American Journal of Clinical Dermatology最新文献

Background

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterized by recurrent pustules on the palms and soles. Current treatments, including topical medications, phototherapy, and systemic therapies, often show limited efficacy. Upadacitinib (UPA), a selective JAK1 inhibitor, has shown potential in treating neutrophilic dermatoses by modulating cytokine activity.

Objective

To evaluate the efficacy and safety of UPA compared with acitretin (ACI) in the acute phase of PPP through a prospective cohort study.

Methods

This study was conducted at the Shanghai Skin Disease Hospital from August 2024 to January 2025. A total of 79 patients with acute PPP were enrolled and randomly assigned to receive UPA (15 mg daily) or ACI (20 mg daily) for 4 weeks. Efficacy was assessed using pustule counts, Palmoplantar Pustulosis Area and Severity Index (PPPASI), and Dermatology Life Quality Index (DLQI). Safety was evaluated by recording adverse events (AEs).

Results

At week 2, the rate of complete pustule clearance was significantly higher in the UPA group (41.9%) than in the ACI group (10.5%, P = 0.003). By week 4, all patients in the UPA group achieved a pustule count < 30, compared with 63.2% in the ACI group. The UPA group also showed greater reductions in PPPASI and higher response rates for PPPASI 50/75/90. Quality of life improvements, as measured by DLQI, were more pronounced in the UPA group. In terms of safety, UPA had a favorable profile with lower overall AE incidence compared with ACI.

Conclusions

UPA demonstrated superior efficacy over ACI in rapidly clearing pustules and improving skin lesions and quality of life in acute PPP episodes. The findings suggest that JAK1 inhibition may be a promising therapeutic approach for PPP, warranting further investigation in larger trials.

Clinical Trial Registration

[www.chictr.org.cn], identifier [ChiCTR2000036186].

Background

The approach to pediatric psoriasis requires special considerations, given the potential for negative consequences on overall physical and psychosocial health.

Objective

The aim of this study was to systematically review the literature to characterize the burden of pediatric psoriasis.

Methods

Papers assessing associations between pediatric psoriasis (in children <18 years old) and quality of life, physical symptoms (e.g., skin pain, itch, sleep disruption), and adverse psychological, social, and financial effects were searched with no date restrictions through July 2023. Databases searched included Ovid MEDLINE^®, CENTRAL, the Cochrane Database of Systematic Reviews, and PsycInfo. Articles were excluded if they focused on comorbidities (including psoriatic arthritis/enthesitis), were of low quality, or were not in English.

Results

64 publications met eligibility criteria. Composite quality of life was the most frequently reported domain (40 publications) and was negatively impacted by psoriasis as a function of severity. Physical burdens, especially itch, occurred in 44.1–96.3% of children with psoriasis, while skin pain was less common. Psychosocial and family burdens were less frequently assessed and often with non-validated tools. Children with psoriasis participated less in social activities, but there were no clear associations between psoriasis and school performance or interpersonal relationships. Psoriasis was associated with a higher mental health burden on caregivers and greater family financial burden.

Conclusions

Psoriasis leads to high burden for pediatric patients and caregivers. Evaluation and management decisions should include and incorporate a thorough assessment of burden. Additional studies using validated tools are necessary to fully assess psychosocial and family burdens of psoriasis.

Immune checkpoint inhibitors, particularly antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4, have transformed the treatment landscape of metastatic melanoma. For a subset of patients, these therapies have led to durable responses and long-term survival. However, despite this progress, more than half of patients experience primary or acquired resistance to anti-PD-1 therapy, highlighting an urgent need for effective alternative treatments. As immune checkpoint inhibitors are increasingly used in neoadjuvant and adjuvant settings, a growing number of patients with newly diagnosed metastatic melanoma will have prior exposure to these agents—posing critical challenges for subsequent treatment strategies after anti-PD-1 failure.

In this review, we outline mechanisms driving resistance to anti-PD-1 therapy, including both tumor-intrinsic and tumor-extrinsic factors, and discuss biomarkers relevant to clinical practice in melanoma. The current treatment landscape is reviewed, with an overview of key clinical trials that have shaped management across metastatic, adjuvant, and neoadjuvant settings. We discuss novel and promising investigational agents targeting immune and cellular pathways, such as cancer vaccines and recent advancements in T-cell therapy.

A key focus is the critical need for predictive biomarkers to guide therapy selection and improve our understanding of long-term outcomes in patients previously treated with immune checkpoint inhibitors. Global efforts are underway to address anti-PD-1 resistance through diverse and innovative strategies, with the aim of developing therapies that maximize the clinical benefit while minimizing toxicity. As the treatment paradigm continues to evolve, overcoming resistance remains central to advancing the care of patients with melanoma.

Background

Data are lacking to guide diagnosis and treatment in patients with skin of color and atopic dermatitis (AD), a population traditionally underrepresented in clinical trials.

Objective

The aim of this study was to evaluate the efficacy and safety of lebrikizumab in adults and adolescents with skin of color and moderate-to-severe AD.

Methods

In the open-label ADmirable trial, 90 adults and adolescents with moderate-to-severe AD, Fitzpatrick skin phototype IV–VI, and self-reported race other than White received lebrikizumab 250 mg subcutaneously every 2 weeks (Q2W), following a 500-mg loading dose at baseline and Week 2, for 16 weeks. From Week 16 to Week 24, responders, defined as patients with at least 75% improvement in Eczema Area and Severity Index (EASI 75) and/or Investigator’s Global Assessment (IGA) score of 0/1 with at least a 2-point improvement from baseline, received lebrikizumab every 4 weeks (Q4W); inadequate responders continued lebrikizumab Q2W. The primary endpoint was the percentage of patients achieving EASI 75 at Week 16. Secondary and exploratory efficacy endpoints and safety were assessed throughout. Data were analyzed as observed and using imputation, with Q2W and Q4W populations pooled for Weeks 16–24.

Results

Mean age at baseline was 40.7 years; 43.3% were female; and 43.3%, 24.4%, and 32.2% had Fitzpatrick skin phototypes IV, V, and VI, respectively. Baseline mean EASI and Pruritus Numeric Rating Scale (NRS) scores were 26.4 and 7.0, respectively; 68.9% of patients had moderate disease (IGA = 3). At Week 16 (number of patients with non-missing values [Nx] = 78), EASI 75, EASI 90 (≥ 90% improvement from baseline in EASI), and IGA 0/1 (IGA response of clear or almost clear) were achieved by 69.2%, 44.9%, and 44.9% of patients, respectively; for Pruritus NRS (Nx = 62), 58.1% of patients reported ≥ 4-point improvement. At Week 24 (Nx = 74) (pooled treatment arms), EASI 75, EASI 90, and IGA 0/1 were achieved by 78.4%, 47.3%, and 54.1% of patients, respectively. EASI 75 was achieved by 62.9%, 88.2%, and 95.5% of patients with Fitzpatrick skin phototype IV (Nx = 35), V (Nx = 17), and VI (Nx = 22), respectively, at Week 24. Most patients (64.4%) with baseline PDCA-Derm™-assessed hyperpigmented areas showed reduced hyperpigmentation at Week 24. Most treatment-emergent adverse events were mild or moderate in severity; none were serious or led to discontinuation. One case of conjunctivitis was reported.

Conclusion

In this first lebrikizumab study in patients with skin of color (Fitzpatrick skin phototype IV, V, and VI) and moderate-to-severe AD, lebrikizumab improved signs and symptoms of AD and confirmed its favorable safety profile.

Trial Registration

ClinicalTrials.gov Identifier: NCT05372419 (registered May 5, 2022).

Patients with, survivors of, and women at increased risk of breast cancer may experience various hair loss disorders, including those related to cancer treatments (such as chemotherapy- or endocrine therapy-induced alopecia), alopecia areata, androgenetic alopecia, and cicatricial alopecias. In the USA, approximately 1 in 8 women (13.1%) will develop breast cancer during their lifetime, emphasizing the importance of understanding safe treatment options for this population. Management of scarring and nonscarring alopecias in patients with or those at high risk of breast cancer requires the selection of therapies that do not impact breast cancer risk, treatment, or outcomes. In this review, we examine the safety of common medications used in the treatment of alopecia areata, androgenetic alopecia, and cicatricial alopecias with regard to breast cancer. We provide evidence-based recommendations for the use of these treatments in patients with and women at elevated risk of breast cancer while highlighting areas where further research is needed.

Background

Multimodal noninvasive imaging is a novel technique in dermatology. Its purpose is to overcome the limitations of unimodal techniques. This is done by combining higher resolution images with deeper imaging depth and/or tissue specificity within a single device for improvement of diagnosis and management of skin lesions.

Objective

Our aim was to systematically review multimodal imaging devices currently used in dermatology clinics and their diagnostic accuracy of skin lesions.

Methods

A comprehensive search was conducted in October 2022 for studies on multimodal imaging technologies in vivo, in human subjects, used in dermatology. An additional search was made in March 2024. Four databases were selected: MEDLINE, Embase, CENTRAL, and Web of Science. This review was registered with the international Prospective Register of Systematic Reviews (PROSPERO record number CRD42022364864). The search strategy used Medical Subject Headings (MeSH) and keywords from two concepts: Multimodal Imaging and Dermatological Conditions. Reference lists were also searched for relevant studies. Selected studies included multimodal techniques in neoplastic, inflammatory, and pigmentary skin disorders. Ex vivo imaging, non-human studies, and non-clinical settings were excluded. Data extraction and quality assessment were performed using QUADAS and STARD criteria. Data extraction was conducted by one researcher and then reviewed by an additional researcher. A third researcher resolved any disagreements. The statistical analysis involved diagnostic accuracy meta-analysis, subgroup comparisons (multimodal vs single modal, multimodal vs multimodal), and SROC curves. The primary outcomes were the diagnostic accuracy, sensitivity, and specificity of multimodal imaging devices in diagnosing dermatological conditions.

Results

The analysis included 92 studies, predominantly case reports or series (83.7%), with basal cell carcinoma (BCC) being the most frequently imaged lesion (11.8%). The studies had a moderate risk of bias (QUADAS score: 0.6) with histology as the reference test in most cases. Meta-analysis showed multimodal devices have high sensitivity and specificity for BCC diagnosis. These results indicate reliable diagnostic accuracy.

Conclusions

In a clinical setting, multimodal imaging can be useful to perform bedside diagnosis and management of skin lesions.

Chemotherapy-induced alopecia and radiation-induced alopecia, the thinning or loss of hair due to cytotoxic chemotherapy and radiation therapy, respectively, are distressing adverse effects of cancer treatment. Chemotherapy, targeted therapies, and radiation therapy used in pediatric oncology often lead to alopecia by damaging hair follicles, with varying degrees of severity depending on the specific treatment type, mechanism of action, and damage-response pathway involved. Pediatric chemotherapy-induced alopecia, radiation-induced alopecia, and permanent alopecia, defined as hair regrowth that remains incomplete 6 months or more after treatment, have significant negative impacts on mental health, self-esteem, and social interactions, highlighting the need for further research into supportive care strategies. There are currently no standard interventions for chemotherapy-induced alopecia or radiation-induced alopecia in children, with most recommendations limited to gentle hair care and camouflaging techniques during treatment. Scalp cooling has demonstrated safety and efficacy in reducing chemotherapy-induced alopecia in adults and is currently under investigation in children and adolescents. Topical and low-dose oral minoxidil have been studied in children for other hair loss disorders and may improve hair regrowth after chemotherapy or radiation. Increased awareness and continued research into management strategies for pediatric chemotherapy-induced alopecia and radiation-induced alopecia are necessary to help mitigate its significant negative impact on quality of life.

Tumor-infiltrating lymphocyte (TIL) therapy is a type of personalized immunotherapy that harnesses the antitumor activity of endogenous immune cells. While TIL therapy has been in clinical investigation since the 1980s and shown promising signs of clinical activity in immunogenic solid tumors such as melanoma, more recent improvements in product manufacturing and characterization have demonstrated consistent efficacy and the feasibility of administering TIL therapy on a larger scale. Lifileucel was granted accelerated approval by the US Food and Drug Administration in February 2024 for the treatment of advanced melanoma, marking the first regulatory approval of a TIL product, and also the first approval of cellular therapy for the treatment of any solid tumor. Despite this landmark event, questions remain surrounding optimal TIL timing, sequencing with other treatment modalities, and the optimal TIL repertoire and phenotype. Innovations in cellular engineering are expected to improve the antitumor efficacy and safety profile of TIL therapy, advance our understanding of how best to deliver TIL therapy, and provide hope for paradigm-shifting approaches in the treatment of advanced melanoma as well as for other solid tumors.

Recent advancements in wound healing are reshaping clinical practice by integrating dermatology, cutaneous microbiome research, and technology. This article discusses new diagnostic tools, such as imaging devices and microbial composition analysis, that enhance our understanding of wound environments. It highlights the importance of wound bed preparation and explores innovative treatment methods for optimal wound healing, including debridement techniques like ultrasound-assisted methods, hydrosurgery, and larval therapy. The evolution of wound management is further illustrated through the use of cellular and acellular matrix products and cellular therapies involving whole blood products. We also present the latest insights on the wound microbiome and antimicrobial treatments, including advanced dressings and antibiofilm surfactants. Finally, the potential of gene therapy for complex conditions like epidermolysis bullosa is discussed as a promising model for advancing wound healing. This review synthesizes current research to improve dermatological practices and patient outcomes in wound care.