Primary Lymphedema with Concomitant Vascular and Lymphatic Lesions

Introduction

Primary extremity lymphedema is a debilitating disease with a reported incidence of approximately 1–3 out of every 10,000 births and with a female to male ratio of 3.5:1. It can be categorized according to the age of onset: congenital (onset at birth), praecox (after birth and before 35 years of age), and tarda (after the age of 35). Specific gene mutations have been identified in primary lymphedema patients, including mutations of VEGFR3 (Milroy’s disease), PIEZO1, EPHB4, CCBE1 (Hennekam’s syndrome), PIK3/AKT/mTOR pathway (PIK3CA-related overgrowth spectrum, SOX18 (hypotrichosis-telangiectasia-lymphedema), FOXC2 (lymphedema distichiasis), and KIF11 (microcephaly-chorioretinopathy-lymphedema-mental retardation). In addition to the clinical history and physical examination needed for diagnosis, recent advances in the use of Tc-99 lymphoscintigraphy and indocyanine green (ICG) lymphography have markedly improved the diagnosis of primary extremity lymphedema. While the definite surgical treatment for patients with primary extremity lymphedema has yet to be proven, studies have shown that microsurgical procedures such as lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) can provide effective treatment. However, there is little to be found in the literature concerning the long-term prognosis of primary extremity lymphedema.

Concomitant vascular and other lymphatic lesions such as venous thrombosis, vascular malformations, arterial occlusions, and retroperitoneal lymphangiomatosis causing chylous ascites may contribute to primary extremity lymphedema and even make primary extremity lymphedema more severe. The incidence of vascular and other lymphatic diseases occurring in primary extremity lymphedema patients has seldom been reported. These other diseases are frequently neglected, and the diagnosis is also much more difficult.

In this chapter, the authors highlight their clinical experience as well as review the relevant literature to provide recommendations for the diagnosis and treatment of primary extremity lymphedema with concomitant vascular and lymphatic diseases.

Concepts

Previous reports show that 20–30% of patients with chronic venous diseases also have associated lymphatic dysfunction, possibly due to cellulitis or overload of the lymphatic system. Therefore, a potential synergistic effect might exist between venous obstruction and lymphatic dysfunction. Szuba et al. reported that 4.6% of patients with extremity lymphedema had concomitant venous obstruction. Sachanandani et al. reported that 15 of 95 (15.8%) patients with extremity lymphedema had concomitant vascular lesions.

Lymphangiomatosis is a rare condition with an unclear incidence where hyperproliferation of lymphatic vasculature causes lymphangiomas and affects soft tissue and viscera, and osseous involvement is sometimes present. The major complications of lymphangiomatosis include chylothorax, chylous pericardial effusion, and chylous ascites. In particular, retroperitoneal lymphangiomatosis may present with chylous ascites as well as concomitant lower limb lymphedema. Previously, the care for retroperitoneal lymphangiomatosis involved symptomatic care with thoracocentesis, pleurodesis, or paracentesis, combined with lymphedema therapy. In one study, 6 of 44 (13.6%) primary extremity lymphedema patients were found to have retroperitoneal lymphangiomatosis.

Considering the relatively high prevalence of concomitant vascular and lymphatic lesions in patients with primary extremity lymphedema and the synergistic severity of lymphedema, early detection and timely intervention of the concomitant diseases to counteract the disease progression are warranted.

Patient Selection

Retroperitoneal Lymphangiomatosis

For the diagnosis of retroperitoneal lymphangiomatosis, the methods that are currently being used include direct lymphangiography followed by computed tomography (CT) and magnetic resonance imaging (MRI). Chen et al. performed MRI in patients with primary extremity lymphedema who also presented with abdominal symptoms and/or ascites in order to view extravasation of chyle into the peritoneal cavity. If the examination was positive, a single photon emission CT (SPECT) scan was then performed to visualize the retroperitoneal lymphatic malformation. Seven patients underwent exploratory laparotomy under the suspicion of retroperitoneal lymphangiomatosis, and six were positive, yielding a specificity of 85.7% when both MRI and SPECT were utilized ( Fig. 5.1 ).