Use this URL to cite or link to this record in EThOS:
Title: The aeitiopathogenesis of cutaneous wound failure in Crohn's disease
Author: Daulatzai, Najibullah
ISNI:       0000 0004 6346 8890
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Access from Institution:
Crohn’s disease (CD) is a multi-system condition with multiple cutaneous manifestations. Perineal wound failure is a common complication following surgery in CD. Despite advancements of our understanding of the underlying disease process in intestinal CD, our knowledge in the aetiopathogenesis of skin involvement is still lacking. Risk factors, which contribute to the development of an unhealed perineum following surgery was assessed. The rate for an unhealed perineum at 12 months following surgery was 23%. Poorer healing took place in patients with pre-existing perineal sepsis, but no significant difference was found between patients with IBD or cancer. Subsequent studies assessed immune cell function as a potential contributor to wound failure in CD. Dendritic cells (DC) are specialised antigen-presenting cells that play a central role in intestinal CD pathogenesis. DC dictate type of T-cell immunity and T-cell homing profiles, however wound DC have yet to be characterised. DC were successfully identified from all wound tissue. Expression of skin- homing molecule (CLA) was reduced on wound DC in CD compared with controls. Wound DC were found to stimulate dose-dependent allogeneic T-cell proliferation; both wound and blood DC from CD patients were significantly less stimulatory than their control DC counterparts. Furthermore, DC from CD patients generated T-cells with enhanced expression of CLA compared to T-cells stimulated by control DC in wound tissue and blood. Aberrant expression of skin-homing marker CLA on DC and T-cells that they stimulate may contribute to alterations in immune cell migration in CD. Taken with the restricted stimulatory capacity of DC in CD wounds, it is likely that a loss of DC function occurs contributing to wound failure. Histological assessment suggested an increase in plasma cells in CD wound tissue compared to non-CD wound tissue, further highlighting an immunological aetiology for the aberrant healing in CD. Finally, a randomised control study to assess quality of life benefits and effects on wound dimensions of regular wound digitation against current standard practice of community nurse-led dressings in the management of open perineal wounds was investigated. Wound digitation had a significant reduction in pain, restriction of daily activities and degree of induration, whilst having a comparable healing rate to regular dressings.
Supervisor: Hart, Ailsa ; Phillips, Robin Sponsor: St. Mark's Hospital for Diseases of the Rectum and Colon (London ; England)
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral