American Journal of Clinical Dermatology最新文献

Background

Psoriasis is a chronic, inflammatory disease requiring long-term therapy. Risankizumab, an anti–interleukin-23 monoclonal antibody, is approved to treat moderate-to-severe plaque psoriasis in adults.

Objective

The aim was to assess the long-term safety and efficacy of continuous risankizumab treatment through 6 years in adults with moderate-to-severe plaque psoriasis.

Methods

LIMMitless, a phase 3, open-label extension study, evaluated the long-term safety and efficacy of risankizumab in patients with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. Patients randomized to risankizumab 150 mg at baseline of the base studies (≤ 52 weeks) were eligible to enroll in the LIMMitless study, in which they received risankizumab 150 mg subcutaneously every 12 weeks for an additional 252 weeks. This final analysis assessed safety (treatment-emergent adverse events [TEAEs]) through 324 weeks and efficacy (including proportions of patients who achieved ≥ 90%/100% improvement from baseline in Psoriasis Area and Severity Index [PASI 90/PASI 100], static Physician’s Global Assessment of clear or almost clear [sPGA 0/1], or Dermatology Life Quality Index of no effect on patient’s quality of life [DLQI 0/1]) through 304 weeks.

Results

Of 897 patients enrolled in the LIMMitless study, 661 completed the study for a total of 4921.2 patient years of exposure to risankizumab. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low and consistent with rates observed in previous studies. During the base studies, risankizumab treatment demonstrated high rates of rapid and durable efficacy through 52 weeks; risankizumab treatment also maintained or further improved efficacy and quality-of-life outcomes in the LIMMitless study. At week 304, 86.0% of patients achieved PASI 90, 54.2% achieved PASI 100, 84.7% achieved sPGA 0/1, and 76.3% achieved DLQI 0/1 (using modified nonresponder imputation).

Conclusions

Long-term risankizumab was well tolerated and demonstrated high and durable efficacy through 6 years of continuous treatment.

Clinical Trial Registration

NCT03047395.

Background

Cholinergic urticaria (CholU) is characterized by pruritic papular wheals induced by various temperature-elevating stimuli such as exercise, bathing, and emotional stress. Although it is considered important to classify CholU into subtype on the basis of the pathogenesis and clinical features for better management, few studies have evaluated the rash type as a clinical feature.

Aim

This study aimed to investigate the associations between different types of rashes in CholU and their clinical phenotypes, and to consider the mechanisms underlying each type of rash.

Methods

We conducted a retrospective study of 64 patients diagnosed with CholU who visited the Dermatological Institute of Kobe University Hospital. Clinical and photographic data obtained after exercise provocation and/or thermoregulatory sweat tests were reviewed and used to classify patients into the red wheal/erythema group (n = 44) or the goosebumps group (n = 20). Intradermal tests, namely the autologous sweat skin test (ASwST) and autologous serum skin test (ASST), were performed to assess sweat and serum reactivity, respectively. The presence of atopic dermatitis and hypohidrosis was evaluated in accordance with established guidelines. Univariable logistic analyses were conducted to assess the associations between rash types and clinical features, namely age, sex, ASwST and ASST results, atopic dermatitis, hypohidrosis, pruritus, and pain. Multivariable logistic analysis was performed using only sex and age. Statistical analyses were performed using GraphPad Prism 10, with significance set at P < 0.05.

Results

The red wheal/erythema group had typical punctate or coalescent erythematous wheals, while the goosebumps group had follicular, goosebump-like rashes with or without erythema. Compared with the red wheal/erythema group, the goosebumps group had a higher proportion of males (85% versus 38.6%) and higher prevalences of hypohidrosis (89.4% versus 35.7%) and pain (89.5% versus 37.8%). In contrast, the red wheal/erythema group had significantly higher prevalences of ASwST positivity (68.4% versus 20%), atopic dermatitis (58.1% versus 5.3%), and pruritus (78.4% versus 10.5%). Univariable analysis revealed that ASwST positivity, atopic dermatitis, and pruritus were significantly associated with the red wheal/erythema group, while hypohidrosis and pain were significantly associated with the goosebumps group. Multivariable logistic analysis showed that male sex was significantly associated with the goosebumps group.

Conclusions

Patients with CholU develop rashes with varying coloration and shapes. Goosebump-like rashes, which differ from typical wheals, were often accompanied by hypohidrosis. The type of rash may help to differentiate the clinical subtypes of CholU.

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.