Approach to Leg Edema of Unclear Etiology

John W. Ely, MD, MSPH; Jerome A. Osheroff, MD; M. Lee Chambliss, MD, MSPH; Mark H. Ebell, MD, MS


J Am Board Fam Med. 2006;19(2):148-160. 

In This Article


Venous Insufficiency

Chronic venous insufficiency is treated with leg elevation and knee-high compression stockings that provide 30 to 40 mm Hg pressure at the ankle.[2,37,38,39,40] If arterial insufficiency is a concern, an ankle-brachial index should be performed because compression stockings are contraindicated in arterial insufficiency. Patients who are refractory to compression stockings may improve with intermittent pneumatic compression pumps.[2] Horse chestnut seed extract (300 mg, standardized to 50 mg of escin, twice a day) has been found to be effective in several studies and can be obtained in health food stores.[41,42,43,44] Horse chestnut seed extract contains escin, which inhibits the activity of elastase and hyaluronidase. These enzymes are thought to play a role in the pathophysiology of chronic venous insufficiency.[45] However, the benefits are modest and the agent has not gained widespread acceptance. Diuretics (eg, furosemide 20 to 40 mg once a day with supplemental potassium) can be used for short periods in severely affected patients. However, venous insufficiency is not a volume overload state, and long-term use of diuretics can lead to adverse metabolic complications.[2]

Idiopathic Edema

Spironolactone is considered the drug of choice for idiopathic edema because of the secondary hyperaldosteronism found in patients with this disorder.[31] The starting dose is 50 to 100 mg daily (maximum 100 mg, 4 times daily).[30,46] If spironolactone is not effective, low doses of a thiazide diuretic (eg, hydrochlorothiazide, 25 mg daily) can be added with close monitoring of the serum potassium. It is best to avoid loop diuretics.[30] The diuretic should be given in the early evening because fluid retention is most noticeable at the end of the day. Other measures include intermittent recumbency, avoiding environmental heat, low salt diet, avoiding excessive fluid intake, and weight loss for obese patients.[31] It may be helpful to ask about depression, eating disorder, and surreptitious diuretic or laxative use. Compression stockings are usually not helpful and not tolerated. Many patients with idiopathic edema are already taking diuretics when first seen and may have "diuretic-induced edema."[46,47,48] Chronic use of diuretics may lead to a state of mild hypovolemia with resulting stimulation of the renin-angiotensin-aldosterone system. When the diuretics are withdrawn, a rebound worsening of edema occurs and patients believe they must continue.[49] However, the treatment of suspected diuretic-induced edema is to withdraw diuretics for 3 to 4 weeks after warning the patient that her edema will probably worsen initially and reassuring her that the diuretic can always be restarted. If the edema does not improve after 4 weeks, spironolactone can be initiated at a dose of 50 to 100 mg daily and increased to a maximum of 100 mg, 4 times daily.[30,46]


Nonspecific treatment of lymphedema includes exercise, elevation, compressive garments, manual lymphatic drainage, intermittent pneumatic compression, and surgery (excisional procedures, microsurgery).[13,21,33] Tinea pedis should be controlled, and prophylactic antibiotics may be indicated for recurrent cellulitis. Diuretics are generally not helpful.[13] Treatment of lymphedema is often disappointing, and psychosocial support is important in such patients.

Deep Vein Thrombosis

An acute deep vein thrombosis is generally treated with low molecular weight heparin, such as enoxaparin 1 mg/kg/dose subcutaneously every 12 hours.[50] Warfarin can be initiated simultaneously with heparin, starting with 5 to 10 mg daily for 2 days with subsequent dosage based on a target international normalized ratio range of 2.0 to 3.0. Heparin is continued for at least 5 days (10 days for severe iliofemoral thrombosis). When the international normalized ratio is between 2.0 and 3.0 for 2 days, the heparin can be withdrawn. A platelet count should be obtained on day 3 and day 10 of heparin therapy to rule out heparin-induced thrombocytopenia. The total duration of oral anticoagulation is reviewed elsewhere.[50] If anticoagulation is contraindicated, an inferior vena cava filter may be an option. Thrombolytic agents are generally reserved for patients with phlegmasia cerula dolens, which is manifested by severe pain, bullae formation, and skin discoloration.