Abstract
It is estimated that 140 to 200 million people are affected by lymphedema worldwide. Many studies have proposed targeted therapies that can be delivered systemically or locally to treat lymphedema. Since lymphedema primarily affects the skin and subcutaneous tissues, topical approaches to therapy should be considered as an attractive proposition as they can avoid systemic complications. In light of this, we conducted a systematic review of publications that analyzed the use of topical approaches to delivering targeted therapies in the treatment of lymphedema. We hypothesized that topical approaches resulted in the satisfactory treatment of lymphedema. We conducted a systematic review of publications on PubMed. The main eligibility criterion was that the articles should primarily investigate the use of topical approaches to delivering targeted therapies in the treatment of lymphedema. Consequently, we excluded papers that investigated any other delivery approaches or medical conditions. Of the 174 potential studies found in the literature, six were found to fulfill our eligibility criteria. All these studies were experimental ones on small animals (mice). The authors generally proposed different types of therapies, which could be clustered into two main groups: 1) induction of lymphangiogenesis [vascular endothelial growth factor C (VEGF-C) hydrogel or fibroblast growth factor]; and 2) modulation of inflammation (tacrolimus or topical collagen gel or troxerutin-phosphatidylcholine). All studies presented positive outcomes, demonstrating that topical therapy is a promising route for delivering growth factors and anti-inflammatory agents in the treatment of lymphedema. However, studies were conducted under heterogeneous protocols, and the safe application of these therapies in humans has not been assessed. Further studies are necessary to confirm the benefits and safety of targeted topical therapy on patients with lymphedema.
Highlights
BackgroundStudies suggest that 140 to 200 million people are affected by lymphedema worldwide [1,2]
The authors generally proposed different types of therapies, which could be clustered into two main groups: 1) induction of lymphangiogenesis [vascular endothelial growth factor C (VEGF-C) hydrogel or fibroblast growth factor]; and 2) modulation of inflammation
Many have proposed different methods of therapy/procedures, which can be clustered into two groups: 1) induction of lymphangiogenesis [vascular endothelial growth factor C (VEGFC) hydrogel or fibroblast growth factor] [14,15,16]; and 2) modulation of inflammation [8,13,17]
Summary
BackgroundStudies suggest that 140 to 200 million people are affected by lymphedema worldwide [1,2]. The most common cause of lymphedema is cancer treatment, affecting one in every six patients that undergo solid tumor resection [3]. Affected patients typically present with symptoms only months after oncologic treatment, and this indicates that the pathophysiology of this medical condition is promoted by an imbalance between lymphatic regeneration and tissue inflammation/fibrosis [4,5,6]. In light of the high prevalence of lymphedema and the lack of any curative approach to the disease, many studies have proposed targeted therapies in the treatment of lymphedema. The two most common rationale used in many studies is the induction of lymphangiogenesis and control of inflammation/fibrosis [7,8,9,10,11,12]. The idea of adopting these targeted therapies in clinical practice remains controversial as there is potential for adverse outcomes such as the increased risk of metastasis among oncology patients [11]
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