American Journal of Clinical Dermatology最新文献

Lichen simplex chronicus (LSC), also known as neurodermatitis, is a common chronic pruritic dermatosis defined by lichenified plaques resulting from persistent scratching. Though often secondary to underlying dermatologic, systemic, or psychological triggers, LSC represents a distinct clinical entity with significant morbidity. The hallmark itch-scratch cycle contributes not only to visible skin changes but also to substantial sleep disruption, emotional distress, and functional impairment. Psychological stress, anxiety, and depression are frequent comorbidities and can further perpetuate disease chronicity. This review provides a comprehensive summary of the evolving understanding of LSC, from its neuroimmune-driven pathogenesis to the wide spectrum of therapeutic strategies currently available. In addition to topical corticosteroids, novel approaches including immunomodulators, neuromodulators, Janus kinase (JAK) inhibitors, and biologics are being increasingly explored. Procedural therapies such as cryotherapy, fractional laser resurfacing, and botulinum toxin injections, have also emerged as valuable tools, particularly in treatment-refractory cases. Recent insights into type 2 inflammation and dysregulated sensory pathways have informed the rationale for these targeted strategies. In anatomically sensitive areas such as the genital region, where topical agents may be poorly tolerated, systemic treatments may be required. Given this complexity, individualized, multimodal treatment plans are critical to optimizing management and improving quality of life (QoL) in patients with LSC. By synthesizing current data on pathophysiology, diagnosis, and both established and emerging therapies, this review aims to guide clinicians in optimizing care for patients with LSC and addressing its far-reaching psychosocial burden.

The growing availability of targeted immunomodulatory therapies has transformed the treatment landscape for chronic inflammatory skin diseases. However, treatment selection remains largely empirical, often guided more by trial-and-error and insurance mandates than by an individual patient’s underlying disease biology. This disconnect between therapeutic strategy and the need to address and calibrate for patient molecular heterogeneity undermines clinical outcomes and contributes to inefficiency in care delivery. Precision medicine offers a solution by tailoring diagnosis and treatment to the molecular and cellular features of each patient’s skin disease. In this Current Opinion, we outline key clinical contexts where precision approaches can be transformative: diagnostic ambiguity, selecting treatments for an established diagnosis, and selecting treatments without a defined diagnosis or disease mechanism. We highlight advances in precision techniques such as single-cell RNA sequencing and spatial transcriptomics that enable more refined skin disease classification and accurate prediction of drug response. Although several challenges remain before these techniques can be widely adopted, such as limited biomarker validation, high costs, and a lack of breadth in research cohorts, we argue that their potential benefits, for patients, clinicians, and the broader field of dermatologic care, substantially outweigh the associated costs. We advocate for expanded funding, population-based research, and scalable diagnostics to successfully integrate precision medicine into dermatology. By combining molecular phenotyping with traditional clinicopathologic diagnosis, precision medicine can reduce therapeutic inefficiency, improve patient outcomes, and redefine care paradigms in chronic inflammatory skin disease.

As women of childbearing potential constitute a considerable portion of the total psoriasis population, dermatologists must consider both the clinical and psychosocial implications of psoriasis when treating these patients. This review summarizes key clinical considerations when treating women of childbearing potential with psoriasis, regarding family planning, pregnancy, and the postpartum period, aiming to assist in identifying common concerns within this population. Many women report initiating the discussion on family planning but having limited access to information. Concerns about the impact of psoriasis and its treatment on fertility, pregnancy, and lactation are common, and lack of adequate information can lead to irrevocable decisions. Despite conflicting results, current evidence suggests a potential negative correlation between moderate-to-severe psoriasis and fertility. Studies on adverse maternal and neonatal events associated with psoriasis show inconsistent outcomes and should be communicated with caution. With the increase in available treatment options during pregnancy and lactation, particularly in cases of severe psoriasis, personalized treatment plans are becoming more achievable, allowing dermatologists to better address the needs of their patients. The majority of patients can be treated during pregnancy with topical treatments or ultraviolet-B irradiation. While the general recommendation is to stop systemic treatment before conception, decisions should be made on an individualized basis. If treatment cannot be discontinued, tumor necrosis factor-α inhibitors and cyclosporine can be used. It is essential to inform parents of the additional risks associated with live or live-attenuated vaccines in cases where the mother has received systemic treatment during pregnancy and to delay vaccinations accordingly.

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.