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Current Issue May 2013 | Volume 12 | Issue 5

Editors

Molecular Skin Research Can Impact Systemic Cancers

William Levis MD and Frank Martiniuk PhD
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Periungual Pyogenic Granuloma Following Imatinib Therapy in a Patient With Chronic Myelogenous Leukemia

Emi Dika MD, Alessia Barisani MD, Sabina Vaccari MD, Pier Alessandro Fanti MD, Alma Ismaili MD, and Annalisa Patrizi MD PhD
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Comorbidities Associated With Leptin and Psoriasis

Shailendra Kapoor MD
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Original Articles

Cosmeceuticals for Recurrence Prevention After Prior Skin Cancer: An Overview

Katlein França MD MSc,^a Joel L. Cohen MD,^b and Lisa Grunebaum MD^c
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INTRODUCTION: Skin cancer is the most common form of cancer in the United States. According to the World Health Organization, the incidence of both nonmelanoma and melanoma skin cancers has increased over the past few decades.
OBJECTIVE: The objective of this article is to review studies about cosmeceuticals that can be used by people who previously had skin cancer and may work as agents that help in some way to prevent new skin cancer lesions.
CONCLUSION: Cosmeceuticals are antiaging skin products that overlap cosmetics and pharmaceuticals and are commonly available over the counter. This article reviewed several substances used in cosmeceuticals formulations that could be useful for individuals who have had previous skin cancers and need to prevent possible new lesions. Further studies are needed to better evaluate these products and their skin cancer preventive properties.

J Drugs Dermatol. 2013;12(5):516-518.

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Targeting the Hedgehog Pathway to Treat Basal Cell Carcinoma

Pieter Geeraert MD,^a,b Jonathan S. Williams BS,^c and Isaac Brownell MD PhD^c
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The discovery of mutations that activate hedgehog (Hh) signaling in basal cell carcinoma (BCC) and other cancers has spurred the development of small molecule inhibitors that target the Hh pathway. High-throughput screens have identified a number of drug candidates that antagonize smoothened (SMO), an essential protein in the Hh signaling pathway. Clinical studies of the oral SMO inhibitor vismodegib (GDC-0449) in patients with inoperable or metastatic BCC have led to its recent approval by the US Food and Drug Administration. This review aims to give the clinician an overview of vismodegib and other Hh pathway inhibitors in the treatment of patients with advanced BCC and basal cell nevus syndrome. Issues of drug mechanism, efficacy, safety, tolerability, and tumor resistance are addressed.

J Drugs Dermatol. 2013;12(5):519-523.

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Nontraditional Management of Basal Cell Carcinoma

Nina Botto MD and Gary Rogers MD
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This review discusses nontraditional modalities available for the treatment of basal cell carcinoma along with the existing evidence to support their respective uses in varying clinical situations. By definition, these modalities are nonsurgical, and in many cases, are not approved by the US Food and Drug Administration as treatments for basal cell carcinoma, including topical chemotherapies, photodynamic therapy, oral therapies, and complementary therapies. Nonetheless, as the population of patients with skin cancer increases at epidemic proportions, many of these modalities are, and will become, increasingly relevant in the dermatologist’s armamentarium.

J Drugs Dermatol. 2013;12(5):525-533.

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Treatment of Facial Photodamage Using a Novel Retinol Formulation

Michael H. Gold MD,^a,b Leon H. Kircik MD,^c-e Vivian W. Bucay MD,^f,g
Monika G. Kiripolsky MD,^h,i and Julie A. Biron BSc^a
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BACKGROUND: Photoaged skin is characterized by a variety of clinical, histologic, and biochemical features.
OBJECTIVE: To determine the efficacy of a new topical formulation of 1% retinol and the effects of this same formulation using a 0.5% retinol concentration to minimize irritation.
METHODS: Patients at 2 sites (n=6, n=5) with photodamaged skin applied a novel suspension of retinol (1%) daily to their faces for 8 to 12 weeks. Clinicians graded improvement in ultraviolet-induced features at 4 to 6 weeks and at 8 to 12 weeks. Positive results of the observational pilot study warranted a follow-up study on the low concentration. At a third site, females (n=30) with facial photodamage applied the same formulation with or without retinol (0.5%) daily for 8 weeks. Twenty-two subjects applied the test product and 8 applied vehicle according to a randomized, double-blinded, institutional review board–approved protocol. Improvements in photodamage features were graded at 4 and 8 weeks.
RESULTS: In the observational pilot study, most participants showed improvement in overall photodamage, crow’s feet, elasticity,wrinkles, brightness, and hyperpigmentation at 60 to 80 days. Improvements at 60 to 80 days were greater than at 30 to 46 days. In the low-concentration study with 0.5% retinol, improvements were modest, most likely due to the lower retinol concentration. Burning, pruritus, dryness, and erythema were minimal with the 0.5% retinol concentration.
CONCLUSIONS: The topical formulation of 1% retinol improves photodamaged skin for at least 8 to 12 weeks. Although improvements with the 0.5% retinol were more modest, side effects such as burning, dryness, pruritus, and erythema during the 8-week study period were minimal. These encouraging results justify a longer-term study to determine whether topically applied 0.5% retinol can provide benefits comparable with those seen with topically applied 1% retinol.

J Drugs Dermatol. 2013;12(5):533-541.

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The Clinical Effects of Zinc as a Topical or Oral Agent on the Clinical Response and Pathophysiologic Mechanisms of Acne: A Systematic Review of the Literature

Staci Brandt PA-C MSMR MBA
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This article reviews the published literature about the efficacy of oral and topical zinc as treatments for acne vulgaris. The medical literature was systematically reviewed to identify relevant articles. Each published study was assessed for pathophysiologic results and the quality of the clinical evidence the study provided based on Strength of Recommendation Taxonomy (SORT) criteria. Finally, the body of evidence for using oral or topical zinc in the treatment of acne was assessed, again using SORT criteria. A SORT strength of recommendation of B (inconsistent or limited-quality patient-oriented evidence) appears to be appropriate for both oral and topical zinc. The preponderance of evidence suggests zinc has antibacterial and anti-inflammatory effects and that it may decrease sebum production.

J Drugs Dermatol. 2013;12(5):542-545.

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Combination Therapy for Psoriasis in the United States

Scott A. Davis MA^a and Steven R. Feldman MD PhD^a-c
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BACKGROUND: Psoriasis is treated with several classes of treatments that may be used in combination, but the ways combination therapies are used are not well characterized.
PURPOSE: To determine the frequency of prescribing calcipotriene and other psoriasis drugs in combination.
METHODS: Visits with a sole diagnosis of psoriasis were selected from 1990-2010 data from the National Ambulatory Medical Care Survey. The number of combination therapies used, the leading therapies in each class of medications, and the leading types used in combination were analyzed.
RESULTS: About 10.2 million of 20.3 million psoriasis visits used multiple treatments. The mean number of prescribed medications increased over time (P=.0003). The top 10 treatments included 6 topical steroids, calcipotriene, 2 other topicals, and methotrexate. The most common combinations were topical steroid plus other topical (15.0%), multiple topical steroids (11.5%), topical steroid plus vitamin D analogue (9.7%), and topical steroid plus systemic treatment (6.9%). Vitamin D analogues and systemic treatments were prescribed with increasing frequency over time, while fewer topical steroids were used, and use of other topicals did not change significantly.
LIMITATIONS: Visits with multiple diagnoses had to be excluded to ensure that the medications listed were for psoriasis.
CONCLUSIONS: Combination therapy is the most common way to treat psoriasis in the United States. The wide range of combination therapies prescribed may reflect increased attention to individualization of treatment to match patients’ diverse preferences.

J Drugs Dermatol. 2013;12(5):546-550.

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Inflammatory Mediators are Inhibited by a Taurine Metabolite in CpG Oligodeoxynucleotide and IFN-r Activated Macrophage Cell Line

Bo Sook Kim DVM PhD,^a Daryl S. Spinner PhD,^b Richard J. Kascsak PhD,^b Seung Yong Park DVM PhD,^c In Soo Cho DVM PhD,^d Georgia Schuller-Levis PhD,^e and Eunkyue Park PhD^e
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Taurine plays an important role in brain and retinal development, and has an antiinflammatory and antioxidant function. Taurine chloramine (Tau-Cl) is produced in polymorphonuclear leukocytes via the myeloperoxidase/halide system. We previously demonstrated that Tau-Cl inhibits the production of nitric oxide (NO) and TNF-α in human and murine macrophages activated with IFN-γ in combination with individual Toll-like receptor (TLR) ligands including those for TLR2 and/or TLR4. In the current study, we further explored the effects of Tau-Cl in RAW 264.7 cells stimulated with the TLR9 ligand CpG oligodeoxynucleotide (ODN). Specifically, we examined the effect of CpG ODN plus IFN-γ on the production of NO and TNF-α, and the effect of Tau-Cl on this process. Our findings show that CpG ODN plus IFN-γ-activated RAW 264.7 cells secrete high levels of NO and TNF-α, and that Tau-Cl (0.8 mM) inhibits this effect in a dose-dependent manner, more potently inhibiting the production of NO (99% inhibition) than that of TNF-α (48% inhibition). Nitric oxide synthase (iNOS) protein was also induced by CpG ODN plus IFN-γ, and was also inhibited by Tau-Cl. Furthermore, while CpG ODN plus IFN-γ induced TNF-α and iNOS mRNAs, Tau-Cl transiently suppressed this effect. Taurine itself had no effects on any of these processes. Our findings in a macrophage cell line demonstrate that Tau-Cl inhibits proinflammatory mediators resulting from TLR9 activation, and have implications for the utility of Tau-Cl in scenarios where such activation is deleterious such as in autoimmune conditions or infections in which overwhelming inflammation may occur. CpG ODNs and Tau-Cl both have potential for topical treatment of autoimmune conditions, including psoriasis, vitiligo, and alopecia areata. As CpG ODNs may, under some conditions, up-regulate Tregs, addition of Tau-Cl to CpG ODN topical formulations has potential for improving cancer immunotherapy.

J Drugs Dermatol. 2013;12(5):551-557.

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Allogeneic Growth Arrested Keratinocytes and Fibroblasts Delivered in a Fibrin Spray Accelerate Healing in Mohs Micrographic Surgery Wounds

Leon Kircik MD,^a-c Jaime E. Dickerson Jr PhD,^d,e Christina Kitten,^f
Kathy A. Weedon BS,^d and Herbert B. Slade MD^d,g
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OBJECTIVES: To determine the effectiveness of HP802-247 compared with bacitracin ointment in healing wounds resulting from Mohs micrographic surgery.
METHODS: Open-label, randomized pilot study conducted at a single center. Subjects were randomized to either HP802-247 (5M cells/mL) applied weekly or bacitracin ointment applied daily. Treatment continued for up to 12 weeks or complete wound closure. Primary efficacy was effectiveness as measured by the Investigator’s Global Assessment of Healing (IGAH) scale. Secondary outcomes included median time to healing, investigator- and subject-scored signs and symptoms, and an assessment of scar by the investigator at 16 weeks postsurgery.
RESULTS: All subjects achieved favorable outcomes within the study period; however, these were reached more quickly for the HP802-247 group than for bacitracin. At 3 weeks postsurgery, healing was assessed as very effective for 75% of subjects in the HP802-247 group compared with 50% for bacitracin. Median time to closure was 24.5 days for HP802-247 and 29 days for bacitracin. Scores for signs and symptoms and scar were similar for both groups but, in general, were numerically better for HP802-247.
CONCLUSION: In this small pilot study, HP802-247 was found to provide a modest, incremental benefit in the healing of Mohs micrographic surgery wounds, suggesting that the healing of uncomplicated acute wounds may be slightly accelerated without enhancement of scarring.

J Drugs Dermatol. 2013;12(5):558-561.

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Treating Hyperpigmentation in Darker-Skinned Patients

Nazanin Saedi MD^a and Anand K. Ganesan MD^b
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BACKGROUND: The treatment of hyperpigmentation in darker-skinned patients (Fitzpatrick skin phototypes III-VI) has remained challenging for dermatologists. No studies have been conducted on hyperpigmentation under the eyes, axilla, and neck in darker-skinned patients. This survey was designed to assess current treatments of hyperpigmentation in these areas.
MATERIALS/METHODS: With approval from the institutional review board at the University of California, Irvine, an electronic survey was sent to practicing dermatologists that contained 18 questions regarding the approach to evaluating and treating hyperpigmentation under the eyes, in the axilla, and along the neck.
RESULTS: Fifty dermatologists completed the survey, and 46 (92%) reported treating patients with darker skin. The ethnic groups treated were Latino (97.8%), African American (97.8%), Middle Eastern (77.6%), and Asian (88.9%). Thirty-six reported treating patients with hyperpigmentation under the eyes, and 22 (61.1%) thought the hyperpigmentation was a result of idiopathic increase in melanin deposition. Forty-two responded to treating hyperpigmentation in the axilla, most of whom thought it was related to acanthosis nigricans (69.0%) or contact dermatitis (59.5%). Forty responded to treating hyperpigmentation on the neck, most of whom treated the condition with hydroquinone (66%). Treatments for these 3 areas were not found to be effective.
CONCLUSIONS: Hyperpigmentation under the eyes, under the arms, or on the neck is a significant problem in darker-skinned patients that is refractory to currently available treatments, highlighting the necessity of developing treatment approaches directed toward this population. Two cases of hyperpigmentation on the neck are presented, describing a new entity that primarily affects dark-skinned individuals.

J Drugs Dermatol. 2013;12(5):563-567.

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Nonmelanoma Skin Cancer in Young Women

Timothy P. Wu BA and Jennifer A. Stein MD PhD
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The increasing incidence of nonmelanoma skin cancer in young women is a growing public health concern. Varying environmental and lifestyle exposures in this specific population highlight the need for a broad understanding of the potential risk factors that may contribute to the early development of these tumors. Reducing the morbidity and mortality in this high-risk population is contingent on developing better strategies for prevention, education, and treatment.

J Drugs Dermatol. 2013;12(5):568-572.

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Melanocytes Transplantation in Patients With Vitiligo Using Needling Micrografting Technique

Khalifa E. Sharquie MD PhD,^a Adil A. Noaimi MD DDV FICMS,^b and Hana A. Al-Mudaris MD^c
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BACKGROUND: Some cases of vitiligo require melanocyte transplantation, but these surgical techniques have varying degrees of success.
OBJECTIVES: To perform melanocytes transplantion in patients with vitiligo using a new needling micrografting technique.
PATIENTS and METHODS: This interventional case study took place at the Department of Dermatology and Venereology at Baghdad Teaching Hospital from December 2010 to September 2011. Twelve patients with vitiligo were included. A split-thickness skin graft was taken from the normal area and cut into micropieces ranging from 0.1 mm to 0.3 mm in diameter. The recipient area was anesthetized, and the micrografts were then implanted into the dermis using the needling technique. The number of implanted micrografts depended on the size of the recipient area. Follow-up was conducted every 2 weeks for the first month and then every 4 weeks for a further 16 weeks.
RESULTS: The intake rate of grafting at week 2 ranged from 90% to 100%. The micrografts started producing noticeable pigmentation at week 2, and pigmentation was obvious at week 4. At week 8, the rate of pigmentation ranged from 10% to 90% (25.24%), and at week 16 it ranged from 10% to 100% (61.36%).
CONCLUSION: This new approach to the treatment of vitiligo delivers rapid and satisfactory pigmentation.

J Drugs Dermatol. 2013;12(5):e74-e78.

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Sign and Pseudo-Sign of Leser-Trélat: Case Reports and a Review of the Literature

Zain Husain MD,^a Joyce K. Ho,^b and Basil M. Hantash MD PhD ^c
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BACKGROUND: Leser-Trélat is distinguished by a rare paraneoplastic sign that is characterized by the sudden eruption of multiple seborrheic keratoses (SKs), associated with underlying internal malignancies. Similar non-malignancy–associated SK eruptions are referred to as the “pseudo-sign of Leser-Trélat” (PLT).
OBJECTIVE: Two cases of rapid SK eruptions, one the sign of Leser-Trélat (SLT) and one PLT, are presented, and the literature on SLT and PLT is reviewed.
METHODS: A literature review of SLT/PLT was performed by searching the PubMed database for all related English published cases.
RESULTS: We identified 109 cases of SLT and 12 cases of PLT, with a mean patient age of 61.8 years. SK eruptions were observed before (68.3%), after (22.1%), and at the time of (9.6%) malignancy diagnosis. The malignancy most frequently associated with SLT was gastric adenocarcinoma. The most common anatomical location of SK eruptions was the trunk (18.9%). Frequently reported associated signs and symptoms included pruritus (52%) and acanthosis nigricans (38.7%). The most common treatment included surgery (35.8%), chemotherapy (26.9%), and radiation therapy (26.9%). Treatment resulted in clinical improvement (45%), no change (30%), exacerbation (15%), or initial improvement followed by exacerbation of SKs. Patient outcomes included disease stability/ improvement (48.4%), recurrence (9.7%), exacerbation/metastasis/new malignancy (4.8%), and death (37.1%).
LIMITATIONS: This was a retrospective study and excluded non-English published cases.
CONCLUSION: This review updates the existing SLT literature and emphasizes the presence of PLT. Clinicians should be aware that SK eruptions may be early manifestations of an internal malignancy or other pathology. To our knowledge, this is the first review examining both SLT and PLT.

J Drugs Dermatol. 2013;12(5):e79-e87.

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The Emervel French Survey: A Prospective Real-Practice Descriptive Study of 1,822 Patients Treated for Facial Rejuvenation With a New Hyaluronic Acid Filler

David Farhi MD,^a,b Patrick Trevidic MD,^c Philippe Kestemont MD,^d Dominique Boineau MD,^e
Hugues Cartier MD,^f Isaac Bodokh MD,^g Patrick Brun MD,^g Benjamin Ascher MD,^h
and Jacques Savary MD,^b,i for the Emervel French Survey Group
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BACKGROUND: Emervel consists of a range of 5 hyaluronic acid (HA) fillers (Touch, Classic, Lips, Deep, and Volume), with a fixed HA concentration (20 mg/mL), and various degrees of cross-linking and calibration.
OBJECTIVES: To describe the current use of Emervel fillers in France.
METHODS: Prospective multicenter, cross-sectional, real-practice, descriptive survey, including 1,822 patients injected with Emervel fillers for face rejuvenation by 58 French physicians between September 2010 and July 2011. The injection modalities were left to the respective physician’s discretion.
RESULTS: The physicians were dermatologists (52.3%), surgeons (43.8%), or general practitioners (14.1%). Nasolabial folds (NLF) with a mean severity 2.4 were mainly injected with Emervel Deep (51.0%) and Emervel Classic (36.0%) (mean volume: 1.0 mL), and primarily with the linear retrograde (LR) technique (89.3%). Marionette lines (ML), with a mean severity 2.6 were mainly injected with Emervel Deep (52.5%) and Emervel Classic (34.6%) (mean volume: 0.8 mL), and mainly with the LR technique (79.5%). More than 90% of patients had scores of 0 or 1 for erythema, bruising, edema, and pain. No serious adverse events were reported up to 15 months after the injection.
CONCLUSION: These data could contribute to upcoming international consensus on optimal injection modalities of the Emervel range of HA fillers.

J Drugs Dermatol. 2013;12(5):e88-e93.

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Case Reports

Iododerma Following Serial Computed Tomography Scans in a Lung Cancer Patient

Lisa R. Rothman BA,^a Michelle M. Levender MD,^a Michelle Duvall Scharf MD,^a,b
Samantha P. Herman MD,^a and Ali Jabbari MD PhD^a
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Iododerma is a rare cutaneous eruption occurring after iodine administration. Nine cases of iododerma following intravenous contrast have been reported in the English-language literature, typically in patients with renal insufficiency. We report a case of iododerma in a patient with relatively unimpaired renal function who underwent serial computer tomography (CT) scans with intravenous contrast. An 81-year-old woman with stage IV lung cancer developed fever and rash following serial CT scans with iodixanol contrast media. On examination, we noted conjunctival injection, enlarged glands, oral ulcers, and erythematous papules and plaques on her forehead, arms, and legs. Random urine iodine was elevated to 106,767 μg/L (normal range, 26-705 μg/L). Skin biopsy revealed diffuse predominantly neutrophilic dermal infiltrate. The patient’s clinical presentation, laboratory findings, and biopsy results were consistent with iododerma. Iododerma can occur in patients with adequate kidney function, and its presentation can include ocular and glandular symptoms, as in this case. Withdrawal of the source of iodine typically leads to resolution of symptoms.

J Drugs Dermatol. 2013;12(5):574-576.

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Cutaneous Clues to Renal Cell Carcinoma: Hereditary Leiomyomatosis and Renal Cell Carcinoma

Melissa A. Michelon MD,^a Christle J. Layton MD,^b Chad J. Jessup MD,^b and Paul F. Lizzul MD PhD MBA MPH^b
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We present a case of a 33-year-old female who was incidentally found to have cutaneous leiomyomata during a routine skin examination. Further history revealed that she also suffered from uterine fibroids and that her mother had died at an early age from renal cell carcinoma. This case serves as a reminder of the often-subtle cutaneous clues, as well as the importance of a multidisciplinary approach, for early diagnosis of potentially fatal conditions.

J Drugs Dermatol. 2013;12(5):578-579.

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Crusted Scabies and Multiple Dosages of Ivermectin

Alex G. Ortega-Loayza MD, Calvin O. McCall MD, and Julia R. Nunley MD
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We present the case of a bone marrow transplant patient who was diagnosed with crusted scabies but did not respond to the usual approach with topical permethrin and ivermectin. The Centers for Disease Control and Prevention were contacted and suggested a 7-dose regimen of ivermectin. The patient started to improve remarkably after the third dose, and the skin eruption was resolved after 7 doses. This case supports the use of a more prolonged course of oral ivermectin for crusted scabies in those who fail the conventional approach.

J Drugs Dermatol. 2013;12(5):584-585.

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Features

Resident Rounds. Part I. Program Spotlight: Mayo Clinic, Arizona

Amanda Pickert MD
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Resident Rounds. Part II. A Quick Reference for Mouth and Tongue Troubles

Amanda Pickert MD
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Resident Rounds. Part III. A Case of Proteus Syndrome

Amanda Pickert MD^a and Harper Price MD^b
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News, Views, & Reviews

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Pipeline Previews

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Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatologic community. This department may include additional information from the manufacturers, plus reports from physicians who wish to share their clinical experience with these new products. In addition, we will inform our readers about the latest drugs receiving Food and Drug Administration (FDA) approval.

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Clinical Trial Review

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Clinical Trial Review is a JDD department designed to provide physicians with information on drugs and devices undergoing clinical testing. It is our goal to inform the reader of the status of select drug and device studies relevant to the practice of dermatology before this information is available through standard channels. To participate in or learn more about these and additional trials, visit www.clinicaltrials.gov.

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Current Issue May 2013 | Volume 12 | Issue 5

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