Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease with a high incidence. It is characterized by eczema-like changes, severe itching, and generalized dryness, frequently co-occurring with other atopic conditions like allergic rhinitis and asthma. AD prevalence reaches up to 20% in children and averages 2.1%–4.9% in adults (1, 2). Although the majority of AD patients with onset in childhood will gradually alleviate in adolescence or later, about 20%–30% of patients will continue to adulthood (3, 4), which can seriously affect the quality of life and mental health of patients (5), and increase the socio-economic burden (6).

The skin barrier consists of four interdependent layers: physical, chemical, microbial, and immune, collectively maintaining its structure and function (7). Increasing research indicates that disruption of the skin barrier is pivotal in AD pathogenesis. Structural and functional impairments contribute to inflammatory symptoms and infection susceptibility in AD patients (8).

Due to the burgeoning research interest in the link between skin barrier damage and AD pathogenesis, alongside the plethora of related publications, researchers face challenges in discerning the latest developments and research trends in this domain. Bibliometric analysis is a statistical method used to comprehensively review academic publications. It analyzes publications from specific periods, examining countries, institutions, journals, authors, keywords, and references to understand the knowledge structure and identify research frontiers or hotspots in a field (9). However, there has been no bibliometric review of studies focused on AD and the skin barrier.

Therefore, we retrieved literature data from the Web of Science (WOS) database¹ to identify the most cited countries, authors, institutions, and journals in the AD and skin barrier field. This paper employs bibliometric analysis to summarize research on the skin barrier’s role in AD pathogenesis and treatment from 1999 to 2023, presenting current advancements, hotspots, and emerging trends. This aims to highlight pivotal research and guide new researchers toward future directions.

In accordance with our search strategy, we retrieved 4,583 articles on AD and the skin barrier from the WOS database. Following the review process conducted by the researchers, a total of 4,227 articles were included in the present study. Based on the literature type, the 4,227 articles were categorized as 3,009 original articles and 1,218 reviews. Figure 1 presents the flowchart illustrating the methodology employed in this study.

This paper presents a comprehensive bibliometric study on the research related to the skin barrier in AD pathogenesis, using visualization tools such as VOSviewer and CiteSpace to thoroughly analyze the existing literature. It is the first study to summarize both historical research findings and the current state of knowledge on the skin barrier in AD, while also identifying development trends and future research hotspots related to skin barrier in AD through the use of these widely adopted bibliometric tools.

Analysis of 4,227 articles from the WOS database reveals a gradual increase in studies on the correlation between the onset of AD and the skin barrier since 1999, with the United States ranking first in terms of the number of published articles and influence, having published 1,268 articles. Additionally, half of the top 10 journals, publishing institutions, and authors are based in the United States, reflecting its dominance, which is closely linked to its significant economic resources and investment in medical research. Furthermore, Figure 3A shows a gradual increase in publications from China, South Korea, and other countries in recent years, indicating growing international interest in the study of the pathogenesis of the skin barrier in AD. It is anticipated that more countries and researchers will engage in this field of study in the future. Consequently, scientific advancement is closely tied to robust national economic support and international collaboration.

Impact factor, JCR and total citations are effective indicators for assessing the influence of journals. Notably, the Journal of Allergy and Clinical Immunology and the Journal of Investigative Dermatology have the highest number of publications, often taking on the responsibility of disseminating significant research in their respective fields. As shown in Table 2, all 10 of the leading journals are from developed countries in Europe and the United States, likely reflecting the influence of their advanced economic development. Despite notable contributions from Japan, South Korea, and China, Asian countries have not yet ranked first in terms of publication volume. This indicates that Japan and other Asian countries possess the potential to establish journals with significant international influence in the future.

As early as 1985, Werner and Lindberg utilized an evaporometer to measure water loss from the stratum corneum of both dry and clinically normal skin in patients with AD. The results showed that patients with AD exhibited a higher rate of water loss from the stratum corneum, particularly in regions of dry skin. This suggests a potential defect in skin barrier function among patients with AD. Additionally, studies have demonstrated that the water-binding capacity of the stratum corneum in AD patients is diminished, and alterations in the lipid composition of the skin surface may contribute to increased water loss. Consequently, alterations in the composition and structure of the stratum corneum may impair skin barrier function in patients with AD (19). The number of citations of a document serves as an indicator of its influence. In the most cited literature, “Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis,” Palmer et al. identified two gene mutations (R510X and 2282del4) significantly associated with AD through genotyping both affected individuals and healthy controls, leading to the identification of filaggrin loss-of-function alleles. Filaggrin, as a crucial protein, facilitates the terminal differentiation of the epidermis and the formation of the skin barrier; thus, its loss of function represents a significant pathogenic factor in AD. These mutations are present in over 9% of the European population (10). This study reveals the critical role of impaired skin barrier function in the development of AD and further investigates the genetic mechanisms and pathogenesis of AD.

Keywords often represent the core content of research, and word frequency can indicate shifts in research hotspots. As illustrated in Supplementary Figures 2B, 3 topics such as “th2,” “mast cell,” “interleukin-13,” “gut microbiota” and “probiotics” have garnered significant attention from researchers in recent years. The pathogenesis of AD, as explored through its diagnosis and treatment, involves genetic susceptibility, epidermal barrier disruption, local and systemic immune imbalances, and interactions with environmental factors (20). Notably, the immune imbalance is primarily characterized by Th1/Th2 imbalance mediated by Th2-type immunity (21). Wang et al., conducted a bibliometric analysis of 2,168 studies related to mast cells (MCs) and AD, concluding that Th2 cytokines, such as IL-4 and IL-13, released by MCs exacerbate the immune imbalance in AD and further promote inflammation. IL-13, IL-4, NFKB1, BGF-1, and CD4 are key genes associated with MCs and AD. These genes primarily regulate inflammatory responses, leukocyte activation, cytokine production, and cell activation. The development of biologics and small-molecule drugs targeting MCs represents a crucial direction for the future treatment of AD (22). Gut microbiota influences the development of AD by modulating immune function, maintaining skin barrier integrity, and regulating neuroendocrine signaling. Probiotics and prebiotics have demonstrated potential therapeutic effects in regulating gut microbiota and restoring intestinal microecological balance. Studies suggest that probiotics can alleviate pruritus in AD patients by modulating gut microbiota, indicating potential therapeutic efficacy in improving AD symptoms (23, 24). Additionally, dysregulation of the skin microbiome plays a significant role in the pathogenesis and progression of AD. The increased colonization of Staphylococcus aureus on the skin of AD patients leads to a reduction in skin bacterial diversity and induces skin inflammation through the release of inflammatory mediators such as IL-1α and IL-24β, which are closely linked to the onset and severity of AD (16, 25, 26). Symbiotic microbes, such as Staphylococcus epidermidis, help maintain skin barrier integrity by secreting ceramides (27). This suggests that future studies will further investigate the complex relationship between the microbiome and AD, potentially providing new therapeutic strategies (28). We anticipate that the diagnosis and treatment of AD will become more diverse in the future.

AD remains a major contributor to the global burden of skin-related diseases. However, research resources are predominantly concentrated in a few developed countries, and international cooperation remains limited. Despite evidence showing a rising prevalence of AD in developing countries, many patients continue to receive ineffective or inappropriate treatments (29). In the current global information age, countries are able to communicate effectively. Developed nations should leverage their advantages to enhance international cooperation and collectively advance research on AD.

It is important to acknowledge that this study has certain limitations. Firstly, this study analyzed literature exclusively from the WOS database. The literature collection is not sufficiently comprehensive, potentially leading to biased results. Future research should expand the search database to achieve a more comprehensive analysis. Secondly, the citation threshold applied to the screened articles may have excluded recent high-quality papers that have not yet reached the ideal number of citations, leading to potential research bias.

In summary, the role of the skin barrier in the pathogenesis of AD has been extensively investigated, and significant progress has been achieved. However, further advancements are still necessary. Developing countries should actively seek and maintain close collaboration with developed nations, such as the United States, Japan, and Germany. Additionally, we anticipate that future research hotspots will focus on the following areas: (1) Targeted factors in inflammatory pathways; (2) The role of gut microbiota in AD and related treatments; 3. Long-term management and comorbidities associated with AD. This bibliometric study facilitates a more accurate and in-depth investigation of the skin barrier in AD.