References
Longitudinal physiological remoulding of lower limb skin as a cause of diabetic foot ulcer: a histopathological examination
Abstract
Objective:
Diabetic foot ulcer (DFU) is recognised as a severe complication in patients with type 2 diabetes. With the increasing incidence of diabetes, it represents a major medical challenge. Several models have been proposed to explain its aetiology; however, they have never been assessed by longitudinal histopathological examination, which this study aims to address.
Method:
Multiplex-immunofluorescence analysis was carried out with lengthwise serial skin specimens obtained from the medial thigh, lower leg, ankle, dorsum of foot and acrotarsium close to the DFU region of a patient with type 2 diabetes receiving above the knee amputation.
Results:
Proximal-to-distal gradual loss of peripheral nerve was demonstrated, accompanied by compromised capillaries in the superficial papillary plexus and distended CD31-positive capillaries in the dorsum of foot. Neural fibres and capillaries were also significantly compromised in the sweat gland acinus in the ankle and dorsum of foot. Injuries in the superficial papillary plexus, sweat gland acinus, and sweat gland-associated adipose tissues were accompanied by significant infiltration of macrophages. These results indicated that longitudinal impairment of local blood circulation could be the cause of peripheral neuropathy, which initiated ulcer formation. Resultant chronic inflammation, involving sweat gland-associated adipose tissue, gave rise to impairment of wound healing, and thus DFU formation.
Conclusion:
Longitudinal histopathological examination demonstrated that impairment of local microvascular circulation (rather than the systemic complication caused by type 2 diabetes) was considered the primary cause of peripheral neuropathy, which initiated ulceration. Together with chronic inflammation in the superficial papillary plexus and sweat gland-associated adipose tissue, it resulted in the development of a DFU. Although this is a study of just one individual's limb, our study provided a unique observation, contributing mechanistic insights into developing novel intervening strategies to prevent and treat DFUs.
Diabetic foot ulcer (DFU) is recognised as a severe complication in patients with type 2 diabetes. DFU is a well-recognised factor compromising patient quality of life, and may even be a fatal complication in patients with diabetes. Thus, it remains an important global medical challenge, particularly with the increasing incidence of diabetes.1,2,3,4
The cause of a DFU is the consequence of two major detrimental disturbances, one of which is diabetes-induced tissue damage, such as callus formation, and subcutaneous haemorrhage, leading to ulcer formation. A further complication is delayed wound healing, which can cause deterioration and persistence of the DFU. These two unfavourable conditions are closely connected, so that integrated study is essential in order to obtain a comprehensive understanding of the aetiology of DFU.
Several mechanisms regarding DFU formation have been demonstrated, including peripheral neuropathy,5,6,7,8 which results in foot deformity, and reduced perspiration. Accordingly, keratosis and callus formation occur, and uneven excess pressure causes foot tissue damage and ulceration. Peripheral neuropathy has been recognised as a consequence of a high glucose level, which in turn generates glucose derivatives, such as polyols and advanced glycation end products (AGEs).9–12 Peripheral arterial disease, which can be caused by diabetes, is also a major contributor to DFU formation. Reduced number and size of capillaries compromise microcirculation. Then, development of occlusive arterial disease has been thought to cause ischaemia and eventually formation of the initial ulcer.1,2,3,4
Register now to continue reading
Thank you for visiting Journal of Wound Care's World Union of Wound Healing Supplement and reading some of our peer-reviewed resources for healthcare professionals. To read more, please register today.