American Journal of Clinical Dermatology最新文献

Background: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis.

Objective: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial.

Methods: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep.

Results: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4-6, and 10 were associated with 0 days, 3-4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0-1, 4-5, and 10 were associated with 0-10%, 20-30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep.

Conclusion: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity.

Clinical trial registration: NCT03575871.

Skin perceives and reacts to external mechanical forces to create resistance against the external environment. Excessive or inappropriate stimuli of pressure may lead to cellular alterations of the skin and the development of both benign and malignant skin disorders. We conducted a comprehensive literature review to delve into the pressure-induced and aggravated skin disorders and their underlying pressure-related mechanisms. Dysregulated mechanical responses of the skin give rise to local inflammation, ischemia, necrosis, proliferation, hyperkeratosis, impaired regeneration, atrophy, or other injurious reactions, resulting in various disease entities. The use of personal devices, activities, occupations, weight bearing, and even unintentional object contact and postures are potential scenarios that account for the development of pressure-related skin disorders. The spectrum of these skin disorders may involve the epidermis (keratinocytes and melanocytes), hair follicles, eccrine glands, nail apparatuses, dermis (fibroblasts, mast cells, and vasculature), subcutis, and fascia. Clarifying the clinical context of each patient and recognizing how pressure at the cellular and tissue levels leads to skin lesions can enhance our comprehension of pressure-related skin disorders to attain better management.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous reaction pattern with a significant impact on quality of life. Type I PRP is the most common PRP variant, presenting as erythematous papules emerging in a follicular distribution and later coalescing into plaques with characteristic islands of sparing; histologically, an alternating pattern of orthokeratosis and parakeratosis is considered the hallmark of PRP (checkerboard hyperkeratosis). Other PRP variants (types II–V) differ in their age of onset and clinical presentation. Type VI PRP is a rare PRP subtype associated with human immunodeficiency virus infection and is occasionally associated with diseases of the follicular occlusion tetrad. Caspase recruitment domain family, member 14 (CARD14)-associated papulosquamous eruption and facial discoid dermatitis are newly described disease states that have an important clinical overlap with PRP, creating shared conundrums with respect to diagnosis and treatment. The etiology inciting PRP often remains uncertain; PRP has been suggested to be associated with infection, malignancy, or drug/vaccine administration in some cases, although these are based on case reports and causality has not been established. Type V PRP is often due to inborn CARD14 mutations. Furthermore, recent literature has identified interleukin-23/T-helper-17 cell axis dysregulation to be a major mediator of PRP pathogenesis, paving the way for mechanism-directed therapy. At present, high-dose isotretinoin, ixekizumab, and secukinumab are systemic agents supported by single-arm prospective studies; numerous other agents have also been trialed for PRP, with variable success rates. Here, we discuss updates on clinical manifestations, present new insights into etiopathogenesis, and offer a survey of recently described therapeutic options.

Abastract

Bullous pemphigoid (BP) is a common autoimmune bullous disease affecting mainly the elderly, with rising incidence due to increased life expectancy. This disease is characterized by tense bullous lesions on normal or erythematous skin, accompanied by pruritus. BP pathogenesis involves autoantibodies against hemidesmosomal proteins BP180 and BP230, leading to detachment at the dermo-epidermal junction as well as blister formation. BP is associated with coexisting comorbidities and drug exposure, and its management often requires high doses or chronic use of systemic glucocorticoids, posing risks of adverse effects. This review focuses on novel treatment options for BP, exploring therapies targeting different immune pathways. Rituximab, a CD20 monoclonal antibody, depletes B-lymphocytes and has shown efficacy in severe cases. Dupilumab, targeting interleukin (IL)-4 receptor α and thus blocking IL-4 and IL-13, downregulates type 2 helper (Th2) responses and has demonstrated promising results. Targeting eosinophil-related molecules using bertilimumab and AKST4290 has yielded positive results in clinical trials. Omalizumab, an immunoglobulin (Ig) E antibody, can reduce disease severity and allows corticosteroid tapering in a number of cases. Complement inhibitors such as nomacopan and avdoralimab are being investigated. IL-17 and IL-23 inhibitors such as secukinumab and tildrakizumab have shown potential in a limited number of case reports. Neonatal Fc receptor antagonists such as efgartigimod are under investigation. Additionally, topical therapies and Janus kinase inhibitors are being explored as potential treatments for BP. These novel therapies offer promising alternatives for managing BP, with potential to improve outcomes and reduce high cumulative doses of systemic corticosteroids and related toxicities. Further research, including controlled clinical trials, is needed to establish their efficacy, safety, and optimal dosing regimens for BP management.

Rare cases of autoinflammatory neutrophilic dermatoses (AINDs) have been reported in patients during pregnancy with associated adverse maternal and fetal outcomes. Due to the rarity and heterogeneous morphology of pregnancy-associated AINDs, clinical diagnosis is often overlooked, and treatment options are limited. In this review, we present the epidemiology, clinical characteristics, therapeutic interventions, maternal and fetal outcomes, and discuss the possible pathophysiology of various pregnancy associated AINDs. Risk factors for the onset and exacerbation of AINDs in pregnancy include older maternal age, disease duration, and specific gestational age. The varied disease courses and conflicting clinical outcomes in both mothers and fetuses demonstrate the importance of symptom recognition and the understanding of the role of pregnancy on AINDs.

Systemic sclerosis (SSc) and morphea are autoimmune sclerosing diseases that cause significant morbidity, and in the case of SSc, mortality. The pathogenesis of both SSc and morphea share vascular dysfunction, auto-reactive T cells and Th2-associated cytokines, such as interleukin 4, and overproduction of transforming growth factor beta (TGFβ). TGFβ stimulates fibroblast collagen and extra-cellular matrix production. Although morphea and SSc have similar pathogenic pathways and histological findings, they are distinct diseases. Recent advances in treatment of morphea, skin sclerosis in SSc, and interstitial lung disease in SSc are focused on targeting known pathogenic pathways.

Atopic dermatitis is one of the most common inflammatory skin diseases among children and adults. Over the last 5 years, the armamentarium for the treatment of this disease, with both topical and systemic drugs, has increased. Treat-to-target is basically the concept where a treatment goal and a time frame for that goal is set at initiation of a new treatment, and if the goals are not achieved in time, treatment will be adjusted. In clinical trials, treatment targets are based on scoring systems for disease severity as recommended by the Harmonizing Outcome Measure for Eczema (HOME) initiative, with the primary endpoint being a reduction of at least 75% of the baseline Eczema Area and Severity Index (EASI) score (EASI-75). The question, however, is if these are useful targets in real-world settings and how this should be implemented in everyday clinical practice. In rheumatology, setting a measurable target and a time frame for an instigated therapy has been shown to lead to more efficient and successful treatment. For atopic dermatitis, the instruments recommended by HOME form the core outcome measures for the treat-to-target frameworks published to date, which are based on expert consensus and Delphi processes. Although atopic dermatitis patients have a high risk of co-morbidities, including physical, psychological and socioeconomic, instruments to measure the severity of co-morbidities have not been included in these existing frameworks. In order to apply a treat-to-target strategy that is meaningful for both the patient and the doctor, validated tools for the measurement of treatment effect on co-morbidities exist and should be included in a shared decision-making process with the individual patient when choosing which targets to aim for and what should be considered treatment success. An obvious limitation for the implementation of a treat-to-target strategy in the clinical setting with atopic dermatitis is that retrieving the data needed is very time consuming. This could to some degree be mitigated by the use of electronic applications in which patients could report their outcomes.

Utilization of telemedicine for dermatology has greatly expanded since the start of the COVID-19 pandemic, with over 500 new teledermatology studies published since 2020. An updated review on teledermatology is necessary to incorporate new findings and perspectives, and educate dermatologists on effective utilization. We discuss teledermatology in terms of diagnostic accuracy and clinical outcomes, patient and physician satisfaction, considerations for special patient populations, published practice guidelines, cost effectiveness and efficiency, as well as administrative regulations and policies. Our findings emphasize the need for dermatologist education, prioritization of reliable reimbursement systems, and technological innovations to support the continued development of teledermatology in the post-pandemic era.