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.

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.

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.

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.

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.

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.

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.

Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study.

Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo. Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975. Findings: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed. Interpretation: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial. Funding: AbbVie Inc.

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.

Lichen planus and lichenoid reactions of the oral mucosa.

Oral lichenoid reactions represent a common end point in response to extrinsic agents (drugs, allergens), altered self-antigens, or superantigens. Oral lichen planus, a common and under-recognized inflammatory disorder, shares many clinical and histopathological features with oral lichenoid drug reaction and oral lichenoid contact reaction. Clinical presentation can vary from asymptomatic white reticular striae to painful erythema and erosions. Cutaneous and additional mucosal involvement is common. Delay in diagnosis of extraoral mucocutaneous lichen planus (LP) results in conjunctival scarring; vaginal stenosis; vulvar destruction; and stricture of the esophagus, urethra, and external auditory meatus. Although the etiology of LP is idiopathic, oral lichenoid reactions may be caused by medications or exogenous agents such as cinnamates and other flavorings. The clinical features, evaluation, and management of these oral lichenoid reactions are discussed.

Approach to the patient with vulvovaginal complaints.

Although vulvovaginal diseases may seem daunting, dermatologists possess all of the requisite tools and skills necessary to comprehensively assess and accurately diagnose primary cutaneous, systemic, and inflammatory diseases that affect the vulva. A simple but comprehensive dermatologic approach to the patient with a vulvovaginal complaint is presented. We begin with a review of the normal vulvar anatomy and normal variants and proceed to the clinical approach with special emphasis on the history, physical examination, and common diagnostic procedures.

Skin cancer prevention education for kidney transplant recipients: a systematic evaluation of Internet sites.

CONTEXT: Repeated patient education about skin cancer prevention is important to self-care after transplant. OBJECTIVE: Examine educational materials for kidney transplant recipients available on the Internet that address sun protection and skin self-examination for early detection of squamous cell carcinoma. DESIGN: Systematic review of Web sites for kidney transplant recipients endorsed by transplant physicians and dermatologists. PARTICIPANTS: An expert panel of 8 dermatologists providing care for kidney transplant recipients and 1 research medical anthropologist. MAIN OUTCOME MEASURES: Reading grade level, inclusion of people with skin of color, sufficient content to support effective sun protection, and description of 4 sun-protection strategies and skin self-examination. Results-Of the 40 sites identified, 11 contained information about sun protection or increased risk of any type of cancer. The Web sites had a ninth-grade median reading level (range, seventh grade to college senior). Interrater reliability for the 25-item assessment tool was assessed by Fleiss' kappa (kappa = 0.87). Skin cancer risk was presented as relevant to those with fair skin. Sites recommended regular use of sunscreen with sun-protection factor of 15 or greater (n=3) to reduce the risk of skin cancer (n=4). Few sites recommended using protective clothing (n=5), seeking shade (n=4), and avoiding deliberate tanning with indoor or outdoor light (n=1). Five sites recommended skin self-examination. CONCLUSION: Because many patients seek self-management information from the Internet, Web sites must provide more thorough educational information about skin cancer prevention and health promotion at a lower reading grade level.

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.

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.

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.