Peripheral edema

Last updated: July 31, 2024

Summary

Peripheral edema is the accumulation of excess fluid in the tissues, particularly in the feet and legs. Although peripheral edema is often a manifestation of underlying systemic diseases, including heart failure, kidney disease (e.g., nephrotic syndrome), and cirrhosis, it can also result from localized issues such as chronic venous insufficiency or lymphatic obstruction and is a common side effect of some medications (e.g., calcium channel blockers). Peripheral edema manifests with swelling of the affected areas, which may be accompanied by skin tightness, discomfort, and, in severe cases, pain. Diagnosis involves a thorough patient history and physical examination, supported by laboratory tests and imaging studies to identify the underlying cause. Management strategies are primarily directed at treating the root cause of the edema, while symptoms can be relieved with limb elevation, compression therapy, and diuretics when fluid overload is a contributing factor.

Pulmonary edema, pleural effusion, ascites, angioedema, and cerebral edema are discussed in separate articles.

Definitions

Edema: abnormal fluid accumulation in the interstitium due to an imbalance in fluid homeostasis caused by either decreased absorption or increased secretion of fluid in the interstitium
Peripheral edema: excess fluid in tissues perfused by the peripheral vascular system
- Dependent edema: the accumulation of fluid in the interstitial space in areas of the body influenced by gravity, e.g., the lower limbs in ambulatory individuals and the sacral area in patients who are not ambulatory
- Pitting edema: residual indentation following the application of pressure to the site of the swelling
- Nonpitting edema: no residual indentation following the application of pressure to the site of swelling

Pitting edema of lower leg Pretibial myxedema

Etiology

Common etiologies by mechanism ^[1]^[2]

Some causes of peripheral edema (e.g., pregnancy, cirrhosis) have more than one pathophysiological mechanism. See “Capillary fluid exchange” for more information on vascular physiology.

Increased capillary pressure
- Chronic venous insufficiency
- Heart failure
- Medications, e.g., calcium channel blockers
- Pregnancy
- Deep vein thrombosis
- Postthrombotic syndrome
- Cirrhosis
Decreased oncotic pressure: resulting from protein deficiency (mainly hypoalbuminemia)
Increased capillary permeability
- Inflammation
- Infection
- Toxins
- Burns
- Allergic reaction
- Trauma
Lymphatic obstruction: lymphedema
Other: myxedema
- Hypothyroidism (generalized edema)
- Hyperthyroidism (typically pretibial myxedema)

The etiology of peripheral edema is often multifactorial. ^[3]

Capillary fluid exchange

Common etiologies by site and acuity

Etiologies of bilateral vs. unilateral peripheral edema ^[3]^[4]^[5]
	Bilateral	Unilateral
Acute (< 72 hours) ^[3]	Acute heart failure Medications Nephrotic syndrome Acute kidney injury Acute decompensated cirrhosis Bilateral or proximal DVT IVC thrombosis or tumor	Unilateral DVT Superficial thrombophlebitis Cellulitis Inflammation or infection Burns Allergic reaction Trauma Insect bites and stings Ruptured popliteal cyst
Subacute (3 days to 3 months) ^[3]
Chronic (> 3 months) ^[3]	Chronic venous insufficiency Heart failure Nephrotic syndrome Cirrhosis Medications Pulmonary hypertension Malnutrition, malabsorption Immobility Pregnancy Lymphedema Obstructive sleep apnea (OSA) Thyroid disease	Chronic venous insufficiency Postthrombotic syndrome Complex regional pain syndrome Lymphedema Iliac vein compression Gastrocnemius weakness ^[5]

Medications that cause edema ^[2]^[3]

The following list includes medications that commonly cause edema. It is not exhaustive.

Subtypes and variants

Anasarca

Extreme generalized peripheral edema
Typically caused by systemic illness, e.g., liver failure, nephrotic syndrome, heart failure, or severe malnutrition

Periorbital edema

Edema of the soft tissues that surround the orbital cavity
Usually secondary to trauma, inflammation, protein deficiency (e.g., nephrotic syndrome), or malignancy

Lipedema ^[6]

Definition: loose connective tissue disease characterized by the excessive accumulation of nodular and fibrotic fat, primarily in the limbs, hips, and buttocks
Epidemiology: occurs almost exclusively in women
Clinical features
- Symmetrical nonpitting swelling
- Pain, and tenderness in the affected areas
- Spares hands and feet
Management includes:
- Weight loss programs: i.e., diet, exercise, and/or bariatric surgery ^[6]
- Compression garments
- Surgical removal (e.g., liposuction)

Clinical evaluation

Medical history ^[3]^[4]^[5]

History of present illness
- Location
- Onset, and tempo
- Exacerbating and alleviating factors
- Associated pain
  - Edema from systemic causes: usually painless; sometimes manifests with discomfort and difficulty walking
  - Chronic edema: Peripheral polyneuropathy may occur.
Evaluation of risk factors
- Risk factors for DVT
- Medications that cause edema
- History of injury, radiation, or surgery to affected limb(s)

Physical examination ^[3]

Peripheral edema
- Location and symmetry of edema
- Examination for pitting edema
Skin changes
- Clinical features of chronic venous insufficiency, e.g., stasis dermatitis
- Erythema, warmth
- Myxedema, e.g., scaly nodules and plaques with orange-peel appearance
- Ecchymosis
Signs of systemic disease, e.g., heart failure, cirrhosis, nephrotic syndrome

Pitting edema of lower leg Cellulitis Pretibial myxedema Ruptured popliteal (Baker) cyst

Diagnosis

Approach ^[3]^[4]

Unilateral edema

The approach depends on the duration:

≤ 3 months (i.e., acute and subacute peripheral edema):
- Follow the diagnostic approach for suspected lower-extremity DVT.
- Consider evaluation for other etiologies based on clinical suspicion, e.g.:
  - Cellulitis
  - Trauma, e.g., tibial fracture, ankle fracture, ankle sprain, compartment syndrome
  - Ruptured popliteal cyst
> 3 months (i.e., chronic peripheral edema): Perform diagnostic studies for chronic venous insufficiency.

Unilateral edema does not require a workup for a systemic cause. ^[5]

Bilateral edema

Initial evaluation: Evaluate for common causes of peripheral edema based on clinical suspicion.
Further evaluation (once systemic causes are ruled out):
- Perform diagnostic studies for chronic venous insufficiency.
- Assess for lymphedema.
- Consider IVC thrombosis in patients with risk factors (e.g., malignancy, thrombophilia).

Laboratory studies ^[3]^[4]

Obtain as indicated to evaluate for systemic causes of peripheral edema.

CMP: liver and/or kidney disease
TFTs: hyperthyroidism or hypothyroidism
BNP: heart failure
Urine protein/creatinine ratio: proteinuria and nephrotic syndrome

Imaging ^[3]^[4]

Duplex ultrasound (preferred)
- Allows for viewing of venous anatomy, patency, and valve function
- Indications
  - Suspected DVT in patients with intermediate or high PTP, or low PTP with positive D-dimer
  - Lower extremity edema with negative workup for other causes
CT or MRI with contrast: if additional imaging is required after duplex ultrasound
Venography with intravascular ultrasound
- If previous imaging was inconclusive
- Also used for endovascular treatments
Lymphoscintigraphy: if lymphedema diagnosis remains uncertain after clinical evaluation

The site of imaging (e.g., lower extremity, pelvis, abdomen) is based on suspected pathology.

Common causes

Common causes of peripheral edema ^[3]^[5]
Condition	Distinguishing clinical features	Diagnostic findings	Management
Chronic venous insufficiency (most common cause)	Chronic, bilateral pitting edema (may be unequal) Typically spares the toes and feet Clinical features of chronic venous insufficiency	Venous duplex ultrasound: reflux or obstruction in leg veins CT or MR venography may be performed if duplex ultrasound is inconclusive.	Treatment of chronic venous insufficiency, e.g.: Elevation Exercise Venous compression therapy Vein ablation therapies or surgery if indicated
Heart failure	Bilateral pitting edema (may be acute or chronic) ↑ JVP Hepatojugular reflux Clinical features of heart failure	Echocardiogram: ↓ ejection fraction ↑ BNP	Guideline-directed medical therapy
Lymphedema	Unilateral or bilateral (may be unequal) Pitting edema in acute stage Nonpitting hyperkeratotic skin in chronic disease Dorsal feet and toes affected Usually develops after injury, surgery, radiation, or infection	Lymphoscintigraphy: lymphatic flow disruption ^[3]	Conservative management (first-line), e.g.: Manual lymphatic drainage Compression garments Skincare Surgical management, e.g., liposuction, for refractory disease ^[7] See “Management of lymphedema.”
Nephrotic syndrome	Bilateral pitting edema (may be acute or chronic) Periorbital edema typically occurs first. Clinical features of nephrotic syndrome	Urine Urine protein: creatinine > 3.5 g/g Nephrotic sediment Blood ↑ Creatinine and/or ↑ BUN ↓ Serum albumin and protein	Treatment of nephrotic syndrome, e.g.: Immunosuppressants Sodium and protein restriction Diuretics
Cirrhosis	Bilateral pitting edema (may be acute or chronic) Clinical features of cirrhosis	Elevated transaminases ↑ ALP, bilirubin, GGT, INR Thrombocytopenia, anemia, leukopenia ↓ Albumin, ↓ total protein Abdominal Doppler ultrasound: nodular liver See “Diagnostics for cirrhosis.”	Treatment of cirrhosis, e.g.: Avoidance of hepatotoxic substances Sodium restriction Diuretics
Medication-induced edema	Bilateral pitting edema (may be acute or chronic) Recent initiation of a medication that causes edema	Clinical correlation with offending medication	Discontinue or reduce the dose of offending medication if possible.
Acute DVT	Acute unilateral pitting edema Clinical features of DVT	Doppler ultrasound: vein obstruction	Anticoagulation for DVT
Graves disease	Chronic bilateral pretibial myxedema Clinical features of thyrotoxicosis	↓ TSH, ↑ free T4	Symptomatic therapy for thyrotoxicosis, e.g., beta blockers Definitive therapy for hyperthyroidism and thyrotoxicosis, e.g.: Methimazole Radioactive iodine ablation
Hypothyroidism	Chronic generalized myxedema Doughy skin texture, puffy appearance Clinical features of hypothyroidism	↑ TSH, ↓ free T4	Management of hypothyroidism, e.g., levothyroxine replacement
Pulmonary hypertension	Bilateral pitting edema Exertional dyspnea and/or syncope Loud and palpable split S2 ↑ JVP Symptoms of right heart failure Nail clubbing Clinical features of pulmonary hypertension	Echocardiogram: right ventricular pressure overload and/or failure	Treatment of pulmonary hypertension
OSA	Bilateral pitting edema Restless sleep with waking, gasping, or choking Loud, irregular snoring with apneic episodes Excessive daytime sleepiness Clinical features of obstructive sleep apnea	Positive STOP-BANG screening ↑ Apnea-hypopnea index on polysomnography	Management of OSA, e.g., continuous positive airway pressure

Unilateral edema is usually caused by venous or lymphatic conditions, while bilateral edema is usually caused by systemic conditions. ^[3]

Edema Chronic venous insufficiency Lymphedema following hysterectomy Periorbital edema Deep vein thrombosis (DVT) Pretibial myxedema

Management

Treat the underlying condition.
Discontinue or reduce dose of causative medications, if possible.
Encourage lifestyle modifications.
- Exercise
- Elevation of legs when seated
- Weight loss if indicated
Initiate venous compression therapy. ^[5]
Prescribe diuretic therapy to treat systemic fluid overload, e.g., in heart failure, cirrhosis, or nephrotic syndrome. ^[4]

Diuretics are not indicated for nonsystemic causes of peripheral edema, e.g., lymphedema. ^[4]

Compression therapy (> 20 mm Hg) is contraindicated in patients with peripheral artery disease with an ankle-brachial index < 0.7. Always measure an ankle-brachial index before starting compression therapy. ^[4]^[5]

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