Evaluation of Leg Edema

Leg edema can be a bothersome complaint and an initial symptom of serious underlying disease. Acute onset of unilateral swelling raises the question of deep vein thrombosis and thrombophlebitis (DVT), which must be addressed promptly. Bilateral disease is particularly common in the elderly and often attributed to chronic venous insufficiency, congestive heart failure, or venodilating medications; however, pulmonary hypertension may account for as much as one fifth of cases and usually goes unrecognized. Noninvasive methods, particularly venous and cardiac ultrasound, have greatly facilitated evaluation, but the clinical estimation of pretest probability is essential to optimal test selection and interpretation. Especially important to the pretest assessment of unilateral edema is knowledge of the incidence, risk factors, symptoms, and signs of DVT. In bilateral edema, awareness of the potential contributions from often overlooked etiologies (such as pulmonary hypertension, hypoalbuminemia, and use of nonsteroidal anti-inflammatory drugs [NSAIDs]) can inform the clinical assessment and guide workup.

PATHOPHYSIOLOGY AND CLINICAL PRESENTATION (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17)

Edema is defined as an increase in extracellular volume. It develops if hydrostatic pressure exceeds colloid oncotic pressure, capillary permeability increases, or lymphatic drainage becomes impaired. Hydrostatic pressure is a function of intravascular volume, blood pressure, and venous outflow. Colloid
oncotic pressure depends on the serum albumin concentration. Inflammation and thrombosis may follow, especially in the setting of poor venous blood flow and hypercoagulability.

Decreased Oncotic Pressure

Decreased oncotic pressures are usually due to hypoalbuminemia, which can occur secondary to malnutrition, hepatocellular failure, or excess renal or gastrointestinal loss of albumin. The resultant fall in intravascular volume from excessive transudation of fluid stimulates salt retention. This compensatory effort to maintain adequate intravascular volume leads to further edema formation because the underlying oncotic deficit remains. Edema sets in when the serum albumin concentration falls to less than 2.5 g/100 mL. Leg swelling due to hypoalbuminemia is typically bilateral, pitting, and sometimes accompanied by edema of the face and eyelids (especially on awakening).

Increased Hydrostatic Pressure

Increased hydrostatic pressure may result from excessive fluid retention (as seen with congestive heart failure or drugs such as NSAIDs and corticosteroids), impairment of venous outflow from venous valvular incompetence, DVT, or pulmonary hypertension (which may be a consequence of sleep apnea, left heart failure, or chronic obstructive lung disease). Venodilating drugs (such as nifedipine and other calcium-channel blockers) may lead to an increase in hydrostatic pressure as blood pools in the lower extremities. A localized increase in hydrostatic pressure develops in the legs during prolonged standing, especially if the valves in the leg veins are incompetent. Increased hydrostatic pressure due to fluid retention produces bilaterally symmetric edema, whereas swelling due to venous insufficiency may be asymmetric and accompanied by varicosities and other signs of venous disease, such as stasis dermatitis, ulcers, and brawny induration. Unilateral lower leg edema can also result from venous compression by a popliteal (Baker’s) cyst. A stroke that causes paresis in one leg may result in unilateral edema due to reductions in vascular tone and venous and lymphatic drainage; thrombophlebitis may ensue.

Increased Capillary Permeability

Increased capillary permeability is another mechanism of leg edema and is associated with immunologic injury, infection, inflammation, or trauma. A permeability defect is also believed to be responsible for idiopathic edema, a poorly understood but common problem seen almost exclusively in women. Although some patients report a periodicity to the problem that seems to parallel the menstrual cycle, careful studies have failed to find sufficient evidence to warrant the label cyclic edema. The condition is especially aggravated by hot weather and standing, more so than occurs with venous insufficiency. Transient abdominal distention is common, and weight may fluctuate by several pounds over the course of the day. The disorder is not progressive, but it can cause considerable discomfort. It is often accompanied by headache, fatigue, anxiety, and other functional symptoms. Some patients are bothered by nocturia.

Lymphatic Obstruction

Lymphatic obstruction hinders reabsorption of interstitial fluid. The resultant lymphedema presents as swelling that usually starts in the feet and progresses upward. Typically, the problem is unilateral. The edema of lymphatic obstruction tends to have a brawny quality and little pitting, except in its early stages. Recumbence provides only minor relief compared with edema from other causes. Lipedema, fatty deposition in the lower legs, may mimic lymphedema in producing nonpitting ankle swelling.

Inflammation and Hypercoagulability

Inflammation and hypercoagulability make important contributions to development of DVT. Changes in blood flow are believed to play a previously unappreciated role in triggering inflammation in chronic venous disease. Valvular incompetence compromises pulsatile venous flow, limiting the normal shear stresses on endothelial cells that inhibit the release of inflammatory mediators. Such loss of normal pulsatile flow, and especially its reversal, is thought to promote an inflammatory response that enhances the risk of thrombosis in compromised veins.

Hypercoagulability also increases the risk of thrombosis. Acquired hypercoagulability is seen with active cancer (five-to sixfold increase in DVT risk), illnesses associated with the production of antiphospholipid antibodies, recent plaster cast/prolonged immobilization, and recent major surgery (especially of the hip or knee). Even prolonged sitting in cramped conditions as occurs on extended airplane flights in coach seating increases the risk of DVT, mostly in persons with preexisting risk factors.

In a significant proportion of cases, venous thrombosis develops without a clear-cut precipitant. As noted, inflammation leading to phlebitis may ensue from loss of normal pulsatile venous flow. Hereditary hypercoagulability often exacerbates the situation. The most common hereditary contributor to hypercoagulability is factor V Leiden mutation, which is found in heterozygous form in up to 20% of some European populations. Others mutations include deficiency of protein S, protein C, or antithrombin III; prothrombin gene mutation; and homocysteinemia (see Chapter 35). Patients with factor V Leiden mutations have odds ratios for DVT of about 3 if they are heterozygous (a relatively weak risk factor) and 18 if they are homozygous. When the mutation is present in conjunction with other hereditary and acquired risk factors, the absolute 10-year risk of DVT can be as high as 10% in heterozygotes and 50% in homozygotes.

Estrogen and progestin increase the risk of DVT by two- to threefold and are additive to other risk factors such as obesity, factor V Leiden mutation, and age. There is some suggestion that esterified estrogens do not increase the DVT risk compared to conjugated estrogens, but this observation requires confirmation; the addition of progestin negates this beneficial difference.

DVT presentation may be subtle, with acute onset of unilateral or asymmetric leg edema as the only manifestation. Such textbook findings as calf tenderness, palpable cord, and positive Homans’ sign are often absent. Most clots due to thrombophlebitis form in the small veins of the calf; 20% to 30% propagate proximally into the popliteal and femoral veins of the knee and thigh. (Clot below the knee poses little risk of pulmonary embolization (<3%), but that which propagates more proximally increases the risk substantially (upwards of 40%). It may also result from extension of superficial thrombophlebitis—24% prevalence of DVT at the time of initial presentation of superficial thrombophlebitis and 10% risk of extension within 3 months.

The physical findings most indicative of significant DVT are swelling of the entire leg, asymmetric leg edema (>3 cm difference in calf circumferences), pitting edema of the involved leg, tenderness along deep veins, and prominent collateral superficial veins. (A ruptured Baker’s cyst due to osteoarthritis of the knee (see Chapter 152) may mimic DVT by causing acute pain and swelling in the calf and popliteal fossa).

Trousseau’s syndrome, DVT associated with underlying malignancy, accounts for as much as 20% of thromboembolic disease
and 10% of idiopathic or so-called unprovoked cases. In about half of cases, the malignancy is already metastatic at the time of initial DVT presentation. Clinical evidence of malignancy often emerges within a year of DVT. Atypical sites of venous thrombosis (e.g., upper extremity, intra-abdominal, bilateral legs) are characteristic as is recurrent idiopathic thrombosis. Overall mortality is increased twofold.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of edema can be organized according to clinical presentations and pathophysiologic mechanisms (Table 22-1). The list of etiologies for bilateral edema is particularly extensive. In primary care practice, the leading causes of bilateral disease include venous insufficiency, heart failure, pulmonary hypertension, and hypoalbuminemia; pulmonary hypertension is the most commonly missed diagnosis. Certain infiltrative conditions may be mistaken for edema, such as pretibial myxedema seen with hyperthyroidism and lipedema (a familial bilateral deposition of excess fat in the lower extremities). A ruptured Baker’s cyst of the knee may mimic DVT of the calf.

WORKUP (2,3,5,8,9,11, 12 and 13,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 and 34)

Diagnosis of leg edema can be challenging. The initial clinical impression often undergoes revision on laboratory testing, underscoring the difficulty in making an accurate diagnosis on the basis of history and physical examination alone. In a study from primary care practice, venous insufficiency was overdiagnosed clinically and heart failure and pulmonary hypertension markedly underdiagnosed. Nonetheless, attention to clinical features is critical to making the best possible pretest probability assessment, which is essential to test selection and interpretation.

Only gold members can continue reading. Log In or Register to continue