This article elucidates the diagnostic and therapeutic challenges, as well as the implications of rare extraintestinal manifestations, through a three-year longitudinal follow-up of a 19-year-old female with metastatic Crohn’s disease (MCD) co-occurring with vulvar Crohn’s disease (VCD). The patient exhibited asynchronous progression of intestinal symptoms and vulvar lesions. Initial treatment with mesalazine proved ineffective; however, significant improvement was observed following infliximab therapy (5-10 mg/kg) in combination with surgical intervention for anal fistulas, as evidenced by normalization of inflammatory markers (CRP/ESR/HGB). Despite this, VCD persisted, underscoring the limitations of anti-TNF? therapy in modulating the gut-skin axis. Key insights include: ? VCD, as a rare manifestation independent of intestinal activity, necessitates accurate diagnosis via multimodal imaging and histopathological biopsy to prevent misclassification; ? The integration of biologics with surgical interventions can effectively manage complex fistulas and inflammation but requires personalized long-term strategies; ? Investigating the immune-microbial interactions within the skin-gut axis may pave the way for novel targeted therapies for MCD; ? Holistic physical and psychological management is essential for optimizing outcomes in chronic conditions. This case provides valuable empirical data for guiding clinical decision-making and advancing mechanistic understanding of MCD.