2-07: Lower Extremity Edema

Acute and chronic lower extremity edema present important diagnostic and treatment challenges. Chronic edema and lymphedema are underrecognized conditions. Lower extremities can swell in response to increased venous or lymphatic pressures, decreased intravascular oncotic pressure, increased capillary leak, and local injury or infection. Chronic venous insufficiency is by far the most common cause, affecting up to 2% of the population, and the incidence of venous insufficiency has not changed over the past 25 years. Venous insufficiency is a common complication of DVT; however, only a small number of patients with chronic venous insufficiency report a history of this disorder. Venous ulceration commonly affects patients with chronic venous insufficiency, and its management is labor-intensive and expensive. Normal lower extremity venous pressure (in the erect position: 80 mm Hg in deep veins, 20–30 mm Hg in superficial veins) and cephalad venous blood flow require competent bicuspid venous valves, effective muscle contractions, normal ankle range of motion, and normal respirations. When one or more of these components fail, venous hypertension may result. Chronic exposure to elevated venous pressure by the postcapillary venules in the legs leads to leakage of fibrinogen and growth factors into the interstitial space, leukocyte aggregation and activation, and obliteration of the cutaneous lymphatic network.

A. Symptoms and Signs

1. Unilateral lower extremity edema

Among common causes of unilateral lower extremity swelling, DVT is the most life-threatening. Clues suggesting DVT include a history of cancer, recent limb immobilization, or confinement to bed for at least 3 days following major surgery within the past month (Table 2–4). Adults with varicose veins have a significantly increased risk of DVT. Lower extremity swelling and inflammation in a limb recently affected by DVT could represent anticoagulation failure and thrombus recurrence but more often are caused by postphlebitic syndrome with valvular incompetence. A search for alternative explanations is equally important in excluding DVT. Other causes of a painful, swollen calf include cellulitis, musculoskeletal disorders (Baker cyst rupture [“pseudothrombophlebitis”]), gastrocnemius tear or rupture, calf strain or trauma, and left common iliac vein compression (May-Thurner syndrome), as well as other sites of nonthrombotic venous outflow obstruction, such as the inguinal ligament, iliac bifurcation, and popliteal fossa. Swelling of the ankle can be a manifestation of Charcot neuropathic osteoarthropathy.

2. Bilateral lower extremity edema

Bilateral involvement and significant improvement upon awakening favor systemic causes (eg, venous insufficiency) and can be presenting symptoms of volume overload (HF, cirrhosis, kidney disease [eg, nephrotic syndrome]). The sensation of “heavy legs” is the most frequent symptom of chronic venous insufficiency, followed by itching. Chronic exposure to elevated venous pressure accounts for the brawny, fibrotic skin changes observed in patients with chronic venous insufficiency as well as the predisposition toward skin ulceration, particularly in the medial malleolar area. Pain, particularly if severe, is uncommon in uncomplicated venous insufficiency.

Lower extremity swelling is a familiar complication of therapy with calcium channel blockers (particularly felodipine and amlodipine), pioglitazone, gabapentin, and minoxidil. Prolonged airline flights (longer than 10 hours) are associated with edema even in the absence of DVT. Lymphedema and lipedema are other causes of bilateral lower extremity edema. Pelvic congestion syndrome worsens symptoms of chronic venous symptoms of the lower extremities.

B. Physical Examination

Physical examination should include assessment of the heart, lungs, and abdomen for evidence of pulmonary hypertension (primary or secondary to chronic lung disease), HF, or cirrhosis. Some patients with cirrhosis have pulmonary hypertension without lung disease. There is a spectrum of skin findings related to chronic venous insufficiency that depends on the severity and chronicity of the disease, ranging from hyperpigmentation and stasis dermatitis to abnormalities highly specific for chronic venous insufficiency: lipodermatosclerosis (thick, brawny skin; in advanced cases, the lower leg resembles an inverted champagne bottle) and atrophie blanche (small depigmented macules within areas of heavy pigmentation). The size of both calves should be measured 10 cm below the tibial tuberosity and pitting and tenderness elicited. Leg edema may also be measured by ultrasonography with a gel pad if physical examination is equivocal. Swelling of the entire leg or of one leg 3 cm more than the other suggests deep venous obstruction. The left calf is normally slightly larger than the right as a result of the left common iliac vein coursing under the aorta.

An ulcer located over the medial malleolus is a hallmark of chronic venous insufficiency but can be due to other causes. Shallow, large, modestly painful ulcers are characteristic of venous insufficiency, whereas small, deep, and more painful ulcers are more apt to be due to arterial insufficiency, vasculitis, or infection (including cutaneous diphtheria). Diabetic vascular ulcers, however, may be painless. When an ulcer is on the foot or above the mid-calf, causes other than venous insufficiency should be considered.

The physical examination is usually inadequate to distinguish lymphedema from venous insufficiency. Sensitivity and specificity of clinical signs in predicting lymphoscintigraphy-confirmed lymphedema were 17% and 88%, respectively. Only the Kaposi-Stemmer sign (the inability to pinch or pick up a fold of skin at the base of the second toe because of its thickness) was a significant predictor of lymphedema (odds ratio, 7.9; P = 0.02).

C. Diagnostic Studies

Patients without an obvious cause of acute lower extremity swelling (eg, calf strain) should have an ultrasound performed, since DVT is difficult to exclude on clinical grounds. A prediction rule allows a clinician to exclude a lower extremity DVT in patients without an ultrasound if the patient has low pretest probability for DVT and a negative sensitive D-dimer test (the “Wells prediction rule”). It is important to ensure a follow-up venous ultrasound is done if the first one incompletely assesses all lower extremity veins. The diagnostic study of choice to detect chronic venous insufficiency due venous incompetence is duplex ultrasonography. Assessment of the ankle-brachial pressure index (ABPI) is important in the management of chronic venous insufficiency, since peripheral arterial disease may be exacerbated by compression therapy. This can be performed at the same time as ultrasound. Caution is required in interpreting the results of ABPI in older patients and diabetics due to the decreased compressibility of their arteries. A urine dipstick test that is strongly positive for protein can suggest nephrotic syndrome, and a serum creatinine can help estimate kidney function. Lymphoscintigraphy can be used to confirm a clinical suspicion of lymphedema. Ambulatory sensors for measuring circumference of lower limbs to assist management of chronic venous insufficiency and lymphedema are being developed.

Treatment of lower extremity edema should be guided by the underlying cause. See relevant chapters for treatment of edema in patients with HF (Chapter 10), nephrosis (Chapter 22), cirrhosis (Chapter 16), and lymphedema and venous stasis ulcers (Chapter 12). Edema resulting from calcium channel blocker therapy responds to concomitant therapy with ACE inhibitors or angiotensin receptor blockers.

In patients with chronic venous insufficiency without a comorbid volume overload state (eg, HF), it is best to avoid diuretic therapy. These patients have relatively decreased intravascular volume, and administration of diuretics may first enhance sodium retention through increased secretion of renin and angiotensin and then result in acute kidney injury and oliguria. Instead, the most effective treatment involves (1) leg elevation, above the level of the heart, for 30 minutes three to four times daily, and during sleep; (2) compression therapy; and (3) ambulatory exercise to increase venous return through calf muscle contractions. There is no evidence for benefit or harm of valvuloplasty in the treatment of patients with deep venous insufficiency secondary to primary valvular incompetence.

A wide variety of stockings and devices are effective in decreasing swelling and preventing ulcer formation. They should be put on with awakening, before hydrostatic forces result in edema. To control simple edema, 20–30 mm Hg compression is usually sufficient, whereas 30–40 mm Hg compression is usually required to control moderate to severe edema associated with ulcer formation. To maintain improvement, consider switching from an elastic stocking to one made of inelastic grosgrain material. Patients with decreased ABPI should be managed in concert with a vascular surgeon. Compression stockings (12–18 mm Hg at the ankle) are effective in preventing edema and asymptomatic thrombosis associated with long airline flights in low- to medium-risk persons. Support stockings are recommended for pregnant women during air travel. For lymphedema, bandaging systems applied twice weekly can be effective. Multi-component compression bandaging may offer additional benefit. Short-term manual lymphatic drainage treatment may improve chronic venous insufficiency severity, symptoms, and quality of life. For patients with reduced mobility and leg edema, intermittent pneumatic compression treatment can reduce edema and improve ankle range of motion.

Liposuction, suction-assisted lipectomy, and subcutaneous drainage may have treatment benefit if conservative measures fail in treatment of lymphedema. Balneotherapy may result in a moderate improvement in pain, quality of life and skin pigmentation changes, but no clear effect on disease severity signs and symptoms score, adverse effects, leg ulcers and edema when compared with no treatment.

• Refer patients with chronic lower extremity ulcerations requiring specialist wound care.

• Refer patients with nephrotic syndrome to a nephrologist.

• Refer patients with coexisting severe arterial insufficiency (claudication) that would complicate treatment with compression stockings to a vascular surgeon.

• Pending definitive diagnosis in patients at high risk for DVT despite normal lower extremity ultrasound.

• Severe, acute swelling raising concern for an impending compartment syndrome.

• Severe edema that impairs ability to ambulate or perform activities of daily living.