurgery, hair transplantation, soft tissue augmentation, tumescent liposuction, laser surgery, phlebology, Mohs chemosurgery, cutaneous reconstruction, wound healing, botulium toxin, blepharoplasty, and rhytidectomy. CONCLUSION: Dermatologic surgeons in the United States have contributed significantly to the history of reconstructive and cosmetic surgery. Dermatologic surgeons have been leaders in advancing this field and are poised to continue in the future.

Morbidity and mortality related to liposuction. Questions and answers.

Reports of fatalities following liposuction have lead to investigations by state medical boards. The risk of complications and fatalities is clearly different for liposuction under local anesthesia and intravenous sedation. Thousands of patients have been treated with true tumescent liposuction as described by dermatologist Dr. Jeffrey A. Klein, with no reports of fatalities. Patients should seek physicians who are experienced in this extremely safe method of liposuction.

Does the location of the surgery or the specialty of the physician affect malpractice claims in liposuction?

BACKGROUND: There is increasing national dialogue on who should perform liposuction and where it should be performed. OBJECTIVE: To determine the effect of the location of liposuction surgery and the specialty of the physician on the incidence of malpractice claims. METHODS: Physicians Insurance Association of America malpractice data from 1995-1997 was analyzed. RESULTS: Hospital-based liposuction had more than 3 times the rate of malpractice settlements than office-based liposuction. Dermatologists accounted for less than 1% of malpractice claim settlements in liposuction. CONCLUSION: Dermatologic liposuction education has emphasized small volume cases performed under local anesthesia using the tumescent technique. The safety of this approach appears to be validated in terms of decreased malpractice settlements.

Cutaneous resurfacing.

Cutaneous resurfacing can be accomplished with application of acids, abrasive modalities, or the new generation of carbon dioxide lasers. Ultimately, the universal goal is removal and replacement of the epidermis and dermal collagen remodeling. The indications range from therapeutic and reconstruction to the treatment of the stigmata associated with senescence. The indications are not technique-specific, and the art of cutaneous resurfacing is identifying the cutaneous defect and selecting the appropriate tool or tools to realize the optimal clinical results.

Prevalence of acne keloidalis nuchae in football players.

BACKGROUND: Acne mechanica (AM) is common in football players. Severe cases of nuchal AM may precede acne keloidalis nuchae (AKN). Factors that may be associated with the progression of nuchal AM to AKN are unknown. The prevalence of AKN in football players has not been reported. OBJECTIVE: We investigated the frequency of nuchal AM and AKN within a susceptible population and attempted to identify factors that may be associated with AKN. METHODS: Four hundred fifty-three high school, collegiate, and professional football players were examined for the presence of nuchal AM or AKN. Those with positive findings completed a questionnaire regarding their disease. RESULTS: Nuchal AM was more prevalent in high school players (15.5%) than older players (1.2%). AKN was more frequent in players beyond the high school level and was found exclusively in blacks. AKN was not associated with a positive family history of AKN nor a positive personal or family history of keloid formation. CONCLUSION: AKN occurs almost exclusively in blacks. The level of football play may be associated with the development of AKN. Positive family history of AKN and positive family or personal history of keloids is not associated with AKN development.

Current status of melanoma vaccines.

BACKGROUND: Malignant melanoma is increasing worldwide faster than any other cancer and the American lifetime risk is estimated to reach 1 in 75 by the year 2000. Active specific immunotherapy with vaccines is evolving as a promising new modality in the treatment of malignant melanoma. OBJECTIVE: To present a concise and understandable summary of the key molecular and clinical concepts of melanoma vaccines currently under investigation, the history that led to their development, and their anticipated clinical response. METHODS: The recent advances in the field of melanoma immunobiology and the newest experiment vaccines are reviewed. RESULTS: There is no effective melanoma vaccine that successfully treats or prevents melanoma. However, their use has been associated with regression or delayed disease progression in some cases. The minority of patients who do have a major clinical response to vaccine therapy experience an improvement in survival. Even in those patients in whom melanoma vaccines cannot improve survival, the paucity of severe side effects has provided a quality of life superior to standard multiagent chemotherapy. CONCLUSION: Melanoma vaccines are relatively safe immunotherapeutic modalities for the management of malignant melanoma. The clinical effectiveness of melanoma vaccines is unclear and adequately controlled studies need yet to be performed. Current melanoma vaccines manipulate antigen presentation networks and combine the best cellular and antibody antitumor immune response effective in mediating tumor protective immunity; these combination vaccines hold the most promise. The ideal melanoma vaccine will ultimately prevent melanoma.

The medical necessity for treatment of port-wine stains.

BACKGROUND: Port-wine stains are congenital vascular malformations that can be disfiguring and may lead to psychosocial as well as medical complications. The 585-nm pulsed dye laser is very effective in treating port-wine stains. Laser treatment is often viewed by insurance companies as a "cosmetic procedure" and not "medically necessary". Consequently many patients are denied coverage for treatment of their disfiguring birthmarks. OBJECTIVE: To determine variability of insurance coverage for laser treatment of port-wine stains from state to state. Natural history, progression, and potential complications of port-wine stains are reviewed and rationale for consistent insurance coverage for laser treatment of port-wine stains is given. METHODS: A questionnaire was mailed to 40 dermatologic surgeons in 22 states and the District of Columbia. We reviewed the literature regarding port-wine stains and their potential complications, and health care policy guidelines regarding "medical necessity" and "cosmetic procedures". RESULTS: Insurance coverage for laser treatment of port-wine stains varies from state to state. CONCLUSION: Based on current health care policy guidelines, laser treatment of port-wine stains should be regarded, and covered, as a medical necessity by all insurance providers.

The molecular basis of xeroderma pigmentosum.

BACKGROUND: Xeroderma pigmentosum is an extremely rare, autosomal recessive disease characterized by a more than 1000-fold increase in nonmelanoma skin cancer. Individuals with this disease can be divided into eight complementation groups: A-G and V for variant. Each one represents a different genetic defect in DNA repair. OBJECTIVE: To review the molecular basis of xeroderma pigmentosum. RESULTS: Deficiencies in various gene products in the nucleotide excision repair pathway cause xeroderma pigmentosum in complementation groups A-G. The molecular basis of the variant group remains to be elucidated. CONCLUSIONS: Research into the genetic defects underlying xeroderma pigmentosum have led to an increased understanding of nucleotide excision repair.