Fig. 15.1
Large foot ulcer in lymphedema of the lower limb stage IV. This ulcer requires debridement and long-term topical therapy concurrently with procedures for decrease of edema of the whole limb
Fig. 15.2
Lymphedema with ulcer
What is specific for obstructive lymphedema is presence of large accumulated mass of bacteria in the swollen tissues deprived of lymphatic outflow [3]. This is predisposed to local inflammation and subsequently ulcer formation. Moreover, patients with obstructive lymphedema suffer from recurrent attacks of dermatolymphangioadenitis (DLA) caused by bacteria present in a dormant state in the stagnant tissue fluid and lymph [2, 4, 5]. This microflora is, together with microbes colonizing from the environment, responsible for non-healing of ulcers and poor healing after the debulking surgery. Interestingly, the detected bacteria are in vitro sensitive to most antibiotics but not penicillin; however, penicillin is clinically most effective [2]. This means that there are other non-defined non-culturable bacterial strains responding to penicillin, which may be responsible for non-healing.
15.3 Role of the Lymphatic System in Ulcer Healing
Wound healing should not be considered as a process limited to the damaged tissues. It is always accompanied by an intensive response of the regional and, in advanced stages, the systemic lymphatic (immune) system (Fig. 15.3). Penetration of microorganisms through the epidermis and cellular changes caused by tissue injury are almost immediately recognized in the local lymphatic system irrespective of the topography of tissue. Blood immune cells and plasma humoral factors extravasate by the process of chemotaxis and increased capillary permeability. The migrating immune cells incorporate the microbial antigens as well as self-antigens from the apoptotic disintegrated tissue parenchymal cells and migrate via initial and collecting lymphatics to the regional lymph nodes. There, the elimination of antigens and raising of antigen-specific lymphocytes take place.
Fig. 15.3
Schematic presentation of how pathological events in the limb evoke reaction of the lymphatic system: lymphatics and nodes
Intensive transport of microbial and self-antigens along lymphatic to lymph nodes and cellular reaction in the lymphoid tissue result in the formation of antigen-specific cohorts of cytotoxic lymphocytes. It remains so far unknown whether these cells migrate back from the bloodstream to the ulcer and, if so, whether they participate in the healing process. The effect of homing lymphocytes may be pro- and anti-inflammatory as well as lymphatic pro- and antiangiogenic. Lymph nodes are sites for quick reaction to bacteria resulting in their elimination. They may also be sites for raising tolerance to own antigens from wound cellular debris. Maybe in delayed wound healing, the low level tolerance is not sufficient to overcome an excessive mass of self-antigens. It may then be suggested that in the non-healing ulcers, the aggressive lymph node-derived cells may prevent healing by attacking own granulation cells. Around 20 % of long-lasting venous ulcers are complicated by systemic allergic reactions. An open question remains whether there is a closed functional loop “wound-regional lymph node-blood circulation-wound” and what may be the tasks of the lymphocytes and precursors of dendritic cells circulating in this loop. The hypothetical loop is “wound-afferent lymphatics-lymph node-efferent lymphatics-blood-wound”: antigens are transported from the wound via afferent lymphatics to the lymph node; once there, a processing of the antigen takes place followed by proliferation of antigen-specific lymphocytes; these cells are released and transported along efferent lymphatic via the thoracic duct to the blood circulation; some of them are trapped in the liver, gut, bone marrow, and spleen and inform local lymphoid tissue about penetration of the body by microbes and release of own cellular debris; these antigen-specific cells are further extracted from blood at the wound site; there, they participate in the healing and reconstruction processes and, however, may also attack own granulation cells in the autoimmune process. Debris help additional colonization by bacteria. This may explain delayed wound healing and systemic allergic reaction seen in some 20 % patients with long-lasting ulcers. Scintigraphy may help in the localization of the pathology (Fig. 15.4).
