American Journal of Clinical Dermatology最新文献

The skin is a physical and immunological barrier to the external environment. Its large surface area is colonized by diverse communities of microorganisms, including bacteria, viruses, fungi, and Demodex species mites. These microorganisms and their genetic material together create the skin microbiome. Physiologic and anatomic properties of skin sites create biogeographical habitats (dry, moist, and sebaceous) where distinct microbiota communities reside. Although, in general, the composition of these habitats is maintained from person to person, the skin microbiome of an individual also has unique microbial features. Dysbiosis occurs when the normal abundance, composition, or location of the microbiota is changed, most notably there is a decrease in flora diversity. Certain skin diseases, including atopic dermatitis, rosacea, and psoriasis are associated with cutaneous dysbiosis, and even disruption of the gut microbiota. Studies have shown that current treatments for these dermatologic conditions can alter/stabilize the skin microbiome, and there is emerging research detailing the impact of prebiotics, probiotics, and postbiotics on these conditions. Although clinical guidelines do not currently exist, clinical studies support the safety and possible benefits of using topical prebiotics and postbiotics and oral probiotics for a variety of skin conditions. Until such guidelines exist, utilizing carefully designed clinical studies to inform clinical practice is recommended.

Background

Ruxolitinib cream is the first topical Janus kinase (JAK) inhibitor approved in the United States (US) for the treatment of mild to moderate atopic dermatitis and nonsegmental vitiligo. A postmarketing study with oral tofacitinib, approved for rheumatoid arthritis, triggered class warnings for JAK inhibitors, including risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis. Because ruxolitinib cream is indicated for inflammatory conditions, it is subject to the same warnings as oral JAK inhibitors in the US. Here, nearly 14,000 patient-years of postmarketing safety data from the first year following market approval of ruxolitinib cream were reviewed.

Methods

The Incyte global safety database (21 September 2021–20 September 2022) and US FDA Adverse Event Reporting System (as of 30 September 2022) were queried for adverse event (AE) reports received for ruxolitinib cream.

Results

The search identified 294 postmarketing individual case safety reports containing 589 events, including four serious AEs and no fatal AEs. AEs (i.e., any unfavorable sign, symptom, or disease) representing >2% of all events included application site pain (n = 16), atopic dermatitis (n = 15), skin irritation (n = 15), scratch (n = 14), and condition aggravated (n = 13). The four serious AEs were skin cancer (n = 2), pericarditis, and thrombocytopenia (both n = 1), none of which had sufficient information to assess possible relatedness to ruxolitinib cream. Serious AEs associated with the class warnings for JAK inhibitors were not reported.

Conclusions

Postmarketing safety data from the year following approval suggest ruxolitinib cream is generally well tolerated, without significant systemic AEs, and with a low incidence of application site reactions.

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.

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.

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.

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.