Giant cell lichenoid dermatitis within healed varicella zoster site.

There are dermatoses that arise within healed zosteriform sites, such as granulomas annulare, acneiform eruptions, psoriasis, lichen planus, and giant cell lichenoid dermatitis "GCLD." Nonetheless, graft-versus-host disease should be considered and ruled out, especially in patients post-bone marrow transplant. Herein, we report a case of GCLD manifesting within healed zosteriform sites.

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.

Low-Intensity Visible and Near-Infrared Light-Induced Cell Signaling Pathways in the Skin: A Comprehensive Review.

Objective: To describe current knowledge regarding established and putative cell signaling pathways involved in skin photobiomodulation. Background: The skin is the largest and most accessible organ of the body. It is the first line of defense against the external environment, including solar radiation. Among solar rays, visible and infrared non-ionizing photons may reach human skin and trigger a cascade of non-thermal cell signaling pathways called photobiomodulation (PBM). The use of PBM using artificial light sources has been known for more than 50 years, but it has not yet been widely accepted due to uncertainty about the cellular mechanisms of action. However, much knowledge has been gained in this field in recent years, which will be summarized in this review. Methods: An extensive literature review was performed using Medline, Embase, and Google Scholar as research databases to acquire relevant publications in this particular field. Results: A comprehensive description of chromophores, primary and secondary effectors is provided in addition to a visual representation of known and putative cell signaling mechanisms involved in such complex light-skin interactions. Also, a summary of clinical indications of skin PBM, key light parameters, and promising skin applications (local and systemic) are mentioned. Conclusions: In PBM, skin cells are the first to absorb photons, triggering specific cell-signaling pathways through primary and secondary effectors, leading to enhanced cell repair and survival, notably in hypoxic or stressed cells. A better understanding of the mechanisms of action will help us optimize known indications and discover new ones.

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.

Incidence of Cutaneous Adverse Events With Phosphoinositide 3-Kinase Inhibitors as Adjuvant Therapy in Patients With Cancer: A Systematic Review and Meta-analysis.

Importance: The phosphoinositide 3-kinase (PI3K) pathway is among the most frequently activated pathways in human cancers. As the use of PI3K inhibitors for cancer treatment grows, there is increasing need for understanding the cutaneous effects associated with these therapies. Objective: To systematically review the published literature reporting incidence of cutaneous adverse events with PI3K inhibitors and to provide pooled incidence estimates using meta-analysis. Data Sources: This systematic review and meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The literature search concerned entries through September 2021 in the following sources: PubMed, Cochrane registry, ClinicalTrials.gov, and evidence from the NHS UK and Trip medical database. To analyze PI3K inhibitors' cutaneous adverse events incidence, only randomized clinical trials (RCTs) were considered. The search strategy used the following keywords: (prevalence OR incidence OR epidemiology) and (phosphoinositide 3 kinase inhibitors OR PI3K inhibitors). No language restriction was applied. Analysis was conducted on July 1, 2022. Study Selection: Studies included phase 2 and phase 3 RCTs that reported incidence of cutaneous adverse events associated with use of PI3K inhibitors. Data Extraction and Measures: Data extracted included sex, medication name and class, sample size, rash incidence, and grade. The bias risk was assessed by the Cochrane tool for risk of bias assessment in RCTs. Main Outcomes and Measures: The primary outcome was incidence of PI3K inhibitor cutaneous adverse events (with 95% CIs) among the overall population and among subgroups. Between-study heterogeneity was assessed using the I2 statistic. Results: The analysis found the incidence of PI3K inhibitor cutaneous events of any grade to be 29.30% in the intervention group, translating to a pooled odds ratio (OR) for incidence of cutaneous adverse events of any grades of 2.55 (95% CI, 1.74-3.75). Incidence of severe grade (grade ≥3) of rash in the intervention group was estimated to be 6.95%, yielding a pooled Peto OR of 4.64 (95% CI, 2.70-7.97). Subgroup analyses revealed that the incidence of severe cutaneous adverse events (grade ≥3) was higher with the use of Pan-class-1 PI3K inhibitors (OR, 6.67; 95% CI, 4.28-10.38) than isoform-selective PI3K inhibitors (OR, 6.37; 95% CI, 3.25-12.48). Conclusions and Relevance: This systematic review and meta-analysis identified an overall incidence of PI3K inhibitor cutaneous adverse events of any grade to be 29.30% with a pooled OR of 2.55; (95% CI, 1.74-3.75). These findings clarify the risk of cutaneous adverse events associated with this important class of anticancer therapies.

Prevalence of inverse psoriasis subtype with immune checkpoint inhibitors.

Background: Cutaneous immune-related adverse events (irAEs) are the most common irAEs caused by immune-checkpoint inhibitors (ICI). Psoriasiform eruptions, both de novo and flares, may occur. Evidence is lacking on inverse psoriasis subtype. Methods: A retrospective study was conducted at Dana-Farber Cancer Institute/Mass General Brigham through February 2020 using databases. Confirmed inverse psoriasis cases pre-/post-ICI initiation either independently or in conjunction with other psoriasis subtypes were included. Known psoriasis cases without flare post-ICI were excluded. Results: A total of 262 (3%) individuals with any ICI-mediated psoriasiform cutaneous irAE were identified out of the 8683 DFCI ICI-treated patients. Of these, 13 (5% of psoriasis patients) had inverse psoriasis (mean age 68.7 years; 7/13 male sex). Median (range) time from ICI initiation to inverse psoriasis development or flare was 7 (4-12) and 3.5 (2-6) weeks, respectively. Pruritus occurred in 12/13 (92.30%) cases. 11 (85%) had inguinal involvement; other sites included gluteal cleft (6; 46%), inframammary (3; 23%), perianal (2; 15%), axilla (2; 15%), umbilicus (2; 15%), and infra-abdominal folds (1; 8%). Most (9/13) individuals had more than one site involved. The Common Terminology Criteria for Adverse Events severity was 1 in 10 (76.92%) individuals and 2 in 3 (15.38%) individuals. Six (46.15%) patients were treated initially by oncology with topical (nystatin, econazole, or clotrimazole) or systemic antifungals (fluconazole) for median (range) of 3.5 (1-7) months without improvement, for presumed candida intertrigo. Conclusion: Patients on ICI may develop inverse psoriasis, which may be initially confused for fungal intertrigo. Delayed diagnosis can prolong symptoms, while patients are treated ineffectively with topical/systemic antifungals for presumed candida infection. Oncologist and dermatologist awareness is important to improve diagnosis of ICI-mediated inverse psoriasis, its management and affected patients' quality of life.

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.

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.