Causes of Peripheral Edema
Peripheral edema is primarily caused by four major pathophysiological mechanisms: sodium/water retention, precapillary vasodilation, increased capillary permeability, and lymphatic insufficiency, with cardiac, hepatic, and renal diseases being the most common underlying conditions. 1
Primary Causes by System
Cardiovascular Causes
- Heart failure: One of the most common causes of peripheral edema
- Right heart failure leads to increased central venous hypertension
- Biventricular failure
- Heart failure with preserved ejection fraction
- Results in increased capillary permeability and plasma volume expansion 1
Hepatic Causes
- Cirrhosis: Causes decreased protein synthesis and decreased plasma oncotic pressure
- Leads to increased systemic venous hypertension and capillary permeability
- Often presents with ascites when severe 1
Renal Causes
- Nephrotic syndrome: Increased protein loss leading to decreased plasma oncotic pressure
- Renal failure: Increased plasma volume through sodium/water retention 1
Endocrine Causes
- Thyroid disorders: Hypothyroidism (myxedema)
- Adrenal disorders: Abnormal water excretion and hyponatremia 1
Medication-Induced Peripheral Edema
Vasodilatory Medications
- Calcium channel blockers (CCBs):
Medications Causing Sodium/Water Retention
- NSAIDs: Inhibit prostaglandin synthesis leading to sodium retention
- Corticosteroids: Promote sodium and water retention
- Thiazolidinediones: Cause fluid retention, particularly when combined with insulin therapy 1
Other Medications
- Gabapentinoids: Can cause peripheral edema
- Minoxidil: Potent vasodilator causing edema
- Estrogens/Hormonal therapies: Can cause fluid retention 4
Other Important Causes
Venous/Lymphatic
- Chronic venous insufficiency: Common cause of bilateral lower extremity edema
- Deep vein thrombosis: Causes acute unilateral edema
- Lymphedema: Primary or secondary to obstruction, surgery, or infection 5
Miscellaneous Causes
- Obstructive sleep apnea: Increases pulmonary vascular resistance leading to increased capillary hydrostatic pressure 1
- Pregnancy: Increased plasma volume
- Premenstrual edema: Hormonal fluctuations causing fluid retention 1
- Malnutrition/Malabsorption: Decreased protein synthesis and decreased plasma oncotic pressure 1
- Allergic causes: Angioedema and urticaria from increased capillary permeability 1
- Idiopathic edema: Diagnosis of exclusion
Clinical Pearls and Pitfalls
- Bilateral vs. unilateral presentation: Bilateral edema typically suggests systemic causes (cardiac, renal, hepatic), while unilateral edema suggests local causes (DVT, lymphatic obstruction) 1, 5
- Timing matters: Acute onset edema requires more urgent evaluation than chronic edema
- Medication review is essential: Always review patient's medication list as a potential cause of edema 4, 2
- Nonthrombotic iliac vein lesions (NIVL) typically cause asymmetrical swelling and rarely present with symmetrical bilateral edema 1
- Heart failure edema signs: Often accompanied by elevated jugular venous pressure, which is the most reliable sign of volume overload 1
Diagnostic Approach
- Assess chronicity and laterality of edema to guide evaluation
- Review medications thoroughly for potential causes
- Basic laboratory testing:
- Basic metabolic panel
- Liver function tests
- Thyroid function tests
- Brain natriuretic peptide (BNP) levels
- Urine protein/creatinine ratio 5
- Imaging studies based on suspected cause:
- Echocardiography for suspected heart failure
- Duplex ultrasonography for chronic venous insufficiency
- Compression ultrasonography for suspected DVT
- Lymphoscintigraphy if lymphedema diagnosis is unclear 5
Remember that peripheral edema is a clinical sign, not a diagnosis, and identifying the underlying cause is essential for appropriate management.