Topical therapy remains a critical component in the management of immune‑mediated inflammatory dermatoses such as psoriasis and atopic dermatitis. In this field, macrolactam immunomodulators, including calcineurin and mammalian target of rapamycin inhibitors, can offer steroid‑free therapeutic alternatives. Despite their potential for skin‑selective treatment compared with topical corticosteroids, the physicochemical properties of these compounds, such as high lipophilicity and large molecular size, do not meet the criteria for efficient penetration into the skin, especially with conventional topical vehicles. Thus, more sophisticated approaches are needed to address the pharmacokinetic limitations of traditional formulations. In this regard, interest has increasingly focused on nanoparticulate systems to optimize penetration kinetics and enhance the efficacy and safety of topical calcineurin and mTOR inhibitors in inflamed skin. Several types of nanovectors have been explored as topical carriers to deliver tacrolimus in both psoriatic and atopic skin, while preclinical data on nanocarrier‑based delivery of topical sirolimus in inflamed skin are also emerging. Given the promising preliminary outcomes and the complexities of drug delivery across inflamed skin, further research is required to translate these nanotherapeutics into clinical settings for inflammatory skin diseases. The present review outlined the dermatokinetic profiles of topical calcineurin and mTOR inhibitors, particularly tacrolimus, pimecrolimus and sirolimus, focusing on their penetration kinetics in psoriatic and atopic skin. It also summarizes the potential anti‑inflammatory benefits of topical sirolimus and explores novel preclinical studies investigating dermally applied nanovehicles to evaluate and optimize the skin delivery, efficacy and safety of these \'hard‑to‑formulate\' macromolecules in the context of psoriasis and atopic dermatitis.

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Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCS) are the mainstays of flare management for atopic eczema or atopic dermatitis (AD). Tacrolimus (an immunomodulator), belongs to the class of calcineurin inhibitors, with promising efficacy in AD. We performed this systematic review to obtain an up-to-date coverage map of controlled clinical trials of sequential or intermittent treatments with TCI as a therapeutic intervention for AD. Articles of interest were retrieved from PubMed, Google Scholar, and EMBASE published between between January 2000 and March 2023. Key words were \"calcineurin inhibitors,\" \"corticosteroids,\" \"atopic dermatitis,\" \"pruritus,\" \"sequential,\" \"intermittent\" and \"consecutive\" while fixed language search consisted of \"Intermittent topical calcineurin inhibitors AND topical corticosteroids AND atopic dermatitis OR eczema\" AD patients who were administered sequential and/or intermittent applications of TCI for management of atopic eczema were included. Outcome measures included but were not limited to Scoring of Atopic Dermatitis (SCORAD) and the Eczema Area Severity Score (EASI). Four clinical trials were considered for the purpose of review. A total of 101 patients with AD were analysed. The risk of bias was low in two studies, while the other two had an unclear risk of bias. Overall, pooled data from two trials revealed that sequential therapy with TCS/TCI was comparable to monotherapy or emollients, as the test for overall effect determined was non-significant with a p-value of 0.33. The two studies were highly heterogeneous, as indicated by a very high I2 of 92% and an extremely significant p-value (p=0.0005). Sequential therapy with TCS and TCIs was effective and well tolerated in the management of AD and it may be considered an important treatment approach during the initial period.

Atopic dermatitis (AD) is the most common inflammatory skin disease. However, recent reports concerning the simple clinical aspects of treatment with topical glucocorticosteroids (TCS) and calcineurin inhibitors (TCI) are lacking. The objective of this study is providing an update on these characteristics of AD management. A group of 150 adults suffering from AD treated with TCS during last year was asked to fill an anonymous questionnaire. The course of topical treatment was analyzed in the context of the severity of symptoms and the knowledge of the patients about therapy. During the last year, the majority of patients (66%) were treated with class IV TCS; however, in the last two weeks, class I TCS was used the most frequently (35%). Only 11% were familiar with the concept of intermittent therapy and 4% used the fingertip unit (FTU). In total, 77% of them used TCI. Most of the patients used the same class of TCS permanently. Unfortunately, patients are unaware of simple approaches (like intermittent therapy or FTU) that increase both the effectiveness and safety of the treatment. Practicians should be aware of these problems to identify and eliminate them, primarily through the education of patients.

UNASSIGNED: Atopic dermatitis (AD) exhibits difference in immune polarization between Caucasians and Asian races due to which an evaluation of the efficacy and safety of Pimecrolimus (PIM) in Asian population is called for. The current study addresses the need via a sub-group analysis of the PETITE study (NCT00120523) to evaluate the safety and efficacy of PIM in Chinese infants.
UNASSIGNED: Patients with AD (≥3 months-<12 months of age) were randomized in a 1:1 ratio to either PIM 1% cream or topical corticosteroids (TCS). The primary endpoint was safety. The secondary endpoint was efficacy.
UNASSIGNED: 120 patients were randomized to either PIM 1% or TCS (n = 61 for PIM, n = 59 for TCS). The most often reported adverse events were reported by similar proportions of patients treated with PIM or TCS. There was a progressive increase in overall IGA treatment success in infants treated with PIM (82.9%, p < .05, 95% CI: 70.4, 95.3) after 26 weeks which was comparable to the TCS group (88.5%, p < .05, 95% CI: 79.8, 97.1).
UNASSIGNED: PIM showed an early and sustained efficacy in the Chinese sub-population with a substantial corticosteroid-sparing effect in patients with AD.

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Topical corticosteroids (TCS) are a mainstay of treatment for atopic dermatitis (AD). There are shared physician and patient concerns that TCS use can result in skin atrophy and systemic absorption. The clinical use of topical calcineurin inhibitors (TCI) for AD is relatively limited despite evidence that TCI are safe and effective. Understanding the differences in efficacy and adverse effects between TCS and TCI can help shape prescription practices to the benefit of patients. The objective of this review is to characterize the difference in efficacy and adverse effects between TCS and TCI. A review of the literature between 2002 and 2022 was performed using the PubMed, EMBASE, and Cochrane Library databases. Ten studies comparing TCS of varying potencies with TCI approved for AD treatment were included in the review. Outcome measures were qualified using percent reductions on the modified Eczema Area and Severity Index score and decreases in physician\'s global evaluation of AD severity. Tacrolimus had statistically significant (P < .05) improvement in disease severity compared with TCS in 4 of the 5 studies that compared tacrolimus with weak TCS. The data suggest greater treatment efficacy of tacrolimus over weak TCS, and inferior efficacy of pimecrolimus (TCI) compared with both tacrolimus and weak TCS. It is difficult to draw conclusions between moderate, potent, and very potent TCS and TCI due to the small number of available studies. TCI can improve disease severity, especially on thin or intertriginous skin regions most vulnerable to adverse events with TCS treatment, and their use may help overcome adherence issues due to patient bias against TCS.

Oral lichen planus (OLP) is a chronic mucosal inflammatory disease associated with T-cell-mediated immunological dysfunction. Symptomatic OLP is a painful condition, and complete healing is often not achieved. The aim of this systematic review was to assess the effectiveness of topical drugs, medications, and other interventions compared to placebo or to other treatments in pain reduction and clinical resolution in adult patients with symptomatic OLP. A detailed electronic literature search was performed through the MEDLINE (PubMed) database between 1 January 2005 and 30 September 2022. Eligible studies were selected based on the inclusion criteria, and a quality assessment was conducted. From 649 titles, 121 articles were selected as abstracts, 75 papers were assessed as full text, along with 15 other papers obtained through a manual search. A total of 15 RCTs were finally included in the review process. Because of the significant heterogeneity in the study design of the included studies, no meta-analysis of the data could be performed. Topical corticosteroids represent the first-line treatment in the management of symptomatic OLP due to their efficacy and minimal adverse effects. Calcineurin inhibitors seem to be equally effective and are indicated in recalcitrant cases, extensive lesions, patients susceptible to oral candidiasis, or cases unresponsive to corticosteroids. Other treatments, such as aloe vera, chamomile, isotretinoin, ozone, and laser therapy, could be beneficial as adjunct therapies in association with first-line treatments.

UNASSIGNED: In recent years, new treatments dedicated to atopic dermatitis (AD) have become available in Israel, including crisaborole, a small molecule with unique benzoxaborole chemistry.
UNASSIGNED: To describe baseline characteristics, history of AD therapies, and use of health-care services of early crisaborole users in real-world settings.
UNASSIGNED: A retrospective cohort study was performed using the data of a large health provider in Israel. AD patients treated with crisaborole since it became commercially available in Israel in July 2019 through end of Sep 2020, were included. Baseline demographics and clinical characteristics, prior AD-related treatments and healthcare resource utilization were collected.
UNASSIGNED: A total of 441 patients were included (57.8% females, median age = 21.1y; interquartile range = 10.5-40.8). In 62.1%, a dermatologist prescribed the first dispensed crisaborole. Median time from AD diagnosis to crisaborole treatment was 6.6 years. Up to 12 months prior to crisaborole treatment, low-, mid- and high-potency TCS were used by 30.8%, 31.1% and 55.8% of patients, respectively. Treatments related to moderate-to-severe AD were dispensed to 38.5% of patients in the prior 5 years. Asthma and allergic rhinitis were documented among 22.2% and 37.2%, respectively. In the past year, patients had a median of 9 visits to primary care physicians, 84.6% visited a dermatologist (≥5 visits: 12.9%).
UNASSIGNED: While crisaborole is indicated for mild-to-moderate disease, results suggest that a significant proportion of patients had history of advanced AD therapies suggestive of moderate-to-severe AD.