American Journal of Clinical Dermatology最新文献

Background

We report pooled safety data for baricitinib treatment of severe alopecia areata in patients in BRAVE-AA1 (phase II/III) and BRAVE-AA2 (phase III), including data from the long-term extension and bridging extension periods.

Methods

Data are reported from the extended dataset (patients receiving continuous baricitinib 2 mg or 4 mg) and the all-baricitinib dataset (all patients receiving any dose of baricitinib at any time during the trials). Safety outcomes include treatment-emergent adverse events, adverse events of special interest, and abnormal changes in laboratory test results. Incidence rates (IRs) per 100 patient-years were calculated based on time at risk. Data cutoff dates were 22 May, 2023, for BRAVE-AA1 and 8 May, 2023, for BRAVE-AA2 and included follow-up through at least 152 weeks.

Results

Data were collected for 1303 patients treated with baricitinib, reflecting 2789.7 patient-years of exposure (median, 825 days; maximum, 1460 days). Most treatment-emergent adverse events were mild to moderate in severity. Incidence rates of serious adverse events (IR = 2.6) and treatment discontinuations because of adverse events (IR = 1.7) were generally low and remained similar to data presented through at least 104 weeks of follow-up. In an additional 1 year of follow-up, no new cases of serious infections, opportunistic infections, major adverse cardiovascular events, deep vein thromboses, or pulmonary embolisms were observed. The IRs for non-melanoma skin cancer (IR = 0.1) and other malignancies (IR = 0.2) remained stable over time. The IR of herpes zoster was comparable to previously reported IRs (IR = 1.9). Laboratory changes were generally consistent over time. No deaths were reported in either study.

Conclusions

Long-term safety data from BRAVE-AA1 and BRAVE-AA2 are consistent with previously reported data from the baricitinib alopecia areata clinical trial program and demonstrate no new safety concerns or signals for baricitinib through a maximum exposure of 4 years.

Clinical Trial Registration

BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) were registered on 18 June, 2018, and 1 April, 2019, respectively.

Management of hidradenitis suppurativa (HS) can be challenging and often requires a multimodal approach with use of on- and off-label medications. There has been a rapid expansion of available HS treatments in the years since the 2019 North American HS (NAHS) clinical management guidelines. Herein we present an up-to-date practical management algorithm based on the diagnosis and management strategies set forth by the 2019 NAHS guidelines using newly available literature. Evaluation and diagnosis of HS disease involves assessment of severity, extent of disease, and impact on patient quality of life. Initial diagnosis of HS should be shortly followed by comorbidity screening. The multimodal approach to HS treatment typically involves use of treatment stacking of topical therapies, systemic and topical antibiotics, retinoids, hormonal and metabolic therapies, biologics and small molecule inhibitors, systemic immunosuppressants, surgical treatment, pain management, lifestyle modifications, adjunctive treatment, wound care, and flare therapy. Thus, the proposed algorithm aims to guide clinicians in their implementation of treatment stacking in HS.

Radiation therapy (RT) is a crucial modality in cancer treatment, functioning through direct DNA damage and immune stimulation. However, RT's effects extend beyond targeted cells, influencing neighboring cells through the bystander effect (ByE) and distant sites via the abscopal effect (AbE). The AbE, first described by Mole in 1953, encompasses biological reactions at sites distant from the irradiation field. While RT can enhance antitumor immune responses, it may also contribute to an immunosuppressive microenvironment. To address this limitation, combining RT with immune checkpoint inhibitors (ICIs) has gained renewed interest, aiming to amplify antitumor immune responses. Evidence of AbEs has been observed in various metastatic or advanced cutaneous cancers, including melanoma, basal cell carcinoma, cutaneous lymphoma, Merkel cell carcinoma, and cutaneous squamous cell carcinoma. Clinical studies suggest combining RT with ICIs targeting CTLA-4 and PD-1/PD-L1 may enhance AbE incidence in these cancers. This review primarily explores the current understanding of AbEs in skin cancers, briefly acknowledging the ByE focusing on combining RT with immunomodulation. It focuses on proposed mechanisms, preclinical and clinical evidence, challenges in clinical translation, and future directions for harnessing AbEs in managing advanced skin malignancies. Alternative modalities for inducing abscopal-like responses are also explored. While promising, challenges remain in consistently reproducing AbEs in clinical practice, necessitating further research to optimize treatment combinations, timing, and patient selection.

Background

Ethnic differences of the clinicopathological characteristics in many immune-mediated skin diseases have been reported, including psoriasis vulgaris (PV). However, the ethnic differences of pustular psoriasis have been less studied.

Objective

The aim of this study was to compare the differences in epidemiology, genetic background, clinical manifestations, treatment patterns and responses among Asian and non-Asian patients with pustular psoriasis, including generalized pustular psoriasis (GPP) and acrodermatitis continua of Hallopeau (ACH).

Methods

This systematic review was based on a comprehensive search of Cochrane, PubMed, and Embase databases from earliest available date to 31 December 2024, and all studies reporting on patients with either GPP or ACH irrespective of study design. Studies with study size below five patients or those focusing on quality of life or economic aspects were excluded. In each publication, the ethnic composition, demographics information, disease course and manifestation, as well as genetic mutations, treatment type and response were collected if available.

Results

Of 2187 screened studies, 141 studies were included, with the majority being cohort studies. Compared with other ethnicities, East Asians with GPP carried more null IL36RN mutations, while AP1S3 mutations seemed absent in Asians. Phenotypically, Asians had younger onset age, bimodal age distribution, less family history of PV, and more scalp/nail involvement. In Asians, absence of coexisting PV was associated with severe disease. GPP with PV had shorter pre-pustular duration among Asians than non-Asians. Use of acitretin appeared higher and more effective among East Asians compared with other populations. In ACH, Asians mostly carried homozygous null IL36RN mutations and had younger onset age, more multi-digit involvement, persistent treatment course, and more coexisting GPP than Europeans. Biologics use was less common in Asia in both GPP and ACH than in Europe and the US.

Conclusions

This systematic review underscores notable ethnic differences in genetic profiles, clinical features, and therapeutic responses in GPP and ACH. The diagnosis of GPP and ACH may differ across studies and the true impacts of ethnicities on these differences remain to be confirmed. Nonetheless, the results from this study enhance our understanding of the heterogeneous characteristics of GPP and ACH, highlighting the necessity of incorporating ethnic differences into the diagnosis, genetic testing, and management strategies for patients with GPP and ACH.

Pyoderma gangrenosum (PG) is a rare, ulcerative, neutrophilic dermatosis that can be challenging to diagnose. Diagnosis of PG is clinical due to a lack of specific histopathologic, immunologic, or imaging findings associated with the disease, although several clinical frameworks exist to guide diagnosis. However, misdiagnosis of PG is frequent and leads to increased patient morbidity and mortality. This article highlights common mimickers of PG and offers clinical pearls to aid in accurate diagnosis with the goal of decreasing diagnostic delay and misdiagnosis and improving patient outcomes.

Vulvovaginal itching is a common yet often under-recognized condition affecting women across all age groups. Despite its prevalence, many dermatologists receive minimal training in vulvar diseases, leading to delayed diagnoses and prolonged discomfort for patients. This review explores the broad spectrum of causes, including infections, inflammatory conditions, neuropathic disorders, and systemic illnesses. The complexity of vulvovaginal pruritus often requires a multidisciplinary approach to accurately diagnose and treat. Contributing factors such as hormonal changes, personal hygiene practices, and environmental exposures must also be considered. Treatment strategies typically begin with lifestyle modifications and topical therapies, such as corticosteroids and antifungals, but can extend to systemic medications and biologics for resistant cases. Additionally, nonpharmaceutical options such as sitz baths and psychological interventions can be crucial for managing chronic symptoms. However, there remains a significant gap in research, particularly regarding the characterization of female-specific pruritus and its long-term impact on quality of life. Despite some advances, the available studies largely focus on isolated causes rather than the holistic nature of the condition. Further research is urgently needed to develop comprehensive, evidence-based guidelines for diagnosing and treating vulvovaginal itching, a condition that has a profound effect on both physical and emotional well-being.

Hidradenitis suppurativa is a chronic inflammatory condition characterized by recurrent abscesses, nodules, tunnels, and scarring. Fluctuations in disease activity are common during pregnancy, and more than half of women with hidradenitis suppurativa report experiencing post-partum flares. Both treatment efficacy and safety of the woman and fetus or infant must be considered when developing a treatment plan for pregnant and lactating women with hidradenitis suppurativa. Although certain commonly used hidradenitis suppurativa medications, such as tetracyclines and spironolactone, are contraindicated during pregnancy, there are still various medical therapies, including topicals, systemic antibiotics, metabolic modulators, and biologics, as well as procedural therapies that may be utilized during pregnancy. This paper aims to provide an updated evidence-based review of the management of hidradenitis suppurativa in pregnancy with an emphasis on safety data.

Background

Tapinarof cream 1% is an aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration to treat atopic dermatitis (AD) in patients down to age 2 years.

Objective

The aim of this study was to evaluate the safety and pharmacokinetics of tapinarof cream 1% once daily (QD) in adolescents and children with extensive AD under maximal usage conditions.

Methods

Patients with a validated Investigator Global Assessment scale for Atopic Dermatitis™ (vIGA-AD™) score ≥ 3 and body surface area (BSA) involvement ≥ 25% (ages 12–17 years) or ≥ 35% (ages 2–11 years) were enrolled into three age cohorts (2–6, 7–11, and 12–17 years) and received tapinarof cream 1% QD for 4 weeks.

Results

Overall, 36 patients (12 per cohort) were enrolled; mean BSA affected was 42.8% (range 26.0–90.0) and mean Eczema Area and Severity Index (EASI) score was 23.8. At baseline, 28 patients (77.8%) had a vIGA-AD™ score of 3 (moderate). No-to-minimal tapinarof systemic exposure was observed (25% of post-treatment plasma samples were below the quantifiable limit of a highly sensitive assay [< 50 pg/mL]). Mean maximum plasma concentration (C_max) was 2.44 ng/mL, and median time to C_max was 2.9 h. Eight patients (22.2%) reported treatment-emergent adverse events (TEAEs), which were mild or moderate; only one patient discontinued due to two unrelated TEAEs. One case of mild folliculitis and no contact dermatitis occurred. Tapinarof was well tolerated, including on sensitive skin and extensor/flexural surfaces.

Conclusion

Tapinarof cream exhibits highly favorable safety and pharmacokinetics in adolescents and children down to age 2 years with extensive AD.

Trial Registration

ClinicalTrials.gov: NCT05186805.

Background

Nail psoriasis (NP) affects up to 90% and 86% of patients with cutaneous psoriasis and psoriatic arthritis, respectively, with a significant impact on quality-of-life. The Nail Psoriasis Severity Index (NAPSI) is infrequently used in clinical practice owing to its labor-intensive nature and variable interobserver reliability.

Objective

The objective of this study was to assess performance and inter-reader agreement between artificial intelligence (AI)-determined NAPSI scores and dermatologist-assigned scores.

Methods

This cross-sectional study used clinical images of psoriatic fingernails captured retrospectively at a specialized nail clinic in New York City. A convolutional neural network (CNN) model was trained and utilized for NAPSI classification of psoriatic fingernail clinical images, with seven dermatologist nail experts scoring identical images. The primary outcome was the interclass correlation coefficient (ICC), using a one-way analysis of variance (ANOVA) fixed effects model for the single-rater absolute agreement, between the average NAPSI score determined by the dermatologists and the AI.

Results

In total, 240 images of psoriatic fingernails were included. The ICC for overall NAPSI, matrix (NAPSIm), and bed (NAPSIb) scores among the dermatologists were 0.43 (95% confidence interval [CI] 0.33–0.55), 0.56 (95% CI 0.46–0.67), and 0.53 (95% CI 0.43–0.65), respectively. Comparing the AI algorithm-assigned NAPSI, NAPSIm, and NAPSIb scores with the average dermatologist-assigned scores, ICCs were 0.81 (95% CI 0.74–0.86), 0.75 (95% CI 0.65–0.82), and 0.81 (95% CI 0.74–0.86), respectively.

Conclusions

We found an excellent correlation between AI-derived NAPSI scores and dermatologist-assigned scores, underscoring the potential of CNNs to improve accuracy and reliability in NAPSI scoring. The limitations of this study include the small sample size, undetermined CNN diagnostic accuracy, incomplete data, and potential racial/ethnic minority group underrepresentation.