Crohn's disease (CD) is a chronic, non-specific inflammatory bowel disease (IBD) of unknown etiology. As a subtype of IBD, CD is characterized by transmural inflammation that disrupts the integrity of the intestinal wall and anal canal mucosa, frequently leading to perianal complications such as fistulae and abscesses. Among these complications, perianal fistulizing CD (PFCD) is particularly prevalent, with its incidence showing a marked increase in recent years (1). Fistulae account for a significant proportion of CD-related perianal lesions, approximately 50% of which are classified as complex. Complex fistulae pose substantial clinical challenges due to their high recurrence rates, potential for sphincter damage, and risk of fecal incontinence (2). Furthermore, intestinal inflammation and rectal ulceration may induce anal strictures, severely compromising patients' quality of life (3). Beyond fistulae, CD-associated perianal manifestations encompass a spectrum of conditions, including skin tags, hemorrhoids, anal fissures, abscesses, rectovaginal fistulae, anorectal stenosis, and malignant transformations (4).

CD manifesting with initial perianal involvement presents significant diagnostic challenges due to its insidious clinical onset. The nonspecific nature of early perianal lesions frequently leads to underdiagnosis or delayed recognition. Moreover, as CD constitutes the underlying etiology, isolated surgical intervention targeting perianal manifestations often results in disease recurrence and refractory lesions. Repeated procedures may further compromise perianal tissue integrity and obliterate characteristic pathological features, thereby impairing subsequent diagnostic accuracy and therapeutic decision-making. Current limitations in clinical practice highlight an urgent need for reliable predictive tools to differentiate CD-associated perianal pathology from isolated anorectal disorders. However, the absence of rapid, minimally invasive, and precise diagnostic modalities continues to hinder early identification and targeted management. We found through literature review that previous visualization analyses have mainly focused on the current status of surgical treatment for PFCD (5), the application status of biologics (6), the diagnosis and treatment status of pediatric Crohn's disease (7), the application status of ustekinumab (8), and the global research trends in Crohn's disease treatment over the past 20 years (9), hotspots and trends of perianal fistula of Crohn's disease (10), the development of surgical treatment for Crohn's disease in the past 20 years (11). Through this in-depth review, we have clearly found that although there have been many excellent studies that have sorted out the overall field of Crohn's disease, there is still no research specifically focused on the specific, important, and clinically complex subfield of “Perianal Lesions Associated with Crohn's Disease”.

In recent years, research on perianal Crohn's disease (pCD) has significantly advanced. However, there remains a paucity of studies focusing on two critical aspects: clinical prediction of CD initially presenting with perianal lesions, and comprehensive literature synthesis regarding perianal CD. To address these gaps, this study employed bibliometric methods using CiteSpace 6.4. R1 software to analyze PubMed-indexed literature on CD with perianal manifestations. Through visualization and interpretation of contributing authors, country distributions, and keyword networks, this investigation aims to elucidate the evolving landscape of this research field, identify current research hotspots and emerging trends, and potentially facilitate future studies on predictive for perianal involvement in CD.

CD is a chronic, relapsing systemic inflammatory disorder that primarily involves the gastrointestinal tract, often presenting with extraintestinal manifestations (12). The intestinal pathology of CD is distinguished by discontinuous transmural inflammation of the intestinal wall. Due to its insidious onset and nonspecific early symptoms, CD frequently experiences significant diagnostic delays (13), with approximately 75% of patients receiving confirmation only two years after symptom onset (14). At initial diagnosis, most patients present with inflammatory disease without stenosis or penetrating complications, typically progressing to stricturing or fistulizing phenotypes over time (15). Clinical data indicate that 20%–30% of CD patients demonstrate perianal involvement at first presentation, with cumulative lifetime risk of perianal disease reaching approximately 50% (16). In CD, perianal lesions most frequently manifest as fistulas, though they may also develop in other regions, including the rectovaginal space, bowel-bladder interface, and intra-abdominal structures. While non-fistulizing perianal CD is less common, it remains a clinically significant presentation (17). Notably, perianal symptoms precede the formal diagnosis of CD in approximately 30% of cases (18). Anal fissures and perianal ulcers occur in roughly 17% of patients, with long-term outcomes favoring fissures over ulcers (19). Additionally, anorectal stenosis develops in about 6% of patients within a decade of disease onset (20).

Our analysis of publication trends in the database reveals a consistent increase in research output on CD with perianal lesions since 1979. The annual growth in publications addressing this condition demonstrates its progressively rising significance in the scientific community, reflecting heightened clinical and academic attention over the past four decades. Professor Ye Byong Duk emerged as the most prolific author with the highest publication output, having authored 26 articles. The analysis revealed a total of 348 collaborative publications within this research network, demonstrating strong academic connections among investigators studying the diagnosis and management of CD with perianal lesions. The United States leads in research output on CD with perianal lesions, producing 452 publications, which more than quadruples Italy's output of 119 publications as the second most productive country. This substantial disparity highlights the dominant contribution of U.S. scholars to this field. Given the rising incidence of perianal complications in CD, expanded international research efforts remain crucial to advance understanding and management of this condition. The observed surge in annual publications post-2010 likely mirrors a paradigm shift in PCD management. This period coincides with the widespread adoption of anti-TNFα therapy (particularly adalimumab for maintenance therapy) and the establishment of high-resolution MRI as the gold standard for fistula classification. These diagnostic and therapeutic advances not only expanded the research landscape but also created new clinical questions, thereby fueling a significant volume of investigative work focused on optimizing treatment sequences and assessing therapy response. Keyword clustering analysis identified six representative clusters based on semantic similarity, with modularity Q = 0.488 (exceeding the threshold of 0.3), demonstrating significant cluster structure. The high mean silhouette = 0.8154 (surpassing the 0.7 benchmark) further confirms the robust validity and distinctiveness of these thematic groupings. The cluster analysis yielded six thematic segments with substantial overlap, demonstrating strong interconnections and conceptual correlations among research domains. Keyword emergence analysis revealed two primary research hotspots: “Crohn's disease perianal fistula” and “inflammatory bowel disease”. Notably, recent scholarly attention has shifted toward several emerging frontiers, including quality of life assessment, therapeutic drug monitoring, biologic therapies, anal function preservation, and mesenchymal stromal cell applications. Among them, quality of life is a keyword with a surge in citation from 2019 to 2024. Currently, commonly used quality of life assessment tools include the Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36, EQ-5D, and IBDQ-32 instruments, which better demonstrate the severity of a patient's condition (21). These all evolving research priorities reflect both the maturing understanding of CD pathogenesis and the trajectory of future investigations in this field.

Current research on CD has predominantly focused on mesenchymal stem cells (MSCs) and intestinal inflammation, while investigations into the pathogenesis and therapeutic interventions for perianal lesions remain relatively limited. This trend underscores the potential significance of IBD mechanisms and mesenchymal stem cell biology in driving the development of perianal complications in CD (22). MSCs, primarily isolated from adipose tissue and bone marrow as well as other organ connective tissues (23), have garnered significant therapeutic interest for CD-associated perianal fistulas due to their regenerative capabilities. These cells demonstrate particular efficacy in promoting healing of CD-related perianal lesions (24), especially fistulous tracts that develop from persistent inflammatory processes leading to epithelial defects and ulceration (25). MSCs demonstrate therapeutic potential for CD-associated perianal lesions through their anti-inflammatory and immunomodulatory properties (26). In contrast, conventional pharmacotherapies such as aminosalicylates and corticosteroids show limited efficacy in IBD management, characterized by low remission rates and high disease recurrence (27). Existing evidence further indicates that aminosalicylate therapy provides no significant clinical benefit for luminal CD (28). Scientific investigation into MSCs for therapeutic applications commenced in 2005 (29). The clinical potential of MSCs in treating perianal fistulizing Crohn's disease (pfCD) primarily stems from their unique capacity for multilineage differentiation and targeted tissue engraftment, which enables effective tissue regeneration and repair (30). A systematic review and meta-analysis on MSCs therapy for perianal fistulizing CD demonstrated both safety and clinical efficacy of this treatment approach (31). MSCs possess two fundamental biological properties: multilineage differentiation potential into mesodermal cell types, and potent immunomodulatory effects that suppress immune cell activation, proliferation, differentiation, and maturation processes (32). Our bibliometric analysis clearly captures the translational journey of MSC therapy in PCD. The initial burst of keywords reflects a foundational research phase focused on mechanistic exploration. This was followed by the emergence and citation classic status of pivotal clinical trials, which shifted the intellectual backbone of the field towards clinical efficacy. The subsequent rise of keywords like in recent years signals the field's current maturation, grappling with the challenges of real-world clinical translation. Thus, the bibliometric trends directly map onto the innovation pathway from bench to bedside.

IBD represents a complex, chronic inflammatory disorder with multifactorial pathogenesis involving dysregulated mucosal immunity and intestinal microbiota dysbiosis. In the United States and Europe, IBD affects over 3.5 million individuals (33). Recent epidemiological studies indicate a rising diagnostic incidence of CD, a principal subtype of IBD, within these populations (34). Perianal fistulizing disease (PFD) represents a particularly debilitating manifestation of IBD, significantly compromising patient quality of life (35). Epidemiological data indicate a prevalence of approximately 34% in CD patients compared to 4% in the general IBD population (36). Diagnostic challenges arise when PFD symptoms precede intestinal manifestations, as these cases are frequently not attributed to CD. This clinical scenario often results in delayed diagnosis, with the condition typically receiving proper medical attention only upon symptom recurrence (37). For patients suspected of PFD caused by CD, a comprehensive diagnostic approach incorporating multiple imaging modalities - such as magnetic resonance imaging, intra-anal ultrasound, computed tomography, or dedicated small bowel CT - is recommended to establish a reliable foundation for clinical diagnosis and subsequent treatment planning (38). The clinical manifestations of IBD, including CD, typically feature bloody diarrhea, fever, and intestinal obstruction. Patients with IBD exhibit marked mucosal vulnerability to bleeding, which characteristically affects the entire rectum and colon. CD is distinguished by transmural inflammation that may occur anywhere along the gastrointestinal tract, from the oral cavity to the anus, often demonstrating a discontinuous, “skip lesion” pattern. In contrast, ulcerative colitis typically presents with continuous inflammation extending proximally from the rectum through the colon. However, it is important to note that discontinuous inflammation alone does not definitively confirm a CD diagnosis, as emerging evidence suggests that even prolonged segments of intestinal inflammation may not always be pathognomonic of CD (39). As CD advances, nearly all patients develop intestinal stenosis and varying degrees of perianal lesions. Current therapeutic strategies primarily focus on maintaining clinical remission as the treatment goal, even when clinical symptoms subside while intestinal mucosal inflammation persists. For IBD patients complicated by perianal fistulae, a combined pharmacological and surgical approach is generally recommended, though conservative management may be appropriate for asymptomatic cases or those with well-tolerated fistulae (36). Notably, there remains a significant gap in research comparing the effectiveness of medical vs. surgical interventions when PFD coexists with IBD (40).

Our bibliometric findings have certain implications for clinical practice and scientific research. Firstly, our research provides a reference for clinical doctors, researchers, and decision-makers in the perianal lesions of Crohn's disease. Currently, research on CD mainly focuses on mesenchymal stem cells (MSCs) and intestinal inflammation. This result not only indicates the direction of previous treatments, but also provides a reference for future research. At the same time, it also suggests the need for more teamwork and optimized new methods and ideas in future research to solve this challenging disease. Although our data is included in a large database, there may still be some missing literature, limitations in search strategies, inherent limitations in bibliometric methods, and subjectivity in parameter selection of software such as CiteSpace, which may lead to certain deficiencies in our research. Therefore, in the future, more refined research directions and a larger number of studies need to be included to present the treatment direction of Crohn's disease perianal lesions as clearly as possible.

While the prevention and treatment of CD have become increasingly standardized, significant research gaps remain, particularly regarding CD cases where perianal symptoms manifest as the initial clinical presentation. Current evidence underscores the need for future investigations to elucidate the underlying pathogenesis of perianal CD lesions and to develop more effective diagnostic and therapeutic strategies. Such research efforts are crucial for improving early detection and intervention in patients presenting with perianal symptoms as their first indication of CD, ultimately enhancing clinical outcomes for this challenging patient population.