American Journal of Clinical Dermatology最新文献

{"title":"OX40 in the Pathogenesis of Atopic Dermatitis—A New Therapeutic Target","authors":"Michael Croft,&nbsp;Ehsanollah Esfandiari,&nbsp;Camilla Chong,&nbsp;Hailing Hsu,&nbsp;Kenji Kabashima,&nbsp;Greg Kricorian,&nbsp;Richard B. Warren,&nbsp;Andreas Wollenberg,&nbsp;Emma Guttman-Yassky","doi":"10.1007/s40257-023-00838-9","DOIUrl":"10.1007/s40257-023-00838-9","url":null,"abstract":"<p>Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient’s overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 3","pages":"447 - 461"},"PeriodicalIF":8.6,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11070399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucocutaneous Manifestations of Recreational Drug Use","authors":"Carolina V. Alexander-Savino,&nbsp;Ginat W. Mirowski,&nbsp;Donna A. Culton","doi":"10.1007/s40257-023-00835-y","DOIUrl":"10.1007/s40257-023-00835-y","url":null,"abstract":"<div><p>Recreational drug use is increasingly common in the dermatology patient population and is often associated with both general and specific mucocutaneous manifestations. Signs of substance use disorder may include changes to general appearance, skin, and mucosal findings associated with particular routes of drug administration (injection, insufflation, or inhalation) or findings specific to a particular drug. In this review article, we provide an overview of the mucocutaneous manifestations of illicit drug use including cocaine, methamphetamine, heroin, hallucinogens, marijuana, and common adulterants to facilitate the identification and improved care of these patients with the goal being to connect this patient population with appropriate resources for treatment.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"281 - 297"},"PeriodicalIF":8.6,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139464121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Systemic Therapies for Adults with Atopic Dermatitis: Selecting from Biologics and JAK Inhibitors","authors":"Richard W. Kim,&nbsp;Megan Lam,&nbsp;Katrina Abuabara,&nbsp;Eric L. Simpson,&nbsp;Aaron M. Drucker","doi":"10.1007/s40257-023-00837-w","DOIUrl":"10.1007/s40257-023-00837-w","url":null,"abstract":"<div><p>Therapeutic options for people with moderate or severe atopic dermatitis refractory to topical therapy have rapidly expanded in recent years. These new targeted immunomodulatory agents—biologics and Janus kinase (JAK) inhibitors—have each demonstrated high levels of efficacy and acceptable safety in mostly placebo-controlled clinical trials for atopic dermatitis, but there is no universally applicable algorithm to help choose between them for a given patient. Hence, patients and physicians should utilize shared decision making, discussing efficacy, safety, mode of delivery, monitoring, costs, speed of onset, and other factors to reach individualized treatment decisions. In this review, we try to aid shared decision making by summarizing the efficacy, safety, and monitoring of biologics and oral JAK inhibitors for adults with atopic dermatitis. Network meta-analyses suggest that higher doses of abrocitinib and upadacitinib are more effective than biologics. They also show that, among biologics, dupilumab is likely more effective than tralokinumab and lebrikizumab. Biologics are generally considered safer than JAK inhibitors, although concerns about JAK inhibitors are mainly extrapolated from older generation JAK inhibitors used in higher-risk populations. We also outline evidence and considerations for choosing and using systemic immunomodulatory treatments for special populations including pregnant individuals, those with human immunodeficiency virus (HIV), hepatitis B and C, end stage kidney disease, and older adults.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"179 - 193"},"PeriodicalIF":8.6,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139431781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to Referees","authors":"","doi":"10.1007/s40257-023-00834-z","DOIUrl":"10.1007/s40257-023-00834-z","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 1","pages":"1 - 4"},"PeriodicalIF":8.6,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pressure and Skin: A Review of Disease Entities Driven or Influenced by Mechanical Pressure","authors":"Wei-Chen Chien,&nbsp;Tsen-Fang Tsai","doi":"10.1007/s40257-023-00833-0","DOIUrl":"10.1007/s40257-023-00833-0","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"261 - 280"},"PeriodicalIF":8.6,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139070189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pityriasis Rubra Pilaris: An Updated Review of Clinical Presentation, Etiopathogenesis, and Treatment Options","authors":"Tejas P. Joshi,&nbsp;Madeleine Duvic","doi":"10.1007/s40257-023-00836-x","DOIUrl":"10.1007/s40257-023-00836-x","url":null,"abstract":"<div><p>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. <i>Caspase recruitment domain family, member 14</i> (<i>CARD14</i>)-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 <i>CARD14</i> 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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"243 - 259"},"PeriodicalIF":8.6,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139070247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update","authors":"Meropi Karakioulaki,&nbsp;Kilian Eyerich,&nbsp;Aikaterini Patsatsi","doi":"10.1007/s40257-023-00832-1","DOIUrl":"10.1007/s40257-023-00832-1","url":null,"abstract":"<p>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.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"195 - 212"},"PeriodicalIF":8.6,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-023-00832-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139070572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare Autoinflammatory Neutrophilic Dermatoses in Pregnancy: Literature Review","authors":"Angela Lo,&nbsp;Brittany Thompson,&nbsp;Naveed Sami","doi":"10.1007/s40257-023-00830-3","DOIUrl":"10.1007/s40257-023-00830-3","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"227 - 242"},"PeriodicalIF":8.6,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138578980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Treatment of Systemic Sclerosis and Morphea","authors":"Noelle Teske,&nbsp;Nicole Fett","doi":"10.1007/s40257-023-00831-2","DOIUrl":"10.1007/s40257-023-00831-2","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"213 - 226"},"PeriodicalIF":8.6,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138579496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treat-to-Target in Atopic Dermatitis","authors":"Christian Vestergaard,&nbsp;Catalina Skovsgaard,&nbsp;Claus Johansen,&nbsp;Mette Deleuran,&nbsp;Jacob P. Thyssen","doi":"10.1007/s40257-023-00827-y","DOIUrl":"10.1007/s40257-023-00827-y","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 1","pages":"91 - 98"},"PeriodicalIF":8.6,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138568291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}