American Journal of Clinical Dermatology最新文献

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.

Acne vulgaris is a chronic inflammatory skin condition with a multifactorial pathogenesis involving follicular hyperkeratinization, sebaceous gland dysregulation, microbial dysbiosis—particularly involving Cutibacterium acnes and Staphylococcus epidermidis—and complex immune-mediated mechanisms, on which T helper cell 1 (T_h1) and T_h17 pathways are central players. This evolving understanding has led to the exploration of biologic therapies targeting cytokines such as tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, IL-17, and IL-23. However, clinical trials to date have not demonstrated efficacy of biologics in moderate to severe acne. In contrast, some case reports and studies suggest clinical improvement with TNFα and IL-17A inhibitors in severe, treatment-resistant acne, although these presentations often overlap with hidradenitis suppurativa (HS), raising questions about diagnosis and underlying disease mechanisms. Furthermore, in various monogenic autoinflammatory syndromes where “acne-like” lesions are part of the clinical spectrum, biologic therapies have shown effectiveness. These observations suggest that in such contexts, the lesions may reflect HS or HS-like pathology rather than true acne, potentially explaining the therapeutic benefit of biologicals in this context. This review synthesizes current insights into the immunopathogenesis of acne and critically evaluates the rationale, evidence, and limitations of biologic therapy in its treatment. While biologics hold promise in defined inflammatory dermatoses, their role in the management of acne vulgaris remains unproven and may be limited to specific phenotypes that overlap with autoinflammatory or HS-related conditions.

The complex interplay between atopic dermatitis (AD) and cutaneous T cell lymphomas (CTCL) has been known as a matter of clinical concern. With the widespread use of dupilumab, a monoclonal antibody inhibiting interleukin-4 receptor alpha (IL-4Ra) and interleukin-13 receptor (IL-13R), potential association between dupilumab and developing CTCL has been reported in patients with AD. Disease progression has also been described in patients with known CTCL who were treated with dupilumab. Although population-based and pharmacovigilance data support an increased risk of CTCL with dupilumab use in patients with AD, it is a rare association, most likely occurring in predisposed patients. No evidence is available to support a direct oncogenic risk of transforming AD into lymphoma by the treatment, and current literature suggests the role of IL-4Ra/IL-13R inhibition in unmasking pre-existing malignant T cell clones through increased IL-13 availability. On the basis of a comprehensive literature review and our experience in a cutaneous lymphoma clinic at a tertiary cancer center, we provide practical clinical care recommendations for the use of dupilumab in patients with AD, CTCL, and non-skin lymphomas. We also highlight the need for further researching alternative diagnostic approaches to differentiate CTCL from AD and other inflammatory skin disorders and studying the roles of IL-13 and its receptors in CTCL and the effect of the newly available IL-13-inhibiting therapies.