Androgens in women: Androgen-mediated skin disease and patient evaluation.

Androgens are produced throughout the body in steroid-producing organs, such as the adrenal glands and ovaries, and in other tissues, like the skin. Several androgens are found normally in women, including dehydroepiandrosterone, dehydroepiandrosterone-sulfate, testosterone, dihydrotestosterone, and androstenedione. These androgens are essential in the development of several common cutaneous conditions in women, including acne, hirsutism, and female pattern hair loss (FPHL)-androgen-mediated cutaneous disorders (AMCDs). However, the role of androgens in the pathophysiology of these diseases is complicated and incompletely understood. In the first article in this Continuing Medical Education series, we discuss the role of the skin in androgen production and the impact of androgens on the skin in women. Specifically, we review the necessary but insufficient role that androgens play in the development of acne, hirsutism, and FPHL in women. Dermatologists face the challenge of differentiating physiologic from pathologic presentations of AMCDs in women. There are currently no dermatology guidelines outlining the indications for endocrinologic evaluation in women presenting with acne, hirsutism, or FPHL. We review the available evidence regarding when to consider an endocrinologic workup in women presenting with AMCDs, including the appropriate type and timing of testing.

Androgens in women: Hormone-modulating therapies for skin disease.

Androgen-mediated cutaneous disorders (AMCDs) in women, including acne, hirsutism, and female pattern hair loss, can be treated with hormone-modulating therapies. In the second article in this Continuing Medical Education series, we discuss the hormone-modulating therapies available to dermatologists for the treatment of AMCDs, including combined oral contraceptives, spironolactone, finasteride, dutasteride, and flutamide. Available hormone-modulating treatments used for each AMCDs are reviewed, along with mechanisms of androgen modulation, safety profile, contraindications, monitoring parameters, and evidence of efficacy. Medications discussed include those that are approved by the US Food and Drug Administration for certain AMCDs and some that are used off-label. Despite the ubiquity of hormone-modulating therapies used for AMCDs, this review highlights the need for more rigorous studies to evaluate these therapies for acne, hirsutism, and female pattern hair loss.

The Use of Hormonal Antiandrogen Therapy in Female Patients with Acne: A 10-Year Retrospective Study.

BACKGROUND: Little is known about how dermatologists prescribe hormonal antiandrogen acne treatment (HAAT). OBJECTIVE: The aim of this study was to investigate dermatologists' HAAT-prescribing habits and HAAT's impact on systemic antibiotic use in women with acne. METHODS: We performed a retrospective study at an academic medical center of female patients receiving HAAT (combined oral contraceptive [COC], spironolactone) for acne from January 2005 to October 2015. Data from a control group of female acne patients who never received HAAT were also collected. RESULTS: A total of 672 female patients received HAAT. Out of all systemic medications for acne, antibiotics were used as first-line treatment in 39% of patients, COCs in 12%, and spironolactone in 21%. Mean antibiotic durations in patients who initiated HAAT for the first time at the study site (250.4 days) were significantly longer than in patients who received HAAT prior to presentation and continued HAAT at the study site (192.0 days) (p = 0.021). A statistically significant inverse association was found between HAAT use and mean antibiotic duration (p = 0.016). CONCLUSIONS: HAAT is not typically used as a first-line systemic therapy in women with acne. HAAT usage is associated with shorter cumulative antibiotic durations and early HAAT initiation can decrease systemic antibiotic use in acne treatment.

Oral Antibacterial Therapy for Acne Vulgaris: An Evidence-Based Review.

BACKGROUND: To some degree, acne vulgaris affects nearly every individual worldwide. Oral antibiotic therapy is routinely prescribed for the treatment of moderate to severe inflammatory acne; however, long-term use of oral antibiotics for acne may have unintended consequences. OBJECTIVE: The aim of this study was to provide a systematic evaluation of the scientific evidence on the efficacy and appropriate use of oral antibiotics in the treatment of acne. METHODS: A systematic search of MEDLINE was conducted to identify randomized controlled clinical trials, systematic reviews, and meta-analyses evaluating the efficacy of oral antibiotics for acne. Overall, 41 articles that examined oral antibiotics compared with placebo, another oral therapy, topical therapy, alternate dose, or duration were included in this study. RESULTS: Tetracyclines, macrolides, and trimethoprim/sulfamethoxazole are effective and safe in the treatment of moderate to severe inflammatory acne. Superior efficacy of one type or class of antibiotic could not be determined, therefore the choice of antibiotic is generally based on the side-effect profile. Although different dosing regimens have been studied, there is a lack of standardized comparator trials to determine optimal dosing and duration of each oral antibiotic used in acne. The combination of oral antibiotics with a topical therapy is superior to oral antibiotics alone. CONCLUSION: This article provides a systematic evaluation of the scientific evidence of the efficacy of oral antibiotics for acne. Due to heterogeneity in the design of the trials, there is insufficient evidence to support one type, dose, or duration of oral antibiotic over another in terms of efficacy; however, due to increasing resistance to antibiotics, dermatologists should heed consensus guidelines for their appropriate use.

Defining Field Cancerization of the Skin Using Noninvasive Optical Coherence Tomography Imaging to Detect and Monitor Actinic Keratosis in Ingenol Mebutate 0.015%- Treated Patients.

OBJECTIVE: The objective of this study was to assess the ability of optical coherence tomography to detect clinical and subclinical actinic keratoses confirmed by histopathology. The efficacy of ingenol mebutate treatment of actinic keratosis was also evaluated using optical coherence tomography, and correlation of treatment efficacy with severity of local skin reactions was determined. DESIGN: Single-arm, open-label, split-face study. SETTING: Hospital outpatient clinic. PARTICIPANTS: Male subjects (N=30) with seven actinic keratoses. MEASUREMENTS: A suspected actinic keratosis and the normal-appearing, perilesional skin were imaged, biopsied for histopathologic analysis, and the results compared with the clinical and a blinded optical coherence tomography diagnosis. Treatment with ingenol mebutate gel 0.015% was randomly administered to three clinically suspected actinic keratoses and the perilesional skin; three additional, suspected actinic keratoses lesions and perilesional areas were left untreated. Clinical and optical coherence tomography images were obtained for all lesions. Severity of local skin reactions was recorded to evaluate the relationship between local skin reaction and treatment effect. RESULTS: Optical coherence tomography analysis had a 100-percent (28/28) correlation with the clinical diagnosis of actinic keratosis and detected 16 of 22 (73%) histopathologically confirmed subclinical lesions from perilesional skin sites. By optical coherence tomography assessment, the clearance rate for clinically observed lesions was 76 percent for ingenol mebutate-treated areas versus 11 percent for untreated areas; the clearance rate for treated subclinical lesions was 88 percent versus 43 percent for untreated areas. Clearance rates did not vary with the severity of the local response. CONCLUSION: Optical coherence tomography is effective at detecting clinical and subclinical actinic keratoses and monitoring their response to treatment.

Improved patient satisfaction using ingenol mebutate gel 0.015% for the treatment of facial actinic keratoses: a prospective pilot study.

Actinic keratoses (AKs), especially on areas of the face, have a negative impact on a patient's quality of life (QoL). These lesions manifest on sun-damaged skin and have the potential to progress to squamous cell carcinoma. Field-directed therapy alone and in combination with lesion-directed treatment is effective in clearing both visible and nonvisible AK lesions. Topical treatments of AKs thus have the potential to improve a patient's well-being. However, evidence demonstrating improvements in patient QoL is limited, and is mostly based on observational or retrospective studies. Some prospective studies have reported unchanged or even worsening QoL despite excellent treatment outcomes. Our prospective, pilot study demonstrated a significant increase in QoL in 28 subjects with AKs of the face treated with ingenol mebutate gel 0.015%. QoL was assessed at days 0 and 60 using the Skindex-16 survey. Mean overall scores improved from 24.5% at baseline to 15.5% at day 60 (P=0.031). Improvements in QoL were consistent with an 80% reduction in AK lesion number at day 60. These improved QoL findings are in line with those from a recent retrospective study using ingenol mebutate 0.015% gel. This study therefore further demonstrates the potential for field therapy to improve both treatment outcomes and patient satisfaction.

Differentiation of Basal Cell Carcinoma Subtypes in Multi-Beam Swept Source Optical Coherence Tomography (MSS-OCT).

BACKGROUND: Optical coherence tomography (OCT) is a technique that enables real-time in-vivo examination of tissue. This technology provides the clinician with the potential to use a non-invasive tool in the identification and diagnosis of many skin lesions. However, the diagnostic features of basal cell carcinoma have not yet been described with comparison to their histopathology.
OBJECTIVES: To identify and describe key features of basal cell carcinoma (BCC) and its subtypes as they present in multi-beam Swept Source - OCT (MSS-OCT), and to correlate those against conventional histopathology.
METHODS: A total of 40 lesions were assessed by MSS-OCT prior to biopsy. 60-slice OCT images of the lesions were obtained and correlated with histology sections taken in the same plane. OCT scans were assessed retrospectively by a panel to determine the OCT criteria for BCC and its subtypes.
RESULTS: The following diagnostic criteria were identified: hyporeflective ovoid structures (40/40), dark halo boundaries (38/40), epidermal thinning (28/40), and collagen compression (14/40). Lesional tissue also showed a destruction of layers when compared to the surrounding normal tissue. In addition to the shared criteria, other subtypes showed distinct diagnostic criteria.
CONCLUSION: With its higher sensitivity, using MSS-OCT allowed for non-invasive, accurate identification of the key diagnostic features of BCC and its subtypes with high correlation to the histopathologic features found with biopsy.

J Drugs Dermatol. 2016;15(5):545-550.

Evaluation of Optical Coherence Tomography as a Means of Identifying Earlier Stage Basal Cell Carcinomas while Reducing the Use of Diagnostic Biopsy.

OBJECTIVE: To determine the diagnostic accuracy of optical coherence tomography for basal cell carcinoma and the proportion of biopsies that could be avoided if optical coherence tomography is used to rule-in surgery. DESIGN: Multicenter, prospective, observational study. SETTING: Dermatology clinics. PARTICIPANTS: Consecutive patients with clinically challenging pink lesions suspicious for basal cell carcinoma. MEASUREMENTS: Clinical, dermoscopic, and optical coherence tomography images were obtained for all subjects. At each stage, the clinician made a diagnosis (pathology + subtype if applicable), and assessed his/her own confidence in the diagnosis. RESULTS: Optical coherence tomography significantly (p<0.01) improved sensitivity and specificity over clinical or dermoscopic evaluation. The percentage of correct diagnoses was 57.4 percent (clinical), 69.6 percent (dermoscopy), and 87.8 percent (optical coherence tomography). Optical coherence tomography significantly increased the certainty of diagnosis; clinicians indicated they were certain (>95% confident) in 17 percent of lesions examined clinically, in 38.6 percent examined with dermoscopy, and in 70 percent examined with optical coherence tomography. With the use of optical coherence tomography in the diagnosis of basal cell carcinoma, more than 1 in 3 patients could avoid a diagnostic biopsy. CONCLUSION: In a population of clinically challenging lesions, optical coherence tomography improved diagnostic certainty by a factor of four over clinical examination alone and improved diagnostic accuracy by 50 percent (57-88%). The addition of optical coherence tomography to other standard assessments can improve the false-positive rate and give a high degree of certainty for ruling in a positive diagnosis for basal cell carcinoma. A reduction of 36 percent in overall biopsies could be achieved by sending high certainty basal cell carcinoma positive optical coherence tomography diagnoses straight to surgery.