Ziwu-Liuzhu-guided combined external therapy promotes wound healing in postoperative perianal fistulizing Crohn’s disease

Abstract

BACKGROUND

Perianal fistulizing Crohn’s disease (PFCD) is one of the most destructive complications of inflammatory bowel disease. Delayed postoperative wound healing, persistent inflammation, and a high risk of recurrence remain major challenges in clinical management. In recent years, external traditional Chinese medicine therapies have attracted increasing attention in postoperative recovery from perianal disorders, and time-specific intervention based on chronomedicine principles, such as the Ziwu-Liuzhu theory, may further optimize therapeutic outcomes.

AIM

To evaluate the effects of Ziwu-Liuzhu-guided combined external therapy on wound healing, disease activity, inflammation, and anxiety in postoperative PFCD patients.

METHODS

This single-center retrospective cohort study included 217 postoperative PFCD patients (2023-2025). They were divided into sitz bath-only (n = 72), sitz bath plus acupoint application (n = 69), and Ziwu-Liuzhu time-specific combined therapy (n = 76) groups. Outcomes included Crohn’s Disease Activity Index (CDAI), Perianal Disease Activity Index (PDAI), wound healing scores, exudate, pain, granulation, healing time, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and Generalized Anxiety Disorder-7 scale (GAD-7). Between-group comparisons, regression, survival analysis, and propensity score matching were performed.

RESULTS

After 4 weeks, all three groups showed significant improvements in CDAI and PDAI, with the greatest reductions observed in the Ziwu-Liuzhu group. This group also exhibited significantly lower wound healing, exudate, pain, and granulation scores, along with a markedly shorter median healing time (18 days vs 24 days and 31 days). Kaplan-Meier analysis demonstrated a higher wound healing probability in the Ziwu-Liuzhu group (log-rank P < 0.001). Levels of CRP, TNF-α, and IL-6 were significantly lower in the Ziwu-Liuzhu group than in the other two groups. The reduction in GAD-7 score was also greatest in this group. Multivariable regression and propensity score matching consistently confirmed that Ziwu-Liuzhu therapy was independently associated with superior healing and overall clinical efficacy.

CONCLUSION

Ziwu-Liuzhu-guided combined external therapy promotes wound healing, reduces inflammation and anxiety, and improves disease activity in postoperative PFCD, representing a valuable adjunctive integrated management approach.

Keywords: Perianal fistulizing Crohn’s disease; Ziwu-Liuzhu; External traditional Chinese medicine therapy; Wound healing; Inflammatory response; Anxiety status

Core Tip: Perianal fistulizing Crohn’s disease (PFCD) is difficult to manage after surgery because delayed wound healing and persistent inflammation are common. In this retrospective cohort study, a Ziwu-Liuzhu-guided time-specific traditional Chinese medicine external therapy was associated with better postoperative recovery than sitz bath alone or non-time-specific combined therapy. Patients in the time-specific group showed faster wound healing, lower inflammatory marker levels, greater improvement in Crohn’s Disease Activity Index and Perianal Disease Activity Index scores, and better anxiety outcomes. These findings suggest that treatment timing may be an important adjunct in integrated postoperative PFCD management.