American Journal of Clinical Dermatology最新文献

Radiotherapy-induced skin fibrosis is a chronic progressive complication of radiotherapy that impairs function, aesthetics, and quality of life yet remains under-recognized and undertreated. While acute cutaneous toxicities are typically transient, chronic sequelae such as fibrosis, lymphedema, atrophy, telangiectasia, and dyspigmentation reflect uncontrolled tissue remodeling driven by sustained inflammation and fibroblast activation. Ionizing radiation generates reactive oxygen species that initiate vascular and epithelial injury, trigger immune infiltration, and perpetuate a cycle of transforming growth factor-β-driven myofibroblast differentiation, epithelial-to-mesenchymal transition, extracellular matrix deposition, and epigenetic reprogramming. Predicting and grading radiotherapy-induced skin fibrosis remains difficult: physician-reported scales lack sensitivity, and emerging imaging modalities and candidate tissue biomarkers require validation. Therapeutic strategies include pentoxifylline with vitamin E, oral statins, corticosteroids, fractional CO₂ and pulsed dye lasers, autologous fat grafting with adipose-derived stem cells, and manual therapies, each with varying efficacy. Investigational approaches such as deferoxamine, microneedling, and mesenchymal stem cell-based interventions show antifibrotic and regenerative potential, while candidate therapies including topical statins, antioxidants, timolol, tamoxifen, and colchicine remain untested. Despite the rising burden among cancer survivors, many patients do not receive a dermatologic evaluation, and consensus guidelines are limited. Dermatology should lead multi-modal efforts to integrate systemic, topical, and procedural interventions, develop standardized diagnostic frameworks, validate biomarkers, and conduct skin-specific clinical trials. Greater involvement of dermatologists in survivorship care, early referral, and advocacy for policy and funding will be essential to address radiotherapy-induced skin fibrosis and improve patient outcomes.

Androgenetic alopecia (AGA) affects nearly 50% of women during their lifetime, representing the most prevalent form of chronic hair loss in this population. Despite its high incidence, AGA in women remains underdiagnosed and undertreated, with significant psychosocial consequences including diminished self-esteem, impaired social functioning, and reduced quality of life that often exceed impacts observed in men. AGA pathophysiology involves complex interactions between hormonal, genetic, and environmental factors. Androgens promote follicular miniaturization through progressive shortening of the anagen phase, while estrogens may provide protective effects. Genetic studies reveal sex-specific differences in disease mechanisms, and environmental factors like oxidative stress and pollution may contribute to disease progression. Clinical evaluation requires careful consideration of differential diagnoses including chronic telogen effluvium, diffuse alopecia areata, and scarring alopecias. Diagnostic tools include trichoscopy, pull testing, and trichometric measurements to assess hair density and miniaturization patterns. Currently, topical minoxidil is the only FDA-approved treatment for female AGA, also referred to as female pattern hair loss (FPHL). Off-label therapies include low-dose oral minoxidil, anti-androgens such as spironolactone and 5-alpha reductase inhibitors (finasteride and dutasteride), and hair transplantation. Adjunctive treatments like low-level light therapy and platelet-rich plasma may further augment improvement and are often best used in conjunction with medical therapies. Critical research gaps persist, including the paucity of randomized controlled trials for AGA that include female patients. There is an urgent need for additional FDA-approved therapies for AGA in women to increase treatment access and reduce its psychosocial burden.

Chronic hand eczema (CHE) is an inflammatory skin disease localized to the hands and wrists that lasts for more than 3 months or relapses at least twice per year. The diagnosis, treatment, and management of CHE presents clinical challenges owing to its multifactorial etiology, heterogeneous presentation, and the absence of a standardized classification system. In the USA there are no specific International Classification of Disease-10 (ICD-10) diagnostic codes, which makes tracking the diagnosis and resultant treatments difficult. Topical delgocitinib is currently the only Food and Drug Administration approved medication for CHE, for patients who have not responded adequately to, or are unable to use, topical corticosteroids. This article provides an overview of the diagnostic and therapeutic considerations of CHE, while presenting practical recommendations to help improve management of the disease within the USA. Diagnostic assessments focusing on detailed patient history and physical examination are proposed, followed by a multi-step approach to treatment. The importance of both clinician, and patient, reported outcome measures are emphasized, to encompass not only disease presentation and severity, but also the impact on patient quality of life.

Background: A growing number of epidemiological studies have suggested a causal link between air pollution and several common skin diseases. However, considerable variation in study design and heterogeneous results make it difficult for clinical dermatologists to judge the true relevance of air pollution as a risk factor for skin diseases.

Objective: We therefore conducted a systematic review of epidemiological studies to investigate the associations of short- and long-term exposure to ambient air pollutants with atopic dermatitis, psoriasis, urticaria, acne, melanoma skin cancer, non-melanoma skin cancer, and skin aging.

Methods: We systematically searched two comprehensive databases, SCOPUS and PubMed, from 1 January, 1990 to 30 April, 2025 for relevant observational studies. After screening 1393 eligible studies, 77 studies were selected. We defined the level of evidence for causality by assessing the risk of bias in such studies. Ambient air pollutants included particulate matter with an aerodynamic diameter of 10 µm or smaller, particulate matter with an aerodynamic diameter of 2.5 µm or smaller, and gaseous pollutants (nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide).

Results: We obtained five major results: (i) the majority of studies strongly advocated the harmful effects of air pollution on the above-mentioned skin diseases, but results across studies were heterogeneous in terms of direction and magnitude. (ii) For all skin diseases, the risk of bias assessment resulted in high risk, which was mainly observed in the domains of confounding, selection bias, and exposure assessment. Consequently, certainty in evidence or causal inference was usually low to very low. (iii) In most studies, high air pollution had a more immediate effect (same day) and lasted up to a week after exposure. (iv) The results on vulnerable subpopulations such as children, older people, or women were inconclusive. (v) Studies were mostly from the upper-middle and higher income countries.

Conclusions: Despite numerous epidemiological studies on air pollution and skin diseases, the overall quality of evidence is low. We encourage more longitudinal studies, such as cohort studies or panel studies, to support causality and study change in disease severity over time and improved exposure assessments, and adjustment for critical confounding factors. Importantly, more studies are needed from low- to middle-income countries and on susceptible groups who are most vulnerable to climate change.

Background: Although clinical trials have demonstrated the efficacy and safety of abrocitinib in atopic dermatitis, there remains a lack of comprehensive long-term real-world studies across diverse patient populations.

Objective: We aimed to characterize long-term treatment responses and adverse events of abrocitinib in adults with moderate-to-severe atopic dermatitis in real-world daily practice.

Methods: We conducted a retrospective observational study of adults with moderate-to-severe atopic dermatitis who were treated with abrocitinib between 1 January, 2022 and 1 January, 2025 at a multi-site hospital system. Final follow-up was defined as each patient's last documented clinic visit before 1 January, 2025. Primary outcomes were changes in clinical severity scores from baseline to the final follow-up. Secondary outcomes included 1-year clinical response rates, laboratory trends, adverse events, and treatment discontinuations.

Results: We identified 50 adults with moderate-to-severe atopic dermatitis (mean age 40 ± 14 years; 56% female) who had been treated with abrocitinib. Most (96%) had not responded to prior systemic therapies, including dupilumab (80%) and prednisone (36%). Clinical response improved over time: at 12-24 weeks (n = 33), 43.5% achieved an improvement of 75% or more in the Eczema Area and Severity Index (EASI-75) and 42.9% achieved an Investigator's Global Assessment (IGA) 0/1; by 36-48 weeks (n = 18), these rates rose to 53.9% and 45.5%, respectively. After 1 year (n = 29), 52.6% maintained EASI-75 and 56.5% achieved IGA 0/1. Final follow-up showed significant reductions from baseline in IGA (- 48.5%), body surface area (- 60.3%), and EASI (- 58.6%) [all p < 0.0001]. Adverse events were mild, the most common were acne (8%) and nausea (6%).

Conclusions: In our real-world study, adults with moderate-to-severe atopic dermatitis treated with abrocitinib had a progressive sustained clinical improvement across various races, ages, doses, disease onsets, atopic comorbidities, and body mass index ranges.

Arboviral infections, notably those caused by West Nile virus (WNV), Dengue virus (DENV), Zika virus (ZIKV), and Chikungunya virus (CHIKV), represent a growing global health concern due to their expanding geographic distribution and evolving clinical spectrum. While systemic and neurologic complications are well recognized, cutaneous manifestations are frequently overlooked despite their diagnostic and prognostic value. These viruses, transmitted primarily by Aedes or Culex mosquitoes, share overlapping symptoms such as fever, headache, arthralgia, myalgia, and malaise but can often be distinguished by specific dermatologic features. WNV may present with a subtle truncal exanthem; DENV is characterized by flushing, petechiae, and the 'white islands in a sea of red' pattern; ZIKV typically is associated with a fine, pruritic maculopapular rash with palmar-plantar involvement, edema and erythema of the malar region of the face, and conjunctival injection; CHIKV frequently shows an asymptomatic or pruritic macular or maculopapular rash that can result in pigmentary changes mostly on the face and mucocutaneous involvement. Other arboviral infections such as Usutu virus (USUV) and Toscana virus (TOSV) more rarely exhibit cutaneous signs. These include transient macular or urticarial rashes, conjunctivitis, and aphthous-like ulcers on the palate during early or prodromal phases. This review synthesizes current clinical, virologic, and pathophysiologic insights into these cutaneous presentations, highlighting their diagnostic relevance, underlying mechanisms, and implications for dermatologic and interdisciplinary care. Recognizing these dermatologic signs can significantly aid early diagnosis and improve patient management in endemic and outbreak settings.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch and eczematous skin lesions. Upadacitinib, a selective oral Janus kinase inhibitor, and dupilumab, a monoclonal antibody, are both approved treatments for moderate-to-severe AD. In period 1 of the LEVEL UP phase 3b/4 head-to-head study, upadacitinib-treated patients demonstrated higher simultaneous achievement of near complete skin clearance and little to no itch compared with dupilumab after 16 weeks of treatment in adults and adolescents with moderate-to-severe AD.

Objective: The objective of period 2 of the LEVEL UP study was to assess the efficacy and safety of switching from dupilumab to upadacitinib in patients with inadequate response to dupilumab.

Methods: Following period 1 of the LEVEL UP study, patients not achieving ≥ 75% improvement in the Eczema Area and Severity Index (EASI 75) from baseline at week 16 entered an additional 16-week extension phase (period 2). In period 2, patients receiving dupilumab were switched to upadacitinib 15 mg, with the potential to escalate to 30 mg based on clinical response. End points in period 2 included EASI 90, Worst Pruritus Numerical Rating Scale (WP-NRS) 0/1, and simultaneous achievement of both EASI 90 and WP-NRS 0/1 at week 20 and week 32.

Results: A total of 208 patients were switched from dupilumab to upadacitinib, entering period 2 of the study. At week 32, response rates for patients who switched were: 79.6%, 58.7%, and 19.9% achieving EASI 75, EASI 90, and EASI 100, respectively; 60.2% achieving Worst Pruritus Numerical Rating Scale improvement ≥ 4 among those with baseline WP-NRS ≥ 4; 37.0% achieving WP-NRS 0/1 among those with baseline WP-NRS > 1; and 26.8% simultaneously achieving EASI 90 and WP-NRS 0/1. Clinically, meaningful outcomes were also observed at week 20. No new safety signals were identified compared with the established safety profile of upadacitinib.

Conclusions: The current findings suggest that switching from dupilumab to upadacitinib may be an effective treatment strategy for patients who do not meet moderate-to-optimal treatment targets with dupilumab.

Clinical trial registration: LEVEL UP (NCT05601882).

Nicotinamide has been widely promoted as a low-cost safe chemopreventive agent against non-melanoma skin cancer. A recent large retrospective study of more than 33,000 US veterans reported a 14% reduction in overall skin cancer risk and a 22% reduction in cutaneous squamous cell carcinoma with nicotinamide use, with greater benefit observed when initiated early. This critical appraisal identifies key methodological limitations of that study, including unmeasured confounders, immortal time bias, exposure misclassification, flexible analytical modelling and limited external validity. The findings are discussed in the context of two recent systematic reviews (2022 and 2023) to provide a balanced appraisal of the evidence and clarify whether nicotinamide should be recommended in routine practice. Current evidence does not yet confirm the chemopreventive efficacy of nicotinamide. Caution is warranted before its widespread clinical adoption-the jury, as it stands, is still out.

Pemphigus is a group of rare autoimmune blistering disorders affecting the skin and mucosal surfaces, caused by pathogenic immunoglobulin G (IgG) autoantibodies targeting desmosomal cadherins, specifically desmoglein-1 and desmoglein-3, which are key components of desmosomes. There are two main forms of pemphigus: pemphigus vulgaris (PV) and pemphigus foliaceus (PF), with PV being the most common. Pemphigus can be life-threatening owing to the progressive loss of the epidermal and epithelial barrier function. However, the introduction of rituximab, an anti-CD20 monoclonal antibody, has significantly improved treatment outcomes in pemphigus. This review provides a comprehensive overview of the current treatment landscape for pemphigus, highlighting both established and emerging therapeutic approaches.