American Journal of Clinical Dermatology最新文献

Background

Menopause is a universal physiological transition, marked by a decline in estrogen, which has important effects on skin and mucosal health. The impact of menopause and menopausal hormone therapy (MHT) on chronic dermatoses remains incompletely defined.

Objective

The aim was to investigate the relationship between menopause, MHT, and common dermatological conditions.

Methods

PubMed, Embase, and Web of Science were searched from inception to September 2024 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies evaluated menopause or MHT in relation to alopecia, psoriasis, acne, rosacea, melasma, and hidradenitis suppurativa (HS). Investigational cohorts largely consisted of menopausal women, although participant characteristics varied. Data on study design, population, hormonal status, and dermatological outcomes were extracted and synthesized.

Results

A total of 40 studies met inclusion criteria. Alopecia, particularly frontal fibrosing alopecia (FFA) and female pattern hair loss (FPHL), showed the strongest postmenopausal associations, with most cases presenting after menopause and earlier or surgical menopause conferring greater risk. Psoriasis frequently persisted or worsened after menopause, though objective assessments are limited. Acne and rosacea generally improved, whereas melasma showed mixed outcomes, including greater extra-facial involvement post menopause. HS responses to menopause were inconsistent. MHT was linked to increased risk of FFA and rosacea, whereas findings for other dermatoses were more variable or absent. Most of the studies involved MHT formulations that are less commonly used in current clinical practice.

Conclusion

Menopause influences the onset and course of several chronic dermatoses, while data on MHT remain more limited and inconsistent. Dermatologists should consider menopausal status and hormone therapy exposure when evaluating skin disease. Longitudinal, dermatology-focused studies—particularly those integrating diverse populations and updated hormone therapies—are needed to inform individualized care.

Psoriasis is a systemic inflammatory disease increasingly recognized for its association with elevated cardiovascular risk, driven by immune-mediated endothelial dysfunction and accelerated atherosclerosis. Non-invasive cardiovascular imaging has consistently demonstrated a spectrum of subclinical abnormalities in patients with moderate-to-severe psoriasis, including coronary microvascular dysfunction, high-risk plaque burden, vascular inflammation, myocardial remodeling, and increased arterial stiffness. This critical review summarizes the role of different imaging modalities in detecting psoriasis-associated cardiovascular alterations and evaluates emerging data on the impact of systemic therapies. Imaging abnormalities in psoriasis often precede clinical events and can support early risk reclassification and referral. Biologic therapy is associated with improved coronary microvascular function and with reductions in noncalcified plaque burden and high-risk plaque features on coronary computed tomography angiography (CCTA), and statins reduce vascular ¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) in psoriasis cohorts. Outcome data that link these imaging changes to reduced events remain limited. Imaging should be used selectively, with coronary calcium scoring or carotid ultrasound for risk refinement in asymptomatic adults and targeted CCTA or transthoracic echocardiography (TTE) when symptoms, examination, or screening suggest cardiovascular involvement.

Background

Oral Janus kinase inhibitors (JAKi) have proven effective in the treatment of atopic dermatitis (AD) in multiple clinical trials, providing rapid response, deep efficacy when given at the highest formulated dose, and in the case of abrocitinib and upadacitinib, superiority to biologics treatments in the first 4–16 weeks. However, it is unclear how this translates to real-world efficacy and safety.

Objectives

To assess the real-world effectiveness and safety of abrocitinib, baricitinib and upadacitinib in the treatment of AD.

Methods

PubMed and EMBASE were systematically searched from inception until 3 January 2025 for observational studies investigating effectiveness and safety of abrocitinib, baricitinib and upadacitinib for the treatment of AD. The primary outcomes were the proportion of patients achieving a ≥ 75% improvement in the Eczema Area and Severity Index (EASI-75) following treatment with abrocitinib, baricitinib or upadacitinib after 12 and 16 weeks. Secondary outcomes included the proportion of patients achieving EASI-50, EASI-90 and the proportion of patients experiencing adverse events (AE). Tertiary outcomes included the Dermatology Life Quality Index (DLQI) and the Peak-Pruritus Numerical rating scale (PP-NRS).

Results

A total of 63 studies including 517 patients treated with abrocitinib (50 mg [0.2%], 100 mg [50.9%], 200 mg [34.2%], mixed/unknown [14.7%]), 574 with baricitinib (2 mg [14.8%], 4 mg [71.9%], mixed/unknown [13.3%]) and 2779 with upadacitinib were included (15 mg [46.6%], 30 mg [33.3%], mixed/unknown [20.0%]). Most studies reported outcomes for doses combined. Across all doses, the proportion of patients achieving EASI-75 and -90 was 75% and 38% for abrocitinib, 51% and 24% for baricitinib and 83% and 55% for upadacitinib after 16 weeks, respectively. Acne and herpes simplex virus (HSV) were frequently reported across all doses of abrocitinib (21%, 2%), baricitinib (8%, 6%) and upadacitinib (15%, 6%), but patients treated with 100 mg abrocitinib and 30 mg upadacitinib reported the highest prevalence of acne and HSV, respectively. Few studies reported serious AEs across all treatments and doses.

Conclusions

Data from real-world studies of JAKis in AD show effectiveness and safety similar to clinical trials using the highest treatment doses. It is important to be aware of HSV and acne risk as these AEs are the most common reasons for discontinuation. Interpretation of results was complicated by the lack of studies reporting dosage information.

The incidence of cutaneous squamous cell carcinoma (CSCC) is on the rise. While the majority of cases are curable with surgery alone, the burden of high-risk tumors that require additional therapies is increasing. While systemic therapy has long been used to treat locally advanced and metastatic CSCC, immunotherapy is a more recent advancement, and use of neoadjuvant and adjuvant systemic therapy in the perioperative setting is an area of ongoing study. While chemotherapy, epidermal growth factor inhibitors, and chemoradiation have all been studied in the perioperative setting, the response is highly variable, and side effects are common. Immunotherapy, in particular programmed cell death protein/ligand-1 inhibitors, have revolutionized treatment of advanced CSCC. Cemiplimab and pembrolizumab have been studied for neoadjuvant and adjuvant use, and atezolizumab for neoadjuvant use. Cemiplimab has shown the most promise, with a 64–75% major or complete pathologic response rate in the neoadjuvant setting, and significantly improved recurrence, metastasis, and disease-free survival rates over placebo in the adjuvant setting. While neoadjuvant and adjuvant immunotherapy has evolved as a promising treatment option for high-risk CSCC, several questions remain unanswered and are subject to ongoing research. This includes investigating optimal treatment regimens, duration, and timing; developing methods to better predict and identify responders; establishing long-term outcomes and safety data; and carrying out further studies in special populations such as organ transplant recipients.

Background

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by intensely pruritic papulonodular lesions. Patients with PN frequently experience comorbid atopic conditions. Dupilumab is the first approved therapy for PN, but the efficacy of dupilumab in patients with PN with or without atopic comorbidities has not been investigated.

Objective

We aimed to assess the efficacy and safety of dupilumab in patients with PN with or without a history of atopic comorbidities.

Methods

Randomized, double-blind, parallel-group, placebo-controlled, 24-week, phase III trials LIBERTY-PN PRIME and PRIME2 were conducted independently in 16 countries in North and South America, Europe, and Asia. Patients were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. In this pre-specified subgroup analysis of pooled data, adults with moderate-to-severe PN, inadequately controlled by topical prescription therapies, were stratified according to the presence or absence of atopic comorbidity history. Investigators assessed itch (Worst Itch Numeric Rating Scale), skin lesions (Investigator’s Global Assessment for PN Stage), and patient-reported quality of life (evaluated using the Dermatology Life Quality Index, Skin Pain Numeric Rating Scale, Hospital Anxiety and Depression Scale, and a Sleep Numeric Rating Scale).

Results

Three hundred and eleven patients were randomized to dupilumab (N = 153; atopic/non-atopic n = 67/86) or placebo (N = 158; atopic/non-atopic n = 68/90). At week 24 in both the atopic and non-atopic subgroups, significantly more patients achieved clinically meaningful improvements with dupilumab treatment compared with placebo in itch (atopic: 58.2% vs 20.6%; P < 0.0001; non-atopic: 59.3% vs 17.8%; P < 0.0001), clear/almost clear skin (atopic: 52.2% vs 16.2%; P < 0.0001; non-atopic: 41.9% vs 17.8%; P = 0.0005), and concomitant itch and skin lesion improvements (atopic: 37.3% vs 7.4%; P = 0.0057; non-atopic 33.7% vs 10.0%; P = 0.007). Patients showed significant improvements in skin pain, Dermatology Life Quality Index, Hospital Anxiety and Depression Scale, and sleep, with dupilumab treatment compared with placebo, regardless of atopic history. Safety was generally consistent with the known dupilumab safety profile.

Conclusions

Dupilumab significantly improved disease signs, symptoms, and health-related quality of life with similar onset time and response magnitude compared with placebo in adult patients with PN, irrespective of the presence or absence of atopic comorbidities.

Clinical Trial Registration

ClinicalTrials.gov Identifiers: NCT04183335 and NCT04202679.

Background

The efficacy and safety of once-daily roflumilast foam 0.3%, a potent phosphodiesterase 4 inhibitor, has been demonstrated in patients with seborrheic dermatitis (SD).

Objectives

To evaluate long-term effects of roflumilast foam 0.3% in patients with SD.

Methods

A phase II, open-label trial (no. NCT04445987) was conducted in patients (aged ≥ 12 years) with SD who completed a prior roflumilast foam trial or were naïve to roflumilast and vehicle. Patients applied roflumilast foam 0.3% once daily to all affected areas, including the scalp, face, trunk, and intertriginous areas, for 24 or 52 weeks (during the course of the trial, the protocol was amended to extend the duration of treatment from 24 weeks to 52 weeks). The primary endpoints were occurrence of treatment-emergent adverse events (AEs); local tolerability and efficacy (via Investigator Global Assessment [IGA]) were also assessed.

Results

Overall, 400 patients participated, among whom 62 were enrolled for 52 weeks. AE rates were low, and ≤ 1.1% reported stinging sensation at the application site at each visit. Durable improvement in signs and symptoms of SD was observed at weeks 24 and 52, with 76.0% and 80.4% of patients, respectively, achieving an IGA of clear or almost clear.

Conclusions

Roflumilast foam 0.3% was well tolerated and improved and/or maintained improvements in signs and symptoms of SD for up to 52 weeks.

ClinicalTrials.gov Listing

NCT04445987.

Background

Acne vulgaris (acne) is a common dermatological condition that can profoundly affect psychosocial well-being. Health-related quality of life (HRQoL) is an important outcome measure to assess the burden of acne in research and clinical practice.

Objective

This systematic review aimed to identify, critically appraise, and synthesize current evidence on the effects of acne on HRQoL and other psychosocial outcomes.

Methods

Structured searches of PubMed and Web of Science were conducted to identify studies measuring any HRQoL or psychosocial outcome in patients with acne vulgaris (all ages). Eligible studies were those that included ≥ 50 patients with acne, measured HRQoL or psychosocial outcomes as primary endpoints, were conducted in Europe and North America, and were published in English from 1 January 2014 to 30 April 2024. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools.

Results

In total, 101 studies were deemed eligible for inclusion. They varied widely in terms of study design, population, outcomes, and quality, but overall demonstrated the adverse impacts of acne on HRQoL, mental health outcomes, and the lived experiences of people with acne. Despite their heterogeneity, studies frequently found that acne predominantly affected the emotional and psychological domains of HRQoL, and was particularly burdensome to adults, females, and those with more severe acne.

Conclusions

This review collated the spectrum of impacts that acne vulgaris can impose on psychosocial well-being, and highlighted the need for consensus outcome measures to streamline future research and improve clinical practice.

PROSPERO Registration

CRD42024539174.

Low-dose oral minoxidil has gained recognition as an off-label treatment for hair loss disorders, including androgenetic alopecia, telogen effluvium, and alopecia areata. Originally developed to treat hypertension, its hair growth-promoting effects are attributed to multiple mechanisms: primarily through direct KATP channel activation in dermal papilla cells, with additional effects from Wnt/β-catenin signaling, enhanced cysteine incorporation, and modulation of inflammatory and androgenic pathways. Clinical studies demonstrate comparable efficacy to topical minoxidil, with the added advantages of improved adherence, lower cost, and reduced application-related side effects. Common adverse effects include dose-dependent hypertrichosis (24% incidence), transient shedding (16–22%), and mild peripheral edema (2%), while serious complications, including pericardial effusion, are rare at doses used for alopecia. International Delphi consensus supports standardized dosing: 1.25 mg/day starting dose for women (range 0.625–5 mg/day) and 2.5 mg/day for men (range 1.25–5 mg/day), with lower doses recommended for adolescents and caution advised in renal/hepatic impairment. Contraindications include pericardial disease, uncontrolled hypertension, and pregnancy. While current evidence supports its safety and efficacy, further research is needed to establish long-term outcomes and optimal use in pediatric populations. With appropriate monitoring, oral minoxidil represents a promising therapeutic option in the management of hair loss disorders.