Jennifer G. Powers

Severe Cutaneous and Neurologic Toxicity in Melanoma Patients during Vemurafenib Administration Following Anti-PD-1 Therapy

Severe systemic toxicities developed in two patients during vemurafenib therapy following disease progression after treatment with anti-PD-1 agents; these results have important implications for the management of melanoma patients and future clinical trials involving anti-PD-1 and BRAF inhibitors. Immune checkpoint inhibitors such as ipilimumab and targeted BRAF inhibitors have dramatically altered the landscape of melanoma therapeutics over the past few years. Agents targeting the programmed cell death-1/ligand (PD-1/PD-L1) axis are now being developed and seem to be highly active clinically with favorable toxicity profiles. We report on two patients with BRAF V600E–mutant melanoma who were treated with anti-PD-1 agents as first-line therapy without significant toxicity, followed by vemurafenib at disease progression. Both patients developed severe hypersensitivity drug eruptions with multiorgan injury early in their BRAF inhibitor treatment course. One patient subsequently developed acute inflammatory demyelinating polyneuropathy, and the other developed anaphylaxis upon low-dose vemurafenib rechallenge. Further investigation of the immune response during combination or sequences of melanoma therapeutics is warranted. Furthermore, clinicians should maintain a high index of suspicion for these toxicities when vemurafenib is administered following an anti-PD-1 agent. Cancer Immunol Res; 1(6); 373–7. ©2013 AACR.

Dressings for chronic wounds.

Covering wounds, acute and chronic, is one of the most fundamental activities of any medical practitioner. Although wound dressings primarily serve to contain the “good” and keep out the “bad,” research has characterized more specifically the sophisticated interaction between the human wound bed and its dressing counterpart. Wound dressings for todays chronic wounds come in many flavors, ranging from the classic types of moisture‐retentive dressings to silver‐coated varieties to biologic dressings serving as skin substitutes. Moisture‐retentive dressing types include foams, films, hydrogels, hydrocolloids, and alginates. Appropriate use of these dressings can help to keep the wound bed moist, which allows for epithelial migration, angiogenesis, retention of growth factors, autolytic debridement, and maintenance of electrical gradients.

Wound healing and treating wounds: Chronic wound care and management

In the United States, chronic ulcers--including decubitus, vascular, inflammatory, and rheumatologic subtypes--affect >6 million people, with increasing numbers anticipated in our growing elderly and diabetic populations. These wounds cause significant morbidity and mortality and lead to significant medical costs. Preventative and treatment measures include disease-specific approaches and the use of moisture retentive dressings and adjunctive topical therapies to promote healing. In this article, we discuss recent advances in wound care technology and current management guidelines for the treatment of wounds and ulcers.

Wound Dressings: Selecting the Most Appropriate Type

Appropriate wound dressing selection is guided by an understanding of wound dressing properties and an ability to match the level of drainage and depth of a wound. Wounds should be assessed for necrosis and infection, which need to be addressed prior to selecting an ideal dressing. Moisture-retentive dressings include films, hydrogels, hydrocolloids, foams, alginates, and hydrofibers and are useful in a variety of clinical settings. Antimicrobial-impregnated dressings can be useful in wounds that are superficially infected or are at higher risk for infection. For refractory wounds that need more growth stimulation, tissue-engineered dressings have become a viable option in the past few decades, especially those that have been approved for burns, venous ulcers, and diabetic ulcers. As wounds heal, the ideal dressing type may change, depending on the amount of exudate and depth of the wound; thus success in wound dressing selection hinges on recognition of the changing healing environment.

The Integrated Skin Exam film: An educational intervention to promote early detection of melanoma by medical students

BACKGROUND Knowledge of the skin cancer examination (SCE) and its practice remain relevant competency gaps among medical students. OBJECTIVE We elaborate on a method of SCE known as the Integrated Skin Exam and discuss the development of an instructional film that illustrates its principles. We assess the tools effect on knowledge, attitudes, and perceptions related to the SCE. METHODS Second-year students among 8 randomized schools viewed the film and completed pre-post questionnaires. RESULTS After viewing The Integrated Skin Exam film, students demonstrated improved melanoma knowledge, including identification of high-risk demographic groups (61% vs 42.9%, P < .001), high-risk anatomic sites in women (88.6% vs 46.5%, P < .001) and men (92.1% vs 34.8%, P < .001), and the ABCDEs of melanoma (98.4% vs 91.2%, P < .001). Students demonstrated increased confidence in the SCE (66.93% vs 16.40%, P < .001) and augmented intentions to practice it (99.05% vs 13.9%, P < .001). A greater proportion (70.4% vs 41.9%, P < .001) of students thought less than 3 minutes were required to integrate SCE into the routine examination. LIMITATIONS Longitudinal impact of the film was not assessed. CONCLUSION The Integrated Skin Exam film introduces an integrated approach to the SCE that addresses knowledge gaps, mitigates perceived barriers, and augments intention related to practice of the SCE.

Coagulation disorders and their cutaneous presentations: Diagnostic work-up and treatment.

Both inherited and acquired hypercoagulable states can present with nonspecific clinical manifestations, such as petechiae, purpura, livedo reticularis, and ulcerations. A good history and physical examination are crucial to diagnoses of these conditions. Inherited conditions tend to present either in neonatal period or later in life, while acquired conditions typically occur later in life. Diagnostic studies are performed to identify the coagulation cascade deficiency or defect. Treatment primarily hinges on anticoagulation and wound care. In this article, we provide an in-depth analysis of the clinical manifestations, diagnostic considerations, and management options of patients in hypercoagulable states.

Effective blue light photodynamic therapy does not affect cutaneous langerhans cell number or oxidatively damage DNA.

BACKGROUND Photodynamic therapy (PDT) using aminolevulinic acid (ALA) with blue light or red light is effective for treating actinic keratoses (AKs). However, immunosuppression follows red light PDT, raising the spectre of skin cancer promotion in treated skin. OBJECTIVE To determine whether broad-area short incubation (BASI)-ALA-PDT using blue light immunosuppression immunosuppresses treated skin. METHODS Patients were evaluated clinically and by standardized facial biopsies of non-AK skin before, 24 hours and 1 month after customary blue light BASI-ALA-PDT. All biopsies were stained for markers of epidermal atypia and Langerhans cells (LCs); and at 24 hours to detect oxidative DNA damage. RESULTS Patients had an 81% reduction in AKs and slight improvement in clinical and histologic signs of photoaging after 1 month. The biopsied chronically photodamaged skin without clinically detectable AKs showed no effect of PDT on the LC number, distribution, or morphology; and no oxidative DNA damage, in contrast to the changes reported after customary red light PDT. CONCLUSION Customary blue light BASI-ALA-PDT does not affect the LC number or produce oxidative DNA damage, the sequelae of red light PDT responsible for immunosuppression in treated skin.

Skin cancer in the military: A systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel

Background: Occupational sun exposure is a well‐studied risk factor for skin cancer development, but more work is needed to assess melanoma and nonmelanoma skin cancer risk among US military personnel to improve education and screening efforts in this population. Objective: To conduct an extensive review of skin cancer risks for US military personnel to inform preventive education, diagnosis, and treatment efforts to better protect these individuals from future skin cancer development. Methods: A systematic review of published studies on the subject of melanoma and nonmelanoma skin cancer in military personnel was conducted. Results: A total of 9 studies describing skin cancer incidence in the US military were identified, with 4 studies specific to melanoma. The study findings reveal an increased risk for melanoma associated with service in the military or prisoner of war status. Service in tropical environments was associated with an increased incidence of both melanoma and nonmelanoma skin cancer among World War II soldiers. Two studies found that increased melanoma risk was also branch dependent, with the highest rates among the United States Air Force. Several of the reviewed studies implicated increased sun exposure during military service and lack of sufficient sun protection as the causes of higher rates of skin cancer among US military and veteran populations as compared with among the nonmilitary population in the United States. Limitations: The reviewed articles have variable results; a prospective randomized controlled trial would be helpful to develop interventions that mitigate skin cancer risk in the US military. Conclusion: This review identifies an abundance of evidence for an increased risk for skin cancer development among US active duty and veteran populations.

Thick Intergluteal Cleft and Lower Extremity Plaques

A 56-year-old white man presented to our dermatology clinic with a 5-year history of hyperkeratotic plaques on his intergluteal cleft, buttocks (Figure, A), and bilateral ankles (Figure, B). These lesions were occasionally pruritic and caused footwear-associated discomfort. The buttock lesion had been previously diagnosed as psoriasis but never responded to treatment. His medical history was remarkable for poorly controlled diabetes mellitus type 2 (hemoglobin A1c, 9.1%), hypertension, hyperlipidemia, and chronic low back pain. There was no family history of skin diseases. Physical examination revealed well-defined, slightly scaly purple to gray expansive plaques on the bilateral medial buttocks. On the anterior shins and proximal heels were well-defined hyperkeratotic plaques with a purple to gray color. He also exhibited 0.5to 2-cm thin pink plaques with hyperkeratotic rims and atrophic centers scattered on his bilateral upper and lower extremities. Two shave biopsy specimens were taken, from his right leg and left buttock (Figure, C). What is your diagnosis?

Successful treatment of minocycline-induced pigmentation with combined use of Q-switched and pulsed dye lasers.

Minocycline is a tetracycline antibiotic that can induce hyperpigmentation and scarring of the skin, nails, mucous membranes, thyroid, teeth, bones, and heart valves. Minocycline-induced cutaneous hyperpigmentation consists of three types. Type I pigmentation occurs in areas of prior inflammation such as scars, and it is not thought to be dependent on treatment dose or duration. Type II pigmentation and type III pigmentation, which occur on normal skin and sun-exposed skin, respectively, appear to be dose-related. This side effect can persist for years if not permanently despite treatment attempts, and definitive therapy does not exist. A few case reports have documented successful treatment of minocycline-induced pigmentation with Q-switched lasers and nonablative fractional photothermolysis, but the potential for combination laser therapy is not well-studied. Additionally, little is known about the efficacy of pulsed dye lasers in treating drug-induced pigmentation. Here, we report a case of successful resolution of minocycline-induced hyperpigmentation with combined Medlite Q-switched and Vbeam pulsed dye laser treatment.