Lymphovenous Anastomosis Aids Wound Healing in Lymphedema: Relationship Between Lymphedema and Delayed Wound Healing from a View of Immune Mechanisms

Abstract

Delayed wound healing in lymphedema is assumed to be caused by two reasons, pathophysiological and immunological effects of lymphedema. The aim of this review is to establish how impaired lymphatics alter wound healing pathophysiologically and immunologically, and to propose treatment modalities that can promote wound healing in lymphedema. Lymphaticovenular anastomoses (lymphovenous anastomoses [LVAs]) were performed on patients who had recurrent cellulitis several times with lymphorrhea and developed severe ulcers that were refractory to skin grafts, flaps, and conservative therapy. The lymphorrhea and the ulcer had healed by 4 weeks. Moreover, the lymphedema improved without compression therapy. Lymphedema is characterized pathophysiologically by localized peripheral edema that compresses the microvasculature and lymphatic vasculature and impairs tissue remodeling. Another suspected mechanism is an imbalance in the differentiation of participating immune cells. Profound suppression of T helper (Th)1 cells is likely to increase the risk of infection, and excessive differentiation of Th2 cells, including M2 macrophage polarization, may promote fibrosis, which disrupts the carefully orchestrated wound healing process. Although negative-pressure wound therapy is useful for the treatment of delayed wound healing in lymphedema, LVAs may be necessary to treat the fundamental problem of lymphedema. LVAs are considered to create a bypass to the lymph nodes through which dendritic cells (DCs) can transmit antigen information to T cells. LVAs are considered to neutralize chronic inflammation by allowing more DCs to return into the circulation, thereby improving wound healing.

Hybrid Treatment Combining Lymphaticovenous Anastomoses and the Oriental Herbal Medicine Bofutsushosan for Obesity-Associated Lower Leg Elephantiasis Nostras Verrucosa: A Case Report

“…4 It is conceivable that the lymphedema associated with ENV results in accumulation of excessive protein-rich fluids in the dermis and the subcutaneous tissues, that the protein-rich fluids reduce the immunity of the skin, and that the poor immunity may lead to the disruption of the skin barrier by cutaneous fissures, erosions, and ulcerations. 5 Yoshida et al 6 found that LVA neutralized chronic inflammation by allowing immune cells to return to the circulation; therefore, LVA facilitated wound healing in patients with lymphedema. In our case, LVA contributed to not only reducing the edema but also improving the skin pathology in the right lower limb.…”

Localized lymphedema after treatment for soft tissue sarcoma in the lower limbs: Comparison of improvement according to duration before lymphaticovenular anastomosis

“…The lymphatic vessels transport not only interstitial fluid but also antigen information with dendritic cells to the lymph nodes. From the standpoint of acquired immunity, LVA is thought to create a bypass to the lymph nodes via which dendritic cells can transmit antigen information to T cells in the blood circulation …”

“…It is important to monitor patients for lymphedema after surgically invasive procedures to the medial knee region. Lymphedema not only causes edema but also increases the risks of infection and delayed wound healing in the affected limb, which is thought to be caused by localized immune deficiency in the area with lymphedema …”

“…From the standpoint of acquired immunity, LVA is thought to create a bypass to the lymph nodes via which dendritic cells can transmit antigen information to T cells in the blood circulation. 6 Secondary lymphedema can also be caused by invasive surgery. Lymph node dissection in the pelvic or inguinal region in particular is a well-known cause of secondary lymphedema.…”

Role of microRNAs in Pressure Ulcer Immune Response, Pathogenesis, and Treatment

“…Lymphedema, or the build-up of lymphatic fluid in the interstitial space, is a component of pressure ulcer pathophysiology, but is often studied as a unique entity that can induce ulcer formation. Acquired lymphedema results in increased levels of pro-inflammatory molecules such as TNFα, IL-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1), which contribute to an increase in the infiltration of pro-inflammatory cells, as well as a decrease in T-regulatory cells involved in the resolution of inflammation [36,37]. The impairment of lymphatic clearance, along with impaired venous drainage described above, leads to the maintenance of high leukocyte infiltrate with poor ROS and cytokine clearance.…”