Diabetic foot ulcers in conjunction with lower limb lymphedema: pathophysiology and treatment procedures

Abstract

Diabetic foot ulcers (DFUs) are complex, chronic, and progressive wounds, and have a significant impact on morbidity, mortality, and quality of life. A particular aspect of DFU that has not been reviewed extensively thus far is its management in conjunction with peripheral limb edema. Peripheral limb edema is a feature of diabetes that has been identified as a significant risk factor for amputation in patients with DFU. Three major etiological factors in development of lymphedema with concurrent DFU are diabetic microangiopathy, failure of autonomic regulation, and recurrent infection. This review outlines the pathophysiology of lymphedema formation in patients with DFU and highlights the cellular and immune components of impaired wound healing in lymphedematous DFU. We then discuss the principles of management of DFU in conjunction with lymphedema.

Drug‐induced peripheral oedema: An aetiology‐based review

“…This leads to increase the vascular permeability and loss of tone regulation, resulting in increased capillary filtration of fluid through the tissues. 33 Diabetic neuropathy can lead to lymphatic pump failure, which impedes interstitial albumin uptake and disrupts the transport of lymphatic fluid along lymphatic vessels. 34 In addition, several diseases such as diabetes and venous hypertension are associated with an altered venoarteriolar reflex.…”

“…In addition to the effect of proteinuria on the capillary oncotic pressure, diabetic microangiopathy also alters the structure and function of the microvasculature. This leads to increase the vascular permeability and loss of tone regulation, resulting in increased capillary filtration of fluid through the tissues 33 . Diabetic neuropathy can lead to lymphatic pump failure, which impedes interstitial albumin uptake and disrupts the transport of lymphatic fluid along lymphatic vessels 34 .…”

The Lymphatic System in Obesity, Insulin Resistance, and Cardiovascular Diseases

“…Increased lymphatic density found in human patient samples seemingly correlates with the phenomenon observed in diabetic rats that have enhanced lymphatic return to the systemic circulation. However, it is possible that the lymphatic function may decompensate after prolonged interstitial fluid overload caused by hyperglycemia (Kanapathy et al, 2015). Increased lymphatic collecting vessel permeability caused by diminished NO availability appears to be a contributing factor for lymphatic dysfunction (Scallan et al, 2015).…”

Materials and Cytokines in the Healing of Diabetic Foot Ulcers

“…[ 93,94 ] Lymph vessel formation can be observed early in wound healing where is it localized to the wound periphery; this formation peaks within ≈1 week and returns to basal levels within 23 d. [ 95 ] Furthermore, decreased lymphatic vessel formation is known to exacerbate chronic diabetic wound healing through excess edema, [ 96 ] and DM is further associated with inflammation of the lymphatic system and the abnormal accumulation of growth factors, neutrophils, and lymphocytes. [ 97 ] These conditions lead to an ideal microenvironment for bacterial growth and abnormal production of collagen, glycosoaminoglycans, and inflammatory cytokines which stimulate fibrosis, leading to further local tissue damage and increased lymphedema. [ 97 ] The local induction of healthy lymphangiogenesis, however, promotes wound healing through ECM remodeling and deposition and increased immune cell migration.…”

“…[ 97 ] These conditions lead to an ideal microenvironment for bacterial growth and abnormal production of collagen, glycosoaminoglycans, and inflammatory cytokines which stimulate fibrosis, leading to further local tissue damage and increased lymphedema. [ 97 ] The local induction of healthy lymphangiogenesis, however, promotes wound healing through ECM remodeling and deposition and increased immune cell migration. [ 94 ]…”