Dermatology:

Advances in inflammatory skin disease management are rapidly redefining dermatologic practice. This issue presents a compelling framework unifying type 2 inflammation across conditions like atopic dermatitis, prurigo nodularis, and chronic urticaria, emphasizing shared cytokine pathways and therapeutic opportunities. Also featured here is new real-world evidence supporting dupilumab efficacy following tralokinumab failure. In psoriasis, a novel "step-down" treatment strategy advocates for earlier biologic use in younger patients, followed by de-escalation. A paired commentary tempers this proposal with methodological and practical concerns. Finally, data on bimekizumab's safety and effectiveness in patients with chronic kidney disease address a critical clinical gap. These contributions highlight a shift toward precision medicine, integrating immunologic insight with patient age, comorbidity profiles, and therapeutic sequencing to inform truly individualized care.

Androgenetic alopecia (AGA) is the most common hair loss type in women, but topical minoxidil is the only Food and Drug Administration-approved treatment option. The pathophysiology involves shortened anagen phases, lengthened telogen phases, and hair follicle miniaturization. Androgens, particularly dihydrotestosterone, play a crucial role in male AGA pathogenesis, but their exact role in female pattern hair loss (FPHL) is unclear. Oral anti-androgens demonstrate some efficacy in women, albeit with considerations for side effects and contraindications. Topical anti-androgens may be used in combination with topical minoxidil or as alternatives to oral medications, likely with fewer systemic adverse effects. Patient-specific factors, including age, signs of hyperandrogenism, or need for contraception may help determine which anti-androgen therapy is most appropriate. This review focuses on current anti-androgen treatments for FPHL available in the US and their limitations, as well as emerging treatments that are investigational, studied in other hair loss types, or available in other countries.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with poor outcomes. Many questions remain regarding its epidemiology.

Despite increasing insights in cytokine pathways involved in T cell-mediated inflammatory skin diseases, the upstream T cell triggering events through antigen-presenting molecules and antigens often remain incompletely understood. Recent studies have proposed an immunopathogenic role for T cells that are activated through CD1a, a lipid antigen-presenting molecule abundantly expressed on antigen-presenting cells in human skin. These CD1a-restricted T cells are thought to play a role in psoriasis, atopic dermatitis, and allergic contact dermatitis. In this review, we discuss modes of T cell activation by CD1a proteins and lipid antigens and bacteria as well as recent insights in local and systemic functions of CD1a-restricted T cells in inflammatory skin disease.

Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin condition thought to be impacted by several risk factors, from genetics to lifestyle. Diet is a lifestyle factor that is of great interest for patients and providers. While there are several diet-related studies that have aimed to understand which dietary patterns and triggers are associated with AD, there exists some conflicting evidence that makes dietary recommendations and decisions difficult and can put patients at risk of inadequate nutrition. A review of dietary patterns and supplements revealed that the most consistent and beneficial dietary patterns associated with improvements in AD were supplementation with probiotics and n-3 polyunsaturated fatty acids and reductions in sodium intake. Data for other diets and supplements like antioxidants and various vitamins were more inconclusive, supporting the need for more high-quality dietary research. Dietary changes have the potential to positively impact the management of AD and should be made in conjunction with a provider to ensure nutritional needs are met.

The information on nail product safety is currently limited, but has been increasing in recent years. This increasing research has shown that some ingredients in nail products are hazardous and can lead to both dermatologic and systemic diseases. This risk is present for nail product consumers and is increased for nail technicians. Another concern with the nail products being used is the mislabeling of ingredients. This paper aims to assess the current literature on nail product safety, promote consumer safety, and encourage the involvement of dermatologists in promoting safe nail product use.

BACKGROUND: Hormonal therapy (HT) is widely administered for contraception and menopausal symptom management. However, its impact on psoriasis risk remains unclear, requiring an evaluation across diverse age groups to inform clinical practice and optimize treatment strategies.

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INTRODUCTION: Vitiligo, a chronic skin disease affecting 1-2% of the global population, is associated with significant impairment in quality of life. Current pharmacological treatment options have limited efficacy and considerable side effects. Recent studies have shown promising results when using Janus kinase inhibitors (JAKis). Despite these favourable findings, there remains a critical need for comprehensive data on the efficacy and safety of JAKi in the treatment of vitiligo.

CONCLUSIONS: The investigated biologics demonstrated improved efficacy and QoL relative to placebo at week 28, with no increased risk of SAEs vs. placebo through week 16. At week 28, efficacy of tildrakizumab, risankizumab, and guselkumab was comparable. Limitations include lack of placebo comparators after week 12 or 16, which could affect results.

Mutant NRAS is the second-most common type of mutation in melanoma. The prognosis is poor in the patients with NRAS mutant melanoma, and effective targeted treatment strategies are still lacking. Mutant NRAS mainly acts through activating the RAF-MEK-ERK signaling to promote the carcinogenesis in melanoma. In recent years, significant clinical advancements have been achieved by targeting the NRAS-MAPK pathway, with novel therapies such as the MEK inhibitor tunlametinib and the combination therapy of the pan-RAF inhibitor naporafenib with trametinib leading the way. In this review, we will systematically summarize the recent advances in the direct targeting of mutant NRAS proteins and their downstream RAF and MEK proteins, as well as targeting the MAPK pathway in combination with other therapeutic targets, including the immunotherapy, to treat NRAS mutant melanoma. Additionally, we will further discuss the current issues and emerging countermeasures related to targeted therapy for NRAS mutant melanoma.

The incidence of melanoma is increasing worldwide, requiring early detection to improve survival rates. Although dermoscopy is the standard non-invasive tool for diagnosing melanoma, it relies on experience and skill. Advances in optical imaging technologies and artificial intelligence have the potential to improve diagnostic accuracy. Our objective was to compare the diagnostic accuracy of novel non-invasive optical imaging techniques for melanoma detection. A systematic literature search was conducted in three databases (Medline, Embase, and CENTRAL) on November 15, 2023. Inclusion criteria focused on studies comparing the accuracy of optical imaging methods against histopathology. Outcomes consisted of measures of diagnostic accuracy. Random-effects meta-analyses were performed for each method with 95% confidence intervals to summarize all relevant effect sizes. Of the 16,239 records, 141 articles met the inclusion criteria, of which 138 articles were eligible for the meta-analysis. Reflectance confocal microscopy (RCM) and dermoscopy combined with artificial intelligence (DSC + AI) had the highest sensitivity (0.93), with DSC + AI showing higher specificity (0.77 [0.70-0.83]) than RCM (0.749 [0.7475-0.7504]). Multispectral imaging combined with AI also showed high sensitivity (0.92 [0.82-0.97]) and relatively high specificity (0.80 [0.67-0.89]). Standalone dermoscopy exhibited balanced sensitivity (0.87 [0.84-0.90]) and specificity (0.82 [0.78-0.86]). In melanoma diagnosis, both RCM and DSC + AI can serve as second-step optical evaluation methods for suspicious lesions following initial screening with DSC. By maintaining a strong emphasis on multimodal imaging, healthcare providers could improve early detection and outcomes for patients with melanoma.

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The management of psoriatic disease has been revolutionized by biologic medications in recent years. Despite their efficacy and safety, patients are often required by insurance plans in the USA or national formulary guidelines in other countries to try and fail other treatments first, which is a strategy called step therapy. Originally designed to contain costs of specialty drugs, step therapy has a number of negative impacts on patients and providers, both personally and clinically. This article is coauthored by a patient with psoriasis and psoriatic arthritis who navigated step therapy. She describes her early experiences with psoriasis and achieving disease control with biologic medication, only to later be diagnosed with psoriatic arthritis and need to revise this treatment plan. She then explains how insurance denials and step therapy impact her life physically, emotionally, socially, and medically. This case is then discussed from the perspective of a dermatologist specializing in inflammatory skin disease. We highlight the psychosocial burden of psoriatic disease, as well as the burden of step therapy and its impacts on patients, providers, and the entire medical system.

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Mycoplasma penetrans has gained attention in relation to non-gonococcal urethritis (NGU), a syndrome where a significant proportion of patients have no identified aetiological agent. In this study, we estimated the prevalence of urethral and rectal M. penetrans in a male population attending a sexually transmitted infection (STI) clinic in Copenhagen, Denmark. Specimens were assessed using M. penetrans-specific real-time polymerase chain reaction (PCR). Demographic characteristics and clinical symptoms were extracted from patient records. A total of 704 urethral specimens and 223 rectal specimens from 721 individual male patients were included. The prevalence of urethral and rectal M. penetrans was 0.3% and 2.7%, respectively. Overall, the prevalence among men who have sex with men (MSM) was 3.6%, significantly higher than in men who have sex with women (p < 0.001). Among MSM, a higher number of partners was associated with M. penetrans infection (p = 0.008). No association was found between the presence of M. penetrans and clinical symptom status, and its pathogenic potential remains unclear.

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Alopecia areata (AA) is an autoimmune condition of non-scarring hair loss that affects 2% of the population worldwide. Topical and intralesional (IL) corticosteroids are the two most commonly used treatments for AA. These locally acting glucocorticoid derivatives are thought to treat AA by reducing the CD8+ T-cell-mediated immune attack on hair follicles. Topical corticosteroids are safe and well tolerated with moderate efficacy in mild AA, but recurrence is common after treatment cessation. They are recommended for children and adults with mild AA who cannot tolerate IL injections. IL steroids are more effective than topical steroids given their ability to penetrate the dermis, where the hair follicle resides. Success rates are higher than topical steroids in mild-to-moderate AA. IL steroids are safe and well tolerated; however, treatment is limited by pain during the procedure. Further research is needed on ideal treatment regimens, long-term safety, preferred candidates, and the role of combination therapy to further elucidate the role of local corticosteroids for AA in clinical practice.