Lymphedema is an imbalance between lymphatic fluid formation and lymphatic fluid absorption, representing a high-output or low-output failure of the lymphatic system or a combination of both. The increase of interstitial fluid leads to a cascade of remodeling that leads to permanent changes in the tissues of the affected limb [1–3, 7].

High-output failure (also known as dynamic insufficiency) occurs when excessive lymphatic fluid formation exceeds the transport capacity of the intact lymphatic system. Increases in lymphatic fluid production may arise when Starling forces shift net pressure to favor the flow of fluid into the interstitium. Increases in venous pressure result in increased hydrostatic pressure within the venules, and capillaries increase the driving force for ultrafiltration [1–3]. The loss of oncotic pressure, as seen in hypoproteinemic states such as malnutrition, has a similar effect. Elevated venous pressure occurs in patients with right heart failure, deep vein thrombosis, and venous insufficiency. Local inflammation increases capillary permeability, accelerating the loss of fluid and plasma proteins into the interstitium [1–3].

In contrast, low-output failure (also known as mechanical insufficiency) occurs when there is injury or impairment of the lymphatic system due to paralysis, obstruction, or inadequacy of the lymphatics (e.g., lymphedema from filarial lymphatic obstruction or congenital hypoplasia) [1–3]. As lymphatic obstruction progresses, tortuosity, dilatation, and pooling of lymphatic fluid give way to massive ectasia, valvular destruction, retrograde lymph flow, and lymph coagulation. Intrinsic truncal contractions fail; intraluminal valves give way, and hydrostatic pressure increases in the superficial valveless lymphatic watersheds. Chronic inflammation results in mast cell infiltration, disruption of the interstitial elastin fiber network, intense lymphangiogenesis and hemangiogenesis, fibrosis, progressive fat deposits, and skin thickening [1–3].

Dermal edema is the hallmark of lymphedema and represents the earliest clinical manifestation of lymphatic impairment [1, 2]. The presence of dilated lymphatic vessels may also be evident. With prolonged lymphatic impairment, tissue changes include fibroplasia, hyperkeratosis, and increases in stromal cells. In addition, elastic tissue fragmentation, clumping, and loss of mature elastic fibers also occur. Abundant subcutaneous fat becomes a predominant component of the swelling seen in the affected limb [3, 7].

The inflammatory cells present in the edematous tissue contribute to the ongoing fibrosis. It is believed that the inflammatory cells fail to migrate to the lymph nodes due to impaired lymphatic transport and dysfunctional lymphangiogenesis, leading to worsening edema and further inflammation. This ultimately results in impaired immune trafficking and decreased clearance of pathogens [1, 2].

Lymphedema is a progressive and usually painless swelling of the limbs or genitals that is the result of decreased transport capacity of the lymphatic system. Lymphedema can be primary or secondary. Primary lymphedema is due to a defect in the lymph conducting pathways. Secondary lymphedema is due to an acquired cause (such as filariasis, previous surgery, radiation therapy, malignancy, infection, and inflammation) that results in injury and impairment of the lymphatic system (Fig. 23.3) [2–4, 7, 8].

Regardless of the etiology, lymphedema is clinically staged by the extent of visible tissue degradation (Table 23.1) [9–12]. In the early stages of lymphedema (stage I), the associated limb swelling resembles other types of edema such as that seen with congestive heart failure, renal insufficiency, and venous disease. At this stage, the swelling is completely relieved with elevation and/or overnight rest. The tissues are soft and usually pitting with no evidence of fibrosis. As the condition progresses (stage II), the edema is no longer relieved with elevation or rest, and skin changes begin to appear such as induration of the skin and progressive hardening. The edema also becomes nonpitting. In the late, chronic stage of lymphedema (stage III), the edema is severe, and the skin is fibrotic with numerous skin changes that include hyperkeratosis, warty projections, cobblestoning, and lichenification (Fig. 23.4). Stage III lymphedema is also known as “elephantiasis” because the affected limb begins to resemble the leg of an elephant [9, 10, 13].

In patients with primary lymphedema, the cause of decreased lymphatic transport can be an intrinsic “defect” or a malfunction of the lymph conducting elements, which is believed to be a genetically determined abnormality of lymph drainage [2]. The majority of lymphedemas classified as primary lymphedema have inborn abnormalities of the lymphatic system that manifest mostly with irregular or abnormal structural development caused by abnormal (mutant) genes [2, 11]. These abnormalities result in lymphatic hypoplasia, aplasia, numerical hyperplasia, or dilation (lymphangiectasia) with valvular incompetence [2, 11].

Primary lymphedemas have been classified into three groups, depending on the age of onset: congenital (before age 2), praecox (onset between ages 2 and 35), and tarda (after age 35). Lymphedema praecox is the most common form of primary lymphedema with a female to male ratio of 10:1. It is usually unilateral and often limited to the foot and calf in most patients (Fig. 23.3) [2, 8, 11].

Secondary lymphedema is far more common than primary lymphedema and represents 90 % of cases of lymphedema. The most common causes of lower extremity lymphedema are tumor (e.g., lymphoma, prostate cancer, ovarian cancer), surgery involving the lymphatics, radiation therapy, obesity, trauma, and infection. Worldwide, infection with the parasitic nematode Wuchereria bancrofti (also known as filariasis) is the most common cause of lymphedema (Fig. 23.3) [2, 4, 8].