The association of wound factors and symptoms of fatigue and pain with wound healing in chronic venous leg ulcers

Int Wound J. 2023 Apr;20(4):1098-1111. doi: 10.1111/iwj.13966. Epub 2022 Sep 30.


The purpose of this study was: (1) to characterise the association of wound area, wound exudate C-reactive protein (CRP), broad-spectrum matrix metalloprotease protein (MMPs), and symptoms of fatigue and pain in individuals with chronic venous leg ulcers (CVLUs) over time and (2) to identify factors associated with the wound healing trajectory in CVLUs. Seventy four participants with CVLU who received weekly sharp debridement were recruited from a wound care clinic during the 8-week study period. To examine associations among wound CRP, MMPs, pain, fatigue, and wound healing trajectory over time, we calculated Bayes factors (BF) based on a linear mixed model. The mean age of participants was 71.8 (SD = 9.8) and the mean wound area was 2278 mm2 (SD = 7085 mm2 ) at baseline. Higher fatigue was strongly associated with higher MMPs (BF = 9, 95% HDI: [-.05, .43]), lower CRP (BF = 11, 95% HDI: [-.02, .002]), and large areas of wound (BF = 20, 95% HDI: [-.001, .01]). Higher CRP and MMPs activity in wound exudate and higher fatigue were associated with a larger wound area. To facilitate wound healing, clinicians need to utilise the multifactorial approach, which includes wound treatment and management of symptoms such as pain and fatigue, because of the molecular and psycho-behavioural factors involved in wound healing.

Keywords: CRP; MMPs; chronic venous leg ulcers; fatigue; wound healing.

MeSH terms

  • Bayes Theorem
  • C-Reactive Protein
  • Fatigue / etiology
  • Fatigue / therapy
  • Humans
  • Pain / diagnosis
  • Varicose Ulcer* / therapy
  • Wound Healing


  • C-Reactive Protein