Perianal fistulizing Crohn’s disease (pfCD) represents one of the most challenging manifestations of CD, often associated with severe phenotypes, refractory luminal inflammation, and a substantial reduction in quality of life. Its pathogenesis is multifactorial and incompletely understood, involving genetic susceptibility, epithelial and stromal dysfunction, and microbiome-related mechanisms. Diagnosis and monitoring rely on advanced imaging, while management requires coordinated medical–surgical strategies. Significant unmet needs persist regarding standardized treatment targets, optimal imaging follow-up, and personalized therapeutic pathways. In this review, we aim to summarise and provide a comprehensive overview of the most recent evidence across pathogenesis, diagnosis, classification systems, and therapeutic approaches in pfCD. We highlight key advances in understanding epithelial–mesenchymal transition, immune–microbiome interactions, and genetic determinants of disease behaviour. Improvements in diagnostic modalities—including MRI-based scores, ultrasound technologies, volumetric assessment, and AI-enhanced imaging—are discussed alongside modern classification systems such as TOPClass. Evidence guiding medical therapy, seton management, and surgical decision-making is reviewed, emphasising integrated, goal-oriented care. Despite substantial progress, pfCD remains a difficult-to-treat condition with persistent gaps in early diagnosis, objective monitoring, and individualized management. Emerging imaging technologies, standardized treatment targets, and structured classification frameworks offer promising strategies to overcome current limitations and improve long-term outcomes.
Faggiani et al. (Thu,) studied this question.