American Journal of Clinical Dermatology最新文献

Psoriasis, a chronic inflammatory skin disease, affects millions of people worldwide. It imposes a significant burden on patients’ quality of life and healthcare systems, creating an urgent need for optimized diagnosis, treatment, and management. In recent years, image-based artificial intelligence (AI) applications have emerged as promising tools to assist physicians by offering improved accuracy and efficiency. In this review, we provide an overview of the current landscape of image-based AI applications in psoriasis. Emphasis is placed on machine learning (ML) algorithms, a key subset of AI, which enable automated pattern recognition for various tasks. Key AI applications in psoriasis include lesion detection and segmentation, differentiation from other skin conditions, subtype identification, automated area involvement, and severity scoring, as well as personalized treatment selection and response prediction. Furthermore, we discuss two commercially available systems that utilize standardized photo documentation, automated segmentation, and semi-automated Psoriasis Area and Severity Index (PASI) calculation for patient assessment and follow-up. Despite the promise of AI in this field, many challenges remain. These include the validation of current models, integration into clinical workflows, the current lack of diversity in training-set data, and the need for standardized imaging protocols. Addressing these issues is crucial for the successful implementation of AI technologies in clinical practice. Overall, we underscore the potential of AI to revolutionize psoriasis management, highlighting both the advancements and the hurdles that need to be overcome. As technology continues to evolve, AI is expected to significantly improve the accuracy, efficiency, and personalization of psoriasis treatment.

Alopecia areata is a common autoimmune disorder characterized by non-scarring hair loss on the scalp or other hair-bearing surface. In recent years, Janus kinase (JAK) inhibitors have shown promise in the treatment of alopecia areata by disrupting the signaling pathways involved in immune-mediated hair follicle damage. However, some patients with alopecia areata exhibit insufficient responses to JAK inhibitors. This review aims to explore the predictive factors for poor responses to JAK inhibitors in patients with alopecia areata and to discuss alternative treatment strategies in such cases. Patients with a longer duration of the current episode and higher baseline severity are at an increased risk of inadequate JAK inhibitor responses. Oral administration rather than topical application, and extended treatment durations, correlate with a favorable response. Notably, the poor response to JAK inhibitors in alopecia areata may be related to the amount and functional depletion of regulatory T cells resulting from an augmented T helper-2-type immune response. For patients with poor responses to JAK inhibitors, treatment adjustments may include increasing the dosage, extending the treatment duration, combination therapies, or switching to alternative JAK inhibitors. For patients with atopic comorbidities or psychological problems, it is important to select corresponding treatment options to optimize patient outcomes. Further research is needed to establish more reliable predictors and improve overall patient care.

Uveal melanoma (UM) is genetically a distinct tumor compared to cutaneous melanoma (CM), and due to its low mutational burden, it is far less perceptible to the immune system. Thus, treatments that have revolutionized the treatment of CM remain widely inefficient in metastatic UM or only demonstrate effectiveness in a small subpopulation of patients. To this end, the therapeutic benefit of immune checkpoint blockade is very limited and may come at the expense of severe immune-related adverse events that could potentially affect all organ systems. Notably, tebentafusp, an entirely novel class of anti-cancer drugs, has received official authorization for the treatment of metastatic UM. It is the first agent that demonstrated a survival advantage in a randomized controlled trial of metastatic UM patients. Despite the survival benefit and approval, the restriction of tebentafusp to HLA-A*02:01-positive patients and the low objective response rate indicate the persistent need for additional therapies. Thus, liver-directed therapies are commonly used for tumor control of hepatic metastases and represent a central pillar of the daily management of liver-dominant disease. Further, promising data from targeted therapies independent of MEK-inhibitors, such as the combination of darovasertib and crizotinib, raise hope for additional options in metastatic UM in the future. This narrative review provides a timely and comprehensive overview of the current treatment landscape for metastatic UM.

Acne scarring is a common sequela of acne vulgaris, which seriously affects facial esthetics. The treatment options for acne scars vary depending on the development stage, color, type, and location of scarring. The objective and precise assessment of acne scars is a prerequisite for treatment, and it is also an important means of monitoring the treatment effect. The traditional methods to evaluate the types and severity grade of acne scars are primarily based on subjective assessment by physicians, which lacks objectivity and accuracy. Novel noninvasive skin imaging techniques, such as skin surface imaging analysis systems, dermoscopy, reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), and multiphoton tomography (MPT), provide new tools for the rapid and objective assessment of acne scars. This article reviews the progress of skin imaging techniques in the diagnosis, classification, and efficacy evaluation of acne scars.

With the continued development of biologics for the treatment of psoriasis, some patients have achieved optimal control, but a recommended biologic sequence if a biologic fails to initially improve the skin, termed primary nonresponse, or loses efficacy after initial improvement, termed secondary nonresponse, is still lacking. Primary and secondary nonresponse can occur with any class of biologics, and the type of nonresponse can drive the choice of whether to switch within a biologic class or to a different biologic class. The choice of biologic can also be challenging when managing psoriasis and concomitant psoriatic arthritis, as treatment differs on the basis of the severity of both diseases and further classification of axial and peripheral joint involvement. When choosing a biologic, each patient's comorbidities and preferences are also taken into account to provide the optimal therapy. With this lack of an established biologic sequence after biologic failure, the objective of our review is to define a therapy sequence for the tumor necrosis factor (TNF), interleukin-17 (IL-17), and interleukin-23 (IL-23) inhibitor classes in the treatment of psoriasis and psoriatic arthritis. Our proposed biologic sequence was derived through an analysis of the efficacy of each biologic class, primary and secondary nonresponse rates from clinical trials, and clinical experience with expert opinion.

Background: Palmoplantar pustulosis (PPP), a refractory skin disease characterized by repeated eruptions of sterile pustules and vesicles on palms and/or soles, involves interleukin-17 pathway activation. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, is being investigated for use in PPP treatment.

Objective: The aim was to assess the efficacy and safety of brodalumab in Japanese PPP patients with moderate or severe pustules/vesicles.

Methods: A phase 3, randomized, double-blind, placebo-controlled trial was conducted between July 2019 and August 2022, at 41 centers in Japan. Patients aged 18-70 years with a diagnosis of PPP for ≥ 24 weeks, a PPP Area Severity Index (PPPASI) score of ≥ 12, a PPPASI subscore of pustules/vesicles of ≥ 2, and inadequate response to therapy were included. Participants were randomized 1:1 to receive brodalumab 210 mg or placebo, subcutaneously (SC) at baseline, weeks 1 and 2, and every 2 weeks (Q2W) thereafter until week 16. Changes from baseline to week 16 in the PPPASI total score (primary endpoint) and other secondary skin-related endpoints and safety endpoints were assessed.

Results: Of the 126 randomized patients, 50 of 63 in the brodalumab group and 62 of 63 in the placebo group completed the 16-week period. Reasons for discontinuation were adverse event (n = 6), withdrawal by patient/parent/guardian (n = 3), progressive disease (n = 3), and lost to follow-up (n = 1) in the brodalumab group and Good Clinical Practice deviation (n = 1) in the placebo group. Change from baseline in the PPPASI total score at week 16 was significantly higher (p = 0.0049) with brodalumab (least-squares mean [95% confidence interval {CI}] 13.73 [10.91-16.56]) versus placebo (8.45 [5.76-11.13]; difference [95% CI] 5.29 [1.64-8.94]). At week 16, brodalumab showed a trend of rapid improvement versus placebo for PPPASI-50/75/90 response (≥ 50%/75%/90% improvement from baseline) and Physician's Global Assessment 0/1 score: 54% versus 24.2%, 36.0% versus 8.1%, 16.0% versus 0.0%, and 32.0% versus 9.7%, respectively. Infection was the dominant treatment-emergent adverse event (TEAE); the commonly reported TEAEs were otitis externa (25.4%/1.6%), folliculitis (15.9%/3.2%), nasopharyngitis (14.3%/4.8%), and eczema (14.3%/12.9%) in the brodalumab/placebo groups, respectively. The severity of most TEAEs reported was Grade 1 or 2 and less frequently Grade ≥ 3.

Conclusions: Brodalumab SC 210 mg Q2W demonstrated efficacy in Japanese PPP patients. The most common TEAEs were mild infectious events.

Trial registration: NCT04061252 (Date of Trial Registration: August 19, 2019).

Background and objective: Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that can be associated with primary immunodeficiency. The pathogenesis of PG has not yet been elucidated, although contributions from dysregulation of the immune system in patients with apparent genetic predispositions have been postulated. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review with the objective of identifying inborn errors of immunity in the presence of PG as well as their clinical characteristics of severity including number of PG lesions and anatomic areas affected, and treatment outcomes.

Methods: A literature search was performed using PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science through August 24, 2023, for studies published in English using the search terms: "pyoderma gangrenosum," "inborn error of immunity," "immune defect*," and a list of genetic mutations potentially associated with PG.

Results: Seventy-four cases of PG associated with inborn errors of immunity were identified. The results demonstrate an association of PG with a variety of inborn errors of immunity, including genetic mutations not classically associated with the condition. Genetic mutations such as BTK, IL1RN, ITGB2, LPIN2, MEFV, NFkB1, NLRP3, NLRP12, NOD2, PSMB8, PLCG2, PSTPIP1, RAG1, TTC37, and WDR1, as well as complement component 2/complement component 4 (C2/C4) and complement component 7 (C7) deficiencies were identified in the presence of either idiopathic or syndromic PG. Of note, mutations in genes such as PSMB8, NLRP3, and IL1RN were found to be associated with a more severe and atypical course of PG, whereas mutations in RAG1 as well as those causing a C2/C4 deficiency were associated with the mildest clinical presentations of PG. Mutations in NFkB1, ITGB2, and PSTPIP1 were associated with the most heterogeneous clinical presentations.

Conclusions: Human inborn errors of immunity may be implicated in the genetic predisposition to PG and may influence the clinical presentation. Due to the rarity of these diseases, further work must be done to describe the association between inborn errors of immunity and PG. Identifying inborn errors of immunity that may contribute to the development of PG may assist in further elucidating the mechanism of PG, guiding targeted treatment, and improving clinical outcomes for these patients.