American Journal of Clinical Dermatology最新文献

Background

Disseminated superficial actinic porokeratosis (DSAP) is a disorder of keratinization characterised by small, brown plaques with elevated keratotic rims, typically occurring on sun exposed areas. DSAP poses a risk for malignant transformation, emphasising the need for effective management strategies.

Objective

The aim of this study was to review the current reported management options for DSAP.

Methods

This systematic review was based on a comprehensive search of databases (Cochrane, PubMed, Medline, Embase, Emcare, ProQuest, Web of Science, CINAHL) from inception to 15 March 2024. Studies reporting management of DSAP were included irrespective of study design.

Results

Of 923 citations, 61 studies were included, predominantly comprising case reports and retrospective case series. A limited number of randomized and open-label trials were identified. Various treatment modalities were reported, including topical and systemic agents, photodynamic therapy, and laser therapy.

Conclusion

Multiple management options are available for DSAP, including topical and systemic agents, photodynamic therapy and laser treatments. However, these approaches vary in their balance between efficacy and toxicity. Currently, there is a paucity of high-quality clinical trial data to guide treatment decisions. Further studies are required to determine the most effective and safe management strategies for DSAP.

Prospero registration

CRD42024514558.

Background

The ALLEGRO phase 2b/3 study investigated the efficacy and safety of ritlecitinib in patients with alopecia areata (AA).

Objective

To describe the impact of ritlecitinib on patient-reported hair loss using the Alopecia Areata Patient Priority Outcomes (AAPPO) instrument and evaluate the relationship between clinically meaningful hair regrowth and improvements in patient-reported impacts.

Methods

In ALLEGRO-2b/3, patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg daily loading dose), 10 mg, or placebo for 24 weeks and then continued ritlecitinib or switched from placebo to ritlecitinib 200/50 or 50 mg for 24 weeks. The AAPPO instrument evaluated improvement in hair loss, emotional symptoms (ES), and activity limitations (AL) from weeks 4 to 48 (secondary endpoint). Mean changes in ES and AL domain scores and individual items at weeks 24 and 48 were calculated for Severity of Alopecia Tool (SALT) score ≤ 20 responders and nonresponders (exploratory endpoint).

Results

Overall, 718 patients were randomized. At week 24, 5–36% of patients receiving ritlecitinib 10–200/50 mg reported improvement in scalp hair loss versus 9% receiving placebo. The results for eyebrow, eyelash, and body hair loss were similar. Mean change from baseline in ES and AL scores at weeks 24 and 48 was small and similar between groups. Mean change was larger for individual hair loss and ES items at weeks 24 and 48 in SALT score ≤ 20 responders versus nonresponders.

Conclusions

The AAPPO instrument demonstrated the beneficial impact of ritlecitinib on patient-reported hair growth, which was consistent with improvements in clinician-reported outcomes.

Clinical Trial Registration

NCT03732807.

Infographic

Neuropathic itch is a type of chronic pruritus resulting from neural dysfunction along the afferent pathway. It is often accompanied by abnormal sensations such as paresthesia, hyperesthesia, or hypoesthesia. This condition, which may involve motor or autonomic neural damage, significantly impacts patients’ quality of life, causing severe itch and associated comorbidities such as depression, disrupted sleep, and social strain. Neuropathic itch accounts for 8% of chronic pruritus cases, though this may be underestimated. This comprehensive review focuses on nerve impingement as the primary pathophysiological mechanism for various forms of neuropathic itch including brachioradial pruritus (BRP), notalgia paresthetica (NP), and anogenital itch. BRP, often seen in middle-aged white women, manifests as pruritus in the dorsolateral forearms typically exacerbated by ultraviolet (UV) exposure and related to cervical spine pathology. NP, prevalent in middle-aged women, presents as pruritus in the upper back due to thoracic spine nerve compression. Anogenital pruritus, affecting 1–5% of adults, is often linked to lumbosacral spine issues after ruling out dermatologic conditions such as lichen sclerosus or lichen simplex chronicus. The pathophysiology of neuropathic itch involves both peripheral and central mechanisms, with nerve damage being a key factor. Diagnosis requires a thorough history, physical examination, and potentially imaging studies. Topical agents such as menthol, capsaicin, and lidocaine are used for mild cases, while systemic medications such as gabapentin, pregabalin, and antidepressants are prescribed for moderate to severe cases; however, no US Food and Drug Administration (FDA)-approved therapies currently exist specifically for neuropathic itch. Understanding the underlying neural dysfunction and appropriate therapeutic strategies is crucial for managing neuropathic itch effectively.

Background

The phase III KEYNOTE-913 study was conducted to evaluate the efficacy and safety of pembrolizumab as first-line therapy in patients with advanced Merkel cell carcinoma (MCC).

Objective

The aim was to report results from the primary analysis of KEYNOTE-913.

Patients and Methods

Patients with recurrent locally advanced or metastatic MCC received pembrolizumab 200 mg intravenously every 3 weeks for up to 35 treatments (~ 2 years). The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary end points were duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety and tolerability.

Results

Fifty-five patients were treated with pembrolizumab. The median time from first dose to data cutoff (February 15, 2024) was 50.3 months (range 38.7–59.4). The ORR was 49% (95% confidence interval [CI] 35–63), with 12 complete responses and 15 partial responses. The median DOR was 39.8 months (range 4.8–52.5+), and the 24-month DOR rate was 69%. The median PFS was 9.3 months (95% CI 3–26), and the 24-month PFS rate was 39%. The median OS was 24.3 months (95% CI 12.4 to not reached), and the 24-month OS rate was 51%. Any-grade treatment-related adverse events (AEs) occurred in 38 patients (69%); 13 patients (24%) experienced grade 3–5 AEs. The most common treatment-related AEs were fatigue (n = 12 [22%]), pruritus (n = 12 [22%]), and lipase increase (n = 10 [18%]). One patient died of treatment-related Guillain-Barré syndrome.

Conclusions

Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or metastatic MCC, supporting its use in this population.

Trial Registration

Clinicaltrials.gov, NCT03783078.

Cannabidiol (CBD) is a non-psychotropic cannabinoid with multiple pharmacological properties. Cannabidiol has attracted growing attention in the cosmetic industry, with an increasing number of CBD-containing skincare products on the market in recent years. The aim of this review is to evaluate the current evidence on the use of CBD for cosmetic purposes. Following an overview of CBD and the endocannabinoid system in the skin, we summarize pre-clinical and clinical studies that address the potential of CBD in cosmetic dermatology. Available in vitro and in vivo evidence suggests that CBD has anti-oxidant, anti-inflammatory, moisturizing, anti-acne, wound-healing, and anti-aging properties. However, only a few clinical studies have been conducted on the use of CBD in the skin. In addition, there is a critical need to develop an efficient drug-delivery system for topical/transdermal application of CBD. Further research, including clinical and pharmacokinetic studies, are needed to fully evaluate the role of CBD in cosmetic dermatology.

Erythroderma, an inflammatory skin condition characterized by widespread erythema with variable degrees of exfoliation, pustulation, or vesiculobullous formation, is associated with high morbidity and mortality. Determining the underlying cause of erythroderma frequently presents a diagnostic challenge, which may contribute to the condition’s relatively poor prognosis. This review covers the clinical presentation, pathophysiology, diagnosis, and treatment of erythroderma. It discusses similarities and differences among the many underlying etiologies of the condition and differences between erythrodermic and non-erythrodermic presentations of the same dermatosis. Finally, this article explores current research that may provide future tools in the diagnosis and management of erythroderma.

Background

Many morphological and histological changes take place in aging skin. Topical tretinoin is the gold standard anti-aging agent used to reduce signs of aging through stimulation of epidermal growth and differentiation and inhibition of collagenase.

Objective

The aim of this systematic review is to summarize studies evaluating the efficacy of tretinoin compared with other topical medications and cosmeceuticals in reducing the appearance of skin aging.

Methods

A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The literature search was conducted using the PubMed and Embase databases from conception to December 2023. Studies were included if they compared anti-aging outcomes of topical medications with those of topical tretinoin (also called all-trans retinoic acid and retinoic acid). Studies were excluded if they compared non-topical anti-aging treatments with tretinoin or were conducted on animal models.

Results

The literature search resulted in 25 studies that met all inclusion and exclusion criteria. The most common study comparators to tretinoin included other forms of vitamin A. Outcomes were reported on the basis of visual reduction of aging signs, histological assessment of the epidermis and dermis, and protein expression. Although comparators to tretinoin had variable efficacy (greater in 7 studies, equivalent in 13 studies, and less in 3 studies), most studies found the comparator to be less irritating and better tolerated by patients than tretinoin.

Discussion

Tretinoin is currently the gold standard therapy for the treatment of photoaging, but its poor tolerability often limits its use. Unfortunately, given that most studies comparing topical therapies with tretinoin are of poor quality and/or demonstrate bias, there is a lack of substantial evidence to support an alternative first-line therapy. However, given there are some data to support the efficacy of retinoid precursors, namely retinaldehyde, pro-retinal nanoparticles, and conjugated alpha-hydroxy acid and retinoid (AHA-ret), these agents can be considered a second-line option for anti-aging treatment in patients who cannot tolerate tretinoin.