Adult-onset Still’s disease (AOSD) is a kind of systemic inflammatory disease with unknown etiology that can accumulate in various systems of the whole body, with a global incidence rate of (0.16–0.40)/100,000 and an estimated prevalence rate of (1-34)/1,000,000 (1). The incidence rate of males in Japan is 0.22/100,000 and that of females is 0.34/100,000 (2). Due to the low prevalence of AOSD, there is still a lack of extensive and reliable epidemiological data in clinics at the present stage (3). A study on Poland revealed that the incidence of AOSD in urban areas of Poland (0.33/100,000) was significantly higher than that in rural areas (0.29/100,000) (4). The age distribution of the AOSD is bimodal, with one peak occurring between 15-25 years and the other between 36-45 years (5). The typical clinical manifestations of AOSD mainly include fever (60-100%), arthritis or arthralgia (70-100%) and maculopapular red rash (60-80%) (6). Atypical clinical manifestations such as sore throat or pharyngitis, myalgia, lymphadenopathy, and hepatosplenomegaly may also occur in some patients (7). In addition, the prevalence of mental disorders in AOSD patients is increased due to the long-term chronic course of the disease, which especially affects their emotions (8). In general, the prognosis of AOSD is good (9), but there is still a mortality rate of 3% (3, 10), and some serious complications can also lead to death (11), such as macrophage activation syndrome (MAS) (12–14%) (12), thrombotic thrombocytopenic purpura (<1%) (13), disseminated intravascular coagulation disease (14), and acute respiratory distress syndrome (15).

Many factors, including genetic factors (16), infection (17), and immune dysfunction (18) may be possible causative factors of AOSD. Several studies have shown that Human leucocyte antigen is closely related to the occurrence of AOSD (19, 20), and the Macrophage migration inhibitory factor gene may increase susceptibility to the disease (21). Bacterial, viral, or parasitic infections may also cause AOSD (22). At present, the pathogenesis is still controversial, and pathophysiology studies are rare (23). Studies have shown that chemokines and pro-inflammatory cytokines, such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL) are involved in the pathogenesis of AOSD (24). In the absence of markers for specific diagnosis and curative effect evaluation (25), AOSD is primarily diagnosed by excluding other diseases (26). For the possibility of misdiagnosis in AOSD (27), the average delay time of diagnosis is about four months (28). Yamaguchi criteria (29) have the highest diagnostic sensitivity of 92%, followed by Fautrel criteria (30) (87%) and Cush criteria (31) (80%). AOSD has been treated symptomatically mainly by using non-steroidal anti-inflammatory drugs (NSAIDs), steroids and disease-modifying anti-rheumatic drugs (DMARDs) (26). With the in-depth understanding of the pathogenesis, Biological Response Modifiers are gradually trying to be used for treatment (32). However, the effect of traditional treatment schemes is not satisfactory, with more than 80% of patients not relieved after only using NSAIDs (33) and 45% of patients developing hormone dependence after the use of steroids (34). At the same time, new treatments, such as Biological Response Modifiers still lack more effective clinical experimental data to verify (35).

In the past few years, a number of scholars have carried out basic and clinical studies on the pathogenesis and treatment of AOSD (36). However, few reports have analyzed the characteristics and development trend of the AOSD over a long period of time, which is not conducive for researchers to accurately grasp the occurrence, development rules and characteristics of the AOSD (37). With an increasing number of reports on the AOSD research, retrieving the research status quickly and efficiently in related fields has become a more realistic problem faced by researchers (38). Bibliometrics and visual analysis provide an important, feasible and systematic method for judging the importance of published literature by showing the author’s networks and academic exchanges, connections between scholars and the development in the field of knowledge (39). Using the results of the bibliometric analysis will not only help researchers understand the global research trends of AOSD and master the information sources of AOSD research but also help researchers understand the advantages and disadvantages of their research and quickly capture the research priorities, hotspots, and trends (40).

In this study, the research articles related to adult-onset Still’s disease in the Scopus database were selected and analyzed by using CiteSpace software. From the perspectives of bibliometrics and visual analysis, the research progress of AOSD is discussed, aiming to understand the research development trends and new trends of AOSD, identify the hotspots in this research field, and provide a reference and basis for better research on AOSD.

In this study, 2,373 articles related to AOSD from the Scopus database were analyzed by bibliometric methods. From 1921 to 2021, the number of published articles showed an overall upward trend ( Figure 1 ), which can be divided into two stages. Before 1972, it was in the initial research period of AOSD, with a few articles published and a slow growth rate of literature. The basic research in this period laid a solid theoretical foundation for the development of AOSD. Since 1972, the number of articles published has increased rapidly, and there is no obvious trend of slowing down, which indicates that the research has not yet entered the mature stage, and the research of AOSD still has great space and potential. For countries, Japan, the United States and France publish the largest number of articles ( Table 5 ), and the United States, France and the United Kingdom engage in relatively more international cooperation ( Figure 4 ), which is basically consistent with the results of other studies (46). This may be because the improvement of gross domestic product and rapidly expanding economies result in more research funding support, thereby increasing scientific productivity (47). In addition, because developed countries have advanced medical levels and abundant scientific research resources, cooperation with developed countries can promote the improvement of scientific productivity. The results show that in scientifically weaker regions, internal cooperation will be more efficient than international cooperation (48). Therefore, we suggest that developed countries strengthen cooperation with wider countries/regions and strengthen internal cooperation and contact in relatively underdeveloped areas to promote the improvement of global standards at the AOSD medical level.

Clinical Rheumatology is the journal with the largest number of published articles, and Journal of Rheumatology is the journal with the most citations ( Table 3 and Figure 1 ). The impact factors of the two journals are above 2, indicating that the quality of AOSD-related research papers is high and has certain academic value. The article Preliminary criteria for classification of adult Still’s disease published by Yamaguchi, Masaya in Journal of Rheumatology in 1992 has the most citations ( Table 2 ). This article describes a preliminary diagnostic criteria of AOSD (29), namely Yamaguchi criteria, which are now widely used.

The most representative and influential authors in the field of AOSD research have formed their own core author groups with little cooperation among them ( Figure 3 ). Ansell, Barbara M.’s group focuses on the pathophysiological changes of AOSD (49, 50). Their study showed that IgG antiglobulin factor levels are elevated in AOSD patients (51). In the FII haemagglutination test for serum antigammaglobulin factors of AOSD patients, the mean FII tube titre increased, and severe incapacity was associated with higher FII titres (52). The group of Kim, Hyoun Ah pointed out that the neutrophil-to-lymphocyte ratio (NLR) can be used as a diagnostic tool and predictor of AOSD recurrence (53). Serum CXCL10, CXCL13 (54) and S100A12 (55) levels can be used as clinical markers to assess the disease activity of AOSD. Chen, D.Y’s team found that there is a fine-tuned mechanism between inflammatory and anti-inflammatory factors in AOSD (56), and IL-18 is an important predictor of active AOSD (57). In addition, galectin-3 (58), C-Type Lectin Domain Family 5-Member A (59), B19-NS1 (60), microRNA-134 (61), and the NLRP3 inflammasome (62) are involved in the pathogenesis of AOSD. Since 2018, the core research team formed by Wang, Zhihong, et al. from Shanghai Jiao Tong University has performed research on biomarkers of AOSD (63) and illustrated the pathogenesis, diagnosis, treatment and nursing of AOSD through clinical case data (64, 65). Their case study pointed out that neutrophils-derived lipocalin-2 can serve as an effective biomarker to identify AOSD with systemic inflammation (66).

The research field of AOSD can be divided into three phases in terms of time ( Figure 6 and Table 7 ) to better determine the research hotspots in different periods and the obvious change in research direction (67). In the early stage of research (1921–1997), researchers paid more attention to the therapeutic medication of disease. JACQUES M. G. W. WOUTERS et al.’s research shows that glucocorticoids can effectively relieve systemic and/or joint symptoms (68). Aydintuǧ, A. Olcay et al. showed that low-dose methotrexate (MTX) can treat AOSD and reduce the dosage of steroids (69). Researchers began to explore the pathological mechanism of disease and biomarkers related to disease in the middle of the research (1998-2011). Chen, Der Yuan’s research showed that Th1 cytokines may promote the pathogenesis of AOSD (70). In the recent stage (2012-2021), the complications of the disease became a hot topic for researchers. As seen, the focus of research has gradually changed from symptoms and treatment of AOSD to the complications and prognosis of diseases. Research on complications and new pathogenesis will become a research trend and hotspot in the future. However, slightly different from our research results, the research results of Xue Zhang et al. show that the research focus in the recent 10 years has mainly been on the treatment of AOSD and its serious complications (46). This difference may be mainly caused by the different literature source databases selected, different data analysis software used, and different literature data time spans included.

Combining the keyword frequency and keyword clustering analysis, the research hotspots and frontier are as follows ( Table 6 and Figure 5 ):

To the best of our knowledge, little research systematically and comprehensively discusses the research progress and changing trends in the AOSD field. Therefore, to eliminate this limitation, we used CiteSpace software to visualize information such as authors, journals, and keywords. This study is the first time to analyze the literature in the field of AOSD in the past 100 years. By retrieving the Scopus database with a large amount of data in the field of AOSD, almost all the original studies in this field were included, and the history, current situation and trend analysis of the field of AOSD were conducted. On the one hand, this research provides valuable information for scholars in this field, which helps them understand the development process of AOSD and master the hot topics at the forefront; on the other hand, it also provides new research perspectives and ideas for exploring the development direction of AOSD.

However, this research inevitably has limitations that need to be solved in the future. Due to the continuous updating of the database and the limited analysis year span of CiteSpace software, only the articles from 1921 to November 30, 2021, were selected for this research, and articles published after that were not included in this research. Therefore, there will be discrepancies between bibliometric analysis and actual publication. Restricted by the capabilities of the analysis software, only articles in the Scopus core database are included in this research, which may result in potentially incomplete analytical data. Due to the limitation of CiteSpace software, a lack of unified parameter setting standards, data loss and partial data overlap will inevitably occur in the process of software clustering, which will also lead to the deviation of analysis results. In addition, according to the general process of bibliometrics research, this study adopts an accurate literature search strategy to ensure the correlation between downloaded literature and research topics and uses Cite Space software to remove duplicate literature. However, it is still possible to have subtle errors due to the database or software issues, which are slightly insufficient in artificial induction.

The number of AOSD-related articles is generally on the rise. Developed countries have more research achievements and closer cooperation among countries and lack cooperation with other countries. The diagnosis and treatment of AOSD have always been the focus of researchers’ attention. In the future, the complications and new pathogenesis of AOSD will become research trends and hotspots.

The original contributions presented in the study are included in the article/supplementary material, Further inquiries can be directed to the corresponding author.

AQ wrote the first draft of the manuscript. JS, CG wrote sections of the manuscript. CL contribute to the search strategy of the study. All authors contributed to manuscript revision, read, and approved the submitted version

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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