The Role of Sex and Gender in Dermatology - From Pathogenesis to Clinical Implications.

BACKGROUND: Sex and gender have increasingly been recognized as significant risk factors for many diseases, including dermatological conditions. Historically, sex and gender have often been grouped together as a single risk factor in the scientific literature. However, both may have a distinct impact on disease incidence, prevalence, clinical presentation, severity, therapeutic response, and associated psychological distress. OBJECTIVES AND PROJECT DESCRIPTION: The mechanisms that underlie differences in skin diseases between males, females, men, and women remain largely unknown. The specific objectives of this review paper are:To highlight the biological differences between males and females (sex), as well as the sociocultural differences between men and women (gender) and how they impact the integumentary system.To perform a literature review to identify important sex- and gender-related epidemiological and clinical differences for various skin conditions belonging to a range of disease categories and to discuss possible biological and sociocultural factors that could explain the observed differences.To discuss dermatological skin conditions and gender-affirming treatments within the transgender community, a population of individuals who have a gender identity which is different than the gender identity they were assigned at birth. FUTURE IMPACT: With the rising number of individuals that identify as non-binary or transgender within our increasingly diverse communities, it is imperative to recognize gender identity, gender, and sex as distinct entities. By doing so, clinicians will be able to better risk-stratify their patients and select treatments that are most aligned with their values. To our knowledge, very few studies have separated sex and gender as two distinct risk factors within the dermatology literature. Our article also has the potential to help guide future prevention strategies that are patient-tailored rather than using a universal approach.

Performance of Ultrasound for Identifying Morphological Characteristics and Thickness of Cutaneous Basal Cell Carcinoma: A Systematic Review.

Advances in ultrasound technology and non-surgical treatments of basal cell carcinomas (BCCs) have raised the need to study the performance of high-frequency ultrasound (HFUS) in BCCs. We aimed to assess the performance of HFUS in the evaluation of BCCs to formulate recommendations for its uses and conducted a systematic review of the literature to do so. A search of Central, Medline, Embase, CINHAL, and Web of Science was performed using key/MESH terms "ultrasonography" and "basal cell carcinoma" (January 2005-December 2020). We included primary studies reporting biopsy-confirmed BCCs for which the target intervention was ultrasound assessment at 15 MHz or higher frequency. Thirty articles were included, studying a total of 1,203 biopsy-confirmed BCCs. HFUS provides accurate depth measurements, especially for BCCs >1 mm. The definition of lateral margins in vivo needs further studies; however, ex vivo margin assessment seems convincing. There is a diagnostic role for HFUS in identifying higher recurrence risk BCC subtypes, which can help in risk stratification. Performance of HFUS is significant in BCC management. Pre-surgical scans may support case selection for Mohs. HFUS can improve safety when used to plan brachytherapy treatments, help with case selection and adjunct treatment choice pre-photodynamic therapy. Finally, HFUS can help follow lesions after intervention, particularly non-surgical management, and support the decision to observe or re-intervene. HFUS can enhance clinical practice by providing useful information that cannot be deducted from the clinical examination. It would be recommended to evaluate the extent, mainly depth, and detect the aggressiveness of the BCCs.

Discriminative deep learning based benignity/malignancy diagnosis of dermatologic ultrasound skin lesions with pretrained artificial intelligence architecture.

BACKGROUND: Deep-learning algorithms (DLAs) have been used in artificial intelligence aided ultrasonography diagnosis of thyroid and breast lesions. However, its use has not been described in the case of dermatologic ultrasound lesions. Our purpose was to train a DLA to discriminate benign form malignant lesions in dermatologic ultrasound images. MATERIALS AND METHODS: We trained a prebuilt neural network architecture (EfficientNet B4) in a commercial artificial intelligence platform (Peltarion, Stockholm, Sweden) with 235 color Doppler images of both benign and malignant ultrasound images of 235 excised and histologically confirmed skin lesions (84.3% training, 15.7% validation). An additional 35 test images were used for testing the algorithm discrimination for correct benign/malignant diagnosis. One dermatologist with more than 5 years of experience in dermatologic ultrasound blindly evaluated the same 35 test images for malignancy or benignity. RESULTS: EfficientNet B4 trained dermatologic ultrasound algorithm sensitivity; specificity; predictive positive values, and predicted negative values for validation algorithm were 0.8, 0.86, 0.86, and 0.8, respectively for malignancy diagnosis. When tested with 35 previously unevaluated images sets, the algorithm´s accuracy for correct benign/malignant diagnosis was 77.1%, not statistically significantly different from the dermatologist's evaluation (74.1%). CONCLUSION: An adequately trained algorithm, even with a limited number of images, is at least as accurate as a dermatologic-ultrasound experienced dermatologist in the evaluation of benignity/malignancy of ultrasound skin tumor images devoid of clinical data.

Acne Scars: An Update on Management

Acne vulgaris is a troubling skin disease known to have both physiologic and psychological effects on patients. Acne scars, a frequent complication, can further impact patients' quality of life. Scars result from an impairment in the healing process. Acne scars can be categorized as follows: atrophic scars (including ice pick, rolling, boxcar subtypes) and trophic (including hypertrophic and keloid scars), the latter being less common. Though various treatment approaches have been suggested, there is a lack of high-quality evidence on effective, type-specific acne scar approaches. Herein, we aim to review the current evidence for treating various acne scars.

Plerixafor on a WHIM - Promise or Fantasy of a New CXCR4 Inhibitor for This Rare, but Important Syndrome?

Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) is a primary immunodeficiency syndrome. Patients with WHIM syndrome are more susceptible to human papillomavirus (HPV) infections and commonly present to a dermatologist with recalcitrant to treatment warts. Other cardinal features of WHIM syndrome include recurrent sinopulmonary bacterial infections, neutropenia/lymphopenia, low levels of immunoglobulins (IgG, IgA, IgM) and myelokathexis. Research demonstrated that truncating gain-of-function mutations of the C-X-C chemokine receptor type 4 gene (CXCR4) are responsible for this disease. Plerixafor, a specific small molecule antagonist of CXCR4, is currently used for peripheral blood hematopoietic stem cell (HSC) mobilization in stem cell transplant recipients. It has recently shown promise for the treatment of WHIM syndrome in phase I/II clinical trials. In this paper we review the emerging patient clinical data for this medication and highlight the role of CXCR4 in other important skin diseases including keratinocyte carcinomas, psoriasis and cutaneous T-cell lymphoma.

Apremilast in dermatology: A review of literature.

Apremilast is an orally administered small molecule that specifically inhibits the phosphodiesterase-4 enzyme and modulates the immune system by increasing the levels of intracellular cyclic adenosine monophosphate (cAMP) and inhibiting IL-2 & 8, interferon-γ and tumor necrosis factor (TNF) production. It is FDA approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers of Behcet's disease. More recently, apremilast has been used off-label to treat varied dermatological diseases where systemic corticosteroids or immunosuppressive agents were not effective. We review the efficacy and safety of apremilast in the treatment of aphthous stomatitis, Behçet's disease, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus in cases where standard treatment has failed.

Hidradenitis Suppurativa: Comprehensive Review of Predisposing Genetic Mutations and Changes.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder. A genetic component in the pathogenesis is highly likely considering that ~30% to 40% of patients with HS report a family history of the disease. The genetic mutations related to HS that have been reported to date suggest HS can be inherited as a monogenic trait because of a defect in either the Notch signaling pathway or inflammasome function, or as a polygenic disorder resulting from defects in genes regulating epidermal proliferation, ceramide production, or in immune system function. This review provides a summary of genetic mutations reported in patients diagnosed with HS and discusses the mechanisms by which these genes are involved in its pathogenesis.

Spontaneous Keloids: A Literature Review.

BACKGROUND: Keloids are benign fibroproliferative tumors that extend beyond the original wound. Spontaneous keloids are those that result without a significant history of trauma. There are multiple reported cases in the literature. OBJECTIVE: This article provides a summary and review of the cases that have been reported with spontaneous keloids and organizes them according to their associated medical conditions. METHODS: A literature review was conducted using PubMed and MEDLINE that included all English published cases and case series from May 1955 to February 2018. RESULTS: Spontaneous keloids have been reported mainly in association with syndromes such as Rubinstein-Taybi syndrome, Dubowitz syndrome, Noonan syndrome, Goeminne syndrome, Bethlem myopathy, conjunctivocorneal dystrophy, X-linked recessive polyfibromatosis and a novel X-linked syndrome with flamin A mutation. Furthermore, spontaneous keloids were reported in atopic patients and a couple of patients who are medically healthy. CONCLUSION: Spontaneous keloids are diagnosed clinically based on the patient's history, and it is challenging to confirm since they might be triggered by minimal injury or inflammation especially if it is a single lesion. Reported syndromes indicate a genetic possibility in the pathogenesis of spontaneous keloids.