Sex differences in initial treatment for genital extramammary Paget disease in the United States: A systematic review.

BACKGROUND: Surgery is the standard treatment for genital extramammary Paget disease (gEMPD). OBJECTIVE: To determine if gEMPD treatments and outcomes differ by sex and US region. METHODS: A systematic review was performed of all English-language studies on initial gEMPD treatment in Medline via PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. At least 2 reviewers performed title and abstract review and data extraction. Surgical categories included total skinning procedures, partial skinning procedures, Mohs micrographic surgery (MMS), or unspecified surgery. Chi-squared tests of association were used for comparisons. RESULTS: A total of 60 studies comprising 302 (79.7%) female and 77 (20.3%) male patients met criteria. Women were most often initially recommended partial skinning procedures. In all, 74 (24.5%) women and 0 men underwent a total skinning procedure. Men were more likely to be offered MMS than women (40.3% vs 1.9%, P < .0001), despite men having a significantly greater extent of disease involving the perineum and perianal skin (21.1% vs 1.7%, P < .0001). Treatment recommendations varied by US region. LIMITATIONS: Only 20 states were represented. CONCLUSION: Women are more frequently offered total skinning procedures for gEMPD while men are more frequently offered MMS. MMS offers less recurrence and morbidity than total skinning procedures and should be recommended equally to both female and male patients with gEMPD.

Comparing clinical acne vulgaris severity to adolescent and parent perceptions of acne severity and impact on quality of life.

BACKGROUND/OBJECTIVES: Little research has compared clinician acne severity assessment with either adolescent- or parent-rated scales of acne severity or impact on quality of life (QOL). We sought to assess how adolescents and their parents perceive the severity and impact of acne on the adolescent's QOL and correlate this with clinical severity. METHODS: Each adolescent and a parent completed a validated QOL survey regarding the adolescent's acne and rated the adolescent's acne severity and QOL impact using a Likert scale. Clinicians assessed the adolescent's acne using a standardized acne severity scale. Statistical analysis compared adolescent scores with respective parent scores or with clinician assessment using a paired t test or Spearman rank-order correlation test. RESULTS: The Likert impact score more accurately reflected acne impact on QOL for adolescents than for parents when considering the validated QOL survey as the gold standard (r2  = .56 vs r2  = .36). Likert scores for adolescents and parents were weakly correlated for acne severity but not for acne QOL impact (r2  = .36 vs r2  = .18). Correlations of acne severity scores between clinician and either adolescent or parent were weak. CONCLUSIONS: Parents and adolescents are in relative agreement regarding acne severity and QOL impact. However, parent and adolescent perceptions are disparate from clinician acne assessment. It is important that physicians identify and consider adolescent and parent perceptions in addition to clinical assessment to better inform the approach to acne management.

Vulvar diseases: Conditions in adults and children.

The most problematic vulvovaginal conditions are familiar to dermatologists but may exhibit distinct clinical features or medication management because of the anatomic location. The second article in this continuing medical education series focuses on management pearls for treating vulvar diseases. We highlight key conditions, such as lichen sclerosus, erosive lichen planus, and vulvodynia. In addition, we review conditions that dermatologists may be less familiar with, such as plasma cell vulvitis, desquamative inflammatory vaginitis, vulvar aphthae, and low estrogen states. Nearly 1 in 6 women experience undiagnosed and untreated vulvovaginal discomfort at some point in their lives. Physicians who treat vulvar disorders will improve the quality of life of countless women.

Vulvar diseases: Approach to the patient.

Patients with vulvar dermatoses often delay seeking medical treatment because of anxiety and embarrassment. Moreover, women frequently self-treat with various home remedies and see multiple clinicians before presenting to a dermatologist. Despite serving as the primary providers for patients with vulvovaginal symptoms, gynecologists typically receive limited training in the causes and management of these conditions. Dermatologists are experts in the evaluation and management of cutaneous disease and should be the caretakers of all skin, including the genitalia. Vulvar disorders are underrecognized by dermatologists for numerous reasons: inadequate training, lack of comfort with both interview and examination techniques, and unfamiliarity with normal anatomic variations. The first article in this continuing medical education series on vulvar dermatoses reviews the fundamentals, approach, and techniques that can be used to ensure a successful visit for both patient and provider.

Hyperkalemia in women with acne exposed to oral spironolactone: A retrospective study from the RADAR (Research on Adverse Drug Events and Reports) program.

PURPOSE: The necessity of serum potassium monitoring for healthy women who are prescribed spironolactone for acne has been debated. The aim of this study was to compare the incidence of hyperkalemia in women 18 to 45 years of age to that in women 46 to 65 years of age, when treated with oral spironolactone for acne. METHODS AND MATERIALS: Data for all women 18 to 65 years of age who were prescribed oral spironolactone by a dermatologist for acne between January 2006 and October 2016 were extracted for analysis. Retrospective data were included for women who exhibited baseline serum potassium within the normal limits and who had repeat serum potassium monitoring within 12 months after initiation of spironolactone. The rate of incident hyperkalemia was determined. RESULTS: Of 618 women who received spironolactone for acne, 133 had serum potassium monitoring both before and after spironolactone initiation. Nine were excluded due to confounding comorbidities. Of the remaining 124 women, the mean age at initiation of spironolactone was 32 years (range, 18-57 years); 112 women were in the 18 to 45 years age group, and 12 were in the 46 to 65 years age group. All women had serum potassium within normal limits at baseline. Women in the 46 to 65 years age group had a significantly higher rate of incident hyperkalemia after spironolactone initiation compared with women 18 to 45 years of age (2 of 12 women [16.7%] vs. 1 of 112 women [< 1%]; p = .0245). CONCLUSIONS: Although controversy surrounds the clinical utility of serum potassium monitoring in healthy women exposed to spironolactone for acne, based on the findings from this large patient population, monitoring of serum potassium is warranted for women over 45 years of age given an age-related greater risk of hyperkalemia.

ASDS Guidelines Task Force: Consensus Recommendations Regarding the Safety of Lasers, Dermabrasion, Chemical Peels, Energy Devices, and Skin Surgery During and After Isotretinoin Use.

BACKGROUND: Currently, the isotretinoin (13-cis-retinoic acid) package insert contains language advising the discontinuation of isotretinoin for 6 months before performing cosmetic procedures, including waxing, dermabrasion, chemical peels, laser procedures, or incisional and excisional cold-steel surgery. It is common practice to follow this standard because of concerns regarding reports of sporadic adverse events and increased risk of scarring. OBJECTIVE: To develop expert consensus regarding the safety of skin procedures, including resurfacing, energy device treatments, and incisional and excisional procedures, in the setting of concurrent or recent isotretinoin use. MATERIALS AND METHODS: The American Society for Dermatologic Surgery authorized a task force of content experts to review the evidence and provide guidance. First, data were extracted from the literature. This was followed by a clinical question review, a consensus Delphi process, and validation of the results by peer review. RESULTS: The task force concluded that there is insufficient evidence to justify delaying treatment with superficial chemical peels and nonablative lasers, including hair removal lasers and lights, vascular lasers, and nonablative fractional devices for patients currently or recently exposed to isotretinoin. Superficial and focal dermabrasion may also be safe when performed by a well-trained clinician.

Assessment of vulvar discomfort with sexual activity among women in the United States.

BACKGROUND: Multidimensional self-report measures of sexual function for women do not include the assessment of vulvar discomfort, limiting our understanding of its prevalence. In an effort to improve the measurement of patient-reported health, the National Institutes of Health funded the creation of the Patient Reported Outcomes Measurement Information System (PROMIS). This included the development of the PROMIS Sexual Function and Satisfaction measure, and version 2.0 of the Sexual Function and Satisfaction measure included 2 scales to measure vulvar discomfort with sexual activity. OBJECTIVES: The objectives of the study were to describe the development of 2 self-reported measures of vulvar discomfort with sexual activity, describe the relationships between these scales and scales for lubrication and vaginal discomfort, and report the prevalence of vulvar discomfort with sexual activity in a large, nationally representative sample of US women. STUDY DESIGN: We followed PROMIS measure development standards, including qualitative development work with patients and clinicians and psychometric evaluation of candidate items based on item response theory, in a probability sample of 1686 English-speaking US adult women. We tested 16 candidate items on vulvar discomfort. We present descriptive statistics for these items, correlation coefficients among the vulvar and vaginal scales, and mean PROMIS scores with 95% confidence intervals separately by menopausal status for the 1046 women who reported sexual activity in the past 30 days. RESULTS: Based on the psychometric evaluation of the candidate items, we created 2 separate 4 item scales, one to measure labial discomfort and pain and one to measure clitoral discomfort and pain. Additional items not included in the scales assess pain quality, numbness, and bleeding. The correlations between the lubrication, vaginal discomfort, and the 2 vulvar discomfort measures ranged from 0.46 to 0.77, suggesting that these measures represent related yet distinct concepts. In our nationally representative sample, 1 in 5 US women endorsed some degree of vulvar discomfort with sexual activity in the past 30 days. Menopausal status was associated with lower lubrication and higher vaginal discomfort but not with vulvar discomfort. CONCLUSION: The PROMIS Vulvar Discomfort with Sexual Activity-Labial and Vulvar Discomfort with Sexual Activity-Clitoral scales are publicly available for use in research and clinical settings. There is limited overlap between vulvar discomfort and lubrication or vaginal discomfort. The importance of measuring vulvar discomfort as part of a comprehensive assessment of sexual function is underscored by its prevalence.

Diseases of the lips.

Heath care providers should be comfortable with normal as well as pathologic findings in the lips, because the lips are highly visible and may display clinical manifestations of local, as well as systemic inflammatory, allergic, irritant, and neoplastic alterations. Fortunately, the lips are easily accessible. The evaluation should include a careful history and physical examination, including visual inspection, as well as palpation of the lips and an examination of associated cervical, submandibular, and submental nodes. Pathologic and microscopic studies, as well as a review of medications, allergies, and habits, may further highlight possible etiologies. Many lip conditions, including premalignant changes, are relatively easy to treat, when the abnormalities are detected early; however, advanced disease and malignancies are challenging for both the patient and clinician. Treatment should be focused on eliminating potential irritants or allergens and treatment of the primary dermatosis. In this paper we review physiologic variants as well as pathologic conditions of the lips.

Guidelines of care for the management of acne vulgaris.

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.

Mind the Gap: Sex Bias in Basic Skin Research.

Given the recent National Institutes of Health proposal for balanced use of male and female cells and animals in preclinical studies, we explored whether sex bias exists in skin research. We surveyed 802 dermatological research articles from 2012 through 2013. No information about the sex of studied cells or animals was provided in 60% of papers. Among keratinocytes of known sex, 70% were male. Few studies compared male versus female cells or animals. Disclosure of sex and comparative studies contribute to our understanding of the biologic basis of sex differences. Addressing sex-specific differences in preclinical research informs subsequent clinical trial design and promotes individualized therapy.

Lichen sclerosus and lichen planus in women and girls.

Lichen planus and lichen sclerosus are common, chronic inflammatory vulvar dermatoses with significant morbidity. The course may wax and wane but disease often persists for decades. These autoimmune diseases have varied clinical presentations that extend beyond the genitalia. Management is best undertaken using a multidisciplinary approach and active patient involvement. The first-line treatment of both conditions is superpotent topical corticosteroids. Supportive measures and adjunct therapies can optimize patient outcomes. Patients who fail to improve despite correct medication use should be re-evaluated, and clinicians should be vigilant in detecting concomitant contact dermatitis, secondary infection, and malignancy.

Mucocutaneous granulomatous disease in a patient with Hermansky-Pudlak syndrome.

IMPORTANCE: Hermansky-Pudlak syndrome (HPS) is a rare genodermatosis characterized by oculocutaneous albinism, platelet dysfunction, and in some patients, pulmonary fibrosis and granulomatous colitis. The granulomatous inflammation in the bowel of patients with HPS can be indistinguishable clinically and histologically from that of Crohn disease (CD); however, mucocutaneous granulomatous lesions have not been considered among the typical skin findings of HPS. OBSERVATIONS: We report a case of an albino woman in her 40s with a history of CD and pulmonary fibrosis who presented with ulcers, plaques, and nodules in the vulva, perineum, inguinal creases, and left axilla. These cutaneous findings had the typical clinical and histologic findings of metastatic cutaneous CD. However, she also had a genetically confirmed diagnosis of HPS. CONCLUSIONS AND RELEVANCE: It is unclear whether our patient's cutaneous findings were due to CD or secondary to HPS. This report reviews the features of HPS and CD, 2 entities characterized by a granulomatous inflammatory reaction pattern but with unique genetic and clinical features, and discusses the possible overlap between the 2 diagnoses.

Alteration of the EphA2/Ephrin-A signaling axis in psoriatic epidermis.

EphA2 is a receptor tyrosine kinase (RTK) that triggers keratinocyte differentiation upon activation and subsequent downregulation by ephrin-A1 ligand. The objective of this study was to determine whether the EphA2/ephrin-A1 signaling axis was altered in psoriasis, an inflammatory skin condition in which keratinocyte differentiation is abnormal. Microarray analysis of skin biopsies from psoriasis patients revealed increased mRNA transcripts for several members of this RTK family in plaques, including the EphA1, EphA2, and EphA4 subtypes prominently expressed by keratinocytes. Of these, EphA2 showed the greatest upregulation, a finding that was confirmed by quantitative reverse-transcriptase-PCR, immunohistochemistry (IHC), and ELISA. In contrast, psoriatic lesions exhibited reduced ephrin-A ligand immunoreactivity. Exposure of primary keratinocytes induced to differentiate in high calcium or a three-dimensional (3D) raft culture of human epidermis to a combination of growth factors and cytokines elevated in psoriasis increased EphA2 mRNA and protein expression while inducing S100A7 and disrupting differentiation. Pharmacological delivery of a soluble ephrin-A1 peptidomimetic ligand led to a reduction in EphA2 expression and ameliorated proliferation and differentiation in raft cultures exposed to EGF and IL-1α. These findings suggest that ephrin-A1-mediated downregulation of EphA2 supports keratinocyte differentiation in the context of cytokine perturbation.

Cutaneous vulvar streptococcal infection.

OBJECTIVE: This study aimed to determine the etiology of fine superficial fissures in women with vulvar pain. MATERIALS AND METHODS: The charts of women with vulvar complaints seen in the Mucosal Disorders Clinic at Northwestern University between April 2006 and May 2008 were reviewed. Outcome measures included mucocutaneous examination findings and results of microbiological swab cultures in the presence of fine, superficial, vulvar and/or perianal fissures. The presence of concomitant vulvar disorders was noted. RESULTS: Sixteen women who presented with vulvar pain were found to have fine, superficial, vulvar and/or perianal fissures with minimal or no erythema on examination. None had inflammatory vaginitis. Group B ß-hemolytic streptococcus (Streptococcus agalactiae) was recovered in 6 (37.5%) patients. All women with group B ß-hemolytic streptococcus-positive cultures had a concomitant vulvar disorder; however, fissures were present despite appropriate treatment directed at the concomitant vulvar dermatosis. Three patients reported improvement in vulvar pain after treatment with antibiotics, and fissures had resolved by the time of follow-up examination in these 3 patients. CONCLUSIONS: Group B ß-hemolytic streptococcus may cause painful fine superficial fissures and minimal erythema of vulvar skin. Obtaining microbiological cultures should be considered in the evaluation of vulvar pain even in the absence of purulent inflammatory vaginitis. The search for documentation and treatment of this relevant pathogen is a departure from published recommendations.

A fixed-dose combination of adapalene 0.1%-BPO 2.5% allows an early and sustained improvement in quality of life and patient treatment satisfaction in severe acne.

INTRODUCTION: Acne has a significant negative impact on quality of life (QoL): lack of self-confidence, depressive symptoms and suicidal thoughts. The objective was to assess the impact of an initial and continued therapy in severe acne patients through patient-related outcomes (PRO). METHODS: In two sequential double-blind randomized studies, patients received either adapalene 0.1% and benzoyl peroxide 2.5% (A-BPO) or vehicle, associated with doxycycline 100 mg for 12 weeks. Patients having obtained at least a good improvement according to investigator global assessment were re-randomized for a 24-week therapy with A-BPO or vehicle. PROs were assessed using the Acne-QoL and a patient treatment satisfaction questionnaire. RESULTS: QoL was improved at week 12 in all domains with a significant difference for the Acne-symptoms domain (p < 0.001) in favor of the A-BPO regimen. Additional 24-week A-BPO treatment showed a sustained improvement, significant (p < 0.001) for all domains except for Acne-symptoms. In the vehicle arm, QoL significantly worsened for all domains (p < 0.03). At weeks 12 and 36, a significantly higher proportion of patients receiving A-BPO vs. vehicle reported high satisfaction for five out of six treatment satisfaction items. CONCLUSIONS: The early and sustained improvement of these PROs is correlated to the fast onset of action of A-BPO, the treatment effectiveness and a good safety profile.