Photodynamic Therapy with 5-aminolevulinic Acid 10% Gel and Red Light for the Treatment of Actinic Keratosis, Nonmelanoma Skin Cancers, and Acne: Current Evidence and Best Practices.

Photodynamic therapy (PDT) can be an effective treatment for actinic keratosis (AK) as well as selected non-melanoma skin cancers (NMSCs), such as Bowen's disease and superficial basal cell carcinoma. PDT has also demonstrated effectiveness in the management of acne vulgaris. Results from controlled clinical trials have shown the safety and efficacy of PDT for these conditions with the use of different photosensitizers and a wide range of light sources. PDT has been employed effectively as monotherapy and in combination with other topicals and alternate light or laser energy therapies. This article provides expert practical guidance for the use of the newest 5-aminolevulinic acid (ALA) product (ALA 10% gel) plus red light as monotherapy for AKs, NMSC, and acne. Here, information from clinical guidelines and a summary of supporting evidence is provided for each cutaneous condition. The authors also provide detailed guidance for employing ALA 10% gel, a photosensitizer precursor, for each of these applications.

Treatment of Actinic Purpura.

Mature skin is prone to bruising, resulting in a condition known as actinic purpura, characterized by unsightly ecchymosis and purple patches. Similar to other skin conditions, the incidence of actinic purpura increases with advancing age and occurs with equal frequency among men and women. The unsightly appearance of actinic purpura may be a source of emotional distress among the elderly. A new product has been formulated specifically for the treatment of actinic purpura. This product contains retinol, α-hydroxy acids, arnica oil, ceramides, niacinamide, and phytonadione, which effectively treat actinic purpura by improving local circulation, thickening the skin, and repairing the skin barrier. The objective of this paper is to review the beneficial properties of these ingredients and their respective roles in the treatment of actinic purpura.

Understanding the Role of Photolyases: Photoprotection and Beyond.

The limitations of photoprotection modalities have been the inability to arrest the progression of photodamage. Chemoprevention strategies involving a sunscreen has been incomplete because of the need to induce sustained repair of mutations and slow carcinogenesis. Photolyases, or photoreactivation enzymes, serve the role of repairing mutations and damage to DNA induced by ultraviolet (UV) radiation and therefore influence the initiation phases of carcinogenesis. As these enzymes are absent in humans, exogenous forms have been manufactured and are now utilized in topical agents to supplement and augment the innate repair mechanisms that are mostly inefficient. J Drugs Dermatol. 2017;16(5 Suppl):61-66.

Expert Consensus on Cosmetic Outcomes After Treatment of Actinic Keratosis.

Dermatologists treat actinic keratosis (AK) primarily because these lesions have the potential to progress to invasive squamous cell carcinoma. Patients, on the other hand, generally seek treatment to remove the lesions and achieve an improved appearance of their skin following treatment. In selecting a treatment option for AK, dermatologists should consider post-treatment cosmesis, because cosmetic outcomes differ across AK treatments. To obtain expert opinion on the cosmetic sequelae related to chronically photodamaged skin and the treatment of AK, an expert panel meeting among dermatologists was conducted in February 2016. These experts reviewed current treatment options for photodamage, including AK, and discussed the relative merits of the various cosmetic assessments commonly used by investigators and patients in both clinical trial and dermatology practice settings. A main goal of the expert panel meeting was to propose assessment tools that could be specifically designed to characterize cosmesis results after treatment of AK. The panel agreed that existing tools for measurement of cosmetic outcomes following treatment of photodamage could also be used to evaluate cosmesis after treatment of AK. Digital photography is probably the best method used for this, with validation by other technologies. Better measurement tools specifically for assessing cosmesis after AK treatment are needed. Once they are developed and validated, regulatory agencies should be educated about the importance of including cosmetic outcomes as a component of product labeling.

J Drugs Dermatol. 2017;16(3):260-265.

Staged Excision for Lentigo Maligna and Lentigo Maligna Melanoma: Analysis of Surgical Margins and Long-term Recurrence in 68 Cases from a Single Practice.

INTRODUCTION: Lentigo maligna is a form of in situ melanoma that occurs commonly on sun-exposed skin of middle-aged to elderly adults. Margin-control surgery offers the highest cure rate for lentigo maligna/lentigo maligna melanoma. MATERIALS AND METHODS: Charts from the authors' private office from the 20-year period from January 1986 to December 2005 were reviewed to identify patients with histologically confirmed lentigo maligna or lentigo maligna melanoma treated by staged excision. RESULTS: Sixty-eight patients (39 men, 29 women; mean age at diagnosis 67.4±10.2 years, range 48-87 years) with 68 tumors were treated in the authors' office for lentigo maligna (58) or lentigo maligna melanoma (10) between January 1986 and December 2005. After excision, patients were followed clinically for a minimum of three years. The mean follow-up duration was 138 months (median 139 months; range 37-330 months). The overall margin for tumor clearance was 7.0±0.55mm with a recurrence rate of 5.9 percent. LIMITATIONS: The limitations of this study include the retrospective nature of the authors' review, and data collected from a single, private practice setting. CONCLUSION: The authors' findings support staged excision as an effective method of treating lentigo maligna and lentigo maligna melanoma, offering a high cure rate while maximally preserving normal tissue.

High-dose Rate Electronic Brachytherapy: A Nonsurgical Treatment Alternative for Nonmelanoma Skin Cancer.

The authors summarized data from a group of physicians with experience using high-dose rate electronic brachytherapy for the treatment of nonmelanoma skin cancer. The data have been published or presented in abstract format at national dermatology and radiation oncology meetings. The data included 1,822 treated lesions from 2009 to 2014 in patients ranging in age from 52 to 104 years. Most lesions were basal cell carcinoma (57%) or squamous cell carcinoma (38%) less than 2cm in size (97%). Median follow-up at the various centers ranged from 4 to 16 months, and results yielded an extremely low recurrence rate of less than one percent. Results show that within the confines of this follow up period, electronic brachytherapy is an effective, convenient, nonsurgical treatment option for patients with nonmelanoma skin cancer with few recurrences and excellent cosmetic results.

Current issues in the management of actinic keratosis.

Actinic keratoses are common sun-induced skin lesions that should be treated to prevent the development of nonmelanoma skin cancer. Although cryotherapy is commonly used to treat individual lesions, it fails to address the actinically damaged field of neighboring sun-damaged skin, which is more effectively treated by field therapies to clear both visible and subclinical lesions. Most topical treatments require prolonged use and cause an inflammatory response that limits tolerability and adherence. Education is essential to teach patients about the chronic nature of actinic keratosis, the risk of nonmelanoma skin cancer, and the importance of correct use of topical medications. The addition of nonphysician clinicians to dermatologic practices provides a valuable source of education, treatment, and follow-up care to the management of actinic keratosis.

Mechanisms of action of topical 5-fluorouracil: review and implications for the treatment of dermatological disorders.

Topical 5-fluorouracil has proved to be a useful therapy since its discovery nearly 50 years ago for the treatment of a range of cancers (e.g. skin, colorectal, breast) and dermatological conditions (e.g. cancerous and precancerous conditions such as actinic keratosis, benign tumors, nail psoriasis, mycosis fungoides, and porokeratoses). As a result of the enduring utility in these conditions, the mechanism of action of 5-fluorouracil has been studied extensively in vivo and in vitro. This review provides an overview of the history and general mechanism of action of 5-fluorouracil and discusses the dermatological implications of the drug, including systemic absorption, selectivity for abnormal skin, targeted delivery, and skin-specific molecular effects. Considerations of 5-fluorouracil treatment in specific dermatological settings are also discussed, as well as recent findings of a role for 5-fluorouracil in the treatment of photoaging.

Advances in topical delivery systems in acne: new solutions to address concentration dependent irritation and dryness.

Formulation development is key to the successful treatment of acne. There has been significant progress over the past few years, but not all developments can be universally applied. An effective topical formulation must provide chemical stability and enhanced penetration of active ingredients at optimal concentrations for efficacy and safety; be cosmetically acceptable; and not add side effects of its own. Both retinoids and fixed combinations containing benzoyl peroxide are commonly used to treat acne, but both have the potential to cause troublesome dose-dependent irritation and dryness. Excipients such as surfactants and alcohol have added to the problem. Two products have recently been introduced where a combination of micronization skills and well-chosen excipients has minimized irritation and dryness without compromising efficacy. Results from two major studies are discussed in this article.

The role of immunohistochemistry in discriminating primary from secondary extramammary Paget disease.

BACKGROUND: Extramammary Paget disease (EMPD) is categorized into 2 groups: primary EMPD or EMPD secondary to underlying malignancy. Primary EMPD has a better prognosis, and the ability to distinguish between the 2 subsets has clinical relevance. Recent studies have suggested that immunostains, including cytokeratin (CK) 7, CK20, and BRST-2, distinguish between the 2 groups. We analyzed a large series of EMPD with an expanded immunohistochemical panel to assess its value in distinguishing primary from secondary disease. DESIGN: Formalin-fixed, paraffin-embedded sections of 98 EMPD specimens from 61 patients (45 primary and 16 secondary) were immunostained with CK7, CK20, HER-2/neu, BRST-2, CDX2, androgen receptor (AR), and cyclin D1. The study included 44 women and 17 men (median age: 73 years). Median follow-up time was 47 months. RESULTS: All EMPD specimens were vibrantly positive for CK7. The frequency of positivity for all EMPD samples was CK20 (28%), BRST-2 (40%), HER-2/neu (64%), CDX2 (10%), AR (16%), and cyclin D1 (76%). For primary EMPD, the frequency of positivity was CK20 (22%), BRST-2 (48%), HER-2/neu (65%), CDX2 (2%), AR (21%), and cyclin D1 (84%). For secondary EMPD, the frequency of positivity was CK20 (50%), BRST-2 (25%), HER-2/neu (60%), CDX2 (33%), AR (0%), and cyclin D1 (53%). Notably, all 6 of 7 cases of EMPD secondary to an anorectal adenocarcinoma tested were HER-2/neu negative and 5 of those 6 cases (80%) were CDX2 positive. CONCLUSIONS: The role of CK7, CK20, and BRST-2 in distinguishing primary and secondary EMPD is limited because CK20 and BRST-2 were positive in large subsets of both groups. An expanded immunohistochemical panel, including HER-2/neu and CDX2, may be useful in discriminating primary EMPD from EMPD secondary to anorectal adenocarcinoma but fails to distinguish primary EMPD from EMPD secondary to urothelial or prostatic malignancy. The consistent overexpression of HER-2/neu in primary EMPD suggests a role for trastuzumab therapy in patients with recurrent disease.

Staged excision versus Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma.

BACKGROUND: Lentigo maligna (LM) is a relatively common tumor with increasing prevalence and substantial morbidity. A variety of treatment modalities are available, though margin-control surgery offers the highest cure rate. We were interested in comparing long-term outcomes of Mohs micrographic surgery (MMS) versus staged excision with permanent sections (SE) for treating LM or LM melanoma (LMM). METHODS: Comparative study consisting of retrospective chart review from our private practice. RESULTS: Fifty-seven patients (31 male, 26 female, mean age at diagnosis 69.1 +/- 10.1 years) were treated in our office for LM (50) or LMM (9) between January 1986 and December 2001. Forty-one tumors (71%) were located on the head and neck. Fifty-three of the 59 tumors (90%) were primary, and 6/59 (10%) were recurrent at the time of initial treatment. Forty-one tumors (36 LM, 5 LMM) were treated with SE, and 18 (14 LM, 4 LMM) were treated with MMS. The mean preoperative lesion size (1.5 +/- 0.2 cm2 for SE; 1.2 +/- 0.4 cm2 for MMS), mean postoperative defect size (7.1 +/- 1 cm2 for SE; 7.1 +/- 1.4 cm2 for MMS), and the ratio of postoperative defect to preoperative lesion size (7.9-fold increase for SE, 11.2-fold increase for MMS) were similar between the cohorts. Mean number of stages for clear margins were similar, with 1.8 +/- 0.2 stages (range: 1-7) for SE and 2.0 +/- 0.2 stages (range: 1-4) for MMS; clear margins were obtained in one or two stages in 85% of cases for SE and in 67% for MMS. Three recurrences (3/41; 7.3%) occurred in the SE group while 6 recurrences (6/18; 33%) occurred in the MMS group (P < .025). The mean follow-up duration was 95 months (range: 60-240) in the SE group and 117.5 months (range: 61-157) in the MMS group. LIMITATIONS: Results are limited to a single practice site and fewer patients underwent MMS compared to SE. Patients were not randomized as cases were ascertained retrospectively. CONCLUSION: Staged excision of LM and LMM is associated with a significantly lower recurrence rate with no difference in surgical defect size compared to MMS. To our knowledge, this is the first study directly comparing these two surgical techniques for managing this form of melanoma. Our extended follow-up duration exceeds that of most previous reports.

Current modalities and new advances in the treatment of basal cell carcinoma.

Basal cell carcinoma (BCC) is one of the most common cancers. Surgical extirpation is currently the standard of care for BCC, which is associated with several advantages and disadvantages. Procedures such as surgical excision used to treat superficial BCC (sBCC) and nodular BCC (nBCC) may have high 5-year recurrence rates if tumors are not completely excised. Curettage with electrodesiccation is a common method for treating primary BCC. However, multiple cycles are recommended and the procedure can have unsatisfactory cosmetic results (e.g. scarring and hypopigmentation). Mohs micrographic surgery has a low rate of disease recurrence but is a specialized procedure usually limited to specific indications (e.g. high-risk tumors). Cryosurgery and photodynamic therapy require multiple cycles and are associated with variable cosmetic outcomes and recurrence rates. As with any procedure, potential risks and patient quality-of-life issues need to be considered. In addition, substantial patient and healthcare provider inconvenience limit the practical utility of some modalities. Pharmacologic interventions provide another treatment option as adjunctive or monotherapy. Investigations of imiquimod, a novel immune response modifier, have indicated that this topical, noninvasive agent is safe and well tolerated and may be efficacious in the treatment of BCC. This review will highlight the role of standard treatment modalities and introduce new advances in the treatment of BCC.

Anti-inflammatory efficacy of Licochalcone A: correlation of clinical potency and in vitro effects.

Licochalcone A (LicA), a major phenolic constituent of the licorice species Glycyrrhiza inflata, has recently been reported to have anti-inflammatory as well as anti-microbial effects. These anti-inflammatory properties might be exploited for topical applications of LicA. We conducted prospective randomized vehicle-controlled clinical trials to assess the anti-irritative efficacy of cosmetic formulations containing LicA in a post-shaving skin irritation model and on UV-induced erythema formation. The clinical trials were accompanied by a series of in vitro experiments to characterize anti-inflammatory properties of LicA on several dermatologically relevant cell types. Topical LicA causes a highly significant reduction in erythema relative to the vehicle control in both the shave- and UV-induced erythema tests, demonstrating the anti-irritative properties of LicA. Furthermore, LicA is a potent inhibitor of pro-inflammatory in vitro responses, including N-formyl-MET-LEU-PHE (fMLP)- or zymosan-induced oxidative burst of granulocytes, UVB-induced PGE(2) release by keratinocytes, lipopolysaccharide (LPS)-induced PGE(2) release by adult dermal fibroblasts, fMLP-induced LTB(4) release by granulocytes, and LPS-induced IL-6/TNF-alpha secretion by monocyte-derived dendritic cells. The reported data suggest therapeutic skin care benefits from LicA when applied to sensitive or irritated skin.

Merkel cell carcinoma in a patient with autoimmune hepatitis.

Merkel cell carcinoma (MCC) has been shown to have a higher incidence in many etiologically distinct immunosuppressed populations. We report a case of aggressive MCC diagnosed in a man with autoimmune hepatitis who was treated with immunosuppressive therapy for more than 30 years.

Advances in the topical treatment of acne and rosacea.

Acne and rosacea are common skin diseases which may present similarly and both involve inflammation. Both can result in significant cosmetic impairment and lead to quality of life decrements if not optimally treated. The conventional approach for both diseases involves the use of topical therapy to treat inflammatory lesions in combination, when needed, with a systemic or topical antibiotic. An important issue in the management of both diseases at present is the need to reduce antibiotic usage due to the increasing problem of bacterial resistance. One of the emerging treatment paradigms that is becoming increasingly useful as an antibiotic-sparing strategy is the use of procedural therapies in combination with medical management. Such procedural modalities include lasers, intense pulsed light (IPL), and photodynamic therapies (PDT). Topical regimens are used pre-treatment and following physical modalities for maintenance of remission.