Edema is a frequent manifestation of systemic illness resulting in maldistribution of total body water. Total body water is divided into intracellular (two-thirds) and extracellular (one-third) compartments. The extracellular compartment is further divided into plasma (one-fourth) and interstitial fluid (three-fourths). Edema is characterized by excess fluid accumulation in the interstitial compartment and occurs because of an imbalance of capillary hemodynamics as a result of one or more of the following mechanisms: increased oncotic pressure of the interstitial space, increased intravascular hydrostatic pressure, increased permeability of the endothelial barrier, decreased oncotic pressure within the capillary, or poor lymphatic drainage.^1,2 Although edema is often localized to the extremities, fluid may also accumulate throughout the entire body (anasarca).²

Although limited data are available on the prevalence of lower-extremity edema, recent estimates indicate that approximately 20% of adults older than 50 years have edema.³ Peripheral edema is a common finding in primary care and can be diagnostically challenging. Edema may be a sign of unrecognized systemic disease and can result in functional impairment. Although often characterized as edema, lipedema is more correctly described as maldistribution of fat in the extremities.⁴ This article focuses on diagnosing and treating localized edema, particularly in the lower extremities.

History and Physical Examination

A detailed history can help narrow the differential diagnosis of edema. Time course and location of symptoms should be determined to help stratify patients based on chronic (more than three months) or acute/subacute (less than three months) edema, as well as unilateral or bilateral edema⁵ (Table 1^5–7). The presence of pain suggests deep venous thrombosis (DVT), chronic venous insufficiency (CVI), or complex regional pain syndrome. Patients with CVI report aching and heaviness of extremities.⁸ Edema that worsens with prolonged standing suggests an underlying venous etiology. The presence of dyspnea or orthopnea should prompt consideration for congestive heart failure (CHF), whereas heat intolerance, fatigue, and weight loss may suggest Graves disease.^5–7

Risk factors for DVT should be assessed, including a history of venous thromboembolism, active malignancy, immobilization, or recent surgery.⁹ Previous radiation or surgery to an extremity may disrupt lymphatic drainage, resulting in lymph-edema.⁴ A comprehensive review of the patient’s medication list is essential because medications may cause or contribute to edema (Table 2).^5–7,10

On physical examination, nonpitting edema suggests pretibial myxedema or later stages of lymphedema, whereas pitting edema is associated with CVI, DVT, or early lymphedema. Pitting edema has been classically graded on a 1 to 4 scale based on depth and rebound time; however, this scale lacks reliability and reproducibility.¹¹ Erythema and tenderness suggest DVT, superficial venous thrombosis, cellulitis, or stasis dermatitis. Lipedema is typically tender, whereas lymphedema often is not. Bilateral lower-extremity edema that spares the dorsum of the feet is highly suggestive of lipedema⁴ (Figure 1). Stemmer sign, the inability to pinch up a fold of skin of the dorsal second toe, is pathognomonic for advanced lymphedema.⁴ Skin changes such as stasis dermatitis, hyperpigmentation, medial ankle ulceration, or lipodermatosclerosis (inflammation of subcutaneous fat leading to hyperpigmentation and thickening) are seen in CVI⁸ (Figure 2). Prominent venous vessels such as telangiectasias, reticular veins, and varicose veins are also common in CVI.⁸ Hyperkeratosis or verrucous lesions are suggestive of lymphedema⁴ (Figure 3¹²). Crescent-shaped ecchymosis of the ankle may suggest a ruptured Baker (popliteal) cyst or gastrocnemius muscle.⁷ The presence of an S3 heart sound (positive likelihood ratio [LR+] = 11.0), abdominojugular reflux (LR+ = 6.4), or jugular venous distention (LR+ = 5.1) increases the likelihood of CHF.¹³ Common findings for cirrhosis include ascites (LR+ = 7.2) and spider nevi (LR+ = 4.3).¹⁴