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Lymphedema: an Overview Here’S a Close Look at This Unappreciated Circulatory System

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Lymphedema: an Overview Here’S a Close Look at This Unappreciated Circulatory System WOUND MANAGEMENT Lymphedema: An Overview Here’s a close look at this unappreciated circulatory system. BY JAMES MCGUIRE, DPM AND CLAIRE-IPHANISE MICHEL, BS, MS What Is Lymphedema? connection between the or- Lymphedema affects ap- Lymph Capillaries in the Tissue Spaces gans—also serve as a great proximately 300 million peo- reservoir of fluid and molec- ple worldwide. Although Tissue cells ular substances that must parasitic filariasis is the most be continually drained from common cause affecting ap- Lymph capillary the spaces. There is a vast proximately 100 million peo- Tissue spaces system of delicate open-end- ple,1 phlebolymphedema or ed lymphatic capillaries and Venule secondary lymphedema due Arteriole pre-collectors that passive- to long-standing chronic ve- ly receive these fluids (Fig- Tissue fluid nous insufficiency (CVI) is Lymphatic vessel ure 1). They actively move 109 the most common type seen them from the periphery in the United States.2 Lymph- through lymphatic capillar- edema occurs because of lym- Figure 1: Lymph capillaries. Source: Wiki Commons ies to the lymph nodes and phatic system dysfunction larger lymphatic veins to a that affects the body’s ability to re- the lack of education of caregivers series of places along the venous move excess fluid from the extremi- in proper treatment of lymphedema, system where the fluids re-enter the ties, or other organs. In addition, the the incidence will almost certainly circulation, the largest of which is lymphatic system is an immunolog- increase in upcoming decades.”2 the thoracic duct (Figure 2). Fluid ical defense system that triggers the production of lymphocytes (natural killer cells, T cells, and B cells). The Lymphedema occurs because of lymphatic system millions of channels of the system collect infecting micro-organisms and dysfunction that affects the body’s ability to remove antigenic substances that find their way into the interstitium and trans- excess fluid from the extremities, or other organs. port them to the lymph nodes, where they are eliminated from the system or antibodies are produced that rap- Anatomy movement is facilitated by a series idly neutralize the offending agents. The lymphatic system is made of one-way valves and delicate mus- Immunodeficiencies ensue when up of three primary components— cles known as lymphangions. the lymphatic system is impaired, the lymph fluid it transports, the The lymph nodes act as a fil- and lymphedema is present, allowing transportation network, and the tration system to remove foreign for infections and increased risk of lymphatic organs. The system is materials and invading organisms malignancies and/or metastases. an open-ended circulatory system from the blood and expose them to Phlebolymphedema is a second- that completes the closed system we the immune cells, which mount an ary lymphedema that develops in are most familiar with. The closed attack on the unwanted invaders. patients with chronic venous insuffi- system consists of the heart, arter- The nodes are part of an adaptive ciency (CVI). There are a number of ies, arterioles, capillaries, venules, immune system where the B and T factors that contribute to an increase and veins. If this were all we had lymphocytes and other white blood in the incidence of lower extremi- to transport nutrients and gather cells recognize and engulf or pro- ty edema in the population. These waste from the tissues, we would duce antibodies to the substances. include: increased survival of heart quickly die because the system is Aberrant cells such as cancer cells failure patients, numerous medica- porous and fluid continually leaks are also identified and engulfed, tions associated with edema, and the out into the interstitial spaces. The whereas toxins are passed on to the increased incidence of obesity. “With myriad nooks and crannies in the liver and kidneys that complete the the aging of the baby boomers and connective tissues—the structural Continued on page 110 www.podiatrym.com AUGUST 2018 | PODIATRY MANAGEMENT WOUND MANAGEMENT Lymphedema (from page 109) Causes of Secondary Lymphedema removal process. Additional Cervical lymph nodes Thoracic duct Cancer-associated lymph- components of the system Thymus edema arises as a result of are the lymphatic organs Lymphatics of the obstructed or infiltrated lym- (the spleen and the thymus), mammary gland Axillary lymph nodes phatic channels or nodes, responsible for regulation of lymphadenectomy, regional Cisterna chyli Spleen the blood components, and lymph node irradiation, or additional immune response the adverse effects of some Lumbar lymph nodes and manufacture of T lym- Lymphatics of the medications.5,8 The most upper limb phocytes (Figure 3). Pelvic lymph nodes common cancer associated with lymphedema is breast Pathophysiology of Lymphatics of the Inguinal lymph nodes cancer secondary to lymph- Lymphedema lower limb adenectomy of the axillary When the normal lym- nodes.9–10 The manifestations phatic flow is disrupted, of lymphedema usually ap- protein-rich fluid accumu- pear within one to five years lates in the tissues, trigger- of the surgery.11 Cancers ing a chronic inflammatory associated with lymphede- reaction that manifests it- Figure 2: Lymph system. Source: Wiki Commons ma include sarcoma, lower self in swelling of what the extremity melanoma, cer- NY Times reported as the newest the dermis and subcutaneous tis- vical, Hodgkin’s lymphoma, and undiscovered organ, the intersti- sues. On a cellular level, this skin prostate.9 The addition of radiation 110 tium.1 White blood cells are attract- change interferes with antigen pro- to lymphadenectomy exponential- ed to the area by the presence of cessing, stagnates immune cells, ly increases the risk of lymphede- extracellular proteins, and release and in some regions impairs Lang- ma compared to lymphadenectomy cytokines, calling other inflamma- erhans cells and keratinocytes, re- alone. In breast cancer treatment, tory cells to the area. The macro- sulting in a thickening of the tissues lymphadenectomy and adjuvant ra- phages ingest foreign materials and and a loss of skin barrier function. diation have an approximately 24% microbes and use lysosomes con- increased rate of lymphedema com- taining free radicals, peroxide, and Types of Lymphedema pared to lymphadenectomy alone.12 hypochlorous acid to denature pro- Primary lymphedema can be de- Parasitic infections such as lym- teins and oxidize cell membranes scribed as a hereditary or congenital phatic filariasis, and skin infections of invading organisms. The macro- disorder, affecting females more than such as cellulitis and erysipelas can phages also release cytokines and males, associated with impaired lym- lead to the development of lower activate fibroblasts, which are stim- phatic vessel development and result- extremity lymphedema. Wuchereria ulated to produces collagen scar ing in lymphedema. Primary lymph- bancrofti, Brugia malayi, and Brugia tissue, resulting in fibrosclerosis of edema can be divided into three forms timori are parasitic roundworms en- depending upon age of demic to Africa, Southeast Asia and Lymph onset: congenital lymphede- Eastern South America that enter the flow ma (at birth), lymphedema body in a larval stage when the host praecox (1-35), and lymph- is bitten by a carrier mosquito. The Lymphatic nodule Capsule edema tarda (35+).4 Some adult nematodes mature in the lym- of the conditions associated Cortex phatic channels and lymph nodes, Trabecula with congenital lymphede- producing a devastating lymphatic ma include: Meige disease, elephantiasis in the affected limb. It Efferent Milroy’s disease, Aagenaes is usually acquired in tropical and Medulla lymphatic vessel syndrome, and Turner syn- subtropical territories during one’s drome. childhood but can be asymptomat- Lymph Secondary lymphedema ic in those younger than five years flow is caused by an acquired old.13 Valve impairment of the lymphat- In the United States, elephan- ic system due to several tiasis from parasites is very rare Vein causes: cancer and its treat- but repetitive cellulitis from mul- Afferent Artery ment, infection, inflamma- tiple insect bites from an infesta- lymphatic Blood capillaries tory disorders, obesity, long vessels around lymphatic tion of mosquitoes or fleas may in nodule standing venous insufficien- rare cases produce an inflammatory cy (phlebolymphedema) secondary lymphedema similar in Figure 3: Lymph node. Source: www.anatomynote.com and other chronic forms of appearance to elephantiasis. In pa- Used with permission, 2018 lymphatic overload.2,5–7 Continued on page 111 AUGUST 2018 | PODIATRY MANAGEMENT www.podiatrym.com WOUND MANAGEMENT Lymphedema (from page 110) tance to infection and inflammation, and an increased risk of carcinogen- tients with chronic lymphedema or in esis. Prolonged lymphostasis leads to the later stages of venous insufficien- a state of chronic localized inflamma- cy, there is an increased risk for recur- tion. Another term, lymphostatic der- rent cellulitis and erysipelas infections. mopathy, refers to the changes in the Cellulitis is a common complication in skin that result in a failure of the skin those who have undergone inguinal as an immune organ (Figure 4).15 lymphadenectomy and have developed subsequent lower extremity lymph- Signs and Symptoms edema. Cellulitis can also be a risk Lymphedema is assessed using factor for the onset and progression of several staging systems, the most pop- lymphedema in patients with chronic ular of which is the International
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